The prevalence of metabolic syndrome and associated factors among adults on antiretroviral therapy in Dar es Salaam, Tanzania.

Background Adults living with HIV (ALHIV) are at increased risk of developing metabolic syndrome (MetS). Several factors are associated with an increase in MetS in these individuals, including certain antiretroviral therapies (ART). There is limited data on the prevalence of MetS among ALHIV in sub-Saharan Africa following scale up of newer integrase inhibitor-containing ART regimens. Objective We assessed the prevalence and correlates of MetS among ALHIV patients receiving tenofovir, lamivudine, and dolutegravir (TLD) in Tanzania. Methods We conducted a retrospective cross-sectional analysis of ALHIV aged > 18 enrolled in a cardiovascular health study at six HIV Care and Treatment Clinics from 11/2020-1/2021 in Dar es Salaam, Tanzania. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). Descriptive statistics were used to summarize the results, and logistic regression was used to assess demographic, behavioral, and HIV-related risk factors associated with MetS. Covariates with a p-value <0.2 at the univariate level were included in the multivariate model. Results Three hundred and eighty nine participants were included in the analysis. The mean age (SD) was 43 years (±11) years, and 286 (73.5%) were female. The prevalence of MetS in this population was 21%. In univariate analysis, MetS components that were significantly higher among women vs. men included abdominal obesity (27.3% vs. 4.9%), reduced HDL (77.9% vs. 53.4% ), and elevated glucose (18.5% vs. 14.6%), all p< 0.05. Age > 50 yrs [AOR 3.25; (95% CI 1.80-5.84), p < 0.01] and BMI [AOR 0.16; (95% CI 0.09-0.30), P < 0.01] were both associated with an increased odds of MetS in multivariate analyses. Conclusion MetS. is prevalent among Tanzanian ALHIV on TLD. Routine screening for MetS and healthy lifestyle promotion, particularly among women and those aging, should be a priority to prevent against cardiovascular disease. Further studies are needed to monitor the long-term impact of these newer ART regimens on MetS and CVD.

Stroke characteristics and outcomes in urban Tanzania: Data from the Prospective Lake Zone Stroke Registry.

BACKGROUND: Stroke is a second leading cause of death globally, with an estimated one in four adults suffering a stroke in their lifetime. We aimed to describe the clinical characteristics, quality of care, and outcomes in adults with stroke in urban Northwestern Tanzania. METHODS: We analyzed de-identified data from a prospective stroke registry from Bugando Medical Centre in Mwanza, the second largest city in Tanzania, between March 2020 and October 2022. This registry included all adults ⩾18 years admitted to our hospital who met the World Health Organization clinical definition of stroke. Information collected included demographics, risk factors, stroke severity using the National Institutes of Health Stroke Scale, brain imaging, indicators for quality of care, discharge modified Rankin Scale, and in-hospital mortality. We examined independent factors associated with mortality using logistic regression. RESULTS: The cohort included 566 adults, of which 52% (294) were female with a mean age of 65 ± 15 years. The majority had a first-ever stroke 88% (498). Premorbid hypertension was present in 86% (488) but only 41% (200) were taking antihypertensive medications before hospital admission; 6% (32) had HIV infection. Ischemic strokes accounted for 66% (371) but only 6% (22) arriving within 4.5 h of symptom onset. In-hospital mortality was 29% (127). Independent factors associated with mortality were severe stroke (adjusted odds ratio (aOR) = 1.81, 95% confidence interval (CI) = 1.47-2.24, p < 0.001), moderate to severe stroke (aOR = 1.49, 95% CI = 1.22-1.84, p < 0.001), moderate stroke (aOR = 1.80, 95% CI = 1.52-2.14, p < 0.001), leukocytosis (aOR = 1.19, 95% CI = 1.03-1.38, p = 0.022), lack of health insurance coverage (aOR = 1.15, 95% CI = 1.02-1.29, p = 0.025), and not receiving any form of venous thromboembolism prophylaxis (aOR = 1.18, 95% CI = 1.02-1.37, p = 0.027). CONCLUSION: We report a stroke cohort with poor in-hospital outcomes in urban Northwestern Tanzania. Early diagnosis and treatment of hypertension could prevent stroke in this region. More work is needed to raise awareness about stroke symptoms and to ensure that people with stroke receive guidelines-directed therapy.

