A Cluster-Randomized Trial of Traditional Healer-Delivered Counseling and Rapid HIV Testing in Tanzania.

Collaborations with traditional healers have been proposed to improve HIV testing uptake. We hypothesized that healer-delivered HIV testing would improve HIV testing uptake, compared with referral to clinic-based HIV testing. We conducted a cluster randomized trial to determine the effectiveness of traditional healers delivering counseling and HIV testing in Mwanza, Tanzania (ClinicalTrials.gov NCT#04071873). Intervention arm healers provided counseling and offered point-of-care HIV tests to adult clients of unknown HIV serostatus. Control arm healers provided referral for clinic-based testing. Primary outcome was receipt of an HIV test within 90 days of enrollment. Secondary outcomes were new HIV diagnosis and linkage to care. In the intervention, 100 clients (100%) received an HIV test, compared with 73 (73%) of control participants (p < 0.001). Two intervention arm participants (2%) had a new diagnosis compared with zero in the control arm (p = 0.50). Engaging traditional healers might provide a culturally concordant opportunity to improve HIV testing uptake.

Understanding the role of traditional healers in the HIV care cascade: Findings from a qualitative study among stakeholders in Mwanza, Tanzania.

Tanzania is HIV-endemic, with 5% prevalence. However, less than half of Tanzanians are aware of their HIV status, and only 75% of adult Tanzanians living with HIV are on antiretroviral therapy (ART). Informal healthcare providers, such as traditional healers, frequently serve as the first line of healthcare in Tanzania. How traditional healers interact with people living with HIV (PLWH) remains unknown. This study sought to understand gaps in HIV care and explore how traditional healers interface with PLWH along the HIV care cascade. We conducted a qualitative study in Mwanza, Tanzania, between November 2019 and May 2020. We invited 15 traditional healers, 15 clients of traditional healers, 15 biomedical healthcare facility staff, and 15 PLWH to participate in a single qualitative interview. Two community focus groups were held with eight male and eight female participants. Participants were 18 years of age or older. Individual experiences with traditional healers and biomedical healthcare facilities, as well as perceptions of traditional healers with respect to HIV care, were explored through interviews. Using a content-analysis approach, codes were grouped into a framework that characterized how traditional healers engage with PLWH throughout the HIV care cascade. PLWH engaged with traditional healers throughout the HIV care cascade, from pre- to post-HIV diagnosis. Traditional healers were described in some cases as facilitating HIV testing, while others were described as delaying testing by providing traditional treatments for HIV symptoms. Traditional medications were frequently used concurrently with ARTs by PLWH. There was concern that healers contributed to ART nonadherence as some PLWH used traditional therapies in search of a "cure" for HIV. Our findings suggest that traditional healers interact with PLWH throughout the HIV care continuum and that collaboration between traditional healers and biomedical healthcare professionals and facilities is needed to improve HIV treatment outcomes.

Short-course High-dose Liposomal Amphotericin B for Human Immunodeficiency Virus-associated Cryptococcal Meningitis: A Phase 2 Randomized Controlled Trial.

