No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Effect of household and community interventions on the burden of tuberculosis in southern Africa: the ZAMSTAR community-randomised trial
Abstract
Southern Africa has had an unprecedented increase in the burden of tuberculosis, driven by the HIV epidemic. The Zambia, South Africa Tuberculosis and AIDS Reduction (ZAMSTAR) trial examined two public health interventions that aimed to reduce the burden of tuberculosis by facilitating either rapid sputum diagnosis or integrating tuberculosis and HIV services within the community.
ZAMSTAR was a community-randomised trial done in Zambia and the Western Cape province of South Africa. Two interventions, community-level enhanced tuberculosis case-finding (ECF) and household level tuberculosis-HIV care, were implemented between Aug 1, 2006, and July 31, 2009, and assessed in a 2×2 factorial design between Jan 9, 2010, and Dec 6, 2010. All communities had a strengthened tuberculosis-HIV programme implemented in participating health-care centres. 24 communities, selected according to population size and tuberculosis notification rate, were randomly allocated to one of four study groups using a randomisation schedule stratified by country and baseline prevalence of tuberculous infection: group 1 strengthened tuberculosis-HIV programme at the clinic alone; group 2, clinic plus ECF; group 3, clinic plus household intervention; and group 4, clinic plus ECF and household interventions. The primary outcome was the prevalence of culture-confirmed pulmonary tuberculosis in adults (≥18 years), defined as Mycobacterium tuberculosis isolated from one respiratory sample, measured 4 years after the start of interventions in a survey of 4000 randomly selected adults in each community in 2010. The secondary outcome was the incidence of tuberculous infection, measured using tuberculin skin testing in a cohort of schoolchildren, a median of 4 years after a baseline survey done before the start of interventions. This trial is registered, number ISRCTN36729271.
Prevalence of tuberculosis was evaluated in 64 463 individuals randomly selected from the 24 communities; 894 individuals had active tuberculosis. Averaging over the 24 communities, the geometric mean of tuberculosis prevalence was 832 per 100 000 population. The adjusted prevalence ratio for the comparison of ECF versus non-ECF intervention groups was 1·09 (95% CI 0·86-1·40) and of household versus non-household intervention groups was 0·82 (0·64-1·04). The incidence of tuberculous infection was measured in a cohort of 8809 children, followed up for a median of 4 years; the adjusted rate ratio for ECF versus non-ECF groups was 1·36 (95% CI 0·59-3·14) and for household versus non-household groups was 0·45 (0·20-1·05).
Although neither intervention led to a statistically significant reduction in tuberculosis, two independent indicators of burden provide some evidence of a reduction in tuberculosis among communities receiving the household intervention. By contrast the ECF intervention had no effect on either outcome.
Bill & Melinda Gates Foundation.
... The global tuberculosis (TB) report reveals a persistent gap between the number of patients identified with active TB and the actual incidence in communities; this is further compounded by the coronavirus disease 2019 (COVID- 19) pandemic. 1 According to this report, despite three decades of efforts to fight the global TB epidemic, 10 million people were living with TB in 2020, but only 5.8 million were diagnosed. ...
... 17,18 Active surveillance for TB is sometimes perceived as expensive and possibly unable to provide value for money. 19,20 This perception is possibly a result of challenges experienced in implementing COPC and additional costs involved in employing and equipping CHW teams that only focus on TB surveillance. 19 However, research shows the cost-effectiveness of CHWs when they work in a generalist and comprehensive approach. ...
... 19,20 This perception is possibly a result of challenges experienced in implementing COPC and additional costs involved in employing and equipping CHW teams that only focus on TB surveillance. 19 However, research shows the cost-effectiveness of CHWs when they work in a generalist and comprehensive approach. 16 The implementation of active surveillance for TB is influenced by factors such as availability of resources, staff experience and motivation as well as collaboration between stakeholders. ...
Background: The high burden of tuberculosis (TB) in South Africa (SA) is associated with uncontrolled transmission in communities and delayed diagnosis of active cases. Active surveillance for TB is provided by community-based services (CBS). Research is required to understand key factors influencing TB screening services in the CBS. This study explored the implementation of active surveillance for TB where community-oriented primary care (COPC) had been successfully implemented to identify these factors.
Methods: This was a qualitative study of four established COPC sites across two provinces in SA where active surveillance for TB is implemented. Semi-structured interviews were conducted with purposively selected healthcare workers in the CBS and citizens in these communities. The recorded interviews were transcribed for data analysis using ATLAS.ti software.
Results: The factors influencing active surveillance for TB were directly related to the major players in the delivery of CBS. These factors interacted in a complex network influencing implementation of active surveillance for TB. Building effective relationships across stakeholder platforms by community health workers (CHWs) was directly influenced by the training, capacity building afforded these CHWs by the district health services; and acceptability of CBS. Each factor interplayed with others to influence active surveillance for TB.
Conclusion: Community health workers were central to the success of active surveillance for TB. The complex interactions of the social determinants of health and TB transmission in communities required CHWs to develop trusting relationships that responded to these issues that have impact on TB disease and linked clients to healthcare.
... We screened 9050 unique abstracts, yielding 361 full-text articles to be assessed for eligibility, of which 314 were excluded. Of the 47 included articles evaluating contact tracing interventions, six were focused on COVID-19 [20][21][22][23][24][25] (table 1), 20 on tuberculosis [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] (table 2), eight on HIV [46][47][48][49][50][51][52][53] (appendix pp [11][12][13][14], 12 on curable STIs (syphilis, [54][55][56] gonorrhea, 57-60 trichomoniasis, 61 23,24,27,[30][31][32][33]35,37,38,[42][43][44][45]49,[51][52][53][54][55]58,62 and two (4·3%) studies (both RCTs on curable STIs 56,63 ) had high risk of bias (appendix pp 7-8). 29 (72·5%) of the 40 studies evaluating the effect of provider-initiated contact tracing, including four (66·7%) of six COVID-19 studies and 11 (68·8%) of 16 RCTs and quasi-RCTs, found contact tracing interventions were associated with improvements in at least one outcome of interest. ...
... 20 studies examined contact tracing for tuberculosis (table 2). [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] These studies included more than 168 000 index patients across a diversity of settings, including urban and rural areas, high-burden and lowerburden areas (in terms of tuberculosis prevalence, incidence, or case notification rate), and all World Bank income levels (appendix pp 9-10). A variety of tracing approaches were described between and within studies, including household contact tracing (17 of 20 studies) 26 [22][23]. ...
... [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] These studies included more than 168 000 index patients across a diversity of settings, including urban and rural areas, high-burden and lowerburden areas (in terms of tuberculosis prevalence, incidence, or case notification rate), and all World Bank income levels (appendix pp 9-10). A variety of tracing approaches were described between and within studies, including household contact tracing (17 of 20 studies) 26 [22][23]. †Other reasons for exclusion were wrong article type (five articles: two conference abstracts, one opinion piece, one clinical trial registration, and one general summary of contact tracing), no separation of outcomes of contact tracing from a broader intervention (one article), only summarising the findings of another study already included in the review (one article), near-identical overlap in study dates, study population, and study results with another study already included in the review (one study), and not having an available manuscript (one study). ...
Background
Contact tracing is used for multiple infectious diseases, most recently for COVID-19, but data regarding its effectiveness in disease control are scarce. To address this knowledge gap and inform public health decision making for COVID-19, we systematically reviewed the existing literature to determine the effectiveness of contact tracing in the control of communicable illness.
Methods
We searched PubMed, Embase, and the Cochrane Library from database inception up to Nov 22, 2021, for published studies evaluating associations between provider-initiated contact tracing for transmissible infectious diseases and one of three outcomes of interest: case detection rates among contacts or at the community level, overall forward transmission, or overall disease incidence. Clinical trials and observational studies were eligible, with no language or date restrictions. Reference lists of reviews were searched for additional studies. We excluded studies without a control group, using only mathematical modelling, not reporting a primary outcome of interest, or solely examining patient-initiated contact tracing. One reviewer applied eligibility criteria to each screened abstract and full-text article, and two reviewers independently extracted summary effect estimates and additional data from eligible studies. Only data reported in published manuscripts or supplemental material was extracted. Risk of bias for each included study was assessed with the Cochrane Risk of Bias 2 tool (randomised studies) or the Newcastle–Ottawa Scale (non-randomised studies).
Findings
We identified 9050 unique citations, of which 47 studies met the inclusion criteria: six were focused on COVID-19, 20 on tuberculosis, eight on HIV, 12 on curable sexually transmitted infections (STIs), and one on measles. More than 2 million index patients were included across a variety of settings (both urban and rural areas and low-resource and high-resource settings). Of the 47 studies, 29 (61·7%) used observational designs, including all studies on COVID-19, and 18 (38·3%) were randomised controlled trials. 40 studies compared provider-initiated contact tracing with other interventions or evaluated expansions of provider-initiated contact tracing, and seven compared programmatic adaptations within provider-initiated contact tracing. 29 (72·5%) of the 40 studies evaluating the effect of provider-initiated contact tracing, including four (66·7%) of six COVID-19 studies, found contact tracing interventions were associated with improvements in at least one outcome of interest. 23 (48·9%) studies had low risk of bias, 22 (46·8%) studies had some risk of bias, and two (4·3%) studies (both randomised controlled trials on curable STIs) had high risk of bias.
Interpretation
Provider-initiated contact tracing can be an effective public health tool. However, the ability of authorities to make informed choices about its deployment might be limited by heterogenous approaches to contact tracing in studies, a scarcity of quantitative evidence on its effectiveness, and absence of specificity of tracing parameters most important for disease control.
Funding
The Sullivan Family Foundation, Massachusetts General Hospital Executive Committee on Research, and US National Institutes of Health.
... We used a novel mixed methods interdisciplinary approach to conduct a secondary analysis of Zambian data sets, collected during a cluster randomised trial (CRT)-the Zambia and South Africa TB and AIDS Reduction study (ZAMSTAR)-and as part of an ancillary study, named the Contact Observations of Daily Activities (CODA). 12 13 The approach combined community level qualitative data, focused on the use of space and daily social interactions, with quantitative measurements of TB prevalence and annual risk of infection (ARI), to investigate whether differences in socio-spatial aspects across communities corresponded to a higher or lower M. tuberculosis transmission efficiency (measured as the ARI per prevalent TB case in a community). ZAMSTAR (2004-2011) compared two interventions to reduce M. tuberculosis transmission and TB prevalence across Zambia and South Africa at a population level. ...
... Details of ZAMSTAR household enumeration, TST data and implied ARI estimates, TB prevalence data and linked methods have been published. 12 14 16 The Zambian communities investigated in this secondary analysis were preselected as a set of 16 for the ZAMSTAR trial. The ZAMSTAR research design needed the potential to detect statistically significant reductions in TB prevalence and infection incidence. ...
... The resulting Zambian ZAMSTAR communities were distributed across 5 provinces and districts with subsequent measures by the ZAMSTAR trial showing that HIV prevalence ranged between 8.1% and 26.6%. 12 All communities were predominantly high-density urban communities (three were peri-urban) located along the line of rail and/or major trading routes. All communities had a broad mix of ethnic groups and four communities had a stronger, yet insignificant presence of non-nationals due to the proximity of international borders and location within the capital city. ...
Objectives
Selected Zambian communities formed part of a cluster randomised trial: the Zambia and South Africa TB and AIDS Reduction study (ZAMSTAR). There was wide variability in the prevalence of Mycobacterium tuberculosis infection and tuberculosis (TB) disease across these communities. We sought to clarify whether specific communities could have been more/less vulnerable to M. tuberculosis transmission as a result of sociological variety relevant to transmission efficiency.
Design
We conducted a mixed methods secondary analysis using existing data sets. First, we analysed qualitative data to categorise and synthesise patterns of socio-spatial engagement across communities. Second, we compared emergent sociological variables with a measure of transmission efficiency: the ratio of the annual risk of infection to TB prevalence.
Setting
ZAMSTAR communities in urban and peri-urban Zambia, spanning five provinces.
Participants
Fifteen communities, each served by a health facility offering TB treatment to a population of at least 25 000. TB notification rates were at least 400 per 100 000 per annum and HIV seroprevalence was estimated to be high.
Results
Crowding, movement, livelihoods and participation in recreational activity differed across communities. Based on 12 socio-spatial indicators, communities were qualitatively classified as more/less spatially crowded and as more/less socially ‘open’ to contact with others, with implications for the presumptive risk of M. tuberculosis transmission. For example, watching video shows in poorly ventilated structures posed a presumptive risk in more socially open communities, while outdoor farming and/or fishing were particularly widespread in communities with lower transmission measures.
Conclusions
A dual dynamic of ‘social permeability’ and crowding appeared relevant to disparities in M. tuberculosis transmission efficiency. To reduce transmission, certain socio-spatial aspects could be adjusted (eg, increasing ventilation on transport), while more structural aspects are less malleable (eg, reliance on public transport). We recommend integrating community level typologies with genome sequencing techniques to further explore the significance of ‘social permeability’.
Trial registration number
ISRCTN36729271 .
... Upstream interventions that can both prevent infection and reduce the intensity of community-wide transmission are critical to ending the TB epidemic. Prior interventions showing an impact on TB transmission were predominantly multi-component TB active case finding interventions [21][22][23][24][25]; however, this study was, to our knowledge, the first to show a population-level impact of a multi-component HIV-specific intervention on incident TB infection, a proxy for community transmission, and an impact on children. Ending the TB epidemic in high HIV and TB burden settings will require multi-factorial interventions that not only scale-up TB specific interventions, such as treating latent TB infection and active TB case finding, but also those addressing the contributing HIV syndemic. ...
... Infection in children is a sentinel of TB transmission, and to our knowledge this study is one of the first to show a population-level impact on incident TB infection in children. The ZAMSTAR trial, a household-based active TB and HIV care intervention in South Africa and Zambia, suggested a reduction of TB transmission as measured by incident TB infection in a TST negative cohort in children, although the effect did not meet statistical significance [25]. Together, findings from the SEARCH and ZAMSTAR trials suggest that community-based interventions focused on adults in the community can reduce TB infection in children. ...
Background
Human immunodeficiency virus (HIV) treatment reduces tuberculosis (TB) disease and mortality; however, the population-level impact of universal HIV-test-and-treat interventions on TB infection and transmission remain unclear.
Methods
In a sub-study nested in the SEARCH trial, a community cluster-randomized trial (NCT01864603), we assessed whether a universal HIV-test-and-treat intervention reduced population-level incident TB infection in rural Uganda. Intervention communities received annual, population-level HIV testing and patient-centered linkage. Control communities received population-level HIV testing at baseline and endline. We compared estimated incident TB infection by arms, defined by tuberculin skin test conversion in a cohort of persons aged 5 and older, adjusting for participation and predictors of infection, and accounting for clustering.
Results
Of the 32 trial communities, 9 were included, comprising 90 801 participants (43 127 intervention and 47 674 control). One-year cumulative incidence of TB infection was 16% in the intervention and 22% in the control; SEARCH reduced the population-level risk of incident TB infection by 27% (adjusted risk ratio = 0.73; 95% confidence interval [CI]: .57–.92, P = .005). In pre-specified analyses, the effect was largest among children aged 5–11 years and males.
Conclusions
A universal HIV-test-and-treat intervention reduced incident TB infection, a marker of population-level TB transmission. Investments in community-level HIV interventions have broader population-level benefits, including TB reductions.
... ACF has been proposed as a way to meet ambitious global TB control targets [2,3,9]. However, these ACF interventions require substantial investment and the evidence for the population-level impact of untargeted community-level ACF interventions has been mixed [10][11][12]. ...
... Although highly targeted case finding interventions such as contact tracing within the homes of newly diagnosed TB cases (household contact tracting: HHCT) are efficient approaches for finding new cases of TB [13][14][15], these interventions produce only modest population-level reductions in TB burden [12,16,17]. Empirical data for ACF interventions implemented at a larger spatial-scale (e.g., neighborhoods) is limited [18]. ...
Mathematical models have suggested that spatially-targeted screening interventions for tuberculosis may efficiently accelerate disease control, but empirical data supporting these findings are limited. Previous models demonstrating substantial impacts of these interventions have typically simulated large-scale screening efforts and have not attempted to capture the spatial distribution of tuberculosis in households and communities at a high resolution. Here, we calibrate an individual-based model to the locations of case notifications in one district of Lima, Peru. We estimate the incremental efficiency and impact of a spatially-targeted interventions used in combination with household contact tracing (HHCT). Our analysis reveals that HHCT is relatively efficient with a median of 40 (Interquartile Range: 31.7 to 49.9) household contacts required to be screened to detect a single case of active tuberculosis. However, HHCT has limited population impact, producing a median incidence reduction of only 3.7% (Interquartile Range: 5.8% to 1.9%) over 5 years. In comparison, spatially targeted screening (which we modeled as active case finding within high tuberculosis prevalence areas 100 m ² grid cell) is far less efficient, requiring evaluation of ≈12 times the number of individuals as HHCT to find a single individual with active tuberculosis. Furthermore, the addition of the spatially targeted screening effort produced only modest additional reductions in tuberculosis incidence over the 5 year period (≈1.3%) in tuberculosis incidence. In summary, we found that HHCT is an efficient approach for tuberculosis case finding, but has limited population impact. Other screening approaches which target areas of high tuberculosis prevalence are less efficient, and may have limited impact unless very large numbers of individuals can be screened.
... Coverage was relatively high (>90%) in most studies, but was notably lower in the one study that used a quasirandomized controlled trial (RCT) design (52.0%) and reported coverage data. This study, called the ZAMSTAR study, tested a community-level enhanced TB case-finding approach including sputum testing versus household-level combined TB and HIV care in Zambia and South Africa, and had a calculated coverage of 52.0% [26]. Supplemental material 3 includes details of the numbers targeted and screened in each category. ...