HIV virologic response, patterns of drug resistance mutations and correlates among adolescents and young adults: A cross-sectional study in Tanzania.

BACKGROUND: The emergence of HIV drug resistance mutations (DRMs) is of significant threat to achieving viral suppression (VS) in the quest to achieve global elimination targets. We hereby report virologic outcomes and patterns of acquired DRMs and its associated factors among adolescents and young adults (AYA) from a broader HIV drug resistance surveillance conducted in Tanzania. METHODS: Data of AYA was extracted from a cross-sectional study conducted in 36 selected facilities using a two-stage cluster sampling design. Dried blood spot (DBS) samples were collected and samples with a viral load (VL) ≥1000 copies/mL underwent genotyping for the HIV-1 pol gene. Stanford HIV database algorithm predicted acquired DRMs, Fisher's exact test and multivariable logistic regression assessed factors associated with DRMs and VS, respectively. FINDINGS: We analyzed data of 578 AYA on antiretroviral therapy (ART) for 9-15 and ≥ 36 months; among them, 91.5% and 88.2% had VS (VL<1000copies/mL) at early and late time points, respectively. Genotyping of 64 participants (11.2%) who had VL ≥1000 copies/ml detected 71.9% of any DRM. Clinically relevant DRMs were K103N, M184V, M41L, T215Y/F, L210W/L, K70R, D67N, L89V/T, G118R, E138K, T66A, T97A and unexpectedly absent K65R. Participants on a protease inhibitor (PI) based regimen were twice as likely to not achieve VS compared to those on integrase strand transfer inhibitors (INSTI). The initial VL done 6 months after ART initiation of ≥1000copies/mL was the primary factor associated with detecting DRMs (p = .019). CONCLUSIONS: VS amongst AYA is lower than the third UNAIDs target. Additionally, a high prevalence of ADR and high levels of circulating clinically relevant DRMs may compromise the long-term VS in AYA. Furthermore, the first VL result of ≥1000copies/ml after ART initiation is a significant risk factor for developing DRMs. Thus, strict VL monitoring for early identification of treatment failure and genotypic testing during any ART switch is recommended to improve treatment outcomes for AYA.

Iron status among HIV-infected adults during the first year of antiretroviral therapy in Tanzania.

BACKGROUND: The influence of inflammation on iron status among people living with HIV (PLWHIV) has not been well explored. We evaluated the trajectory of iron status among PLWHIV during the first year of highly active antiretroviral therapy (HAART), compared alternative approaches for inflammation correction, and assessed the associations of iron status with HIV-1 viral load and anthropometric outcomes. METHODS: We conducted a secondary analysis of data from a randomized trial among 400 adults initiating HAART in Tanzania. Ferritin and C-reactive protein (CRP) were measured at baseline, 1, 6 or 12 months. Ferritin was considered in four ways: unadjusted, and adjusted for inflammation using higher cut-off (HC), Thurnham-corrected (TC) and regression-corrected (RC) approaches. For unadjusted, TC and RC ferritin, iron deficiency (ID) was defined using ferritin < 15 µg/L and elevated iron status was defined using ferritin > 150 µg/L among females and > 200 µg/L among males. For HC ferritin, elevated iron status was defined based on serum ferritin > 500 µg/L, while ID was defined using ferritin < 70 µg/L in the presence of inflammation and < 15 µg/L in the absence of inflammation. Regression models evaluated the trajectory of ferritin concentration across categories of baseline characteristics, and assessed the association of iron status with viral and anthropometric outcomes. RESULTS: The prevalence of iron deficiency at HAART initiation was 9% for unadjusted, 17% for HC, 12% for TC and 22% for RC ferritin. The prevalence of elevated iron status was 42% for unadjusted, 18% for HC, 31% for TC, and 15% for RC ferritin. The prevalence of iron deficiency for all three methods increased during the first year of HAART, while the prevalence of elevated iron status decreased. Baseline elevated iron status defined using HC ferritin was associated with a greater risk of HIV-1 viral load > 1000 copies/mL [relative risk (RR) = 4.29, 95% CI: 1.38-13.3] and incidence of being underweight [body mass index (BMI) < 18.5 kg/m2 , hazard ratio (HR) = 3.65, 95% confidence interval (CI): 1.38-9.67]. Neither baseline-elevated iron status defined using TC or RC ferritin nor baseline iron deficiency defined using any of the three methods was associated with HIV-1 viral load or anthropometric outcomes. CONCLUSIONS: Whether and how inflammation correction is done influences findings of studies of iron status among PLWHIV.