Background: We performed a phase 2 noninferiority trial examining the early fungicidal activity (EFA) of 3 short-course, high-dose liposomal amphotericin B (L-AmB) regimens for cryptococcal meningitis (CM) in Tanzania and Botswana. Methods: Human immunodeficiency virus (HIV)-infected adults with CM were randomized to (i) L-AmB 10 mg/kg on day 1 (single dose); (ii) L-AmB 10 mg/kg on day 1 and 5 mg/kg on day 3 (2 doses); (iii) L-AmB 10 mg/kg on day 1 and 5 mg/kg on days 3 and 7 (3 doses); or (iv) L-AmB 3 mg/kg/day for 14 days (control). All patients also received oral fluconazole 1200 mg/day for 14 days. Primary endpoint was mean rate of clearance of cerebrospinal fluid cryptococcal infection (EFA). Noninferiority was defined as an upper limit of the 2-sided 95% confidence interval (CI) of difference in EFA between intervention and control <0.2 log10 colony-forming units (CFU)/mL/day. Results: Eighty participants were enrolled. EFA for daily L-AmB was -0.41 log10 CFU/mL/day (standard deviation, 0.11; n = 17). Difference in mean EFA from control was -0.11 (95% CI, -.29 to .07) log10 CFU/mL/day faster with single dose (n = 16); -0.05 (95% CI, -.20 to .10) log10 CFU/mL/day faster with 2 doses (n = 18); and -0.13 (95% CI, -.35 to .09) log10 CFU/mL/day faster with 3 doses (n = 18). EFA in all short-course arms was noninferior to control. Ten-week mortality was 29% (n = 23) with no statistical difference between arms. All arms were well tolerated. Conclusions: Single-dose 10 mg/kg L-AmB was well tolerated and led to noninferior EFA compared to 14 days of 3 mg/kg/day L-AmB in HIV-associated CM. Induction based on a single 10 mg/kg L-AmB dose is being taken forward to a phase 3 clinical endpoint trial. Clinical Trials Registration: ISRCTN 10248064.

Drug adherence and efficacy of smear microscopy in the diagnosis of pulmonary tuberculosis after 2 months of medication in North-western Tanzania.

OBJECTIVES: The study aimed at assessing the Tuberculosis (TB) medication adherence level and the efficacy of smear microscopy in the diagnosing pulmonary TB at month 2. METHODS: A prospective study was conducted at the four sites located in the Northern-western Tanzania. New smear positive, pulmonary TB patients were followed up and their adherence to TB medication assessed after 2 months of the treatment. In addition, the acid fast bacilli (AFB) smear microscopy was performed after 2 and 5 months of the treatment. All smear positive samples were subjected to geneXpert (MTB/RIF) assay and culture on the Lowenstein Jensen (LJ) media. RESULTS: A total of 331 smear positive, newly diagnosed patients with pulmonary TB were enrolled. The median age was 36 [Interquartile range (IQR): 28-45] years and males formed the slightly majority, 187 (56.5%) of the participants. A total of 105 (31.7%) patients were infected with HIV. Out of 331 patients, 36 (10.9%) were still AFB smear positive at the end of two month. Of these 19 (52.8%) were positive on GeneXpert MTB RIF and none was Rifampicin resistant. Of note, only 13 (31.1%) were culture positive (viable). None of the patients was positive at month 5. Poor adherence to TB medications in the first 2 months of treatment was observed in 56/331 (16.9%) [95% CI=12.9-21.0] of the patients. CONCLUSION: Over two thirds of smear positive patients are wrongly put in one month extension of the intensive phase treatment; this may cause increased costs and drug toxicity. Culture should be advocated to confirm smear positivity after 2 months of medications. TB treatment drug adherence in our setting is good and is associated with successful cure. No multidrug resistant tuberculosis (MDR-TB) was observed. Continued surveillance and emphasizing of TB drug adherence should be kept upbeat in order to control tuberculosis in developing countries.

Resistance to Cotrimoxazole and Other Antimicrobials among Isolates from HIV/AIDS and Non-HIV/AIDS Patients at Bugando Medical Centre, Mwanza, Tanzania.

