Farida Bani's research while affiliated with Ifakara Health Institute and other places

We assessed the diagnostic yield of urine GeneXpert MTB/RIF Ultra (Ultra) and factors associated with a positive test among adult patients suspected to have extrapulmonary tuberculosis. Urine Ultra was positive in 14% of participants with definite or probable tuberculosis. Hospitalization, disseminated tuberculosis and HIV infection were associated with a positive result.

Background: Patients with suspected extrapulmonary tuberculosis are often treated empirically. We hypothesized that extended Focused Assessment of Sonography for HIV and Tuberculosis (eFASH), in combination with other tests, would increase the proportion of correctly managed patients with suspected extrapulmonary tuberculosis. Methods: This trial in adults with suspected extrapulmonary tuberculosis was performed in a rural and an urban hospital in Tanzania. Participants were randomised 1:1 to intervention or routine care, stratified by site and HIV status. All participants received a clinical evaluation, chest X-ray, sputum Xpert MTB/RIF, and urine Xpert MTB/RIF Ultra. The intervention was a management algorithm based on eFASH plus microbiology, adenosine deaminase (ADA) and chest X-ray. The primary outcome was the proportion of correctly managed patients. Presence of positive microbiology or ADA defined definite tuberculosis. An independent endpoint review committee determined diagnoses of probable or no tuberculosis. We evaluated outcomes using logistic regression models, adjusted for randomisation stratification factors. Results: From 09/2018 to 10/2020, 1,036 patients were screened and 701 randomised (350 intervention, 351 control). 251 (72%) intervention participants had a positive eFASH. 258 (74%) intervention and 227 (65%) control participants were initiated anti-tuberculosis treatment at baseline. More intervention participants had definite tuberculosis (n = 124, 35%) compared to controls (n = 85, 24%). There was no difference between groups for the primary outcome (intervention 266/286 (93%); control: 245/266 (92%); odds ratio 1.14 (95% confidence interval 0.60-2.16, p = 0.68)). There were no procedure-associated adverse events. Conclusion: eFASH did not change the proportion of correctly managed patients, but increased the proportion of definite tuberculosis.

Background The extent to which drug–drug interactions (DDIs) between antiretrovirals (ARVs) and co-medications are recognized and managed has not been thoroughly evaluated in limited-resource settings. Objectives This prospective questionnaire-based study aimed to determine the prevalence and risk factors for unrecognized/incorrectly managed DDIs in people living with HIV followed-up at the Chronic Diseases Clinic of Ifakara (CDCI) and enrolled in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO). Methods We prospectively included ARV-treated adults receiving ≥1 co-medication coming for a follow-up visit at the CDCI between March and July 2017. Using a structured questionnaire, physicians were requested to identify potentially clinically significant DDIs in the prescribed treatment, to provide recommendations for their management and to indicate any hurdles to implement the recommendations. Prescriptions were subsequently screened for DDIs using the Liverpool DDIs database. Identified clinically significant DDIs and their recommended management according to the DDIs database were compared with the information provided in the questionnaires. Results Among 334 participants, the median age was 47 years (IQR = 40–56 years), 69% were female and 82% had ≥1 non-communicable disease (NCD). Overall, 129 participants had ≥1 clinically relevant DDI, which was not recognized and/or incorrectly managed in 56 participants (43%). Of those, 6 (11%) were due to limited monitoring options or medication affordability issues. In the multivariable logistic regression, the presence of ≥1 NCD was associated with an increased risk for unrecognized/incorrect DDI management (OR = 15.8; 95% CI = 1.8–139.6). Conclusions Recognition/appropriate management of DDIs is suboptimal, highlighting the need for educational programmes, pharmacovigilance activities and increased access to medications and monitoring options. This should become a focus of HIV programmes given the increasing burden of NCDs in sub-Saharan Africa.

Background: Patients with clinically suspected tuberculosis are often treated empirically, as diagnosis - especially of extrapulmonary tuberculosis - remains challenging. This leads to an overtreatment of tuberculosis and to underdiagnosis of possible differential diagnoses. Methods: This open-label, parallel-group, superiority randomized controlled trial is done in a rural and an urban center in Tanzania. HIV-positive and -negative adults (≥18 years) with clinically suspected extrapulmonary tuberculosis are randomized in a 1:1 ratio to an intervention- or control group, stratified by center and HIV status. The intervention consists of a management algorithm including extended focused assessment of sonography for HIV and tuberculosis (eFASH) in combination with chest X-ray and microbiological tests. Treatment with anti-tuberculosis drugs is started, if eFASH is positive, chest X-ray suggests tuberculosis, or a microbiological result is positive for tuberculosis. Patients in the control group are managed according national guidelines. Treatment is started if microbiology is positive or empirically according to the treating physician. The primary outcome is the proportion of correctly managed patients at 6 months (i.e patients who were treated with anti-tuberculosis treatment and had definite or probable tuberculosis, and patients who were not treated with anti-tuberculosis treatment and did not have tuberculosis). Secondary outcomes are the proportion of symptom-free patients at two and 6 months, and time to death. The sample size is 650 patients. Discussion: This study will determine, whether ultrasound in combination with other tests can increase the proportion of correctly managed patients with clinically suspected extrapulmonary tuberculosis, thus reducing overtreatment with anti-tuberculosis drugs. Trial registration: PACTR, Registration number: PACTR201712002829221, registered December 1st 2017.