Cholecalciferol Supplementation Does Not Affect the Risk of HIV Progression, Viral Suppression, Comorbidities, Weight Loss, and Depression among Tanzanian Adults Initiating Antiretroviral Therapy: Secondary Outcomes of a Randomized Trial.

BACKGROUND: Observational studies suggest that blood concentrations of 25-hydroxyvitamin D [25(OH)D] are associated with morbidity, viral suppression, and mortality among adults living with HIV. OBJECTIVES: We evaluated the effect of cholecalciferol (vitamin D3) supplementation on the risk of HIV disease progression, HIV-1 viral suppression, comorbidities, weight change, and depression among HIV-infected individuals that were initiating antiretroviral therapy (ART) in Dar es Salaam, Tanzania. METHODS: We conducted a randomized, double-blind, placebo-controlled trial of vitamin D3 supplementation among 4000 HIV-infected adult men and nonpregnant women initiating ART with insufficient serum 25(OH)D concentrations (<30 ng/mL). Participants were randomly assigned to receive either weekly 50,000-IU doses for 4 wk followed by daily 2000 IU vitamin D3 until 1 y or a matching placebo regimen given in weekly followed by daily doses until 1 y. Participants were followed up at weekly visits for the first month followed by monthly visits thereafter. We conducted intent-to-treat analyses to assess the effect of vitamin D3 supplementation on the secondary trial outcomes of HIV progression or death, viral suppression, comorbidities, change in BMI, >10% weight loss, incident wasting, and depression. RESULTS: During follow-up, 345 participants (17.2%) in the vitamin D3 group and 371 participants (18.6%) in the placebo group experienced HIV disease progression or death and there was no difference in risk between groups (RR: 0.91; 95% CI: 0.79, 1.06). Vitamin D3 supplementation did not affect the risk of an unsuppressed HIV-1 viral load (>1000 copies/mL) after 6 mo (RR: 1.10; 95% CI: 0.87, 1.41) and there was also no effect on change in BMI, risk of >10% weight loss, wasting, comorbidities, and depression (P values >0.05). CONCLUSIONS: Vitamin D supplementation did not affect the risk of HIV progression, viral suppression, common morbidities, weight-related indicators, or depression among adults initiating ART in Tanzania.This trial was registered at clinicaltrials.gov as NCT01798680.

Acquired HIV drug resistance among children and adults receiving antiretroviral therapy in Tanzania: a national representative survey protocol.

INTRODUCTION: Tanzania is making an enormous effort in scaling-up of antiretroviral therapy (ART). However, people living with HIV (PLHIV) continue to succumb to the challenge of drug resistance. Evidence on drug resistance for a national survey is unavailable in Tanzania. Therefore, we sought to assess viral suppression (vs) rates and magnitude of acquired drug resistance (ADR) among PLHIV. METHODS AND ANALYSIS: A national survey will be conducted from 26 July to 29 October 2021 in 22 regions, recruiting 2160 participants. These will include adults on ART for 9-15 months and ≥48 months and children on ART for 9-15 months and ≥36 months. A standardised questionnaire will capture participants' demographic and clinical data. Plasma and dried blood spot will be prepared for viral load testing and drug resistance genotyping. Statistical analyses to determine the burden of ADR, characteristics and factors associated therewith will be done using STATA V.15. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the National Health Research Ethics Committee of Tanzania (NIMR/HQ/R.8a/Vol.IX/3432). Appropriate participant informed consent or parental consent and assent will be obtained. Dissemination will include a survey report, conference presentations, policy briefs and peer-reviewed publications.