... Specifically, the ZAMSTAR Quasi RCT was an ambitious study that enumerated and sought to consent individuals in 24 communities in Zambia and South Africa. In this study using community enhanced case finding, household-based screening and clinic-based interventions, screening completion was impacted by refusals to participate, long distances for transporting specimen, missing or contaminated sputum culture samples excluded for failure to meet quality assurance standards [26]. Successful screening completion requires simple methods, including point-of care tests that are easy to use in the field. ...
Background:
Active case finding (ACF) for tuberculosis (TB) is a key strategy to reduce diagnostic delays, expedite treatment, and prevent transmission.
Objective:
Our objective was to identify the populations, settings, screening and diagnostic approaches that optimize coverage (proportion of those targeted who were screened) and yield (proportion of those screened who had active TB) in ACF programs.
Methods:
We performed a comprehensive search to identify studies published from 1980-2016 that reported the coverage and yield of different ACF approaches. For each outcome, we conducted meta-analyses of single proportions to produce estimates across studies, followed by meta-regression to identify predictors. Findings. Of 3,972 publications identified, 224 met criteria after full-text review. Most individuals who were targeted successfully completed screening, for a pooled coverage estimate of 93.5%. The pooled yield of active TB across studies was 3.2%. Settings with the highest yield were internally-displaced persons camps (15.6%) and healthcare facilities (6.9%). When compared to symptom screening as the reference standard, studies that screened individuals regardless of symptoms using microscopy, culture, or GeneXpert®MTB/RIF (Xpert) had 3.7% higher case yield. In particular, microbiological screening (usually microscopy) as the initial test, followed by culture or Xpert for diagnosis had 3.6% higher yield than symptom screening followed by microscopy for diagnosis. In a model adjusted for use of Xpert testing, approaches targeting persons living with HIV (PLWH) had a 4.9% higher yield than those targeting the general population. In all models, studies targeting children had higher yield (4.8%-5.7%) than those targeting adults.
Conclusion:
ACF activities can be implemented successfully in various populations and settings. Screening yield was highest in internally-displaced person and healthcare settings, and among PLWH and children. In high-prevalence settings, ACF approaches that screen individuals with laboratory tests regardless of symptoms have higher yield than approaches focused on symptomatic individuals.
... Previous randomized trials have investigated the effectiveness of TB household contact tracing interventions on screening completion, community TB prevalence, and TB notification, showing mixed results [10][11][12][13]. Evidence suggests that more intensive TB screening approaches increase diagnostic yield and could reduce transmission by identifying and treating people with subclinical infectious TB earlier [5,14,15]. ...
... Our trial differs from previous randomized trials of household contact tracing for TB. In the ZAMSTAR Study, conducted in South Africa and Zambia, household contacts received TB symptom screening, followed by sputum smear microscopy if symptomatic, HIV testing, and TPT [11]. There was weak evidence that household interventions reduced TB prevalence and childhood TB transmission. ...
Background
Household contact tracing for tuberculosis (TB) may facilitate TB diagnosis and identify individuals who may benefit from TB preventive therapy (TPT). In this cluster-randomised trial, we investigated whether household contact tracing and intensive TB/HIV screening would improve TB-free survival.
Methods
Household contacts of index TB patients in two Provinces of South Africa were randomised to home tracing and intensive HIV/TB screening (sputum Xpert and culture; HIV testing with treatment linkage; and TPT, if eligible), or standard of care (SOC, clinic referral letters). The primary outcome was incident TB or death at 15-months. Secondary outcomes included tuberculin skin test (TST) positivity in children ≤14 years and undiagnosed HIV. (ISRCTN16006202).
Results
From December 2016-March 2019, 1,032 index patients (4,459 contacts) and 1,030 (4,129 contacts) were randomised to the intervention and SOC arms. 3.2% (69/2166) of intervention arm contacts had prevalent microbiologically-confirmed TB. At 15-months, the cumulative incidence of TB or death did not differ between the intensive screening (93/3230, 2.9%) and SOC (80/2600, 3.1%) arms (hazard ratio: 0.90, 95% confidence interval (CI): 0.66-1.24). TST positivity was higher in the intensive screening arm (38/845, 4.5%) compared to the SOC arm (15/800, 1.9%, odds ratio: 2.25, 95% CI: 1.07-4.72). Undiagnosed HIV was similar between arms (41/3185, 1.3% vs. 32/2543, 1.3%; odds ratio: 1.02, 95% CI: 0.64-1.64).
Conclusions
Household contact tracing with intensive screening and referral did not reduce incident TB or death. Providing referral letters to household contacts of index patients is an alternative strategy to home visits in high TB/HIV-prevalence settings.
... South Africa is a high-burden country; in 2018, the TB incidence rate was 737 per 100,000 people, as opposed to the global average of 132 per 100,000 in the same year [22,23] The country has high rates of HIV, poverty, and poor living conditions, constituting a population vulnerable to TB [2,14,24] Cape Town, on the southwestern tip of South Africa, had one of the highest TB burdens in the world; in 2013, corresponding with the time period of our study, the city had an annual notification rate of 713 per 100,000 inhabitants [25]. ...
Objectives
Although the link between poverty and tuberculosis (TB) is widely recognised, limited studies have investigated the association between neighbourhood factors and TB incidence. Since the factors influencing different episodes of TB might be different, this study focused on the first episode of TB disease (first‐episode TB).
Methods
All first episodes in previously linked and geocoded TB notification data from 2007 to 2015 in Cape Town, South Africa, were aggregated at the neighbourhood level and merged with the 2011 census data. We conducted an ecological study to assess the association between neighbourhood incidence of first‐episode TB and neighbourhood factors (total TB burden [all episodes] in the previous year, socioeconomic index, mean household size, mean age, and percentage males) using a negative binomial regression. We also examined the presence of hotspots in neighbourhood TB incidence with the Global Moran's I statistic and assessed spatial dependency in the association between neighbourhood factors and TB incidence using a spatial lag model.
Results
The study included 684 neighbourhoods with a median first‐episode TB incidence rate of 114 (IQR: 0–345) per 100,000 people. We found lower neighbourhood socioeconomic index (SEI), higher neighbourhood total TB burden, lower neighbourhood mean household size, and lower neighbourhood mean age were associated with increased neighbourhood first‐episode TB incidence. Our findings revealed a hotspot of first‐episode TB incidence in Cape Town and evidence of spatial dependency in the association between neighbourhood factors and TB incidence.
Conclusion
Neighbourhood TB burden and SEI were associated with first‐episode TB incidence, and there was spatial dependency in this association. Our findings can inform targeted interventions to reduce TB in high‐risk neighbourhoods, thereby reducing health disparities and promoting health equity.
... Complete data were unavailable for analysis for a substantial proportion of control participants, reasons for which are discussed elsewhere [8,19,20]. This has resulted in reduced study power but is unlikely to have introduced bias to our study results. ...
Objectives
To determine if HIV modifies the association between hyperglycaemia and active tuberculosis in Lusaka, Zambia.
Methods
A case–control study among newly—diagnosed adult tuberculosis cases and population controls in three areas of Lusaka. Hyperglycaemia is determined by random blood glucose (RBG) concentration measured at the time of recruitment; active tuberculosis disease by clinical diagnosis, and HIV status by serological result. Multivariable logistic regression is used to explore the primary association and effect modification by HIV.
Results
The prevalence of RBG concentration ≥ 11.1 mmol/L among 3843 tuberculosis cases was 1.4% and among 6977 controls was 1.5%. Overall, the adjusted odds ratio of active tuberculosis was 1.60 (95% CI 0.91–2.82) comparing those with RBG concentration ≥ 11.1– < 11.1 mmol/L. The corresponding adjusted odds ratio among those with and without HIV was 5.47 (95% CI 1.29–23.21) and 1.17 (95% CI 0.61–2.27) respectively; p -value for effect modification by HIV = 0.042. On subgroup analysis, the adjusted odds ratio of smear/Xpert-positive tuberculosis was 2.97 (95% CI 1.49–5.90) comparing RBG concentration ≥ 11.1– < 11.1 mmol/L.
Conclusions
Overall, no evidence of association between hyperglycaemia and active tuberculosis was found, though among those with HIV and/or smear/Xpert-positive tuberculosis there was evidence of association. Differentiation of hyperglycaemia caused by diabetes mellitus and stress-induced hyperglycaemia secondary to tuberculosis infection is important for a better understanding of these findings.
... Unmatched controls were recruited between January and December 2010 as part of a cross-sectional survey that measured prevalent TB for a large cluster randomised trial (the ZAMSTAR trial). [13,14] They were sampled randomly from all adults living in the catchment areas of the clinics, using a 2-stage cluster sampling technique within each community. Exclusion criteria for controls were age < 18 years, refusal to submit a respiratory sample, diagnosed TB at the time of the survey (culture positive sputum for Mycobacterium tuberculosis), currently on treatment for TB at the time of the survey (self-report), inability to give consent due to disability/incapacitation or any persons living in institutional settings. ...
Objectives
To determine if HIV modifies the association between hyperglycaemia and active tuberculosis in Lusaka, Zambia.
Methods
A case-control study among newly-diagnosed adult tuberculosis cases and population controls in three areas of Lusaka. Hyperglycaemia is determined by random blood glucose (RBG) concentration measured at the time of recruitment; active tuberculosis disease by clinical diagnosis, and HIV status by serological result. Multivariable logistic regression is used to explore the primary association and effect modification by HIV.
Results
The prevalence of RBG concentration ≥ 11.1mmol/L among 3,843 tuberculosis cases was 1.4% and among 6,977 controls was 1.5%. Overall, the adjusted odds ratio of active tuberculosis was 1.60 (95%CI 0.91–2.82) comparing those with RBG concentration ≥ 11.1mmol/L to < 11.1mmol/L. The corresponding adjusted odds ratio among those with and without HIV was 5.47 (95%CI 1.29–23.21) and 1.17 (95%CI 0.61–2.27) respectively; p-value for effect modification by HIV = 0.042. On subgroup analysis, the adjusted odds ratio of smear/Xpert-positive tuberculosis was 2.97 (95%CI 1.49–5.90) comparing RBG concentration ≥ 11.1mmol/L to < 11.1mmol/L.
Conclusions
Overall, no evidence of association between hyperglycaemia and active tuberculosis was found, though among those with HIV and/or smear/Xpert-positive tuberculosis there was evidence of association. Differentiation of hyperglycaemia caused by diabetes mellitus and stress-induced hyperglycaemia secondary to tuberculosis infection is important for a better understanding of these findings.
... Tuberculosis (TB) has been a leading infectious disease killer globally for decades despite the availability of robust diagnostics, effective prevention, and treatment [1]. One challenge has been poor implementation of comprehensive TB programs in low-resource settings where the majority of the global TB burden lies [2][3][4][5][6][7][8][9][10][11][12]. Additionally, one billion people are estimated to be infected with TB globally, with 5-15% of people at risk of becoming sick with TB disease [1]. ...
Background
The use of systems engineering tools, including the development and use of care cascades using routinely collected data, process mapping, and continuous quality improvement, is used for frontline healthcare workers to devise systems level change. South Africa experiences high rates of tuberculosis (TB) infection and disease as well as HIV co-infection. The Department of Health has made significant gains in HIV services over the last two decades, reaching their set “90–90-90” targets for HIV. However, TB services, although robust, have lagged in comparison for both disease and infection. The Systems Analysis and Improvement Approach (SAIA) is a five-step implementation science method, drawn from systems engineering, to identify, define, and implement workflow modifications using cascade analysis, process mapping, and repeated quality improvement cycles within healthcare facilities.
Methods
This stepped-wedge cluster randomized trial will evaluate the effectiveness of SAIA on TB (SAIA-TB) cascade optimization for patients with TB and high-risk contacts across 16 clinics in four local municipalities in the Sarah Baartman district, Eastern Cape, South Africa. We hypothesize that SAIA-TB implementation will lead to a 20% increase in each of: TB screening, TB preventive treatment initiation, and TB disease treatment initiation during the 18-month intervention period. Focus group discussions and key informant interviews with clinic staff will also be conducted to determine drivers of implementation variability across clinics.
Discussion
This study has the potential to improve TB screening, treatment initiation, and completion for both active disease and preventive measures among individuals with and without HIV in a high burden setting. SAIA-TB provides frontline health care workers with a systems-level view of their care delivery system with the aim of sustainable systems-level improvements.
Trial registration
Clinicaltrials.gov, NCT06314386. Registered 18 March 2024, https://clinicaltrials.gov/study/NCT06314386. NCT06314386.
... Of the two cluster-randomised trials considered in the WHO Guideline Development Group meeting, the ZAMSTAR Study in Zambia and South Africa-which included a combination of ECF activities and sputum drop-off points for microscopy-did not affect TB prevalence [29]. In contrast, the ACT3 Study in Vietnam, a more intensive intervention comprising 3 years of repeated rounds of TB screening with sputum Xpert testing for all able to produce a sample, resulted in a 44% relative reduction in the prevalence of microbiologically confirmed TB [30]. ...
Community-based active case finding (ACF) for tuberculosis (TB) involves an offer of screening to populations at risk of TB, oftentimes with additional health promotion, community engagement and health service strengthening. Recently updated World Health Organization TB screening guidelines conditionally recommend expanded offer of ACF for communities where the prevalence of undiagnosed pulmonary TB is greater than 0.5% among adults, or with other structural risk factors for TB. Subclinical TB is thought to be a major contributor to TB transmission, and ACF, particularly with chest X-ray screening, could lead to earlier diagnosis. However, the evidence base for the population-level impact of ACF is mixed, with effectiveness likely highly dependent on the screening approach used, the intensity with which ACF is delivered, and the success of community- and health-system participation. With recent changes in TB epidemiology due to the effective scale-up of treatment for HIV in Africa, the impacts of the COVID-19 pandemic, and the importance of subclinical TB, researchers and public health practitioners planning to implement ACF programmes must carefully and repeatedly consider the potential population and individual benefits and harms from these programmes. Here we synthesise evidence and experience from implementing ACF programmes to provide practical guidance, focusing on the selection of populations, screening algorithms, selecting outcomes, and monitoring and evaluation. With careful planning and substantial investment, community-based ACF for TB can be an impactful approach to accelerating progress towards elimination of TB in high-burden countries. However, ACF cannot and should not be a substitute for equitable access to responsive, affordable, accessible primary care services for all.
... The research conducted base on the Mathematical Modelling on Infectious Diseases by means of stochastic on TB and HIV epidemiology in South Africa (2012) [7]. In the model, they includes TB and HIV record at an individual-level, with population level incidence sustained by M.TB spread [8]. The model incorporated data on age-structured of social involvement forms, as well as demography [9]. ...
Many countries' researchers have researched the Tuberculosis (TB) disease intensively and tremendously. The TB disease and HIV/AIDS continue to be great threat in South Sudan, to minimize the risks and causing factors that clue to effective control of TB disease and highlighted the most detected factors that impacts TB disease elimination on HIV/AIDS. We aimed at detected factors and test them whether can contribute to TB elimination or has significance impact on TB and HIV/AIDS. In the research, we includes the various approaches to different age groups, medical staffs, patients and some knowledgeable persons in Juba Teaching Hospital. Since the research work is applied quantitative and qualitative method, we collect the information of recorded admitted sick patients in 2017. The particular software used in analysis is SPSS, the statistical methodology of implementation were ANOVA to find level of significance of different means, Chi-Square Test to compare the relationship between TB and HIV/AIDS. Therefore, in this project's recommendations, if is noted well and embraced, it would address the TB disease elimination in the population. This project is proposed towards Tuberculosis disease elimination by looking into current cases detected on individuals with active cases finding within special groups.
... Because of the high cost, and risk of false-positive and false-negative screening results, community-wide ACF is conditionally recommended only for general populations with undiagnosed TB of 500 per 100,000 population or higher [10,13]. Evaluating impact is technically difficult and costly, and a recent systematic review [9] identified just eight randomised controlled trials, only two of which had community TB infection incidence or prevalence outcomes [14,15]. ...
Active case-finding (ACF) for tuberculosis can help find the “missing millions” with undiagnosed tuberculosis. In a cluster-randomised trial, we investigated impact of ACF on case-notifications in Blantyre, Malawi, where ACF has been intensively implemented following 2014 estimates of ~1,000 per 100,000 adults with undiagnosed TB. Following a pre-intervention prevalence survey (May 2019 to March 2020), constrained randomisation allocated neighbourhoods to either door-to-door ACF (sputum microscopy for reported cough >2 weeks) or standard-of-care (SOC). Implementation was interrupted by COVID-19. Cluster-level bacteriologically-confirmed case-notification rate (CNR) ratio within 91 days of ACF was our redefined primary outcome; comparison between arms used Poisson regression with random effects. Secondary outcomes were 91-day CNR ratios comparing all tuberculosis registrations and all non-ACF registrations. Interrupted time series (ITS) analysis of CNRs in the SOC arm examined prevalence survey impact. (ISRCTN11400592). 72 clusters served by 10 study-supported tuberculosis registration centres were randomised to ACF (261,244 adults, 58,944 person-years follow-up) or SOC (256,713 adults, 52,805 person-years). Of 1,192 ACF participants, 13 (1.09%) were smear-positive. Within 91 days, 113 (42 bacteriologically-confirmed) and 108 (33 bacteriologically-confirmed) tuberculosis patients were identified as ACF or SOC cluster residents, respectively. There was no difference by arm, with adjusted 91-day CNR ratios 1.12 (95% CI: 0.61–2.07) for bacteriologically-confirmed tuberculosis; 0.93 (95% CI: 0.68–1.28) for all tuberculosis registrations; and 0.86 (95%CI: 0.63–1.16) for non-ACF (routinely) diagnosed. Of 7,905 ACF and 7,992 SOC pre-intervention survey participants, 12 (0.15%) and 17 (0.21%), respectively, had culture/Xpert-confirmed tuberculosis. ITS analysis showed no survey impact on SOC CNRs. Despite residual undiagnosed tuberculosis of 150 per 100,000 population, there was no increase in tuberculosis notifications from this previously successful approach targeting symptomatic disease, likely due to previous TB ACF and rapid declines in TB burden. In such settings, future ACF should focus on targeted outreach and demand creation, alongside optimised facility-based screening.