Bacterial resistance has increased in the AIDS era and is attributed to the widespread use of cotrimoxazole prophylaxis against opportunistic infections in HIV/AIDS patients. In Tanzania, cotrimoxazole prophylaxis has been used for more than ten years. Little is known, however, about its impact on the spread of antibiotic resistance in HIV positive patients. This cross-sectional study was done to compare magnitude of bacterial resistance to cotrimoxazole and other antimicrobials among isolates from HIV infected patients on cotrimoxazole prophylaxis and those not on prophylaxis and non-HIV patients attending Bugando Medical Centre (BMC). Susceptibility testing on obtained urine and swab specimens followed Clinical Laboratory Standard Institute, 2010, Guidelines. Of 945 samples collected, 155 had positive bacterial growth after 24 hours of incubation. Of the positive samples (72), 46.4% were from HIV positive patients. The common isolates were E. coli 41.3% (64/155), Klebsiella pneumoniae 17.5% (27/155), and Staphylococcus aureus 16.1% (25/155). Overall, bacterial resistance to cotrimoxazole was 118 (76.1%); among isolates from HIV patients bacterial resistance was 54 (75%), and for isolates from HIV patients on prophylaxis bacterial resistance was 36 (81.3%). HIV seropositivity and cotrimoxazole prophylaxis are not associated with antibiotic resistance observed in bacteria infecting patients attending BMC, Mwanza, Tanzania.

Effects on mortality of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy: a randomised controlled trial.

BACKGROUND: Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality. METHODS: The study was an individually-randomised phase III trial conducted in ART clinics in Mwanza, Tanzania, and Lusaka, Zambia. Participants were 1,815 ART-naïve non-pregnant adults with body mass index (BMI) <18.5 kg/m² who were referred for ART based on CD4 count <350 cells/µL or WHO stage 3 or 4 disease. The intervention was a lipid-based nutritional supplement either without (LNS) or with additional vitamins and minerals (LNS-VM), beginning prior to ART initiation; supplement amounts were 30 g/day (150 kcal) from recruitment until 2 weeks after starting ART and 250 g/day (1,400 kcal) from weeks 2 to 6 after starting ART. The primary outcome was mortality between recruitment and 12 weeks of ART. Secondary outcomes were serious adverse events (SAEs) and abnormal electrolytes throughout, and BMI and CD4 count at 12 weeks ART. RESULTS: Follow-up for the primary outcome was 91%. Median adherence was 66%. There were 181 deaths in the LNS group (83.7/100 person-years) and 184 (82.6/100 person-years) in the LNS-VM group (rate ratio (RR), 0.99; 95% CI, 0.80-1.21; P = 0.89). The intervention did not affect SAEs or BMI, but decreased the incidence of low serum phosphate (RR, 0.73; 95% CI, 0.55-0.97; P = 0.03) and increased the incidence of high serum potassium (RR, 1.60; 95% CI, 1.19-2.15; P = 0.002) and phosphate (RR, 1.23; 95% CI, 1.10-1.37; P <0.001). Mean CD4 count at 12 weeks post-ART was 25 cells/µL (95% CI, 4-46) higher in the LNS-VM compared to the LNS arm (P = 0.02). CONCLUSIONS: High-dose vitamin and mineral supplementation in LNS, compared to LNS alone, did not decrease mortality or clinical SAEs in malnourished African adults initiating ART, but improved CD4 count. The higher frequency of elevated serum potassium and phosphate levels suggests high-level electrolyte supplementation for all patients is inadvisable but the addition of micronutrient supplements to ART may provide clinical benefits in these patients. TRIAL REGISTRATION: PACTR201106000300631, registered on 1st June 2011.

International health research monitoring: exploring a scientific and a cooperative approach using participatory action research.

