Marian Loveday

South African Medical Research Council | MRC · HIV Prevention Research Unit (HPRU)

Background:There have been advances in drug-resistant tuberculosis (DR-TB) diagnosis, treatment, and service delivery. However, as DR-TB often affects those with limited resources, people with DR-TB struggle with socioeconomic and psychosocial challenges, which may impact retention in care. Consequently, advances in DR-TB diagnostics and treatment...

Background Despite HIV's evolution to a chronic disease, the burden of advanced HIV disease (AHD) remains high among PLHIV on ART, due in part to treatment interruptions. TB is the most common cause of hospital admission and death in PLHIV. As little is known about the experiences of patients hospitalised with AHD, this study sought to discern patt...

Objectives Treatment for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) is increasingly transitioning from hospital-centred to community-based care. A national policy for decentralised programmatic MDR/RR-TB care was adopted in South Africa in 2011. We explored variations in the implementation of care models in response to this c...

BACKGROUND Each year more than 200,000 pregnant people become sick with TB, but little is known about how to optimize their diagnosis and therapy. Although there is a need for further research in this population, it is important to recognize that much can be done to improve the services they currently receive. METHODS Following a systematic review...

Abstract Background Tuberculosis (TB)-associated mortality in South Africa remains high. This review aimed to systematically assess risk factors associated with death during TB treatment in South African patients. Methods We conducted a systematic review of TB research articles published between 2010 and 2018. We searched BioMed Central (BMC), PubM...

Tuberculosis (TB) is a leading cause of death globally. In 2015, the World Health Organization hailed patient-centred care as the first of three pillars in the End TB strategy. Few examples of how to deliver patient-centred care in TB programmes exist in practice; TB control efforts have historically prioritised health systems structures and proces...

Objective Champions are recognised as important to driving organisational change in healthcare quality improvement initiatives in high-income settings. In low-income and middle-income countries with a high disease burden and constrained human resources, their role is highly relevant yet understudied. Within a broader study on policy implementation...

Background Adolescents who have acquired HIV perinatally (ALHIV) face unique challenges in taking lifelong antiretroviral therapy (ART), but little is known about what factors affect their adherence over the course of their lifelong treatment journey. Methods We conducted a qualitative study with ALHIV who had periods of poor adherence to ART in K...

Breast milk is the preferred method of infant nutrition. Breastfeeding infants born to mothers treated for TB may be at risk of drug toxicity through breast milk exposure, or potentially be vulnerable to select for drug resistance with low level drug exposure. Except for isoniazid, the quantification of first-line TB drugs including rifabutin in br...

Background: Adolescents who have acquired HIV perinatally (ALHIV) face unique challenges in taking lifelong antiretroviral therapy (ART), but little is known about what factors affect their adherence over the course of their lifelong treatment journey. Methods: We conducted a qualitative study with ALHIV who had periods of poor adherence to ART in...

Background People living with HIV need to take lifelong, combination antiretroviral therapy (cART), but there have been only limited explorations of how factors affecting adherence can change over the course of an individual’s lifetime. Methods We carried out a qualitative study of men and women living with HIV in KwaZulu, Natal, South Africa who...

Background: Adolescents are a unique population with significant unmet health needs. They are often excluded from research that may benefit them as they are perceived as vulnerable and needing protection from research participation. For Research Ethics Committees, conflicting positions in statutes, regulations and ethical guidelines about who provi...

Background: People living with HIV need to take lifelong, combination antiretroviral therapy (cART) for, but there have been only limited explorations of how factors affecting adherence can change over the course of an individual’s lifetime. Methods: We carried out a qualitative study of men and women living with HIV in KwaZulu, Natal, South Afric...

Aims We aimed to explore the effect of pregnancy on bedaquiline pharmacokinetics (PK) and describe bedaquiline exposure in the breast milk of mothers treated for rifampicin‐resistant tuberculosis (TB), where there are no human data available. Methods We performed a longitudinal PK study in pregnant women treated for rifampicin‐resistant TB to expl...

Background: The concept of multi-morbidity is typically defined as the concurrent existence of more than one infectious and/or chronic condition in one person. We conducted a systematic review to quantify and describe the extent of multi-morbidities associated with tuberculosis (TB) in South Africa. Methods: This systematic review and meta-analysis...