Trial Registration : ISRCTN11400592 .
... This is highlighted by the fact that while transmission models find significant potential of ACF in reducing transmission, [8][9][10] the impact observed in controlled trials has been mixed. [11][12][13][14] Analyses exploring the impact of ACF on case notification at the national level are unlikely to show large effects because the majority of ACF projects is subnational, and the impact is, therefore, primarily localised. This disconnect may partially be driven by the fact that detailed and informed models are not incorporated early in the planning and design phase of ACF. 14 Incorporating ...
Objectives
Active case finding (ACF) is an important tuberculosis (TB) intervention in high-burden settings. However, empirical evidence garnered from field data has been equivocal about the long-term community-level impact, and more data at a finer geographic scale and data-informed methods to quantify their impact are necessary.
Methods
Using village development committee (VDC)-level data on TB notification and demography between 2016 and 2017 in four southern districts of Nepal, where ACF activities were implemented as a part of the IMPACT-TB study between 2017 and 2019, we developed VDC-level transmission models of TB and ACF. Using these models and ACF yield data collected in the study, we estimated the potential epidemiological impact of IMPACT-TB ACF and compared its efficiency across VDCs in each district.
Results
Cases were found in the majority of VDCs during IMPACT-TB ACF, but the number of cases detected within VDCs correlated weakly with historic case notification rates. We projected that this ACF intervention would reduce the TB incidence rate by 14% (12–16) in Chitwan, 8.6% (7.3–9.7) in Dhanusha, 8.3% (7.3–9.2) in Mahottari and 3% (2.5–3.2) in Makwanpur. Over the next 10 years, we projected that this intervention would avert 987 (746–1282), 422 (304–571), 598 (450–782) and 197 (172–240) cases in Chitwan, Dhanusha, Mahottari and Makwanpur, respectively. There was substantial variation in the efficiency of ACF across VDCs: there was up to twofold difference in the number of cases averted in the 10 years per case detected.
Conclusion
ACF data confirm that TB is widely prevalent, including in VDCs with relatively low reporting rates. Although ACF is a highly efficient component of TB control, its impact can vary substantially at local levels and must be combined with other interventions to alter TB epidemiology significantly.
... It is generally challenging to collect sputum samples from people in the community as some will struggle to produce a sample, especially children [49]. The sputum collection rate achieved in our study was comparable to other studies in community and household settings [16,50]. The younger median age of those with no sputum result could bias results in the direction of an underestimate of subclinical TB prevalence, given previous evidence of an association between younger age and subclinical TB [46,47]. ...
Background
People with subclinical tuberculosis (TB) have microbiological evidence of disease caused by Mycobacterium tuberculosis , but either do not have or do not report TB symptoms. The relationship between human immunodeficiency virus (HIV) and subclinical TB is not yet well understood. We estimated the prevalence of subclinical pulmonary TB in household contacts of index TB patients in two South African provinces, and how this differed by HIV status.
Methods
This was a cross-sectional, secondary analysis of baseline data from the intervention arm of a household cluster randomised trial. Prevalence of subclinical TB was measured as the number of household contacts aged ≥ 5 years who had positive sputum TB microscopy, culture or nucleic acid amplification test (Xpert MTB/Rif or Xpert Ultra) results on a single sputum specimen and who did not report current cough, fever, weight loss or night sweats on direct questioning. Regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the association between HIV status and subclinical TB; adjusting for province, sex and age in household contacts; and HIV status in index patients.
Results
Amongst household contacts, microbiologically confirmed prevalent subclinical TB was over twice as common as symptomatic TB disease (48/2077, 2.3%, 95% CI 1.7–3.1% compared to 20/2077, 1.0%, 95% CI 0.6–1.5%). Subclinical TB prevalence was higher in people living with HIV (15/377, 4.0%, 95% CI 2.2–6.5%) compared to those who were HIV-negative (33/1696, 1.9%, 95% CI 1.3–2.7%; p = 0.018). In regression analysis, living with HIV (377/2077, 18.2%) was associated with a two-fold increase in prevalent subclinical TB with 95% confidence intervals consistent with no association through to a four-fold increase (adjusted OR 2.00, 95% CI 0.99–4.01, p = 0.052). Living with HIV was associated with a five-fold increase in prevalent symptomatic TB (adjusted OR 5.05, 95% CI 2.22–11.59, p < 0.001).
Conclusions
Most (70.6%) pulmonary TB diagnosed in household contacts in this setting was subclinical. Living with HIV was likely associated with prevalent subclinical TB and was associated with prevalent symptomatic TB. Universal sputum testing with sensitive assays improves early TB diagnosis in subclinical household contacts.
... Previous randomised controlled trials have evaluated the effects of household contact symptom screening on tuberculosis detection, but none has evaluated TPT management. [22][23][24][25][26] In the CONTACT study, the primary endpoint was assessed among all declared child contacts in the TPT target group to account for potential increased enrolment under the community-based approach and to have a more stringent comparison between the two groups. ...
... The HIV Prevention Trials Network (HPTN) 071 (PopART) community-randomised trial was conducted during 2013 to 2018 in 21 communities in Zambia and the Western Cape Province of South Africa and was designed to measure the impact of a combination HIV prevention package (the PopART intervention) on HIV incidence [9]. The study built on previous TB and HIV research that was conducted in many of the same communities, including the ZAMSTAR trial during 2004 to 2011 [10,11]. The PopART package of interventions was centred on universal HIV testing and support for linkage to HIV care, with or without universal ART, and included systematic screening for TB based on TB symptoms. ...
Background:
Tuberculosis (TB) prevalence remains persistently high in many settings, with new or expanded interventions required to achieve substantial reductions. The HIV Prevention Trials Network (HPTN) 071 (PopART) community-randomised trial randomised 14 communities to receive the "PopART" intervention during 2014 to 2017 (7 arm A and 7 arm B communities) and 7 communities to receive standard-of-care (arm C). The intervention was delivered door-to-door by community HIV care providers (CHiPs) and included universal HIV testing, facilitated linkage to HIV care at government health clinics, and systematic TB symptom screening. The Tuberculosis Reduction through Expanded Anti-retroviral Treatment and Screening (TREATS) study aimed to measure the impact of delivering the PopART intervention on TB outcomes, in communities with high HIV and TB prevalence.
Methods and findings:
The study population of the HPTN 071 (PopART) trial included individuals aged ≥15 years living in 21 urban and peri-urban communities in Zambia and South Africa, with a total population of approximately 1 million and an adult HIV prevalence of around 15% at the time of the trial. Two sputum samples for TB testing were provided to CHiPs by individuals who reported ≥1 TB suggestive symptom (a cough for ≥2 weeks, unintentional weight loss ≥1.5 kg in the last month, or current night sweats) or that a household member was currently on TB treatment. Antiretroviral therapy (ART) was offered universally at clinics in arm A and according to local guidelines in arms B and C. The TREATS study was conducted in the same 21 communities as the HPTN 071 (PopART) trial between 2017 and 2022, and TB prevalence was a co-primary endpoint of the TREATS study. The primary comparison was between the PopART intervention (arms A and B combined) and the standard-of-care (arm C). During 2019 to 2021, a TB prevalence survey was conducted among randomly selected individuals aged ≥15 years (approximately 1,750 per community in arms A and B, approximately 3,500 in arm C). Participants were screened on TB symptoms and chest X-ray, with diagnostic testing using Xpert-Ultra followed by culture for individuals who screened positive. Sputum eligibility was determined by the presence of a cough for ≥2 weeks, or ≥2 of 5 "TB suggestive" symptoms (cough, weight loss for ≥4 weeks, night sweats, chest pain, and fever for ≥2 weeks), or chest X-ray CAD4TBv5 score ≥50, or no available X-ray results. TB prevalence was compared between trial arms using standard methods for cluster-randomised trials, with adjustment for age, sex, and HIV status, and multiple imputation was used for missing data on prevalent TB. Among 83,092 individuals who were eligible for the survey, 49,556 (59.6%) participated, 8,083 (16.3%) screened positive, 90.8% (7,336/8,083) provided 2 sputum samples for Xpert-Ultra testing, and 308 (4.2%) required culture confirmation. Overall, estimated TB prevalence was 0.92% (457/49,556). The geometric means of 7 community-level prevalence estimates were 0.91%, 0.70%, and 0.69% in arms A, B, and C, respectively, with no evidence of a difference comparing arms A and B combined with arm C (adjusted prevalence ratio 1.14, 95% confidence interval, CI [0.67, 1.95], p = 0.60). TB prevalence was higher among people living with HIV than HIV-negative individuals, with an age-sex-community adjusted odds ratio of 2.29 [95% CI 1.54, 3.41] in Zambian communities and 1.61 [95% CI 1.13, 2.30] in South African communities. The primary limitations are that the study was powered to detect only large reductions in TB prevalence in the intervention arm compared with standard-of-care, and the between-community variation in TB prevalence was larger than anticipated.
Conclusions:
There was no evidence that the PopART intervention reduced TB prevalence. Systematic screening for TB that is based on symptom screening alone may not be sufficient to achieve a large reduction in TB prevalence over a period of several years. Including chest X-ray screening alongside TB symptom screening could substantially increase the sensitivity of systematic screening for TB.
Trial registration:
The TREATS study was registered with ClinicalTrials.gov Identifier: NCT03739736 on November 14, 2018. The HPTN 071 (PopART) trial was registered at ClinicalTrials.gov under number NCT01900977 on July 17, 2013.
... An individually randomised, controlled trial in Brazil found that intensified TB screening among household contacts (including as-needed home visits and follow-up evaluation and treatment of latent and active TB in clinics) decreased TB incidence by 15% over five years relative to usual care without contact investigation [10]. The ZAMSTAR study, a cluster-randomised trial in 24 communities in Zambia and South Africa, found that household contact investigation with TB preventive therapy (TPT) for eligible contacts decreased TB transmission by 55% and active TB prevalence by 18% relative to clinic-based enhanced casefinding plus TPT, although the differences were not statistically significant [11]. A cluster-randomised trial in 70 districts in Vietnam demonstrated that inviting household TB contacts for clinic-based TB symptom and chest x-ray screening every six months for two years significantly increased the cumulative incidence of TB diagnoses and treatments by 2.5-fold compared with usual care without contact investigation [12]. ...
Background
Tuberculosis(TB) is among the leading causes of infectious death worldwide. Contact investigation is an evidence-based, World Health Organisation-endorsed intervention for timely TB diagnosis, treatment, and prevention but has not been widely and effectively implemented.
Methods
We are conducting a stepped-wedge, cluster-randomised, hybrid Type III implementation-effectiveness trial comparing a user-centred to a standard strategy for implementing TB contact investigation in 12 healthcare facilities in Uganda. The user-centred strategy consists of several client-focused components including (1) a TB-education booklet, (2) a contact-identification algorithm, (3) an instructional sputum-collection video, and (4) a community-health-rider service to transport clients, CHWs, and sputum samples, along with several healthcare-worker-focused components, including (1) collaborative improvement meetings, (2) regular audit-and-feedback reports, and (3) a digital group-chat application designed to develop a community of practice. Sites will cross-over from the standard to the user-centred strategy in six, eight-week transition steps following a randomly determined site-pairing scheme and timeline. The primary implementation outcome is the proportion of symptomatic close contacts completing TB evaluation within 60 days of TB treatment initiation by the index person with TB. The primary clinical effectiveness outcomes are the proportion of contacts diagnosed with and initiating active TB disease treatment and the proportion initiating TB preventative therapy within 60 days. We will assess outcomes from routine source documents using intention-to-treat analyses. We will also conduct nested mixed-methods studies of implementation fidelity and context and perform cost-effectiveness and impact modelling. The Makerere School of Public Health IRB(#554), the Uganda National Council for Science and Technology(#HS1720ES), and the Yale Institutional Review Board(#2000023199) approved the study and waived informed consent for the main trial implementation-effectiveness outcomes. We will submit results for publication in peer-reviewed journals and disseminate findings to local policymakers and representatives of affected communities.
Discussion
This pragmatic, quasi-experimental implementation trial will inform efforts to find and prevent undiagnosed persons with TB in high-burden settings using contact investigation. It will also help assess the suitability of human-centred design and communities of practice for tailoring implementation strategies and sustaining evidence-based interventions in low-and-middle-income countries.
Trial registration
The trial was registered(ClinicalTrials.gov Identifier NCT05640648) on 16 November 2022, after the trial launch on 7 March 2022.
... More recently, high-quality randomized controlled trials have added comparative data showing that contact investigation effectively reduced active TB prevalence in one Brazilian community [6] and increased TB case notifications across 36 districts in Vietnam [7]. Three other randomized trials were inconclusive, with one strongly suggesting but unable to confirm a benefit of contact tracing over clinic-based case-finding [8] and two others showing no benefit over facility-based approaches [9,10]. As a result, WHO now endorses TB contact investigation in all settings, including low-and middle-income countries (LMICs) [11,12]. ...
Background
Implementation science offers a systematic approach to adapting innovations and delivery strategies to new contexts but has yet to be widely applied in low- and middle-income countries. The Fogarty Center for Global Health Studies is sponsoring a special series, “Global Implementation Science Case Studies,” to address this gap.
Methods
We developed a case study for this series describing our approach and lessons learned while conducting a prospective, multi-modal study to design, implement, and evaluate an implementation strategy for TB contact investigation in Kampala, Uganda. The study included formative, evaluative, and summative phases that allowed us to develop and test an adapted contact investigation intervention involving home-based sample collection for TB and HIV testing. We concurrently developed a multi-component mHealth implementation strategy involving fingerprint scanning, electronic decision support, and automated reporting of test results via text message. We then conducted a household-randomized, hybrid implementation-effectiveness trial comparing the adapted intervention and implementation strategy to usual care. Our assessment included nested quantitative and qualitative studies to understand the strategy’s acceptability, appropriateness, feasibility, fidelity, and costs. Reflecting on this process with a multi-disciplinary team of implementing researchers and local public health partners, we provide commentary on the previously published studies and how the results influenced the adaptation of international TB contact investigation guidelines to fit the local context.
Results
While the trial did not show improvements in contact investigation delivery or public health outcomes, our multi-modal evaluation strategy helped us identify which elements of home-based, mHealth-facilitated contact investigation were feasible, acceptable, and appropriate and which elements reduced its fidelity and sustainability, including high costs. We identified a need for better tools for measuring implementation that are simple, quantitative, and repeatable and for greater attention to ethical issues in implementation science.
Conclusions
Overall, a theory-informed, community-engaged approach to implementation offered many learnings and actionable insights for delivering TB contact investigation and using implementation science in low-income countries. Future implementation trials, especially those incorporating mHealth strategies, should apply the learnings from this case study to enhance the rigor, equity, and impact of implementation research in global health settings.
... Yet, published data on the individual-and population-level impacts of community-based active case finding are mixed. Systematic screening in the general population has been shown to lead to reductions in tuberculosis prevalence in some [6,7] but not all [8,9] settings, and limited evidence suggests that while screening may reduce time to diagnosis and mortality, it may also be associated with higher pretreatment loss to follow-up compared with standard "passive" case finding [10]. Importantly, the answer to the key question of whether community-wide systematic screening increases tuberculosis case detection remains open to debate. ...
(See the Major Article by Burke et al. on pages 94–100.)
In 2021, of the estimated 10.6 million cases of tuberculosis worldwide, only 6.4 million were detected and notified [1], a disheartening indication that global efforts to find and treat all people with tuberculosis remain inadequate. Results of national prevalence surveys suggest that, in many high-burden settings, for every case of tuberculosis detected, there exist between 2 and 5 undiagnosed cases in the community [1]. With tuberculosis consistently ranked a leading infectious cause of death and the top killer of people with human immunodeficiency virus (HIV), improving case detection has long been a global health priority. Systematic screening for tuberculosis, also referred to as active case finding, involves the systematic identification of people at risk for tuberculosis disease and is a central component of the World Health Organization (WHO) End TB Strategy [2, 3]. To help facilitate the implementation of evidence-based approaches, in 2013, WHO published guidelines on systematic screening for tuberculosis, primarily emphasizing screening in targeted populations such as household contacts and people with HIV [4]. In 2021, WHO additionally endorsed community-wide systematic screening in settings with a high tuberculosis prevalence (≥500 per 100 000 population) [5] based on evidence suggesting potential public health benefits.
... [3][4][5] Adding community-based active case finding (ACF) interventions to facility-based services can increase the number of number of people diagnosed with tuberculosis, with somebut not allstudies reporting reductions in tuberculosis prevalence. [6][7][8][9][10] Community-based ACF in populations with a high prevalence of undiagnosed disease is one of the approaches recommended by WHO. Ideally, ACF should be combined with scale-up of HIV testing and antiretroviral treatment (ART) services, and strengthening of facility-based tuberculosis diagnostics and infection control, with combined interventions most likely to maximize and maintain individual and public-health benefits from early tuberculosis diagnosis. ...