Background In sub-Saharan Africa, diagnosis and management of extrapulmonary tuberculosis (EPTB) in people living with HIV (PLHIV) remains a major challenge. This study aimed to characterize the epidemiology and risk factors for poor outcome of extrapulmonary tuberculosis in people living with HIV (PLHIV) in a rural setting in Tanzania. Methods We included PLHIV >18 years of age enrolled into the Kilombero and Ulanga antiretroviral cohort (KIULARCO) from 2013 to 2017. We assessed the diagnosis of tuberculosis by integrating prospectively collected clinical and microbiological data. We calculated prevalence- and incidence rates and used Cox regression analysis to evaluate the association of risk factors in extrapulmonary tuberculosis (EPTB) with a combined endpoint of lost to follow-up (LTFU) and death. Results We included 3,129 subjects (64.5% female) with a median age of 38 years (interquartile range [IQR] 31–46) and a median CD4+ cell count of 229/μl (IQR 94–421) at baseline. During the median follow-up of 1.25 years (IQR 0.46–2.85), 574 (18.4%) subjects were diagnosed with tuberculosis, whereof 175 (30.5%) had an extrapulmonary manifestation. Microbiological evidence by Acid-Fast-Bacillus stain (AFB-stain) or Xpert® MTB/RIF was present in 178/483 (36.9%) patients with pulmonary and in 28/175 (16.0%) of patients with extrapulmonary manifestations, respectively. Incidence density rates for pulmonary Tuberculosis (PTB and EPTB were 17.9/1000person-years (py) (95% CI 14.2–22.6) and 5.8/1000 py (95% CI 4.0–8.5), respectively. The combined endpoint of death and LTFU was observed in 1058 (33.8%) patients, most frequently in the subgroup of EPTB (47.2%). Patients with EPTB had a higher rate of the composite outcome of death/LTFU after TB diagnosis than with PTB [HR 1.63, (1.14–2.31); p = 0.006]. The adjusted hazard ratios [HR (95% CI)] for death/LTFU in EPTB patients were significantly increased for patients aged >45 years [HR 1.95, (1.15–3.3); p = 0.013], whereas ART use was protective [HR 0.15, (0.08–0.27); p <0.001]. Conclusions Extrapulmonary tuberculosis was a frequent manifestation in this cohort of PLHIV. The diagnosis of EPTB in the absence of histopathology and mycobacterial culture remains challenging even with availability of Xpert® MTB/RIF. Patients with EPTB had increased rates of mortality and LTFU despite early recognition of the disease after enrollment.

Objective: HIV-1 rapidly establishes a persistent infection that can be contained under life-long antiretroviral therapy (ART) but not cured. One major viral reservoir is the peripheral lymph node (LN) follicles. Studying the impact of novel HIV-1 treatment and vaccination approaches on cells residing in germinal centers is essential for rapid progress towards HIV-1 prevention and cure. Results: We enrolled 9 asymptomatic adult volunteers with a newly diagnosed HIV-1 infection and CD4 T cell counts ≥ 350/ml. The patients underwent venous blood collection and inguinal lymph node excision surgery in parallel. Mononuclear cells were extracted from blood and tissues simultaneously. Participants were followed up regularly for 2 weeks until complete healing of the surgical wounds. All participants completed the lymph node excision surgery without clinical complications. Among the 9 volunteers, one elite controller was identified. The number of mononuclear cells recovered from lymph nodes ranged from 68 to 206 million and correlated positively with lymph node size. This is the first study to show that lymph node biopsy is a safe procedure and can be undertaken with local experts in rural settings. It provides a foundation for detailed immune response investigations during future clinical trials.