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 resu...

Aim We aimed to explore the effect of pregnancy on bedaquiline pharmacokinetics and describe bedaquiline exposure in the human milk of mothers treated for rifampicin-resistant TB, where there is no human data available. Methods We performed a longitudinal pharmacokinetic study in pregnant women treated for rifampicin-resistant TB to explore the eff...

Background There are few data on the on post-treatment experiences of people who have been successfully treated for rifampicin-resistant (RR-)TB. Objective To describe the experiences and impact of RR-TB disease and therapy on post-treatment life of individuals who were successfully treated. Methods In this qualitative study in-depth interviews w...

Introduction: In South Africa, mortality rates among HIV-TB coinfected patients are among the highest in the world. The key to reducing mortality is integrating HIV-TB services, however, a generalizable implementation method and package of tested change ideas to guide the scale-up of integrated HIV-TB services are unavailable. We describe the impl...

Objective: To describe the medical, socio-economic and geographical profiles of patients with rifampicin-resistant TB (RR-TB) and the implications for the provision of patient-centred care. Setting: Thirteen districts across three South African provinces. Design: This descriptive study examined laboratory and healthcare facility records of 194...

Background A quality improvement (QI) collaborative approach to enhancing integrated HIV-Tuberculosis (TB) services may be effective in scaling up and improving the quality of service delivery. Little is known of the role of organizational contextual factors (OCFs) in influencing the success of QI collaboratives. This study aims to determine which...

Introduction : Tuberculosis (TB) remains the most common cause of death among people living with HIV. Integrating HIV and TB services reduces mortality but is sub-optimally implemented. Quality improvement (QI) methods offer a low-cost and easily implementable approach to strengthening healthcare delivery systems. This trial assessed a QI intervent...

Background Tuberculosis (TB) is a major public health concern in South Africa and TB-related mortality remains unacceptably high. Numerous clinical studies have examined the direct causes of TB-related mortality, but its wider, systemic drivers are less well understood. Applying systems thinking, we aimed to identify factors underlying TB mortality...

In 2011, the South African National TB Programme launched a policy of decentralized management of drug-resistant tuberculosis (DR-TB) in order to expand the capacity of facilities to treat patients with DR-TB, minimize delays to access care and improve patient outcomes. This policy directive was implemented to varying degrees within a rapidly evolv...

This brief report presents a series of 5 pregnant women treated for rifampicin-resistant tuberculosis with the novel drugs bedaquiline, delamanid, and linezolid as part of an optimized backbone regimen and reviews the outcomes of the children born to them. Although the case series is small, all children had excellent birth outcomes suggesting pregn...

Background There are few data on the on the care experiences of pregnant women with rifampicin-resistant TB. Objective To describe the treatment journeys of pregnant women with RR-TB—including how their care experiences shape their identities—and identify areas in which tailored interventions are needed. Methods In this qualitative study in-depth...

The COVID-19 pandemic and phased nationwide lockdown have impacted negatively on individuals with tuberculosis (TB) and routine TB services. Through a literature review and the perspective of members of a national TB Think Tank task team, we describe the impact of the pandemic and lockdown on TB patients and services as well as the potential long-t...

Rapid diagnostics, newer drugs, repurposed medications, and shorter regimens have radically altered the landscape for treating rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB). There are multiple ongoing clinical trials aiming to build a robust evidence base to guide RR/MDR-TB treatment, and both observational studies and program...

Breast milk provides optimal nutrition, and is recommended for neonates and infants. In women with TB, there has been uncertainty about optimal feeding practices due to the risk of transmission to the neonate and the possibility of drug exposure via breast milk. For women who have drug-susceptible TB (DS-TB) who are no longer infectious, it is safe...

Tuberculosis (TB) is a curable disease, but continues to contribute to large numbers of deaths globally and remains among the leading causes of death in South Africa (SA). Evaluating trends in TB deaths and progress towards the End TB strategy target of zero deaths is particularly important to guide policy and practice in SA. TB deaths are complica...