Background:
Tuberculosis case-finding interventions are critical to meeting World Health Organization End TB strategy goals. We investigated the impact of community-wide tuberculosis active case-finding (ACF) alongside scale-up of HIV testing and care on trends in adult tuberculosis case notification rates (CNRs) in Blantyre, Malawi.
Methods:
Five rounds of ACF for tuberculosis (1-2 weeks of leafleting, door-to-door enquiry for cough and sputum microscopy) were delivered to neighbourhoods ("ACF areas") in North-West Blantyre between April 2011 and August 2014. Many of these neighborhoods also had concurrent HIV testing interventions. The remaining neighbourhoods in Blantyre City ("non-ACF areas") provided a non-randomised comparator. We analyzed TB CNRs from January 2009 until December 2018. We used interrupted time series analysis to compare tuberculosis CNRs before ACF and after ACF, and between ACF and non-ACF areas.
Findings:
Tuberculosis CNRs increased in Blantyre concurrently with start of ACF for tuberculosis in both ACF and non-ACF areas, with a larger magnitude in ACF areas. Compared to a counterfactual where pre-ACF CNR trends continued during ACF period, we estimated there were an additional 101 (95% confidence interval [CI] 42 to 160) microbiologically confirmed (Bac+) tuberculosis diagnoses per 100,000 person-years in the ACF areas in three and a half years of ACF. Compared to a counterfactual where trends in ACF area were the same as trends in non-ACF areas, we estimated an additional 63 (95% CI 38 to 90) Bac+ diagnoses per 100,000 person-years in the same period.
Interpretation:
Tuberculosis ACF was associated with a rapid increase in people diagnosed with tuberculosis in Blantyre.
... 6 The monetary value of YPLL captured in the present study is an understatement given that TB fatalities in Somalia are grossly underreported because of lack of resources and conflict and fragility conditions. Evidence suggests that undetected TB cases are common, especially for high-risk groups in high-burden countries 54-57 and lack of resources limit strategies to control TB. [58][59][60] For the case of Somalia where TB is a serious public health problem, fewer than half of the estimated cases are detected. 61 That said, it should be noted that there is also the possibility that fragility conditions directedly kill people via armed conflicts before they can die of TB. ...
Background:
Low tuberculosis (TB) detection and conflict and fragility have overburdened Somalia. This study estimated economic loss associated with TB deaths among persons aged >14 years.
Method:
Using epidemiologic and economic data, we calculated the cost based on the framework of the World Health Organization guide of identifying the economic consequences of disease and injury. Baseline loss is the product of years of life lost, non-health expenditure, and number of deaths. Adjusting for conflict and fragility conditions and growth of non-health expenditure, we discounted the loss at 3% rate. We conducted a sensitivity analysis of epidemiologic and economic factors.
Results:
In 2017 values, the 9180 reported deaths result in a loss of US$ 44.77 million, a US$ 4877 per death over the discounted years. Conflict conditions would increase the loss by 5.3%, while simultaneous adjustment for conflict and attunement to growth of non-health expenditure would increase the burden by 54% to US$ 67.28 million. Male fatalities account for 59% of the burden. The baseline result is robust to input variations, although sensitivity analysis suggests conflict and fragility conditions account for greater uncertainty of the loss.
Conclusion:
Stakeholders in the healthcare system should minimise the sizeable economic loss by taking measures to enhance surveillance of TB and security.
... In Maharashtra, one of the highest TB burden states in India [50], NTEP policymakers and implementers are enthusiastic about studying the effectiveness of telephonic active case finding (TACF) and home-based active case finding (HACF). HACF strategies have been successful at identifying high proportions of TB among HHCs in high incidence settings [51][52][53]. However, HACF may be resourceintensive and difficult to scale. ...
Background:
Approximately 7% of all reported tuberculosis (TB) cases each year are recurrent, occurring among people who have had TB in the recent or distant past. TB recurrence is particularly common in India, which has the largest TB burden worldwide. Although patients recently treated for TB are at high risk of developing TB again, evidence around effective active case finding (ACF) strategies in this population is scarce. We will conduct a hybrid type I effectiveness-implementation non-inferiority randomized trial to compare the effectiveness, cost-effectiveness, and feasibility of two ACF strategies among individuals who have completed TB treatment and their household contacts (HHCs).
Methods:
We will enroll 1076 adults (≥ 18 years) who have completed TB treatment at a public TB unit (TU) in Pune, India, along with their HHCs (averaging two per patient, n = 2152). Participants will undergo symptom-based ACF by existing healthcare workers (HCWs) at 6-month intervals and will be randomized to either home-based ACF (HACF) or telephonic ACF (TACF). Symptomatic participants will undergo microbiologic testing through the program. Asymptomatic HHCs will be referred for TB preventive treatment (TPT) per national guidelines. The primary outcome is rate per 100 person-years of people diagnosed with new or recurrent TB by study arm, within 12 months following treatment completion. The secondary outcome is proportion of HHCs < 6 years, by study arm, initiated on TPT after ruling out TB disease. Study staff will collect socio-demographic and clinical data to identify risk factors for TB recurrence and will measure post-TB lung impairment. In both arms, an 18-month "mop-up" visit will be conducted to ascertain outcomes. We will use the RE-AIM framework to characterize implementation processes and explore acceptability through in-depth interviews with index patients, HHCs and HCWs (n = 100). Cost-effectiveness will be assessed by calculating the incremental cost per TB case detected within 12 months and projected for disability-adjusted life years averted based on modeled estimates of morbidity, mortality, and time with infectious TB.
Discussion:
This novel trial will guide India's scale-up of post-treatment ACF and provide an evidence base for designing strategies to detect recurrent and new TB in other high burden settings.
Trial registration:
NCT04333485 , registered April 3, 2020. CTRI/2020/05/025059 [Clinical Trials Registry of India], registered May 6 2020.
... These drugs are less effective, far more toxic than first-line agents and more difficult to administer, as most regimens contain injectable agents such as amikacin. Treating MDR-TB using conventional regimens is also resource intensive, costing from US$2,500 to US$10,000 per patient compared with US$100-US$1,000 for drug-susceptible TB cases (91) . Nevertheless, it has been possible to achieve treatment success rate for MDR-TB of only 56% worldwide (2) . ...
Tuberculosis (TB) is a public health threat and is among the world’s most lethal infectious diseases. Globally, Cambodia ranks 15th among the 30 countries with the highest TB incidence rate. The increasing emergence of MDR-TB as well as pre-XDR and XDR-TB has been observed in this country. However, the mechanisms underlying this escalation of resistance are still poorly understood. In this context, this thesis aims to understand the emergence, spread and evolution of antibiotic resistance in Mycobacterium tuberculosis (M.tb) in Cambodia.Two collections of M.tb are included in the study: (i) 404 isolates from MDR-TB presumptive patients between 2012 and 2017, (ii) 19 isolates from bears from a wildlife rescue center and one isolate from a staff member. The isolates were analyzed by two techniques: spoligotyping, 24-MIRU-VNTR, sequencing of drug resistance genes and drug susceptibility testing for first (FLD) and second line (SLD) drugs.First, this work describes the genetic diversity of the clinical M.tb isolates and their link with FLD resistance. The two predominant families, Beijing and EAI, represent almost 90% of the sample. The analysis showed a significant association between the Beijing family and phenotypic drug resistance, in particular with MDR and quadruple resistance. The clustering suggests the existence of recent transmissions also associated with the Beijing family.Second, while focusing on resistance to SLD, the data suggest that the proportion of XDR and pre-XDR isolates remains low but is on the rise compared to previous reports. The Beijing family was predominant among these highly resistant isolates. One Beijing isolate, named XDR+, was resistant to all anti-TB drugs tested (FLD and SLD). A cluster comprising 2 pre-XDR and XDR isolates was observed, suggesting recent transmission of these strains.Third, the genetic determinants of resistance to FLD and SLD and the evolution of resistance over time were studied. The data demonstrated a diversity of drug resistant patterns from mono-resistance to XDR, an important diversity of mutation patterns in each M.tb family and each cluster and the existence of compensatory mutations in some resistant isolates. These results suggest various evolutionary trajectories towards resistance to FLD and SLD. The Beijing family was also associated with MDR and XDR and low fitness cost mutations in resistant genes. Our data suggest a cumulative effect of mutations, a role of epistasis in the acquisition of multiple resistance and the spread of highly resistant and transmissible isolates in the population.Finally, concerning the M.tb in bear population and the staff isolate, my work has confirmed a human-animal transmission of M.tb sensitive and resistant with the presence of two clusters; EAI cluster and Beijing streptomycin and isoniazid resistant cluster including the human case. The timing and exposure indicated probable transmission from bear to human and back to bear.In conclusion, this work provides knowledge on the diversity, population structure of M.tb and resistance to FLD and SLD in our sample collected from MDR-TB presumptive patients between 2012 and 2017. These data predict an evolution of resistance to a more problematic situation in the future. First, the Beijing family is associated with MDR and XDR as well as mutations associated with high level of resistance and low fitness cost and recent transmission. Second, the proportion of XDR and pre-XDR isolates remains low but appears to be increasing over time. This study strongly indicates the need for rapid interventions in terms of diagnostic and treatment to prevent the spread of the Beijing pre-XDR and XDR isolates in the population and the emergence of more resistant strains. This work also illustrates that the susceptibility of the endangered species, Helarctos malayanus sun bear, to human TB in particular to resistant TB poses problems in terms of conservation of the species but also of public health.
... 119 Similarly, reductions in the prevalence of latent tuberculosis infection have been demonstrated among children in clusters in which door-to-door tuberculosis screening was done. 119,120 Compared with door-to-door strategies, a mobile clinic-based approach has been reported to be more effective for case detection. 121 Mobile clinics equipped with point-of-care (POC) molecular tools provide additional opportunities for community-based active case finding. ...
The global tuberculosis burden remains substantial, with more than 10 million people newly ill per year. Nevertheless, tuberculosis incidence has slowly declined over the past decade, and mortality has decreased by almost a third in tandem. This positive trend was abruptly reversed by the COVID-19 pandemic, which in many parts of the world has resulted in a substantial reduction in tuberculosis testing and case notifications, with an associated increase in mortality, taking global tuberculosis control back by roughly 10 years. Here, we consider points of intersection between the tuberculosis and COVID-19 pandemics, identifying wide-ranging approaches that could be taken to reverse the devastating effects of COVID-19 on tuberculosis control. We review the impact of COVID-19 at the population level on tuberculosis case detection, morbidity and mortality, and the patient-level impact, including susceptibility to disease, clinical presentation, diagnosis, management, and prognosis. We propose strategies to reverse or mitigate the deleterious effects of COVID-19 and restore tuberculosis services. Finally, we highlight research priorities and major challenges and controversies that need to be addressed to restore and advance the global response to tuberculosis.
... Health system strengthening is dependent on the established health system, the type of intervention, screening and diagnostic tools used, and planned steps for people who screen negative, people who screen false positive and people diagnosed with TB. Examples of health system strengthening include training of lay health workers to conduct screening [19], improved storage and transport of sputum specimens [20,21], laboratory strengthening, health information system augmentation, and improved TB treatment and preventive therapy support [22]. Also see Additional file 3: WHO case-finding definitions have evolved over the development of successive guidelines. ...
Background
Tuberculosis case-finding interventions often involve several activities to enhance patient pathways, and it is unclear which activity defines the type of case-finding intervention. When conducting studies to identify the most effective case-finding intervention it is important to have a clear understanding of these interventions for meaningful comparisons. This review aimed to construct a systems-based logic model of all pathways to tuberculosis case detection through a synthesis of intervention designs.
Methods
We identified an existing systematic review on the effectiveness of interventions to increase tuberculosis case detection and updated the search from December 2016 to October 2020. We included randomized controlled trials, as these designs encourage detailed description of interventions. Taking each study in turn, intervention descriptions were read in detail. The texts were analysed qualitatively by constantly comparing emerging codes to construct patient journeys, visualized as logical chains. Actions taken as part of interventions were positioned along patient journeys to theorize the sequence of outcomes. Patient journeys formed the basis of the model, which was refined through discussion.
Results
Based on intervention descriptions from 17 randomized controlled trials, our model distinguishes two care-seeking pathways and four screening pathways. An open invitation to people with tuberculosis symptoms creates care-seeking pathways. On care-seeking pathways, systematic screening can be conducted at general health services, but not at specific TB care services. People invited to tuberculosis services regardless of symptoms follow tuberculosis screening pathways and may be identified with presumptive tuberculosis even if they do not seek care for tuberculosis symptoms. Tuberculosis screening pathways include screening offered to all people accessing care at general health services, screening at a mobile clinic or health facility with open invitation to a whole population or tuberculosis contacts, screening personally offered to a whole population or tuberculosis contacts at home, work or school, and screening offered to people receiving care for human immunodeficiency virus or other clinical risk-group care.
Conclusion
This systems-based logic model of tuberculosis case-finding pathways may support standardized terminology, consistency, transparency and improved communication among researchers, policy-makers, health workers and community members when implementing and evaluating interventions to improve tuberculosis case detection.
... The sample size for the clinic survey was based on a precision estimate, assuming the prevalence of TB in the general population was 1.5% [21], and among PHC attendees to be around 3%. To allow for estimation of an overall TB prevalence of 3% with a precision of ±0.8%, the study aimed to enroll 3400 adult attendees (1700 per clinic) to obtain the target sample size of 2000 participants with a sputum sample, assuming that 60% could produce a specimen. ...
Background
Tuberculosis (TB) case finding efforts typically target symptomatic people attending health facilities. We compared the prevalence of Mycobacterium tuberculosis (Mtb) sputum culture-positivity among adult clinic attendees in rural South Africa with a concurrent, community-based estimate from the surrounding demographic surveillance area (DSA).
Methods
Clinic: Randomly-selected adults (≥18 years) attending two primary healthcare clinics were interviewed and requested to give sputum for mycobacterial culture. HIV and antiretroviral therapy (ART) status were based on self-report and record review. Community: All adult (≥15 years) DSA residents were invited to a mobile clinic for health screening, including serological HIV testing; those with ≥1 TB symptom (cough, weight loss, night sweats, fever) or abnormal chest radiograph were asked for sputum.
Results
Clinic: 2,055 patients were enrolled (76.9% female, median age 36 years); 1,479 (72.0%) were classified HIV-positive (98.9% on ART) and 131 (6.4%) reported ≥1 TB symptom. Of 20/2,055 (1.0% [95% CI 0.6–1.5]) with Mtb culture-positive sputum, 14 (70%) reported no symptoms. Community: 10,320 residents were enrolled (68.3% female, median age 38 years); 3,105 (30.3%) tested HIV-positive (87.4% on ART) and 1,091 (10.6%) reported ≥1 TB symptom. Of 58/10,320 (0.6% [95% CI 0.4–0.7]) with Mtb culture-positive sputum, 45 (77.6%) reported no symptoms.
In both surveys, sputum culture positivity was associated with male sex and reporting >1 TB symptom.
Conclusions
In both clinic and community settings, most participants with Mtb culture-positive sputum were asymptomatic. TB screening based only on symptoms will miss many people with active disease in both settings.
... Public health practitioners increasingly view community health workers as adherence promoters. More patient-centered approaches have included the use of trained community volunteers to visit patients often in their homes (Ayles et al. 2013;Shin et al. 2004). 13 Some researchers have shown that family members might serve as viable treatment supporters , an idea that has generated some controversy about the role of family in DOT (Freiden and Sbarbaro 2007), even as family members are already playing substantial, informal roles in treatment support. ...
... This report adds to a small but growing body of literature that community-based approaches supporting TPT for drug-resistant and drug-susceptible TB result in higher rates of completion than has typically been reported using facility-based approaches [25]. It also expands on research suggesting that household engagement and symptom-based TPT delivery are effective strategies for reducing TB prevalence and providing TPT in high burden settings [13,15,26,27]. Building on this work, this report is among the first descriptions of a fully decentralized contact management program where screening, prevention and follow-up took place at patient homes. ...
BACKGROUND
The prevention of tuberculosis (TB) in child contacts of TB cases and people living with HIV is a public health priority, but global access to TB preventive therapy (TPT) remains low. In 2019, we implemented Vikela Ekhaya, a novel community-based TB contact management program in Eswatini designed to reduce barriers to accessing TPT.
METHODS
Vikela Ekhaya offered differentiated TB and HIV testing for household contacts of TB cases, by utilizing mobile contact management teams to screen contacts, assess their TPT eligibility, and initiate and monitor TPT adherence in participants’ homes.
RESULTS
In total, 945 contacts from 244 households were screened for TB symptoms; 72 (8%) contacts reported TB symptoms, and five contacts (0.5%) were diagnosed with prevalent TB. 322 of 330 (98%) eligible asymptomatic household contacts initiated TPT. Of 322 contacts initiating TPT, 248 children initiated 3 months of isoniazid and rifampicin and 74 children and adults living with HIV initiated 6 months of isoniazid; 298 (93%) completed TPT. In clustered logistic regression analyses, unknown HIV status (aOR 5.7, p = 0.023), positive HIV status (aOR 21.1, p = 0.001), urban setting (aOR 5.6, p = 0.006), and low income (aOR 5.9, p =0.001) predicted loss from the cascade of care among TPT eligible contacts.
CONCLUSION
Vikela Ekhaya demonstrated that community-based TB household contact management is a feasible, acceptable and successful strategy for TB screening and TPT delivery. The results of this study support the development of novel, differentiated, community-based interventions for TB prevention and control.
... [13][14][15] The population prevalence of HIV among adults was estimated at 19.2% in 2010 in the province. 16 Vertical HIV transmission was <5% during the study period. 17 According to national guidelines, bacillus Calmette-Guérin (BCG) vaccination was routinely administered to all newborns at birth, with >90% coverage in the province in 2012. ...