Minimizing the impact of the triple burden of COVID-19, tuberculosis and HIV on health services in sub-Saharan Africa.

In this perspective, we discuss the impact of COVID-19 on tuberculosis (TB)/HIV health services and approaches to mitigating the growing burden of these three colliding epidemics in sub-Saharan Africa (SSA). SSA countries bear significantly high proportions of TB and HIV cases reported worldwide, compared to countries in the West. Whilst COVID-19 epidemiology appears to vary across Africa, most countries in this region have reported relatively lower-case counts compared to the West. Nevertheless, the COVID-19 pandemic has added an additional burden to already overstretched health systems in SSA, which, among other things, have been focused on the longstanding dual epidemics of TB and HIV. As with these dual epidemics, inadequate resources and poor case identification and reporting may be contributing to underestimations of the COVID-19 case burden in SSA. Modelling studies predict that the pandemic-related disruptions in TB and HIV services will result in significant increases in associated morbidity and mortality over the next five years. Furthermore, limited empirical evidence suggests that SARS-CoV-2 coinfections with TB and HIV are associated with increased mortality risk in SSA. However, predictive models require a better evidence-base to accurately define the impact of COVID-19, not only on communicable diseases such as TB and HIV, but on non-communicable disease comorbidities. Further research is needed to assess morbidity and mortality data among both adults and children across the African continent, paying attention to geographic disparities, as well as the clinical and socio-economic determinants of COVID-19 in the setting of TB and/or HIV.

Clinical and Imaging Features of Adults with Recurrent Pulmonary Tuberculosis - A Prospective Case-Controlled Study.

BACKGROUND: Recurrent pulmonary tuberculosis (RPTB) is a growing, important and neglected problem affecting treated TB patients and TB health services across the world, particularly in sub-Saharan Africa. Analyses and identification of differences in clinical features between recurrent PTB and newly diagnosed PTB may lead to improved management recommendations. METHODS: Between September 1st 2019 and January 31st 2020, we performed a prospective case controlled study of clinical and imaging features of patients with recurrent pulmonary tuberculosis and compared them with those of newly diagnosed PTB cases. Recurrent PTB was defined as a patient with bacteriologically confirmed active PTB who was previously successfully treated for PTB and was cured. A control was defined as a patient who presents for the first time with bacteriologically confirmed PTB. Clinical and radiological features were assessed and documented. Chi-square and t-test were used to test the difference between proportion and continuous data, respectively. Logistic regression analysis was done to determine factors associated with RPTB using SPSS version 23 software. RESULTS: A total of 312 patients with PTB were enrolled (104 RPTB cases and 208 newly diagnosed controls). Clinically hemoptysis was more common in RPTB compared to controls 28/104 (26.9%) vs 35/208 (16.8%), P = 0.036. Chest pain was significantly less common among patients with RPTB compared to controls 33 (31.7%) vs 92 (44.2%), P = 0.034. A higher proportion of RPTB presented with cavitation 34/104 (32.7%) compared to control 44/208 (21.2%) P = 0.027. The median score for lung pathology was higher among patients with RPTB (50) compared to controls (30); P = 0.001. Lung function of patients with RPTB at diagnosis of index TB were more likely to show mixed restrictive and obstructive pattern 36/104 (34.6%) compared to controls 31/208 (14.9%). p<0.001. Multivariate analysis showed that patients older than 45 years of age (adjusted odds ratio [aOR]: 3.59, 95% CI: 1.38 - 9.32), those with hemoptysis (aOR 1.96, 95% CI: 1.04 - 3.69) p=0.04) and fibrosis on chest x rays (aOR 2.18, 95% CI: 1.16 - 4.10) were significantly associated with recurrent PTB. CONCLUSIONS: Hemoptysis, lung parenchymal damage, and patients being older than 45 years of age are significant features of RPTB. Management should focus on risk factors for recurrence, and a more holistic model of care to prevent long term lung injury.

Depression and Viral Suppression Among Adults Living with HIV in Tanzania.