OBJECTIVES: To evaluate and determine the value of monitoring models developed by the Mahidol Oxford Tropical Research Unit and the East African Consortium for Clinical Research, consider how this can be measured and explore monitors' and investigators' experiences of and views about the nature, purpose and practice of monitoring. RESEARCH DESIGN: A case study approach was used within the context of participatory action research because one of the aims was to guide and improve practice. 34 interviews, five focus groups and observations of monitoring practice were conducted. SETTING AND PARTICIPANTS: Fieldwork occurred in the places where the monitoring models are coordinated and applied in Thailand, Cambodia, Uganda and Kenya. Participants included those coordinating the monitoring schemes, monitors, senior investigators and research staff. ANALYSIS: Transcribed textual data from field notes, interviews and focus groups was imported into a qualitative data software program (NVIVO V. 10) and analysed inductively and thematically by a qualitative researcher. The initial coding framework was reviewed internally and two main categories emerged from the subsequent interrogation of the data. RESULTS: The categories that were identified related to the conceptual framing and nature of monitoring, and the practice of monitoring, including relational factors. Particular emphasis was given to the value of a scientific and cooperative style of monitoring as a means of enhancing data quality, trust and transparency. In terms of practice the primary purpose of monitoring was defined as improving the conduct of health research and increasing the capacity of researchers and trial sites. CONCLUSIONS: The models studied utilise internal and network wide expertise to improve the ethics and quality of clinical research. They demonstrate how monitoring can be a scientific and constructive exercise rather than a threatening process. The value of cooperative relations needs to be given more emphasis in monitoring activities, which seek to ensure that research protects human rights and produces reliable data.

Plasma concentrations of efavirenz and nevirapine among HIV-infected patients with immunological failure attending a tertiary hospital in North-western Tanzania.

BACKGROUND: Sub-therapeutic and supra-therapeutic plasma concentrations of antriretrovirals are the significant causes of treatment failure and toxicity respectively among HIV-infected patients. We conducted this study to determine the pattern of efavirenz and nevirapine plasma drug concentrations among adult HIV-infected patients with immunological failure attending at a tertiary hospital in North-western Tanzania. MATERIALS AND METHODS: A cross-sectional study was conducted among adult HIV-infected patients with immunological failure who have been on either efavirenz or nevirapine based antiretroviral regimen for more than 6 months. Patients were serially enrolled through routine Care and Treatment Clinic (CTC) activities. Plasma drug concentrations for efavirenz and nevirapine were determined by high performance liquid chromatography (HPLC) and Gas Chromatography (GC) respectively. Demographic, clinical and laboratory data such as viral load and CD4 counts were collected. Data analysis was done using STATA 12. RESULTS: Of the 152 patients with immunological failure enrolled, the sub-therapeutic, therapeutic and supra-therapeutic plasma antiretroviral drug concentrations were found in 43/152 (28.3%), 76/152 (50.0%) and 33/152 (21.7%) respectively. Half of the patients were outside therapeutic window with either sub-therapeutic or supra-therapeutic plasma ARV drug concentrations. There was a significant difference in distribution of ARV adherence (p-value<0.001), NRTI backbone (p-value = 0.039), HIV stage (p-value = 0.026) and viral load (p-value = 0.007) within sub-therapeutic, therapeutic and supra-therapeutic ARV plasma drug concentrations. CONCLUSION: There is a wide inter-individual variability of plasma ARV concentrations among HIV patients with immunological failure, with a large proportion of patients being outside therapeutic window. This variability is significant based on ARV adherence, NRTI backbone, viral load and HIV stage. Routine therapeutic drug monitoring (TDM) could assist identifying these patients early and making timely correction to avoid virological failure, poor immunological outcome and prevent associated drug toxicities. Nonetheless, ARV adherence should be strictly emphasized on HIV patients with immunological failure.

The prevalence of latent Mycobacterium tuberculosis infection based on an interferon-γ release assay: a cross-sectional survey among urban adults in Mwanza, Tanzania.