Background:
The clinical utility of the magnitude of interferon gamma (IFNγ) in response to mycobacterial antigens is unknown. We assessed the association between quantitative IFNγ response and degree of Mycobacterium tuberculosis exposure, infection and tuberculosis (TB) disease status in children.
Methods:
We completed cross-sectional analysis of children (≤15 years) exposed to an adult with bacteriologically confirmed TB, 2007-2012 in Cape Town, South Africa. IFNγ values were reported as concentrations and spot forming units for the QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB, respectively. Random-effects linear regression was used to investigate the relation between the M. tuberculosis contact score, clinical phenotype (TB diseased, infected, uninfected) and IFNγ▪response as outcome, adjusted for relevant covariates.
Results:
We analyzed data from 669 children (median age, 63 months; interquartile range, 33-108 months). A 1-unit increase in M. tuberculosis contact score was associated with an increase of IFNγ 0.60 international unit/mL (95% confidence interval [CI], 0.44-0.76 international unit/mL), and IFNγ spot forming unit 2 counts (95% CI, 1-3). IFNγ response was significantly lower among children with M. tuberculosis infection compared with children with TB disease (β = -1.42; 95% CI, -2.80 to -0.03) for the QFT-GIT, but not for the T-SPOT.TB. This association was strongest among children 2-5 years (β = -2.35 years; 95% CI, -4.28 to -0.42 years) and absent if <2 years.
Conclusions:
The magnitude of IFNγ response correlated with the degree of recent M. tuberculosis exposure, measured by QFT-GIT and T-SPOT.TB, and was correlated with clinically relevant TB phenotypes using the QFT-GIT. IFNγ values are not only useful in estimating the risk of M. tuberculosis infection but may also support the diagnosis of TB disease in children.
Discussion:
The magnitude of IFNγ response correlated with the degree of recent M. tuberculosis exposure, measured by QFT-GIT and T-SPOT.TB, and was correlated with clinically relevant TB phenotypes using the QFT-GIT. IFNγ values are not only useful in estimating the risk of M. tuberculosis infection but may also support the diagnosis of TB disease in children.
Background
The persistence of tuberculosis today and its global disparity send a powerful message that effective tuberculosis control must respond to its regional epidemiology. Active case finding through contact investigation is a standard protocol used for tuberculosis control, but its effectiveness has not been established, especially in endemic areas.
Methods
To quantify the potential effectiveness of contact investigation in Kampala, Uganda, we used a cross-sectional design to evaluate the social networks of 123 tuberculosis index cases and 124 controls without tuberculosis.
Results
Tuberculous infection was present in 515 of 989 tuberculosis case contacts (52.1%) and 396 of 1026 control contacts (38.6%; adjusted prevalence ratio, 1.4; 95% CI, 1.3–1.6). The proportion of infected participants with known exposure within the social network of the tuberculosis case was 35%. The population-attributable fraction was 11.1% for any known exposure, with 7.3% attributable to household exposure and 3.4% attributable to extrahousehold exposure.
Conclusions
This low population-attributable fraction indicates that contact tracing in the social networks of index cases will have only a modest effect in reducing tuberculous infection in a community. New approaches to community-level active case finding are needed.
Aim: A rapid and precise diagnostic method is crucial for timely intervention and management of tuberculosis. The present study compared the diagnostic accuracy of a novel lipoarabinomannan (LAM) antigen test, AIMLAM, for tuberculosis in urine samples. Methodology: The study subjected 106 TB suspects to smear microscopy, MGIT, GeneXpert and AIMLAM. Results: Among 106, smear microscopy identified 36 as positive (33%) (sensitivity; 70.93%, 95% CI (60.14–80.22%), while MGIT showed 38 positive (36.8%). GeneXpert detected 59 positives (sensitivity; 96.83, 95% CI (89.00–99.61%)). AIMLAM declared 61 as positive (57.5%) (sensitivity; 100.00, 95% CI (94.13–100.00%) and 45 as negative (42.5%). Conclusion: Overall, AIMLAM demonstrated better diagnostic accuracy than GeneXpert Assay, smear microscopy and MGIT liquid culture in urine samples.
Background:
Active case finding (ACF) refers to the systematic identification of people with tuberculosis in communities and amongst populations who do not present to health facilities, through approaches such as door-to-door screening or contact tracing. ACF may improve access to tuberculosis diagnosis and treatment for the poor and for people remote from diagnostic and treatment facilities. As a result, ACF may also reduce onward transmission. However, there is a need to understand how these programmes are experienced by communities in order to design appropriate services.
Objectives:
To synthesize community views on tuberculosis active case finding (ACF) programmes in low- and middle-income countries.
Search methods:
We searched MEDLINE, Embase, and eight other databases up to 22 June 2023, together with reference checking, citation searching, and contact with study authors to identify additional studies. We did not include grey literature.
Selection criteria:
This review synthesized qualitative research and mixed-methods studies with separate qualitative data. Eligible studies explored community experiences, perceptions, or attitudes towards ACF programmes for tuberculosis in any endemic low- or middle-income country, with no time restrictions.
Data collection and analysis:
Due to the large volume of studies identified, we chose to sample studies that had 'thick' description and that investigated key subgroups of children and refugees. We followed standard Cochrane methods for study description and appraisal of methodological limitations. We conducted thematic synthesis and developed codes inductively using ATLAS.ti software. We examined codes for underlying ideas, connections, and interpretations and, from this, generated analytical themes. We assessed the confidence in the findings using the GRADE-CERQual approach, and produced a conceptual model to display how the different findings interact.
Main results:
We included 45 studies in this synthesis, and sampled 20. The studies covered a broad range of World Health Organization (WHO) regions (Africa, South-East Asia, Eastern Mediterranean, and the Americas) and explored the views and experiences of community members, community health workers, and clinical staff in low- and middle-income countries endemic for tuberculosis. The following five themes emerged. • ACF improves access to diagnosis for many, but does little to help communities on the edge. Tuberculosis ACF and contact tracing improve access to health services for people with worse health and fewer resources (High confidence). ACF helps to find this population, exposed to deprived living conditions, but is not sensitive to additional dimensions of their plight (High confidence) and out-of-pocket costs necessary to continue care (High confidence). Finally, migration and difficult geography further reduce communities' access to ACF (High confidence). • People are afraid of diagnosis and its impact. Some community members find screening frightening. It exposes them to discrimination along distinct pathways (isolation from their families and wider community, lost employment and housing). HIV stigma compounds tuberculosis stigma and heightens vulnerability to discrimination along these same pathways (High confidence). Consequently, community members may refuse to participate in screening, contact tracing, and treatment (High confidence). In addition, people with tuberculosis reported their emotional turmoil upon diagnosis, as they anticipated intense treatment regimens and the prospect of living with a serious illness (High confidence). • Screening is undermined by weak health infrastructure. In many settings, a lack of resources results in weak services in competition with other disease control programmes (Moderate confidence). In this context of low investment, people face repeated tests and clinic visits, wasted time, and fraught social interaction with health providers (Moderate confidence). ACF can create expectations for follow-up health care that it cannot deliver (High confidence). Finally, community education improves awareness of tuberculosis in some settings, but lack of full information impacts community members, parents, and health workers, and sometimes leads to harm for children (High confidence). • Health workers are an undervalued but important part of ACF. ACF can feel difficult for health workers in the context of a poorly resourced health system and with people who may not wish to be identified. In addition, the evidence suggests health workers are poorly protected against tuberculosis and fear they or their families might become infected (Moderate confidence). However, they appear to be central to programme success, as the humanity they offer often acts as a driving force for retaining people with tuberculosis in care (Moderate confidence). • Local leadership is necessary but not sufficient for ensuring appropriate programmes. Local leadership creates an intrinsic motivation for communities to value health services (High confidence). However, local leadership cannot guarantee the success of ACF and contact tracing programmes. It is important to balance professional authority with local knowledge and rapport (High confidence).
Authors' conclusions:
Tuberculosis active case finding (ACF) and contact tracing bring a diagnostic service to people who may otherwise not receive it, such as those who are well or without symptoms and those who are sick but who have fewer resources and live further from health facilities. However, capturing these 'missing cases' may in itself be insufficient without appropriate health system strengthening to retain people in care. People who receive a tuberculosis diagnosis must contend with a complex and unsustainable cascade of care, and this affects their perception of ACF and their decision to engage with it.
In recognition of the high rates of undetected tuberculosis in the community, the World Health Organization (WHO) encourages targeted active case finding (ACF) among “high-risk” populations. While this strategy has led to increased case detection in these populations, the epidemic impact of these interventions has not been demonstrated. Historical data suggest that population-wide (untargeted) ACF can interrupt transmission in high-incidence settings, but implementation remains lacking, despite recent advances in screening tools. The reservoir of latent infection—affecting up to a quarter of the global population –complicates elimination efforts by acting as a pool from which future tuberculosis cases may emerge, even after all active cases have been treated. A holistic case finding strategy that addresses both active disease and latent infection is likely to be the optimal approach for rapidly achieving sustainable progress toward TB elimination in a durable way, but safety and cost effectiveness have not been demonstrated. Sensitive, symptom-agnostic community screening, combined with effective tuberculosis treatment and prevention, should eliminate all infectious cases in the community, whilst identifying and treating people with latent infection will also eliminate tomorrow’s tuberculosis cases. If real strides toward global tuberculosis elimination are to be made, bold strategies are required using the best available tools and a long horizon for cost-benefit assessment.
Background:
HPTN071 (PopART) was a cluster randomized trial conducted in Zambian and South African (SA) communities, between 2013-2018. The PopART intervention (universal HIV-testing and treatment (UTT) combined with population-level TB symptom screening) was implemented in 14 communities. The TREATS study (2017-2021) was conducted to evaluate the impact of the PopART intervention on TB outcomes. We report on the impact of the combined TB/HIV intervention on the incidence of TB infection in a cohort of adolescents and young adults (AYA) aged 15-24 years.
Methods:
A random sample of AYA was enrolled between July 2018 and July 2019 in 7 intervention vs 7 standard-of-care communities. We collected questionnaire data on risk factors for TB, and blood for measuring TB infection using QuantiFERON (QFT) Plus. AYA were seen at months 12 and 24 with all procedures repeated. Primary outcome was incidence of TB infection comparing intervention and standard-of-care communities. An incident case was defined as a participant with QFT interferon-gamma response of < 0.2 IU/ml plasma ('negative') at baseline and a QFT interferon-gamma response of > = 0.7 IU/ml ('positive') at follow up.
Results:
We enrolled 4,648 AYA, 2,223 (47.8%) had a negative QFT-plus result at baseline, 1,902 (85.6%) had a follow up blood sample taken at 12 months or 24 months. Among the 1,902 AYA, followed for 2,987 person-years, 213 had incident TB infection giving (7.1 per 100 person-years). TB infection incidence rates were 8.7 per 100 person-years in intervention communities compared to 6.0 per 100 person-years in standard-of-care communities. There was no evidence the intervention reduced the transmission of TB (incidence-rate-ratio of 1.45, 95%CI 0.97-2.15, p = 0.063).
Conclusion:
In our trial setting, we found no evidence that UTT combined with TB active case finding reduced the incidence of TB infection at population level. Our data will inform future modelling work to better understand the population level dynamics of HIV and TB.
Contact investigation is recommended for close contacts of TB patients to identify undiagnosed cases of active and latent TB to initiate them on curative and preventive therapy respectively. Because contact invitation is conducted in Kenya, the value of TB contact investigation in childhood TB control is unknown. To compare the yield of contact investigation (intervention arm) to contact invitation (control arm) in contributing to childhood TB control, a cluster randomized trial was conducted in Kisumu County between 2014 and 2015 a period prior to the implementation of standardized contact investigation. This was done to compare TB cases diagnosed and children receiving IPT in the pre- intervention (2012-2013) and intervention (2014-2015) years, and in the intervention years using a minimum sample size of 15 per arm. Of 77 facilities identified for the study, 65 facilities were randomized to a contact screening strategy; a TB contact investigation strategy in isolation (n=4), in combination with health facility screening (n=19), or in combination with both enhanced facility screening and mobile units (n=31) with the remainder, (n=11) randomized to the standard approach i.e. TB contact invitation. Facilities distribution did not differ by category of services or patient type. In the pre-intervention and post-intervention years, TB number of TB cases diagnosed in children increased by 20 (75% from intervention arm). During the intervention years TB cases decreased by 17 (29% from intervention arm); the intervention arm contributed to 100% and 75% of the children put on IPT whose implementation had just begun. Contact investigation enhanced childhood TB control in comparison to routine approaches. Critical support ought to be availed to the TB screening cascade to facilitate contact investigation and IPT implementation as well as ingrain contact investigation within existing community health systems.
Introduction:
Tuberculosis is the second most common infectious cause of death globally. Low TB case detection remains a major challenge to achieve the global End TB targets. This systematic review and meta-analysis aimed to determine whether training of health professionals and volunteers increase TB case detection.
Methods:
We performed a systematic review and meta-analysis of randomized control trials and non-randomized control trials reporting on the effectiveness of health professionals and volunteers training on TB case detection. We searched PubMed, SCOPUS, Cochrane Library, and reference sections of included articles from inception through to 15 February 2021, for studies published in English. Study screening, data extraction, and bias assessments were performed independently by two reviewers with third and fourth reviewers participating to resolve conflicts. The risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist. Meta-analyses were performed with a random effect model to estimate the effectiveness of training intervention on TB case detection.
Results:
Of the 2015 unique records identified through our search strategies, 2007 records were excluded following the screening, leaving eight studies to be included in the final systematic review and meta-analysis. The results showed that providing training to health professionals and volunteers significantly increased TB case detection (RR: 1.60, 95% CI: 1.53, 1.66). There was not a significant degree of heterogeneity across the included study on the outcome of interest (I2 = 0.00%, p = 0.667).
Conclusions:
Providing training to healthcare workers and volunteers can increase TB case detection.
Expansion of tuberculous preventive therapy (TPT) is essential to curb TB incidence and mortality among people with HIV (PWH), yet implementation has been slow. Innovative strategies to operationalize TPT are urgently needed. Here we present an evaluation of community-based identification and referral of PWH on completion of a six-month course of isoniazid in a highly prevalent region in rural South Africa. Using a community-based TB/HIV intensive case finding strategy, a team of nurses and lay workers identified community members with HIV who were without fever, night sweats, weight loss, or cough and referred them to the government primary care clinics for daily oral isoniazid, the only available TPT regimen. We measured monthly adherence and six-month treatment completion in the community-based identification and referral (CBR) group compared to those already engaged in HIV care. Adherence was measured by self-report and urine isoniazid metabolite testing. A multivariable analysis was performed to identify independent predictors of TPT completion. Among 240 participants, 81.7% were female, median age 35 years (IQR 30–44), and 24.6% had previously been treated for TB. The median CD4 count in the CBR group was 457 (IQR 301–648), significantly higher than the clinic-based comparison group median CD4 of 344 (IQR 186–495, p
The HPTN 071 (PopART) trial of universal HIV testing and treatment to reduce HIV incidence was conducted in nine communities in South Africa and 12 in Zambia. The trial's primary outcome results were complicated to explain. Dissemination of these complicated results in participating communities in Zambia was done using a community dialogue approach. The approach, which involved interactive activities and a gradual and systematic approach to discussion of results in each community, facilitated respect and inclusion of participants in the dissemination process. The use of local language, pictures, images, and familiar analogies enhanced comprehension of the findings and created a two-way communication process between researchers and participants. The dialogue approach enabled both groups to use community perspectives, lived experiences, and local socio-structural features to interpret the trial results. Further, community members reflected on what the results meant to them individually and collectively. Although this community dialogue was both productive and appreciated, making this community interpretation apparent across disciplines in key quantitative scientific outputs remained a challenge.
Importance:
Delayed engagement in tuberculosis (TB) services is associated with ongoing transmission and poor clinical outcomes.
Objective:
To assess whether patients with TB have differential preferences for strategies to improve the public health reach of TB diagnostic services.
Design, setting, and participants:
A cross-sectional study was undertaken in which a discrete choice experiment (DCE) was administered between September 18, 2019, and January 17, 2020, to 401 adults (>18 years of age) with microbiologically confirmed TB in Lusaka, Zambia. The DCE had 7 attributes with 2 to 3 levels per attribute related to TB service enhancements. Latent class analysis was used to identify segments of participants with unique preferences. Multiscenario simulations were used to estimate shares of preferences for different TB service improvement strategies.
Main outcomes and measures:
The main outcomes were patient preference archetypes and estimated shares of preferences for different strategies to improve TB diagnostic services. Collected data were analyzed between January 3, 2022, to July 2, 2022.
Results:
Among 326 adults with TB (median [IQR] age, 34 [27-42] years; 217 [66.8%] male; 158 [48.8%] HIV positive), 3 groups with distinct preferences for TB service improvements were identified. Group 1 (192 participants [58.9%]) preferred a facility that offered same-day TB test results, shorter wait times, and financial incentives for testing. Group 2 (83 participants [25.4%]) preferred a facility that provided same-day TB results, had greater privacy, and was closer to home. Group 3 (51 participants [15.6%]) had no strong preferences for service improvements and had negative preferences for receiving telephone-based TB test results. Groups 1 and 2 were more likely to report at least a 4-week delay in seeking health care for their current TB episode compared with group 3 (29 [51.3%] in group 1, 95 [35.8%] in group 2, and 10 [19.6%] in group 3; P < .001). Strategies to improve TB diagnostic services most preferred by all participants were same-day TB test results alone (shares of preference, 69.9%) and combined with a small financial testing incentive (shares of preference, 79.3%), shortened wait times (shares of preference, 76.1%), or greater privacy (shares of preference, 75.0%). However, the most preferred service improvement strategies differed substantially by group.