Limited information is available on the association between depression and viral suppression among people living with HIV (PLH) in sub-Saharan Africa. We conducted a prospective cohort study of 3996 adults initiating antiretroviral therapy (ART) in Dar es Salaam, Tanzania. Log-binomial models were used to assess the association between depression and the risk of an unsuppressed viral load (> 400 copies/mL) after 6 months of ART. Women who had depression at both initiation and after 6 months of treatment had 1.94 times (95% CI 1.22, 3.09; z = 2.78, p < 0.01) the risk of an unsuppressed viral load after 6 months of treatment as compared to women who did not have depression at either time point. Men with the top tertile of depressive symptoms after 6 months of treatment had 1.58 times the risk of an unsuppressed viral load (95% CI 1.04, 2.38; z = 2.15, p = 0.03) as compared to the lowest tertile. Research should be pursued on interventions to prevent and address depression among adults initiating ART to potentially support achievement of viral suppression.

Efficacy of vitamin D3 supplementation for the prevention of pulmonary tuberculosis and mortality in HIV: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Observational data suggest that low vitamin D status is associated with an increased incidence of pulmonary tuberculosis and mortality among people living with HIV. The primary aims of this study were to assess the effect of vitamin D3 supplementation on the risk of mortality and incidence of pulmonary tuberculosis among adults initiating antiretroviral therapy (ART). METHODS: This was a randomised, double-blind, placebo-controlled trial of vitamin D3 supplementation among adults living with HIV who initiated ART and had serum 25-hydroxyvitamin D concentrations of less than 30 ng/mL at four large HIV care and treatment centres in Dar es Salaam, Tanzania. Patients were excluded if they were younger than 18 years, pregnant at the time of randomisation, or were enrolled in any other clinical trial. Patients were randomly assigned 1:1 to receive either weekly oral 50 000 IU vitamin D3 supplements (cholecalciferol) for the first month of ART followed by daily 2000 IU vitamin D3 supplements or a matching weekly and daily placebo regimen. The randomisation list was computer-generated by a non-study statistician with sequence blocks of ten that were stratified by study clinic. Complete allocation concealment was ensured and patients, field team, and investigators were masked to group assignment. The trial follow-up duration was 1 year and the primary efficacy outcomes were death and incident pulmonary tuberculosis. An intention-to-treat analysis was followed for all-cause mortality; participants diagnosed with or receiving treatment for pulmonary tuberculosis at randomisation, or suspected to have tuberculosis at randomisation and who later had that diagnosis confirmed, were excluded from analyses of pulmonary tuberculosis incidence. Safety was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT01798680, and is completed. FINDINGS: Between Feb 24, 2014, and Feb 24, 2017, 6250 adults initiating ART had serum 25-hydroxyvitamin D screening, 4000 of whom were enrolled in the trial and followed up for 1 year (follow-up of all participants was completed on March 7, 2018). 2001 patients were randomly assigned to the vitamin D3 supplementation group, and 1999 to the placebo group. 415 deaths were recorded: 211 in the vitamin D3 group and 204 in the placebo group. Among all randomly assigned participants, there was no overall effect of vitamin D3 supplementation on the risk of mortality (hazard ratio [HR] 1·04, 95% CI 0·85-1·25; p=0·73). There was also no difference in the overall incidence of pulmonary tuberculosis between the vitamin D3 (50 events in 1812 patients analysed) and placebo groups (64 events in 1827 patients; HR 0·78, 0·54-1·13; p=0·19). The vitamin D3 regimen did not increase the risk of hypercalcaemia (three events in the vitamin D3 group and two events in the placebo group; relative risk 1·25, 95% CI 0·43-3·66; Fisher's exact p=1·00). 101 hospital admissions were reported in the vitamin D3 group and 94 in the placebo group (incidence rate ratio 1·06, 95% CI 0·80-1·41; p=0·66). INTERPRETATION: Additional research is needed before vitamin D3 supplementation should be considered for implementation in HIV care and treatment programmes for the prevention of pulmonary tuberculosis or mortality. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases.