INTRODUCTION: One third of the world's population is estimated to be latently infected with Mycobacterium tuberculosis (LTBI). Surveys of LTBI are rarely performed in resource poor TB high endemic countries like Tanzania although low-income countries harbor the largest burden of the worlds LTBI. The primary objective was to estimate the prevalence of LTBI in household contacts of pulmonary TB cases and a group of apparently healthy neighborhood controls in an urban setting of such a country. Secondly we assessed potential impact of LTBI on inflammation by quantitating circulating levels of an acute phase reactant: alpha-1-acid glycoprotein (AGP) in neighborhood controls. METHODS: The study was nested within the framework of two nutrition studies among TB patients in Mwanza, Tanzania. Household contacts- and neighborhood controls were invited to participate. The study involved a questionnaire, BMI determination and blood samples to measure AGP, HIV testing and a Quantiferon Gold In tube (QFN-IT) test to detect signs of LTBI. RESULTS: 245 household contacts and 192 neighborhood controls had available QFN-IT data. Among household contacts, the proportion of QFT-IT positive was 59% compared to 41% in the neighborhood controls (p = 0.001). In a linear regression model adjusted for sex, age, CD4 and HIV, a QFT-IT positive test was associated with a 10% higher level of alpha-1-acid glycoprotein(AGP) (10(B) 1.10, 95% CI 1.01; 1.20, p = 0.03), compared to individuals with a QFT-IT negative test. CONCLUSION: LTBI is highly prevalent among apparently healthy urban Tanzanians even without known exposure to TB in the household. LTBI was found to be associated with elevated levels of AGP. The implications of this observation merit further studies.

The role of diabetes co-morbidity for tuberculosis treatment outcomes: a prospective cohort study from Mwanza, Tanzania.

BACKGROUND: Due to the association between diabetes and pulmonary tuberculosis (TB), diabetes may threaten the control of TB. In a prospective cohort study nested in a nutrition trial, we investigated the role of diabetes on changes in anthropometry, grip strength, and clinical parameters over a five months follow-up period. METHODS: Among pulmonary TB patients with known diabetes status, we assessed anthropometry and clinical parameters (e.g. haemoglobin) at baseline and after two and five months of TB treatment. A linear mixed-effects model (repeated measurements) was used to investigate the role of diabetes during recovery. RESULTS: Of 1205 TB patients, the mean (standard deviation) age was 36.6 (13.0) years, 40.9% were females, 48.9% were HIV co-infected, and 16.3% had diabetes. TB patients with diabetes co-morbidity experienced a lower weight gain at two (1.3 kg, CI95% 0.5; 2.0, p = 0.001) and five months (1.0 kg, CI95% 0.3; 1.7, p = 0.007). Similarly, the increase in the level of haemoglobin was lower among TB patients with diabetes co-morbidity after two (Δ 0.6 g/dL, CI95% 0.3; 0.9 p < 0.001) and five months (Δ 0.5 g/dL, CI95% 0.2; 0.9 p = 0.004) of TB treatment, respectively. CONCLUSION: TB patients initiating TB treatment with diabetes co-morbidity experience delayed recovery of body mass and haemoglobin, which are important for the functional recovery from disease.

CD4 lymphocyte dynamics in Tanzanian pulmonary tuberculosis patients with and without HIV co-infection.

BACKGROUND: The interaction of HIV and tuberculosis (TB) on CD4 levels over time is complex and has been divergently reported. METHODS: CD4 counts were assessed from time of diagnosis till the end of TB treatment in a cohort of pulmonary TB patients with and without HIV co-infection and compared with cross-sectional data on age- and sex-matched non-TB controls from the same area. RESULTS: Of 1,605 study participants, 1,250 were PTB patients and 355 were non-TB controls. At baseline, HIV was associated with 246 (95% CI: 203; 279) cells per µL lower CD4 counts. All PTB patients had 100 cells per µL lower CD4 counts than the healthy controls. The CD4 levels were largely unchanged during a five-month of TB treatment. HIV infected patients not receiving ART at any time and those already on ART at baseline had no increase in CD4 counts after 5 months of TB treatment, whereas those prescribed ART between baseline and 2 months, and between 2 and 5 months increased by 69 (22;117) and 110 (52; 168) CD4 cells per µL after 5 months. CONCLUSIONS: The increase in circulating CD4 levels observed in PTB in patients is acquired after 2 months of treatment irrespective of HIV status. Initiation of ART is the strongest factor correlated with CD4 increase during TB treatment. TRIAL REGISTRATION NUMBER: Clinical trials.gov: NCT00311298.