Tuberculosis (TB) remains among the top 10 infectious diseases with highest mortality globally since the 1990s despite effective chemotherapy. Among 10 million patients that fell ill with tuberculosis in the year 2017, 36 % were undiagnosed or detected and not reported; the number goes as high as 55 % in Tanzania, showing that the diagnosis of TB is a big challenge in the developing countries. There have been great advancements in TB diagnostics with introduction of the molecular tests such as Xpert MTB/RIF, loop-mediated isothermal amplification, lipoarabinomannan urine strip test, and molecular line-probe assays. However, most of the hospitals in Tanzania still rely on the TB score chart in children, the WHO screening questions in adults, acid-fast bacilli and chest x-ray for the diagnosis of TB. Xpert MTB/RIF has been rolled-out but remains a challenge in settings where the samples for testing must be transported over many kilometers. Imaging by sonography - nowadays widely available even in rural settings of Tanzania - has been shown to be a useful tool in the diagnosis of extrapulmonary tuberculosis. Despite all the efforts and new diagnostics, 30-50 % of patients in high-burden TB countries are still empirically treated for tuberculosis. More efforts need to be placed if we are to reduce the death toll by 90 % until 2030.

Background: Cryptococcal meningitis accounts for 15% of all AIDS-mortality globally. Most cases in low- and middle-income countries are treated with fluconazole monotherapy, which is associated with a high mortality. New available therapies are needed. Short course amphotericin B has been shown to be a safe and efficient therapeutic option. Sertraline has in vitro fungicidal activity against Cryptococcus and bi-directional synergy with fluconazole. Methods: We conducted an open label clinical trial to assess the safety and efficacy of sertraline 400 mg/day and fluconazole 1200 mg/day (n=28) vs. sertraline, fluconazole and additional 5-days of amphotericin B deoxycholate 0.7-1 mg/kg (n=18) for cryptococcal meningitis. Results: 2-week survival was 64% (18/28) without amphotericin and 89% (16/18) with amphotericin, and 10-week survival was 21% (6/28) vs. 61% (11/18), respectively (p=0.012). The cerebrospinal fluid (CSF) Cryptococcus clearance rate was 0.264 log10 colony forming units (CFU)/mL of CSF/day (95%CI: 0.112-0.416) without amphotericin and 0.473 log10 CFU/mL/day (95%CI: 0.344-0.60) with short-course amphotericin (p=0.03). Sertraline was discontinued in one participant due to side effects. Four participants receiving amphotericin B experienced hypokalemia <2.4 mEq/L. Conclusions: Short-course amphotericin substantially increased CSF clearance and 10-week survival. Adjunctive sertraline improved 2-week CSF fungal clearance but did not improve 10-week mortality compared with published data using fluconazole 1200 mg/day monotherapy (early fungicidal activity 0.15 log10 CFU/mL/day). This article is protected by copyright. All rights reserved.

Background Patients with suspected tuberculosis are often overtreated with anti-tuberculosis drugs. We evaluated the diagnostic value of the Focused Assessment with Sonography for HIV-associated Tuberculosis (FASH) in rural Tanzania. Methods In a prospective cohort study the frequency of FASH-signs was compared between patients with confirmed tuberculosis and those without tuberculosis. Clinical and laboratory examination, chest x-ray, Xpert MTB/RIF assay and culture from sputum, sterile body fluids, lymph node aspirates, and Xpert MTB/RIF urine assay was done. Results Of 191 analysed patients with a 6 months follow-up, 52.4% were HIV-positive, 21.5% had clinically suspected pulmonary, 3.7% extrapulmonary, and 74.9% extrapulmonary and pulmonary tuberculosis. Tuberculosis was microbiologically confirmed in 57.6%, probable in 13.1%, and excluded in 29.3%. Ten of 11 patients with splenic or hepatic hypoechogenic lesions had confirmed tuberculosis. In a univariate model, abdominal lymphadenopathy was significantly associated with confirmed tuberculosis. Pleural- and pericardial effusion, ascites, and thickened ileum wall lacked significant association. In a multiple regression model, abnormal chest x-ray (OR 6.19, 95% CI 1.96-19.6, p<0.002), ≥1 FASH-sign (OR 3.33, 95% CI 1.21-9.12, p=0.019), and body temperature (OR 2.48, 95% CI 1.52-5.03, p=0.001 per °C increase) remained associated with tuberculosis. A combination of ≥1 FASH sign, abnormal chest x-ray, and temperature ≥37.5 °C had 99.1% sensitivity (95% CI 94.9-99.9), 35.2 % specificity (95% CI 22.7-49.4), and a positive and negative predictive value of 75.2% (95% CI 71.3-78.7) and 95.0% (95%CI 72.3-99.3). Conclusion The absence of FASH-signs combined with a normal chest x-ray and body temperature <37.5 °C might exclude tuberculosis.