Trends in Hospitalisation for Human Immunodeficiency Virus in a Tertiary Hospital in Dar es Salaam, Tanzania: A Case study.

BACKGROUND: Reports on systematic evaluation of the impact of antiretroviral therapy(ART) on patients' hospitalisation in Sub Saharan Africa (SSA) and Tanzania in particular are scarce. We aimed at documenting the trends of hospital admissions at Muhimbili National Hospital (MNH) following scale up of free access to ART in Tanzania. METHODS: Records for all admissions at MNH from June 2005 to June 2015 were reviewed. We extracted data from Hospital Information Management System as well as from patients' charts. Data extracted included diagnosis at discharge, reason for admission and thereafter assessed admission trends over the decade. We summarised the data as frequency and percentages. We compared proportions using Chi squared test, P<0.05 was deemed significant. RESULTS: Overall there were 209,101 admissions during the study period (June 2005 to June 2015) and 7864/209,101 (3.8%) were due to HIV infection. Whereas 598/4,519 (13.2%) of all admissions in 2005 were due to HIV, only 345/13,119 (2.6%) of admissions in 2015 were HIV-related; showing a significant drop over time (P value for trend < .001). Generally, females 3887/6679 (58.2%) were more likely to be admitted than males (41.8%). Median CD4 count for admitted HIV patients was 143 cells/µl. Majority of admissions occured in the medical wards 3643/5310 (68.6%). Discharge diagnoses were Tuberculosis 1396/6482 (21.5%), anaemias 1016/6482 (15.6 %), malignancies 789/6482(12.2%), CNS infections 541/6482 (8.3%) and chronic kidney disease 308/6482 (4.8%). Three leading AIDS defining malignancies among hospitalised patients included Kaposi's sarcoma 380/789 (48.2%), carcinoma of the cervix 77/789 (9.8%), and Non-Hodgkin's lymphoma 44/789 (5.6%). CONCLUSION: Despite drastic drop of HIV related admissions at Muhimbili National Hospital over the years, the infection remains a problem of the adults, largely females suffering from medical conditions and presenting with severe immunosuppression. Tuberculosis remained the most common opportunistic infection among hospitalized HIV infected patients. Anaemia and cancers became more important causes of admission than was diarrhoea which had been the most common among HIV infected patients in pre- ART era.

Prevalence and factors associated with alcohol drinking among HIV and tuberculosis co-infected patients in Dar es Salaam, Tanzania.

There is scarcity of information on the burden of alcohol use among people living with HIV in Tanzania despite the high burden of HIV. We examined the prevalence and factors associated with alcohol use among HIV and tuberculosis (TB) co-infected patients in fourteen clinics with highest notification of TB in Dar es Salaam, Tanzania, between October 2010 and December 2011. Proportions were used to describe the prevalence and pattern of alcohol use. Logistic regression was used to assess the association of various participant characteristics with alcohol use. Out of the 515 participants, 38 (7.4%) were current alcohol drinkers, 183 (35.5%) were ex-drinkers and the rest, 294 (57.1%) denied ever drinking alcohol. Approximately, 15% of past and current drinkers were classified as heavy drinkers. Patients with normal BMI, cigarette smokers, and those with higher income were more likely to be drinkers. Similarly, compared to civil servants, those in petty trade and other occupations were more likely to be drinkers. We concluded that, the level of current alcohol use among HIV positive people receiving pulmonary TB treatment in this population was low. Nevertheless, alcohol use screening and assessment should be added as an integral part of service provision in HIV clinics given the effect of alcohol on health outcomes among HIV positive patients.

Hepatitis B vaccination coverage among healthcare workers at national hospital in Tanzania: how much, who and why?