Prevalence of bacterial vaginosis and associated factors among pregnant women attending at Bugando Medical Centre, Mwanza, Tanzania.

Bacterial vaginosis (BV) is an extremely common reproductive tract condition worldwide with reported high prevalence among African population. Factors associated with this condition include preterm labour, premature rupture of membranes, preterm delivery and possibly spontaneous abortion. Nevertheless, antenatal screening and treatment is not routinenly available in most poor-resource countries including Tanzania. A cross-sectional descriptive study was conducted among delivering women at Bugando Medical Centre (BMC), Mwanza, Tanzania to determine the magnitude of the BV using the Nugent's criteria and to document factors associated with the condition. A total of 284 women who presented for delivery at BMC labour ward from February to March 2011 were recruited into the study. For each consented women, a vaginal swab was taken, samples collected tested and a Nugent's score of at least seven indicated bacterial vaginosis. Overall, bacterial vaginosis was diagnosed in 28.5% (n=81) of all participants. Gardnerella was the commonest morphotypes found in approximately 66.2% (n=188) of all participants while 11.6% (33 participants) had Mobilincus. There were no evidence for the association between bacterial vaginosis having formal education, (OR, 1.42[95%CI, 0.29-6.97; p=0.6671). Urban residence (OR, 1.29 [95% CI, 0.76-2.19; p=0.352]), ever delivered before (OR 0.66[95%CI, 0.39-1.12; p=0.126]), vaginal practice to enhance dry sex (OR, 1. 16[95%CI, 0.43-3.17; p=0.768]) or wet sex (OR 1.31[95%CI, 0.46-3.7; p=0.613]), gestation age less than 37 weeks (OR 0.82[95%CI, 0.45-1.51; p=0.534]) and HIV infection (OR 0.90[95%CI, 0.28-2.92; p=0.863]) were not associated with bacterial vaginosis. Bacterial vaginosis is common among women delivering at Bugando Medical Centre and more studies to include antenatal clinic attendees initiating care are required to reliably document the magnitude the condition.

Infrequent detection of Pneumocystis jirovecii by PCR in oral wash specimens from TB patients with or without HIV and healthy contacts in Tanzania.

BACKGROUND: In tuberculosis (TB) endemic parts of the world, patients with pulmonary symptoms are managed as "smear-negative TB patients" if they do not improve on a two-week presumptive, broad-spectrum course of antibiotic treatment even if they are TB microscopy smear negative. These patients are frequently HIV positive and have a higher mortality than smear-positive TB patients. Lack of access to diagnose Pneumocystis jirovecii pneumonia might be a contributing reason. We therefore assessed the prevalence of P. jirovecii by PCR in oral wash specimens among TB patients and healthy individuals in an HIV- and TB-endemic area of sub-Saharan Africa. METHODS: A prospective study of 384 patients initiating treatment for sputum smear-positive and smear-negative TB and 100 healthy household contacts and neighbourhood controls. DNA from oral wash specimens was examined by PCR for P. jirovecii. All patients delivered sputum for TB microscopy and culture. Healthy contacts and community controls were clinically assessed and all study subjects were HIV tested and had CD4 cell counts determined. Clinical status and mortality was assessed after a follow-up period of 5 months. RESULTS: 384 patients and 100 controls were included, 53% and 8% HIV positive respectively. A total number of 65 patients and controls (13.6%) were at definitive risk for PCP based on CD4 counts <200 cells per mm3 and no specific PCP prophylaxis. Only a single patient (0.3% of the patients) was PCR positive for P. jirovecii. None of the healthy household contacts or neighbourhood controls had PCR-detectable P. jirovecii DNA in their oral wash specimens regardless of HIV-status. CONCLUSIONS: The prevalence of P. jirovecii as detected by PCR on oral wash specimens was very low among TB patients with or without HIV and healthy individuals in Tanzania. Colonisation by P. jirovecii was not detected among healthy controls. The present findings may encourage diagnostic use of this non-invasive method.