Conclusions and relevance:
In this study, patients with TB had heterogenous preferences for TB diagnostic service improvements associated with differential health care-seeking behavior. Tailored strategies that incorporate features most valued by persons with undiagnosed TB, including same-day results, financial incentives, and greater privacy, may optimize reach by overcoming key barriers to timely TB care engagement.
Trial designs using cluster-level randomization are necessary when interventions have intended effects that cannot be measured with individual randomization. When an intervention is intrinsically only able to be delivered to a cluster or when implementation of an individual level intervention is only feasibly implemented at a cluster level, cluster-level randomization is required. In designing the strategy for evaluation of the primary outcome of a cluster randomized trial, there are a multitude of important decisions to consider. While these decisions are guided primarily by the intervention—who benefits, what is the intended effect and when will it be achieved—there are important detailed choices that affect potential bias and statistical power, and implementation considerations that require compromise for considerations of feasibility and practicality. Through the lens of three large completed cluster randomized trials in HIV prevention, we present specific choices made for the overall evaluation plan, together with some of the detailed considerations, compromises and modifications that occurred during trial implementation.
Since 2012, the World Health Organization has recommended household contact investigation as an evidence-based intervention to find and treat individuals with active tuberculosis (TB), the most common infectious cause of death worldwide after COVID-19. Unfortunately, uptake of this recommendation has been suboptimal in low- and middle-income countries, where the majority of affected individuals reside, and little is known about how to effectively deliver this service. Therefore, we undertook a systematic process to design a novel, theory-informed implementation strategy to promote uptake of contact investigation in Uganda, using the COM-B (Capability-Opportunity-Motivation-Behavior) model and the Behavior Change Wheel (BCW) framework. We systematically engaged national, clinic-, and community-based stakeholders and collectively re-examined the results of our own formative, parallel mixed-methods studies. We identified three core behaviors within contact investigation that we wished to change, and multiple antecedents (i.e., barriers and facilitators) of those behaviors. The BCW framework helped identify multiple intervention functions targeted to these antecedents, as well as several policies that could potentially enhance the effectiveness of those interventions. Finally, we identified multiple behavior change techniques and policies that we incorporated into a multi-component implementation strategy, which we compared to usual care in a household cluster-randomized trial. We introduced some components in both arms, including those designed to facilitate initial uptake of contact investigation, with improvement relative to historical controls. Other components that we introduced to facilitate completion of TB evaluation—home-based TB-HIV evaluation and follow-up text messaging—returned negative results due to implementation failures. In summary, the Behavior Change Wheel framework provided a feasible and transparent approach to designing a theory-informed implementation strategy. Future studies should explore the use of experimental methods such as micro-randomized trials to identify the most active components of implementation strategies, as well as more creative and entrepreneurial methods such as human-centered design to better adapt the forms and fit of implementation strategies to end users.
Background:
Systematic screening in high-burden settings is recommended as a strategy for early detection of pulmonary tuberculosis disease, reducing mortality, morbidity and transmission, and improving equity in access to care. Questioning for symptoms and chest radiography (CXR) have historically been the most widely available tools to screen for tuberculosis disease. Their accuracy is important for the design of tuberculosis screening programmes and determines, in combination with the accuracy of confirmatory diagnostic tests, the yield of a screening programme and the burden on individuals and the health service.
Objectives:
To assess the sensitivity and specificity of questioning for the presence of one or more tuberculosis symptoms or symptom combinations, CXR, and combinations of these as screening tools for detecting bacteriologically confirmed pulmonary tuberculosis disease in HIV-negative adults and adults with unknown HIV status who are considered eligible for systematic screening for tuberculosis disease. Second, to investigate sources of heterogeneity, especially in relation to regional, epidemiological, and demographic characteristics of the study populations.
Search methods:
We searched the MEDLINE, Embase, LILACS, and HTA (Health Technology Assessment) databases using pre-specified search terms and consulted experts for unpublished reports, for the period 1992 to 2018. The search date was 10 December 2018. This search was repeated on 2 July 2021.
Selection criteria:
Studies were eligible if participants were screened for tuberculosis disease using symptom questions, or abnormalities on CXR, or both, and were offered confirmatory testing with a reference standard. We included studies if diagnostic two-by-two tables could be generated for one or more index tests, even if not all participants were subjected to a microbacteriological reference standard. We excluded studies evaluating self-reporting of symptoms.
Data collection and analysis:
We categorized symptom and CXR index tests according to commonly used definitions. We assessed the methodological quality of included studies using the QUADAS-2 instrument. We examined the forest plots and receiver operating characteristic plots visually for heterogeneity. We estimated summary sensitivities and specificities (and 95% confidence intervals (CI)) for each index test using bivariate random-effects methods. We analyzed potential sources of heterogeneity in a hierarchical mixed-model.
Main results:
The electronic database search identified 9473 titles and abstracts. Through expert consultation, we identified 31 reports on national tuberculosis prevalence surveys as eligible (of which eight were already captured in the search of the electronic databases), and we identified 957 potentially relevant articles through reference checking. After removal of duplicates, we assessed 10,415 titles and abstracts, of which we identified 430 (4%) for full text review, whereafter we excluded 364 articles. In total, 66 articles provided data on 59 studies. We assessed the 2 July 2021 search results; seven studies were potentially eligible but would make no material difference to the review findings or grading of the evidence, and were not added in this edition of the review. We judged most studies at high risk of bias in one or more domains, most commonly because of incorporation bias and verification bias. We judged applicability concerns low in more than 80% of studies in all three domains. The three most common symptom index tests, cough for two or more weeks (41 studies), any cough (21 studies), and any tuberculosis symptom (29 studies), showed a summary sensitivity of 42.1% (95% CI 36.6% to 47.7%), 51.3% (95% CI 42.8% to 59.7%), and 70.6% (95% CI 61.7% to 78.2%, all very low-certainty evidence), and a specificity of 94.4% (95% CI 92.6% to 95.8%, high-certainty evidence), 87.6% (95% CI 81.6% to 91.8%, low-certainty evidence), and 65.1% (95% CI 53.3% to 75.4%, low-certainty evidence), respectively. The data on symptom index tests were more heterogenous than those for CXR. The studies on any tuberculosis symptom were the most heterogeneous, but had the lowest number of variables explaining this variation. Symptom index tests also showed regional variation. The summary sensitivity of any CXR abnormality (23 studies) was 94.7% (95% CI 92.2% to 96.4%, very low-certainty evidence) and 84.8% (95% CI 76.7% to 90.4%, low-certainty evidence) for CXR abnormalities suggestive of tuberculosis (19 studies), and specificity was 89.1% (95% CI 85.6% to 91.8%, low-certainty evidence) and 95.6% (95% CI 92.6% to 97.4%, high-certainty evidence), respectively. Sensitivity was more heterogenous than specificity, and could be explained by regional variation. The addition of cough for two or more weeks, whether to any (pulmonary) CXR abnormality or to CXR abnormalities suggestive of tuberculosis, resulted in a summary sensitivity and specificity of 99.2% (95% CI 96.8% to 99.8%) and 84.9% (95% CI 81.2% to 88.1%) (15 studies; certainty of evidence not assessed).
Authors' conclusions:
The summary estimates of the symptom and CXR index tests may inform the choice of screening and diagnostic algorithms in any given setting or country where screening for tuberculosis is being implemented. The high sensitivity of CXR index tests, with or without symptom questions in parallel, suggests a high yield of persons with tuberculosis disease. However, additional considerations will determine the design of screening and diagnostic algorithms, such as the availability and accessibility of CXR facilities or the resources to fund them, and the need for more or fewer diagnostic tests to confirm the diagnosis (depending on screening test specificity), which also has resource implications. These review findings should be interpreted with caution due to methodological limitations in the included studies and regional variation in sensitivity and specificity. The sensitivity and specificity of an index test in a specific setting cannot be predicted with great precision due to heterogeneity. This should be borne in mind when planning for and implementing tuberculosis screening programmes.
BACKGROUND: Early presentation to healthcare facilities is critical for early diagnosis and treatment of TB. We studied self-reported time to care-seeking from the onset of TB symptoms among primary healthcare clinic (PHC) attendees in Limpopo Province, South Africa. METHODS: We used data from participants enrolled in a cluster-randomized trial of TB case finding in 56 PHC clinics across two health districts. We fitted log-normal accelerated failure time regression models and we present time ratios (TRs) for potential risk factors. RESULTS: We included 2,160 participants. Among the 1,757 (81%) diagnosed with active TB, the median time to care-seeking was 30 days (IQR 14–60); adults sought care later than children/adolescents (adjusted TR aTR 1.47, 95% CI 1.10–1.96). Among those not diagnosed with TB, the median was 14 days (IQR 7–60); being HIV-positive (aTR 1.57, 95% CI 1.03–2.40); having less than grade 8 education and currently smoking were associated with longer time to care-seeking. In the combined analysis, living with HIV and having underlying active TB was associated with faster care-seeking (TB status x HIV interaction: TR 0.68, 95% CI 0.48–0.96). CONCLUSION: Delay in care-seeking was associated with age, lower education and being a current smoker. TB awareness campaigns targeting these population groups may improve care-seeking behavior and reduce community TB transmission.
Background
Spatially-targeted approaches to screen for tuberculosis (TB) could accelerate TB control in high-burden populations. We aimed to estimate gains in case-finding yield under an adaptive decision-making approach for spatially-targeted, mobile digital chest radiography (dCXR)-based screening in communities with varying levels of TB prevalence.
Methods
We used a Monte-Carlo simulation model to simulate a spatially-targeted screening intervention in 24 communities with TB prevalence estimates derived from a large community-randomized trial. We implemented a Thompson sampling algorithm to allocate screening units based on Bayesian probabilities of local TB prevalence that are continuously updated during weekly screening rounds. Four mobile units for dCXR-based screening and subsequent Xpert Ultra-based testing were allocated among the communities during a 52-week period. We estimated the yield of bacteriologically-confirmed TB per 1,000 screenings comparing scenarios of spatially-targeted and untargeted resource allocation.
Results
We estimated that under the untargeted scenario, an expected 666 (95% uncertainty interval 522-825) TB cases would be detected over one year, equivalent to 8.9 (7.5-10.3) per 1,000 individuals screened. Allocating the screening units to the communities with the highest (prior-year) cases notification rates resulted in an expected 760 (617-926) TB cases detected, 10.1 (8.6-11.8) per 1,000 screened. Adaptive, spatially-targeted screening resulted in an expected 1,241 (995-1502) TB cases detected, 16.5 (14.5-18.7) per 1,000 screened. Numbers of dCXR-based screenings needed to find detect one additional TB case declined during the first 12-14 weeks as a result of Bayesian learning.
Conclusion
We introduce a spatially-targeted screening strategy that could reduce the number of screenings necessary to detect additional TB in high-burden settings and thus improve the efficiency of screening interventions. Empirical trials are needed to determine whether this approach could be successfully implemented.
The failure to control tuberculosis (TB) in recent times stems, at least in part, from complacency towards TB control in the 1970s and 1980s and the subsequent devastating impact of the HIV-1 pandemic, the rising emergence of drug resistance as well as the growing disparity in disease burden between developed and developing countries. Progress has also been hindered by the slow development of more effective tools such as point-of-care diagnostics and treatments for active and latent disease, preventive vaccines, and laboratory assays of disease progression, immune protection, and cure. This lack of progress is, in turn, related to a poor understanding of the fundamental relationship between Mycobacterium tuberculosis and the human host and especially the nature of what is referred to as ‘latent TB infection’. An increased focus on understanding the mechanics and drivers of transmission together with a concerted effort to translate research findings into policy and practice contextualized to local needs and resources is required. This chapter reviews recent advances in tackling tuberculosis, highlighting key unmet needs and strategies for an accelerated effort to achieve control.
Background
Household contact tracing for tuberculosis (TB) may facilitate TB diagnosis and identify individuals who may benefit from TB preventive therapy (TPT). In this cluster-randomised trial, we investigated whether household contact tracing and intensive TB/HIV screening would improve TB-free survival.
Methods
Household contacts of index TB patients in two Provinces of South Africa were randomised to home tracing and intensive HIV/TB screening (sputum Xpert and culture; HIV testing with treatment linkage; and TPT, if eligible), or standard of care (SOC, clinic referral letters). The primary outcome was incident TB or death at 15-months. Secondary outcomes included tuberculin skin test (TST) positivity in children ≤14 years and undiagnosed HIV. (ISRCTN16006202).
Results
From December 2016-March 2019, 1,032 index patients (4,459 contacts) and 1,030 (4,129 contacts) were randomised to the intervention and SOC arms. 3.2% (69/2166) of intervention arm contacts had prevalent microbiologically-confirmed TB. At 15-months, the cumulative incidence of TB or death did not differ between the intensive screening (93/3230, 2.9%) and SOC (80/2600, 3.1%) arms (hazard ratio: 0.90, 95% confidence interval (CI): 0.66-1.24). TST positivity was higher in the intensive screening arm (38/845, 4.5%) compared to the SOC arm (15/800, 1.9%, odds ratio: 2.25, 95% CI: 1.07-4.72). Undiagnosed HIV was similar between arms (41/3185, 1.3% vs. 32/2543, 1.3%; odds ratio: 1.02, 95% CI: 0.64-1.64).
Conclusions
Household contact tracing with intensive screening and referral did not reduce incident TB or death. Providing referral letters to household contacts of index patients is an alternative strategy to home visits in high TB/HIV-prevalence settings.
Background
As a part of Competency Based Medical Education (CBME) the competencies related to Communication skills, survey technique, can be improvised by exposing the students in community based Active Case Finding for Tuberculosis which helps in sustaining the activity.
Methods
Community based house-to-house survey using “Student centered approach” was carried out to identify Presumptive TB cases as per the program definition among fourteen villages covered by Thirubhuvanai, Primary Health Centre. The team comprised of trained MBBS student, medical interns supervised by Post graduates, Medical social workers posted at the Department of Community Medicine, of a medical college, Puducherry. After training Mobile based application (Epicollect5) was used for survey. Feedback from students were obtained to explore their experience from ACF. Free listing and pile sorting was done among interns to explore their experience on Epicollect using Visual Anthropic software.
Results
The major learning of the medical students from ACF activities were communication skills, rapport building with the community people, Screening for TB and their problem. Free listing identified 14 salient variables depending on the cut-off value of 0.083 (Smith’s Salience Score) and subjected to pile sorting. Cognitive map identified their experiences into three categories namely knowledge on TB screening, uses of Epicollect and paper-based questionnaire. Totally 19,134households were screened, among them 77 presumptive TB cases were identified, three positive pulmonary TB cases were detected and linked to TB care pathway.
Conclusion
“Student centered approach” proved to be effective strategy in ACF for TB from student’s reflection. This rigorous ACF outreach activity shares dual benefits individual and community level benefit and also programme level benefits. Implementing this approach of involving MBBS students in ACF activity was successful and it is feasible to continue every year propounded byNational TB Elimination Program (NTEP) guidelines.
Background:
Health services have traditionally been developed to focus on specific diseases or medical specialties. Involving consumers as partners in planning, delivering and evaluating health services may lead to services that are person-centred and so better able to meet the needs of and provide care for individuals. Globally, governments recommend consumer involvement in healthcare decision-making at the systems level, as a strategy for promoting person-centred health services. However, the effects of this 'working in partnership' approach to healthcare decision-making are unclear. Working in partnership is defined here as collaborative relationships between at least one consumer and health provider, meeting jointly and regularly in formal group formats, to equally contribute to and collaborate on health service-related decision-making in real time. In this review, the terms 'consumer' and 'health provider' refer to partnership participants, and 'health service user' and 'health service provider' refer to trial participants. This review of effects of partnership interventions was undertaken concurrently with a Cochrane Qualitative Evidence Synthesis (QES) entitled Consumers and health providers working in partnership for the promotion of person-centred health services: a co-produced qualitative evidence synthesis.
Objectives:
To assess the effects of consumers and health providers working in partnership, as an intervention to promote person-centred health services.
Search methods:
We searched the CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL databases from 2000 to April 2019; PROQUEST Dissertations and Theses Global from 2016 to April 2019; and grey literature and online trial registries from 2000 until September 2019.
Selection criteria:
We included randomised controlled trials (RCTs), quasi-RCTs, and cluster-RCTs of 'working in partnership' interventions meeting these three criteria: both consumer and provider participants meet; they meet jointly and regularly in formal group formats; and they make actual decisions that relate to the person-centredness of health service(s).
Data collection and analysis:
Two review authors independently screened most titles and abstracts. One review author screened a subset of titles and abstracts (i.e. those identified through clinical trials registries searches, those classified by the Cochrane RCT Classifier as unlikely to be an RCT, and those identified through other sources). Two review authors independently screened all full texts of potentially eligible articles for inclusion. In case of disagreement, they consulted a third review author to reach consensus. One review author extracted data and assessed risk of bias for all included studies and a second review author independently cross-checked all data and assessments. Any discrepancies were resolved by discussion, or by consulting a third review author to reach consensus. Meta-analysis was not possible due to the small number of included trials and their heterogeneity; we synthesised results descriptively by comparison and outcome. We reported the following outcomes in GRADE 'Summary of findings' tables: health service alterations; the degree to which changed service reflects health service user priorities; health service users' ratings of health service performance; health service users' health service utilisation patterns; resources associated with the decision-making process; resources associated with implementing decisions; and adverse events.