Background: Data on safety and efficacy of second-line tuberculosis drugs in pregnant women and their infants are severely limited due to exclusion from clinical trials and expanded access programmes. Methods: Pregnant women starting treatment for multidrug/rifampicin-resistant (MDR/RR)-tuberculosis at King Dinuzulu Hospital in KwaZulu-Natal, So...

Introduction As the management of MDR-TB expands and is decentralised to resource-limited settings, ensuring patients are managed in line with country guidelines optimises the chances of cure, and minimises transmission and development of further resistance. We aimed to develop sustainable quality MDR-TB services in a rural South African district h...

Objectives: Drug-resistant tuberculosis (DR-TB) is a growing concern in many low-income and middle-income countries. Facing rising numbers of DR-TB patients, South Africa (SA) introduced a decentralised model of care for DR-TB in 2011. We aimed to document the introduction and implementation of the new models of care for patients with DR-TB in four...

Background: Patient-centered care is pillar 1 of the "End TB" strategy, but little has been documented in the literature about what this means for people living with rifampicin-resistant (RR-TB). Optimizing care for such individuals requires a better understanding of the challenges they face and the support they need. Methods: A qualitative stud...

SETTING: Thirteen districts in Eastern Cape (EC), KwaZulu-Natal (KZN) and Western Cape (WC) Provinces, South Africa. OBJECTIVE: To pilot a methodology for describing and visualising healthcare journeys among drug-resistant tuberculosis (DR-TB) patients using routine laboratory records. DESIGN: Laboratory records were obtained for 195 patients with...

Although the neonatal mortality rate in South Africa (SA) has remained stagnant at 12 deaths per 1 000 live births, the infant and under-5 mortality rates have significantly declined since peaking in 2003. Policy changes that have influenced this decline include policies to prevent vertical HIV transmission, earlier treatment of children living wit...

Health policy and systems research (HPSR) guides health system reforms and is essential for South Africa (SA)'s progress towards universal coverage of high-quality healthcare. For HPSR evidence to inform and strengthen health systems, it needs to flow efficiently between evidence producers, evidence synthesisers, evidence processers and disseminato...

Objectives Multidrug-resistant tuberculosis (MDR-TB) is a global public health priority. The advent of the World Health Organisation’s Short Course regimen for MDR-TB, which halves treatment duration, has transformed outcomes and treatment acceptability for affected patients. Bedaquiline, a cornerstone of the Short Course regimen, has unknown terat...

South Africa (SA) is committed to reducing tuberculosis (TB) mortality rates in line with the World Health Organization's End TB Strategy and the Sustainable Development Goal (SDG) targets. From mortality reports released by Statistics South Africa, this study analysed reported TB mortality in SA from 2006 to 2016 to inform our understanding of TB...

Little is known about the treatment experiences of pregnant women with rifampin-resistant tuberculosis. We conducted qualitative interviews with 10 women who had this condition; 9 reported facing discrimination from healthcare providers. Our findings underscore an urgent need to ensure a human-rights-based, patient-centered approach for women with...

Background: South Africa has a high burden of MDR-TB, and to provide accessible treatment the government has introduced different models of care. We report the most cost-effective model after comparing cost per patient successfully treated across 5 models of care: centralized hospital, district hospitals (2), and community-based care through clini...

Unit cost per type of activity per site. (DOCX)

Comparison of populations included in this study. (DOCX)

Criteria for home-based treatment of MDR-TB patients. (DOCX)

Treatment outcome definitions. (DOCX)

Additional methodology regarding the propensity analysis. (DOCX)

Background Globally, preventable and treatable childhood conditions such as pneumonia, diarrhoea, malaria, malnutrition and newborn conditions still account for 75% of under-five mortality. To reduce the mortality rate from these conditions, Ethiopia launched an ambitious Health Extension Programme (HEP) in 2003. Trained Community Health Workers (C...

Mortality in patients with human immunodeficiency virus (HIV)-associated tuberculosis (TB) is high, particularly in sub-Saharan Africa. This study aimed to compare mortality and predictors of mortality in those who were antiretroviral therapy (ART) naïve to those with prior ART exposure. This retrospective cohort study was conducted in Serowe/Palap...

This annual publication provides an overview of the performance of public health services in South Africa and has become an important planning and management resource for health service providers, managers, researchers and policy makers in the country.

Setting: Referral hospital for drug-resistant tuberculosis (TB) in KwaZulu-Natal, South Africa. Objectives: We conducted interviews with primary care givers of children admitted with multidrug-resistant TB (MDR-TB) during a 3-month period in 2015 to identify broader household challenges. Results: We interviewed 26 care givers, most of whom wer...

In this chapter we review the emergence of DR-TB in South Africa and progress towards universal access to diagnosis and effective treatment; we also discuss key policy initiatives that have contributed to treatment access and patient outcomes, and highlight opportunities and challenges moving forward.

SETTING: Referral hospital for drug-resistant tuberculosis (DR-TB) in KwaZulu-Natal Province, South Africa. OBJECTIVE: To review the clinical outcomes of patients (age  14 years) with a laboratory-confirmed diagnosis of DR-TB who had minimal symptoms and/or did not have chest radiographic evidence of active disease at referral. These patients were...

The District Health Barometer 2015/16, now in its 11th edition, seeks to highlight, health system performance, inequities in health outcomes, and health-resource allocation and delivery, and to track the efficiency of healthcare delivery processes across all provinces and districts in South Africa. Over the years, the DHB has become an important pl...

Increasing rates of anti-TB drug resistance coupled with the narrow pipe-line of anti-TB drug development, highlights the need for judicious use of new and old anti-TB drugs. New drugs, such as bedaquiline and delamanid have become available for the treatment of resistant TB. The introduction of repurposed drugs, such as linezolid, is also seen as...

Background: The Xpert MTB/RIF assay has been widely implemented in South Africa for rapid tuberculosis (TB) screening. However, its usefulness in management and improving treatment outcomes in patients with multidrug-resistant TB (MDR-TB) remains undefined. The aim of this study was to evaluate the clinical impact of introduction of the Xpert MTB/...

Background The diagnosis of drug-resistant tuberculosis (DR-TB) in children is challenging and treatment is associated with many adverse effects. Objective We aimed to assess if careful observation, without initiation of second-line treatment, is safe in asymptomatic children referred with ‘culture-confirmed’ DR-TB. Setting KwaZulu-Natal, South Afr...

The annually published District Health Barometer (DHB) is designed and compiled to assist South Africa’s National Department of Health in making health and related information available for monitoring progress in health service delivery at district level. The Barometer provides current information on functioning and associated fluctuations in all...

KwaZulu-Natal, South Africa, a predominantly rural province with a high burden of tuberculosis (TB), multidrug-resistant TB (MDR-TB) and human immunodeficiency virus (HIV) infection. To determine the most effective care model by comparing MDR-TB treatment outcomes at community-based sites with traditional care at a central, specialised hospital. A...

Objective: Assess coverage of selected case management and care-seeking indicators of diarrhoea, malaria and pneumonia, after an integrated health system strengthening (IHSS) intervention in six African countries – Ethiopia, Ghana, Malawi, Mali, Mozambique and Niger. Methods: Fixed mixed-methods evaluation were utilised. Baseline data and secular...

We examine some aspects of the South African health system that have contributed to the current multi- and extensively drug-resistant tuberculosis (M(X)DR-TB) epidemic and identify opportunities for change and improvement. Implementation of several recent major scientific advances have the potential to accelerate the control of M(X)DR-TB, but healt...

South Africa is a global hotspot of the tuberculosis (TB), drug-resistant TB and HIV syndemics, and will not achieve the TB targets contained in the Millennium Development Goals. Using information from National Department of Health databases (the District Health Information System and electronic TB register), this chapter identifies areas of sub-op...

To improve the treatment of MDR-TB and HIV co-infected patients, we investigated the relationship between health system performance and patient treatment outcomes at 4 decentralised MDR-TB sites. In this mixed methods case study which included prospective comparative data, we measured health system performance using a framework of domains comprisin...

The Xpert MTB/RIF RIF assay has been rapidly introduced in public health facilities in South Africa. This retrospective study assesses the impact of Xpert MTB/RIF in reducing time to treatment initiation and morbidity in MDR-TB patients co-infected with HIV. In this expedited record review, between 2008 and 2010 813 MDR-TB patients diagnosed with t...