Main results:
We included five trials (one RCT and four cluster-RCTs), with 16,257 health service users and more than 469 health service providers as trial participants. For two trials, the aims of the partnerships were to directly improve the person-centredness of health services (via health service planning, and discharge co-ordination). In the remaining trials, the aims were indirect (training first-year medical doctors on patient safety) or broader in focus (which could include person-centredness of health services that targeted the public/community, households or health service delivery to improve maternal and neonatal mortality). Three trials were conducted in high income-countries, one was in a middle-income country and one was in a low-income country. Two studies evaluated working in partnership interventions, compared to usual practice without partnership (Comparison 1); and three studies evaluated working in partnership as part of a multi-component intervention, compared to the same intervention without partnership (Comparison 2). No studies evaluated one form of working in partnership compared to another (Comparison 3). The effects of consumers and health providers working in partnership compared to usual practice without partnership are uncertain: only one of the two studies that assessed this comparison measured health service alteration outcomes, and data were not usable, as only intervention group data were reported. Additionally, none of the included studies evaluating this comparison measured the other primary or secondary outcomes we sought for the 'Summary of findings' table. We are also unsure about the effects of consumers and health providers working in partnership as part of a multi-component intervention compared to the same intervention without partnership. Very low-certainty evidence indicated there may be little or no difference on health service alterations or health service user health service performance ratings (two studies); or on health service user health service utilisation patterns and adverse events (one study each). No studies evaluating this comparison reported the degree to which health service alterations reflect health service user priorities, or resource use. Overall, our confidence in the findings about the effects of working in partnership interventions was very low due to indirectness, imprecision and publication bias, and serious concerns about risk of selection bias; performance bias, detection bias and reporting bias in most studies.
Authors' conclusions:
The effects of consumers and providers working in partnership as an intervention, or as part of a multi-component intervention, are uncertain, due to a lack of high-quality evidence and/or due to a lack of studies. Further well-designed RCTs with a clear focus on assessing outcomes directly related to partnerships for patient-centred health services are needed in this area, which may also benefit from mixed-methods and qualitative research to build the evidence base.
Screening for tuberculosis (TB) disease aims to improve early TB case detection. The ultimate goal is to improve outcomes for people with TB and to reduce Mycobacterium tuberculosis transmission in the community through improved case detection, reduction in diagnostic delays and early treatment. Before screening programmes are recommended, evidence is needed of individual and/or community-level benefits.
We conducted a systematic review of the literature to assess the evidence that screening for TB disease 1) initially increases the number of TB cases initiated on anti-tuberculosis treatment, 2) identifies cases earlier in the course of disease, 3) reduces mortality and morbidity, and 4) impacts on TB epidemiology.
A total of 28 798 publications were identified by the search strategy: 27 087 were excluded on initial screening and 1749 on full text review, leaving 62 publications that addressed at least one of the study questions. Screening increases the number of cases found in the short term. In many settings, more than half of the prevalent TB cases in the community remain undiagnosed. Screening tends to find cases earlier and with less severe disease, but this may be attributed to case-finding studies using more sensitive diagnostic methods than routine programmes. Treatment outcomes among people identified through screening are similar to outcomes among those identified through passive case finding. Current studies provide insufficient evidence to show that active screening for TB disease impacts on TB epidemiology.
Individual and community-level benefits from active screening for TB disease remain uncertain. So far, the benefits of earlier diagnosis on patient outcomes and transmission have not been established.
South Africa has a high prevalence of tuberculosis (TB) and HIV-coinfected adults in whom TB is often diagnosed late in the course of disease.
Improved case-finding approaches for TB and HIV are needed to reduce mortality and prevent transmission.
We identified newly diagnosed index TB cases in a rural district and enrolled their households in a TB-HIV contact-tracing study. A group of randomly selected control households were enrolled to determine community prevalence of undetected TB and HIV. Field teams screened participants for TB symptoms, collected sputum specimens for smear microscopy and culture, provided HIV counseling and testing, and collected blood for CD4 testing. Participants were referred to public clinics for TB treatment and antiretroviral therapy.
We evaluated 2,843 household contacts of 727 index patients with TB and 983 randomly selected control household members. The prevalence of TB in household contacts was 6,075 per 100,000 (95% confidence interval, 5,789-6,360 per 100,000), whereas the prevalence detected in randomly selected households was 407 per 100,000 (95% confidence interval, 0-912 per 100,000; prevalence difference, 5,668 per 100,000; P < 0.001). TB detected among contacts was less likely to be smear-positive than in the index patients (6% vs. 22%; P < 0.001). Most contacts with culture-confirmed TB were asymptomatic. At least one case of undiagnosed TB was found in 141 (19%) of 727 contact versus 4 (1%) of 312 control households. HIV testing was positive in 166 (11%) of 1,568 contacts tested versus 76 (14%) of 521 control participants tested (odds ratio, 1.48; P = 0.02).
Active case finding in TB contact households should be considered to improve TB and HIV case detection in high-prevalence settings, but sensitive diagnostic tools are necessary.
Limited information exists on the prevalence of tuberculosis and adequacy of case finding in African populations with high rates of HIV. Objectives: To estimate the prevalence of bacteriologically confirmed pulmonary tuberculosis (PTB) and the fraction attributable to HIV, and to evaluate case detection.
Residents aged 15 years and older, from 40 randomly sampled clusters, provided two sputum samples for microscopy; those with chest radiograph abnormalities or symptoms suggestive of PTB provided one additional sputum sample for culture.
PTB was defined by a culture positive for Mycobacterium tuberculosis or two positive smears. Persons with PTB were offered HIV testing and interviewed on care-seeking behavior. We estimated the population-attributable fraction of HIV on prevalent and notified PTB, the patient diagnostic rate, and case detection rate using provincial TB notification data. Among 20,566 participants, 123 had PTB. TB prevalence was 6.0/1,000 (95% confidence interval, 4.6-7.4) for all PTB and 2.5/1,000 (1.6-3.4) for smear-positive PTB. Of 101 prevalent TB cases tested, 52 (51%) were HIV infected, and 58 (64%) of 91 cases who were not on treatment and were interviewed had not sought care. Forty-eight percent of prevalent and 65% of notified PTB cases were attributable to HIV. For smear-positive and smear-negative PTB combined, the patient diagnostic rate was 1.4 cases detected per person-year among HIV-infected persons having PTB and 0.6 for those who were HIV uninfected, corresponding to case detection rates of 56 and 65%, respectively.
Undiagnosed PTB is common in this community. TB case finding needs improvement, for instance through intensified case finding with mobile smear microscopy services, rigorous HIV testing, and improved diagnosis of smear-negative TB.
Control of tuberculosis in settings with high HIV prevalence is a pressing public health priority. We tested two active case-finding strategies to target long periods of infectiousness before diagnosis, which is typical of HIV-negative tuberculosis and is a key driver of transmission.
Clusters of neighbourhoods in the high-density residential suburbs of Harare, Zimbabwe, were randomised to receive six rounds of active case finding at 6-monthly intervals by either mobile van or door-to-door visits. Randomisation was done by selection of discs of two colours from an opaque bag, with one disc to represent every cluster, and one colour allocated to each intervention group before selection began. In both groups, adult (≥16 years) residents volunteering chronic cough (≥2 weeks) had two sputum specimens collected for fluorescence microscopy. Community health workers and cluster residents were not masked to intervention allocation, but investigators and laboratory staff were masked to allocation until final analysis. The primary outcome was the cumulative yield of smear-positive tuberculosis per 1000 adult residents, compared between intervention groups; analysis was by intention to treat. The secondary outcome was change in prevalence of culture-positive tuberculosis from before intervention to before round six of intervention in 12% of randomly selected households from the two intervention groups combined; analysis was based on participants who provided sputum in the two prevalence surveys. This trial is registered, number ISRCTN84352452.
46 study clusters were identified and randomly allocated equally between intervention groups, with 55 741 adults in the mobile van group and 54,691 in the door-to-door group at baseline. HIV prevalence was 21% (1916/9060) and in the 6 months before intervention the smear-positive case notification rate was 2·8 per 1000 adults per year. The trial was completed as planned with no adverse events. The mobile van detected 255 smear-positive patients from 5466 participants submitting sputum compared with 137 of 4711 participants identified through door-to-door visits (adjusted risk ratio 1·48, 95% CI 1·11-1·96, p=0·0087). The overall prevalence of culture-positive tuberculosis declined from 6·5 per 1000 adults (95% CI 5·1-8·3) to 3·7 per 1000 adults (2·6-5·0; adjusted risk ratio 0·59, 95% CI 0·40-0·89, p=0·0112).
Wide implementation of active case finding, particularly with a mobile van approach, could have rapid effects on tuberculosis transmission and disease.
Wellcome Trust.
The annual risk of tuberculous infection (ARTI) is a key epidemiological indicator of the extent of transmission in a community. Several methods have been suggested to estimate the prevalence of tuberculous infection using tuberculin skin test data. This paper explores the implications of using different methods to estimate prevalence of infection and ARTI. The effect of BCG vaccination on these estimates is also investigated.
Tuberculin surveys among school children in 16 communities in Zambia and 8 in South Africa (SA) were performed in 2005, as part of baseline data collection and for randomisation purposes of the ZAMSTAR study. Infection prevalence and ARTI estimates were calculated using five methods: different cut-offs with or without adjustments for sensitivity, the mirror method, and mixture analysis. A total of 49,835 children were registered for the surveys, of which 25,048 (50%) had skin tests done and 22,563 (90%) of those tested were read. Infection prevalence was higher in the combined SA than Zambian communities. The mirror method resulted in the least difference of 7.8%, whereas that estimated by the cut-off methods varied from 12.2% to 17.3%. The ARTI in the Zambian and SA communities was between 0.8% and 2.8% and 2.5% and 4.2% respectively, depending on the method used. In the SA communities, the ARTI was higher among the younger children. BCG vaccination had little effect on these estimates.
ARTI estimates are dependent on the calculation method used. All methods agreed that there were substantial differences in infection prevalence across the communities, with higher rates in SA. Although TB notification rates have increased over the past decades, the difference in cumulative exposure between younger and older children is less dramatic and a rise in risk of infection in parallel with the estimated incidence of active tuberculosis cannot be excluded.
Harare's high density suburbs.
To investigate the burden, duration and risk factors for prevalent tuberculosis (TB) and explore potential control strategies.
Randomly selected adults had TB culture, symptom screen and human immunodeficiency virus (HIV) serology. Prevalent TB was defined as undiagnosed or still culture-positive. Notification data and HIV prevalence in TB out-patients were used to estimate duration of infectiousness (prevalence/estimated incidence).
Among 10 092 participants, 40 (0.40%, 95%CI 0.28-0.54) had prevalent smear-positive TB. HIV (adjusted odds ratio [aOR] 3.1, 95%CI 1.6-6.3, population attributable fraction [PAF] 33%), male sex (aOR 3.1, 95%CI 1.5-6.4, PAF 40%), and overcrowding (PAF 34%) were significant risk factors, with past TB treatment significant for HIV-negative participants only (PAF 7%). Recent household TB contact was not significant (PAF 10%). HIV prevalence was 21.1%; 76.9% of HIV-positive participants were previously untested. Duration of infectiousness was at least 18 weeks in HIV-positive and approximately 1 year in HIV-negative patients.
Overcrowding, male sex and HIV infection were major risk factors for prevalent smear-positive TB. Reducing diagnostic delay may have greater potential to improve the control of prevalent TB than interventions targeted at household contacts, TB treatment outcomes, or TB-HIV interventions under current levels of awareness of HIV status.
The Stop TB Partnership target for tuberculosis is to have reduced the prevalence of tuberculosis by 50% comparing 2015 to 1990. This target is challenging as few prevalence surveys have been conducted, especially in high burden tuberculosis and HIV countries. Current tuberculosis control strategies in high HIV prevalent settings are therefore based on limited epidemiological evidence and more evidence is needed from community-based surveys to inform improved policy formulation.
8044 adults were sampled from 2 sub-districts (wards) in Lusaka province, Zambia. Questionnaires were used to screen for symptoms, respiratory samples were obtained for culture and oral secretions collected for HIV testing. 79 individuals were found to have Mycobacterium tuberculosis in their sputum, giving an adjusted overall prevalence of tuberculosis of 870/100,000 (95% CI 570-1160/100,000). The adjusted overall prevalence of HIV was 28.61% (95% CI 26.04-31.19). HIV- infection was significantly associated with prevalent tuberculosis (Adj OR 2.3, 95% CI 1.42-3.74) and the population attributable fraction of HIV for prevalent tuberculosis was 36%. Symptoms such as prolonged cough (adj OR 12.72, 95% CI 7.05-22.94) and fever (Adj OR 2.04, 95%CI 1.23-3.39), were associated with prevalent tuberculosis, but 8 (10%) individuals with prevalent tuberculosis denied having any symptoms at all and only 34 (43%) would have been classified as a TB suspect by current guidelines.
Undiagnosed tuberculosis is a challenge for tuberculosis control and new approaches are needed if we are to reach international targets. Epidemiological studies can inform screening algorithms for both detection and prevention of active tuberculosis.
TB and HIV form a deadly synergy in much of the developing world, especially Africa. Interventions to reduce the impact of these diseases at community level are urgently needed. This paper presents the design of a community randomised trial to evaluate the impact of two complex interventions on the prevalence of tuberculosis (TB) in high HIV prevalence settings in Zambia and South Africa.
The interaction between TB and HIV is reviewed and possible interventions that could reduce the prevalence of TB in HIV-endemic populations are discussed. Two of these interventions are described in detail and the design of a 2 x 2 factorial community randomised trial to test these interventions is presented. The limitations and challenges of the design are identified and discussed.
There is an urgent need to reduce the prevalence of TB in communities highly affected by HIV. Potential interventions are complex and require innovative trial designs to provide the rigorous evidence needed to inform health policy makers and to ensure that resources are used optimally.
Number: ISRCTN36729271.
The objective of this study was to identify risk factors for ongoing community transmission of tuberculosis (TB) in two densely populated urban communities with a high incidence rate of TB in Cape Town, South Africa.
Between 1993 and 1998 DNA fingerprints of mycobacterial isolates from TB patients were determined by restriction fragment length polymorphism (RFLP). Cases whose isolates shared identical fingerprint patterns were considered to belong to the same cluster and to be attributable to ongoing community transmission.
The average annual notification rate of new smear positive TB was 238/100000. In all, 1023/1526 reported patients were culture positive, and RFLP was available for 768 (75%) of the isolates from these patients. Since some patients experienced more than one infection during the study period, 797 cases were included in the analysis. Of the cases, 575/797 (72%) were clustered. Smear-positive cases and those who were retreated after default were more likely to be clustered than smear-negative and new cases, respectively. Patients from Uitsig were more often part of large clusters than were patients from Ravensmead. Age, sex, year of diagnosis, and outcome of disease were not risk factors for clustering, nor for being the first case in a cluster, although various analytical approaches were used.
The incidence and proportion of cases that are clustered in this area are higher than reported elsewhere. An overwhelming majority of TB cases in this area is attributed to ongoing community transmission, and only very few to reactivation. This may explain the lack of demographic risk factors for clustering.
Neonatal deaths in developing countries make the largest contribution to global mortality in children younger than 5 years. 90% of deliveries in the poorest quintile of households happen at home. We postulated that a community-based participatory intervention could significantly reduce neonatal mortality rates.
We pair-matched 42 geopolitical clusters in Makwanpur district, Nepal, selected 12 pairs randomly, and randomly assigned one of each pair to intervention or control. In each intervention cluster (average population 7000), a female facilitator convened nine women's group meetings every month. The facilitator supported groups through an action-learning cycle in which they identified local perinatal problems and formulated strategies to address them. We monitored birth outcomes in a cohort of 28?931 women, of whom 8% joined the groups. The primary outcome was neonatal mortality rate. Other outcomes included stillbirths and maternal deaths, uptake of antenatal and delivery services, home care practices, infant morbidity, and health-care seeking. Analysis was by intention to treat. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN31137309.
From 2001 to 2003, the neonatal mortality rate was 26.2 per 1000 (76 deaths per 2899 livebirths) in intervention clusters compared with 36.9 per 1000 (119 deaths per 3226 livebirths) in controls (adjusted odds ratio 0.70 [95% CI 0.53-0.94]). Stillbirth rates were similar in both groups. The maternal mortality ratio was 69 per 100000 (two deaths per 2899 livebirths) in intervention clusters compared with 341 per 100000 (11 deaths per 3226 livebirths) in control clusters (0.22 [0.05-0.90]). Women in intervention clusters were more likely to have antenatal care, institutional delivery, trained birth attendance, and hygienic care than were controls.
Birth outcomes in a poor rural population improved greatly through a low cost, potentially sustainable and scalable, participatory intervention with women's groups.
The proportion of cases of tuberculosis due to recent infection can be estimated in long-term population-based studies using molecular techniques. Here, we present what is, to our knowledge, the first such study in an area with high human immunodeficiency virus (HIV) prevalence.
All patients with tuberculosis in Karonga District, Malawi, were interviewed. Isolates were genotyped using restriction-fragment-length polymorphism (RFLP) patterns. Strains were considered to be "clustered" if at least 1 other patient had an isolate with an identical pattern.
RFLP results were available from 83% of culture-positive patients from late 1995 to early 2003. When strains with <5 bands were excluded, 72% (682/948) were clustered. Maximum clustering was reached using a 4-year window, with an estimated two-thirds of cases due to recent transmission. The proportion clustered decreased with age and varied by area of residence. In older adults, clustering was less common in men and more common in patients who were HIV positive (adjusted odds ratio, 5.1 [95% confidence interval, 2.1-12.6]).
The proportion clustered found in the present study was among the highest in the world, suggesting high rates of recent transmission. The association with HIV infection in older adults may suggest that HIV has a greater impact on disease caused by recent transmission than on that caused by reactivation.
Lack of health insurance adversely affects children's health. Eight million US children are uninsured, with Latinos being the racial/ethnic group at greatest risk for being uninsured. A randomized, controlled trial comparing the effectiveness of various public insurance strategies for insuring uninsured children has never been conducted.
To evaluate whether case managers are more effective than traditional methods in insuring uninsured Latino children.
Randomized, controlled trial conducted from May 2002 to August 2004.
A total of 275 uninsured Latino children and their parents were recruited from urban community sites in Boston.
Uninsured children were assigned randomly to an intervention group with trained case managers or a control group that received traditional Medicaid and State Children's Health Insurance Program (SCHIP) outreach and enrollment. Case managers provided information on program eligibility, helped families complete insurance applications, acted as a family liaison with Medicaid/SCHIP, and assisted in maintaining coverage.
Obtaining health insurance, coverage continuity, the time to obtain coverage, and parental satisfaction with the process of obtaining insurance for children were assessed. Subjects were contacted monthly for 1 year to monitor outcomes by a researcher blinded with respect to group assignment.
One hundred thirty-nine subjects were assigned randomly to the intervention group and 136 to the control group. Intervention group children were significantly more likely to obtain health insurance (96% vs 57%) and had approximately 8 times the adjusted odds (odds ratio: 7.78; 95% confidence interval: 5.20-11.64) of obtaining insurance. Seventy-eight percent of intervention group children were insured continuously, compared with 30% of control group children. Intervention group children obtained insurance significantly faster (mean: 87.5 vs 134.8 days), and their parents were significantly more satisfied with the process of obtaining insurance.
Community-based case managers are more effective than traditional Medicaid/SCHIP outreach and enrollment in insuring uninsured Latino children. Case management may be a useful mechanism to reduce the number of uninsured children, especially among high-risk populations.
Although failure of tuberculosis (TB) control in sub-Saharan Africa is attributed to the HIV epidemic, it is unclear why the directly observed therapy short-course (DOTS) strategy is insufficient in this setting. We conducted a cross-sectional survey of pulmonary TB (PTB) and HIV infection in a community of 13,000 with high HIV prevalence and high TB notification rate and a well-functioning DOTS TB control program.
Active case finding for PTB was performed in 762 adults using sputum microscopy and Mycobacterium tuberculosis culture, testing for HIV, and a symptom and risk factor questionnaire. Survey findings were correlated with notification data extracted from the TB treatment register.
Of those surveyed, 174 (23%) tested HIV positive, 11 (7 HIV positive) were receiving TB therapy, 6 (5 HIV positive) had previously undiagnosed smear-positive PTB, and 6 (4 HIV positive) had smear-negative/culture-positive PTB. Symptoms were not a useful screen for PTB. Among HIV-positive and -negative individuals, prevalence of notified smear-positive PTB was 1,563/100,000 and 352/100,000, undiagnosed smear-positive PTB prevalence was 2,837/100,000 and 175/100,000, and case-finding proportions were 37 and 67%, respectively. Estimated duration of infectiousness was similar for HIV-positive and HIV-negative individuals. However, 87% of total person-years of undiagnosed smear-positive TB in the community were among HIV-infected individuals.
PTB was identified in 9% of HIV-infected individuals, with 5% being previously undiagnosed. Lack of symptoms suggestive of PTB may contribute to low case-finding rates. DOTS strategy based on passive case finding should be supplemented by active case finding targeting HIV-infected individuals.
The tuberculosis (TB) notification rate is high and increasing in 2 communities in Cape Town, South Africa. In 2002, we conducted a prevalence survey among adults > or = 15 years of age to determine the TB prevalence rate; 15% of households in these communities were randomly sampled. All persons living in sampled households were eligible for chest radiography and sputum examination. Of the 3,483 adults who completed a questionnaire, 2,608 underwent chest radiography and sputum examination. We detected 26 bacteriologically confirmed TB cases and a prevalence of 10.0/1,000 (95% confidence interval [CI] 6.2-13.8 per 1,000). We found 18 patients with smear-positive TB, of whom 8 were new patients (3.1/1,000, 95% CI 0.9-5.1/1,000). More than half of patients with smear-positive TB (10, 56%) had previously been treated. Such patients may contribute to transmission of Mycobacterium tuberculosis and the high TB prevalence rate. Successful treatment of TB patients must be a priority.
Antiretroviral therapy (ART) has been proposed as an intervention for reducing tuberculosis (TB) burdens in areas with high HIV prevalence. However, little data is available on the impact of ART on population-level TB.
Trends in adult TB case fatality and notifications were assessed before and during increasing ART coverage in a well-defined periurban community, from 1997 to 2008. Mean changes in TB rates were measured using linear autoregression models. ART coverage increased from 1% in 2003 to 5%, 13%, and 21% of HIV-infected population in 2004, 2005, and 2008, respectively.
From 1997 to end of 2004 TB notification rates increased by an average of 187 cases/100,000/year (P < 0.001), reaching a peak of 2536/100,000 in 2005. From 2005 to 2008, TB notification rates declined by approximately 202 cases/100,000/year (P < 0.001). TB rates were initially stable in HIV-uninfected individuals, but declined moderately from 2005. TB rates declined in HIV-infected adults from 6513/100,000 in 2005 to 4741/100,000 in 2008. The predominant decline in TB notifications occurred among HIV-infected patients receiving ART (1156 cases/100,000/year) and was less marked in those not receiving ART (416 cases/100,000/year). Similarly, TB case fatality was constant for HIV-uninfected individuals, but declined in HIV-infected individuals from 23% in 2002 to 8% in 2008 (P = 0.01).
In this community heavily affected by both HIV and TB epidemics, rapid and high ART coverage was associated with significant reductions in TB notifications and TB-associated case fatality.
A large, impoverished squatters' settlement (favela), Rio de Janeiro, Brazil.
To assess the community impact of active case finding for tuberculosis (TB) compared to an enhanced case-finding strategy.
A pair-matched, cluster-randomized trial comparing household symptom screening and spot sputum collection (Arm 1) vs. distribution of an educational pamphlet (Arm 2) was performed in a large Brazilian favela. We compared TB case-notification rates, time from symptom onset to treatment start and treatment completion proportions between arms. Fourteen neighborhoods (estimated population 58,587) were pair-matched by prior TB case rates and randomly allocated to one of two interventions. TB was diagnosed using acid-fast bacilli smears. New TB cases were interviewed and clinic records were reviewed.
A total of 193 TB cases were identified in the 14 study neighborhoods (incidence proportion 329 per 100,000 population). The case identification rate in Arm 1 was 934/100,000 person-years (py) vs. 604/100,000 py in Arm 2 (RR 1.55, 95%CI 1.10-1.99). No significant differences were found in time from cough onset to treatment start or proportion completing treatment.
A door-to-door case-finding campaign was more effective (while ongoing) at detecting prevalent cases and influencing people to come for care than leafleting, but no differences were seen in time to treatment start or treatment completion.
Central Rio de Janeiro, Brazil.
To compare the impact of routine DOTS vs. enhanced DOTS (DOTS-Ampliado or DOTS-A) on tuberculosis (TB) incidence.
Cluster-randomized trial in eight urban neighborhoods pair-matched by TB incidence and randomly assigned to receive either the DOTS-A or DOTS strategy. DOTS-A added intensive screening of household contacts of active TB cases and provision of treatment to secondary cases and preventive therapy to contacts with latent TB infection (LTBI) to the standard DOTS strategy. The primary endpoint was the TB incidence rates in communities after 5 years of intervention.
From November 2000 to December 2004, respectively 339 and 311 pulmonary TB cases were enrolled and 1003 and 960 household were identified in DOTS and DOTS-A communities. Among contacts from DOTS-A communities, 26 (4%) had active TB diagnosed and treated, 429 (61.3%) had LTBI detected and 258 (60.1%) started preventive therapy. TB incidence increased by 5% in DOTS communities and decreased by 10% in DOTS-A communities, for a difference of 15% after 5 years (P = 0.04).
DOTS-A was associated with a modest reduction in TB incidence and may be an important strategy for reducing the burden of TB.
A small number of clusters and substantial variation between clusters increase the chance of unbalanced randomization in cluster randomized trials. Baseline imbalances between groups may distort intervention effects. When adjusting for imbalances in the cluster-level analysis, this results in loss of degrees of freedom. Variance reduction that can be achieved through stratification and blocking is limited. Restricted randomization is an alternative approach that ensures balanced allocation.
We present the randomization scheme used in the ZAMSTAR trial of tuberculosis control interventions in Southern Africa.
We used stratification and restriction to randomize 24 clusters (16 Zambian, 8 South African) into four intervention groups in a 2 x 2 factorial design. Stratification was by country and tuberculous infection prevalence and restriction by tuberculous infection prevalence, HIV prevalence, urban/rural, social context, and geographical location. Balance was defined in terms of covariate-specific tolerance thresholds for the measure of imbalance. For binary (0/1) covariates we defined imbalance = max(S(i)) - min(S(i)), where, S(i) was the number of 1s in group i = 1,2,3,4. For continuous covariates we defined imbalance = (max(M(i)) - min(M(i)))/ min(M(i) ), where, M( i) was the average in group i = 1,2,3,4.We used simulation to estimate the restriction factor (proportion of unacceptable allocations) both for individual covariates and overall. Simulation was also used to investigate the validity of the restricted randomization design, with the use of the validity matrix, by monitoring the probability that any given pair of clusters is allocated to the same intervention group.
There were 3 657 930 400 possible ways of allocating the 24 clusters to the four groups after stratification. With a combined restriction factor of 0.998 this still left 7 million acceptable allocations. The final allocation was selected at a public ceremony from a randomly-generated list of acceptable allocations. The design of the allocation process was observed to be valid.
The restricted randomization scheme significantly decreased the total number of available allocations of clusters into intervention groups.
Our restricted randomization was successful in that it achieved good balance while preserving the impartiality and validity of the trial.
During recruitment to a prospective study of tuberculosis patients in Lusaka, Zambia, 109 had pulmonary disease proven by sputum culture for Mycobacterium tuberculosis, of whom 72 were HIV-1 antibody-positive and 37 were HIV-negative. Among these culture-proven cases, 43% of the HIV-positive patients had a negative sputum smear, compared with 24% of the HIV-negative cases. There was a strong trend towards lower grade or negative sputum smear in the HIV-positive group (P = 0.003). HIV-positive cases also had lower colony counts on culture and colonies took longer to appear. The findings imply that cases of HIV-associated pulmonary tuberculosis may frequently be missed and emphasise the need for new diagnostic methods.
This Supplement provides an update on guidelines first published in 1996 on conducting a tuberculin skin test survey and analyzing the resulting data. The updated guidelines add experiences gained from community surveys, revisit the proposed sampling strategies, and provide additional information on ethical considerations.
Many aspects of the natural history of tuberculosis are poorly understood. Though it is recognized that clinical tuberculosis may follow shortly after initial infection (‘primary’ disease), or many years thereafter through either endogenous reactivation or after reinfection, the relative importance of these mechanisms is often disputed. The issue is complicated by the fact that the risks of developing disease are age-dependent, and reflect infection risks which may change over time.
This paper estimates the age-dependent risks of developing tuberculosis using an age-structured deterministic model of the dynamics of tuberculous infection and disease in England and Wales since 1900. The work extends the classical studies of Sutherland and colleagues. The best estimates of the risks of developing ‘primary’ disease (within 5 years of initial infection) were approximately 4%, 9% and 14% for individuals infected at ages 0–10, 15 years and over 20 years respectively, and a previous infection appeared to impart little protection against (further) reinfection, but 16–41% protection against disease subsequent to reinfection for adolescents and adults. We also provide evidence that reinfection made an important contribution to tuberculous morbidity in the past, as (i) exclusion of exogenous disease from the model considerably worsened the fit to observed notification rates, and (ii) the dramatic decline in the risk of tuberculous infection from 1950 in England and Wales accelerated the decline in morbidity among all individuals, even among the older age groups with a high prevalence of tuberculous infection. We conclude that the risk of infection is the single most important factor affecting the magnitude of the tuberculous morbidity in a population, as it determines both the age pattern of initial infection (and hence the risk of developing disease) and the risk of reinfection.
Gold miners have very high rates of tuberculosis. The contribution of infections imported into mining communities versus transmission within them is not known and has implications for control strategies.
We did a prospective, population-based molecular and conventional epidemiological study of pulmonary tuberculosis in a group of goldminers. Clusters were defined as groups of patients with Mycobacterium tuberculosis isolates with identical IS6110 DNA fingerprints. We compared the frequency of possible risk factors in the clustered and non-clustered patients whose isolates had fingerprints with more than four bands, and re-interviewed members of 45 clusters.
Of 448 patients, ten were excluded because they had false-positive cultures. Fingerprints were made in 419 of 438, of which 371 had more than four bands. 248 of 371 were categorised into 62 clusters. At least 50% of tuberculosis cases were due to transmission within the community. Patients who had failed treatment at entry to the study were more likely to be in clusters (adjusted odds ratio 3.41 [95% CI 1.25-9.27]). Patients with multidrug-resistant isolates were more likely to have failed treatment but were less likely to be clustered than those with a sensitive strain (0.27 [0.09-0.83]). HIV infection was common (177 of 370 tested) but not associated with clustering.
Despite a control programme that cures 86% of new cases, most tuberculosis in this mining community is due to ongoing transmission. Persistently infectious individuals who have previously failed treatment may be responsible for one third of tuberculosis cases. WHO targets for cure rates are not sufficient to interrupt transmission of tuberculosis in this setting. Indicators that are more closely linked to the rate of ongoing transmission are needed.
The fight against AIDS, TB and malaria is dependent on many inputs. Among these are drugs, diagnostics and vaccines. Starting with drugs, the world urgently needs drugs against the three diseases which are low-cost, easy to administer, safe, and effective. The picture today is not good. For HIV/AIDS, the current drugs prolong life but do not cure. Although prices have fallen dramatically in the past three years, they remain expensive. They have substantial side effects for many patients and need to be taken for the remainder of a person's life. For tuberculosis, the main problem is that the drugs, while effective, have to be taken for six months or more in order to effect a cure. In addition, resistance of the bacillus to a range of the more commonly used drugs is rising rapidly, creating the phenomenon of multi-drug resistant tuberculosis. This is both very expensive and very difficult to treat. For malaria, widespread resistance to the first and second generation antimalarial drugs is now forcing country after country to switch to the more expensive, but highly effective, artemisinin-combination therapies (ACTs). These products are not ideal; they have a relatively short shelf-life, their safety for pregnant women is not certain, and the production process involves cultivation of plant material in China.
Despite a history of remarkable scientific achievements in microbiology and therapeutics, tuberculosis (TB) continues to pose an extraordinary threat to human health. Case finding and treatment of TB disease are the principal means of controlling transmission and reducing incidence. This review presents a historical perspective of active case finding (ACF) of TB, detailing case detection strategies that have been used over the last century. This review is divided into the following sections: mass radiography, house-to-house surveys, out-patient case detection, enhanced case finding, high-risk populations and cost-effectiveness. The report concludes with a discussion and recommendations for future case finding strategies. Understanding the strengths and weaknesses of these methods will help inform and shape ACF as a TB control policy in the twenty-first century.
The Lancet Maternal Health series is largely uncontroversial: there is unanimity about the need for more investment political commitment and research to reduce the unacceptable annual burden of half a million maternal deaths. There is also no doubt that a delivery attended by a skilled attendant in a health facility should be a womans right if that is her choice. However the final paper of the series goes further: "The Millennium Development Goal for maternal health (MDG-5)--to reduce maternal mortality by two-thirds by 2015--will best be achieved by adopting a core strategy of health centre-based intrapartum care (HCIC)." This statement echoes the recommendations of the US Institute of Medicine and the WHO2 and indicates accepted wisdom in safer motherhood policy. We are concerned about a one-size-fits-all core strategy and believe that policies need to be context-specific. Intrapartum care based in health centres is appropriate for all as a longer-term strategy but might not be the best option for reducing maternal mortality in all contexts in the shorter term. In many communities with high maternal mortality this strategy is simply not achievable with current resources and infrastructure and without other evidence-based options countries could be left without adequate guidance about how to proceed. (excerpt)
Rio de Janeiro City, Brazil.
To compare community-based directly observed treatment (DOT) for tuberculosis (TB), using community health workers (CHWs), with clinic-based DOT.
In a longitudinal study in a cohort of TB patients in a region of Rio de Janeiro city, we evaluated treatment modalities and outcomes in 1811 patients diagnosed with TB between 1 January 2003 and 30 December 2004. Patients were offered DOT when they presented to out-patient clinics for an initial diagnosis. DOT was provided in the clinic or in the community, using CHWs, for patients living in a large favela. Outcomes of treatment were assessed using treatment registry databases.
Of the 1811 TB patients, 1215 (67%) were treated under DOT; among these, 726 (60%) received clinic-based treatment and 489 (40%) community-based treatment. Patients offered community-based treatment were more likely to accept DOT (99%) than those offered clinic-based treatment (60%, P<0.001). Treatment success rates for new smear-positive and retreatment TB cases were significantly higher among those treated with community-based DOT compared to clinic-based DOT.
We conclude that using CHWs to deliver DOT in the community may improve TB treatment outcomes in selected areas such as urban slums.
A household-based HIV and TB intervention increases HIV testing in households and reduces prevalence of TB at the community level: the ZAMSTAR community randomized trial
- Ayles