To improve the treatment of patients co-infected with multidrug-resistant tuberculosis (MDR-TB) and the human immunodeficiency virus, we measured the relationship between treatment outcomes and hospital performance at four decentralised MDR-TB sites in South Africa. We describe hospital performance from the patient's perspective by the use of a gra...

Drug-resistant tuberculosis (TB) is an occupational hazard for health-care workers (HCWs) in South Africa. We undertook this qualitative study to contextualize epidemiological findings suggesting that HCWs' elevated risk of drug-resistant TB is related to workplace exposure. A total of 55 HCWs and 7 hospital managers participated in focus groups an...

Introduction: As the South African province of KwaZulu-Natal addresses a growing multidrug-resistant tuberculosis (MDR-TB) epidemic by shifting care and treatment from trained specialty centers to community hospitals, delivering and monitoring MDR-TB therapy has presented new challenges. In particular, tracking and reporting adverse clinical event...

Most patients with multidrug-resistant tuberculosis (MDR-TB) in South Africa are HIV-infected, but the safety and tolerability of co-treatment is unknown. We reviewed all adverse events (AEs) for MDR-TB patients in a home-based treatment program in rural KwaZulu-Natal. Of 91 MDR-TB patients, 74 (81%) were HIV-positive and receiving antiretroviral t...

Treatment outcomes for multidrug-resistant tuberculosis (MDR-TB) in South Africa have suffered as centralized, in-patient treatment programs struggle to cope with rising prevalence and human immunodeficiency virus (HIV) co-infection rates. A new treatment model is needed to expand treatment capacity and improve MDR-TB and HIV outcomes. To describe...

In KwaZulu-Natal, South Africa, a setting endemic for tuberculosis (TB) and the human immunodeficiency virus (HIV), prolonged hospitalisation for the treatment of the growing number of multidrug-resistant TB (MDR-TB) patients is neither possible nor effective. To compare early treatment outcomes in patients with MDR-TB with and without HIV co-infec...

Despite the prioritisation of TB, HIV and STI programmes in South Africa, service targets are not achieved, have had little effect, and the magnitude of the epidemics continues to escalate. Objective. To report on a participatory quality improvement intervention designed to evaluate these priority programmes in primary health care (PHC) clinics in...

To determine whether women in KwaZulu-Natal, South Africa, with drug-resistant tuberculosis (TB) were more likely than men to have extensively drug-resistant TB, we reviewed 4,514 adults admitted during 2003-2008 for drug-resistant TB. Female sex independently predicted extensively drug-resistant TB, even after we controlled for HIV infection. This...

To identify key obstacles to operational integration of TB and HIV services and to suggest strategies to promote integration in the prevention, treatment and care of patients with TB and HIV. This is a health systems research case study of operational integration of TB and HIV in South Africa. Peer-reviewed and grey literature together with the exp...

Little is known about the time to sputum culture conversion in MDR-TB patients co-infected with HIV, although such patients have, historically, had poor outcomes. We describe culture conversion rates among MDR-TB patients with and without HIV-co-infection in a TB-endemic, high-HIV prevalent, resource-limited setting. Patients with culture-proven MD...

This community situational analysis determined factors impacting the utilization of maternal health services in South Africa. Quantitative and qualitative research methods were used, including semistructured household interviews, case studies of women with no antenatal care and/or home birth, and verbal/social autopsies of maternal and infant death...

To determine the clinical profile and outcomes of health care workers (HCWs) with extensively drug resistant tuberculosis (XDR-TB) in the Eastern and Western Cape Provinces of South Africa. Retrospective case record review of 334 patients with XDR-TB reported during the period 1996-2008 from Western and Eastern Cape Province, Cape Town, South Afric...

Nosocomial transmission has been described in extensively drug-resistant tuberculosis (XDR-TB) and HIV co-infected patients in South Africa. However, little is known about the rates of drug-resistant tuberculosis among health care workers in countries with high tuberculosis and HIV burden. To estimate rates of multidrug-resistant tuberculosis (MDR-...

High mortality and high transmission rates of extensively drug-resistant tuberculosis (XDR-TB) in KwaZulu-Natal Province of South Africa have highlighted the role of hospitals in the spread of TB and drug-resistant TB. To determine the operational effectiveness of the National TB Programme (NTP) at a regional/district hospital and its referral clin...