BACKGROUND: Hepatitis B vaccination for healthcare workers (HCWs) is a key component of the WHO Hepatitis B Elimination Strategy 2016-2021. Data on current hepatitis B vaccine coverage among health care workers in Sub-Saharan Africa are scarce, but these data are vital for effective programming. We assessed the proportion of HCWs vaccinated for hepatitis B and the factors associated with adequate vaccination coverage at a national hospital in Tanzania. METHODS: A descriptive cross-sectional study was conducted among consenting healthcare workers between 30th July and 30th September 2015. Vaccination histories were obtained through self-administered questionnaires. Means and proportions were used to summarize the data. Student's t and chi-squared tests were used as appropriate. Logistic regression was used to determine the factors associated with vaccination. RESULTS: A total of 348 HCWs were interviewed, of whom 198 (56.9%) had received at least one dose of hepatitis B vaccination, while only 117 (33.6%) were fully vaccinated. About half of the 81 HCWs with partial vaccination (49.4%) had missed their subsequent vaccination appointments. Among unvaccinated HCWs, 14 (9.3%) had either HBV infection or antibodies against HBV infection upon pre-vaccination screening. However, the remaining participants were not vaccinated and did not know their immune status against HBV. Nearly all respondents (347, 99.3%) had heard about the hepatitis B viral vaccine. The following reasons for non-vaccination were given: 98 (65.3%) reported that they had not been offered the vaccine; 70 (46.7%) observed standard precautions to ensure infection prevention and 60 (41.3%) blamed a low level of awareness regarding the availability of the hepatitis B vaccine. CONCLUSION: The current vaccination coverage among practicing healthcare workers at Muhimbili National Hospital is low, despite a high level of awareness and the acceptance of the vaccine. Expedited and concerted efforts to scale vaccine uptake should include improved access to the vaccine, especially for newly recruited HCWs. The extension of the study to private healthcare settings and lower-level facilities would be useful.

Strong anti-Epstein Barr virus (EBV) or cytomegalovirus (CMV) cellular immune responses predict survival and a favourable response to anti-tuberculosis therapy.

BACKGROUND: Intact immune responses to cytomegalovirus (CMV) and Epstein-Barr virus (EBV) represent a biologically and clinically relevant correlate of 'immunological fitness' in humans. However, there is a lack of knowledge concerning anti-EBV or anti-CMV responses in patients with pulmonary tuberculosis (TB), in whom aberrant immune responses may promote progression of clinical disease. METHODS: Venous blood samples were obtained at the time of (sputum smear positive) pulmonary TB diagnosis. A whole blood assay was performed by exposing PBMCs (peripheral blood mononuclear cells) to a panel of infectious antigens, including CMV, EBV and mycobacterial proteins. Cell culture supernatants were collected after seven days and interferon gamma (IFN-γ) was measured using a sandwich ELISA. Patients received standard first line anti-tuberculosis rifampicin (R)/isoniazid (H)/ethambutol (E)/pyrazinamide (Z) for two months followed by RH for four months. RESULTS: PBMCs from cured patients (after treatment completion) exhibited significantly stronger IFN-γ responses to CMV (p=0.035), EBV (p=0.006) or Mycobacterium tuberculosis ESAT-6 (p=0.043) at the time of diagnosis as compared to patients who succumbed to TB during treatment. IFN-γ responses to other viral (H5N1, HSV-1) as well as other mycobacterial (Ag85A, Rv2958c, Rv0447c) antigens were not found to be significantly different among patients who were cured or those who succumbed to TB. CONCLUSIONS: Increased cellular immune responses to CMV and EBV antigens at the time of diagnosis of pulmonary tuberculosis are associated with increased survival after a standard six months anti-TB therapy. CVM and EBV antigens may represent "intrinsic markers for immune fitness" and guide improved TB therapies including host-directed therapies.

Efficacy of vitamin D3 supplementation in reducing incidence of pulmonary tuberculosis and mortality among HIV-infected Tanzanian adults initiating antiretroviral therapy: study protocol for a randomized controlled trial.

BACKGROUND: HIV-infected adults initiating antiretroviral therapy (ART) in sub-Saharan Africa continue to experience high rates of morbidity and mortality during the initial months of treatment. Observational studies in high-income and resource-limited settings indicate that HIV-infected adults with low vitamin D levels may be at increased risk of mortality, HIV disease progression, and incidence of pulmonary tuberculosis (TB). As a result, vitamin D3 supplementation may improve survival and treatment outcomes for HIV-infected adults initiating ART. METHODS/DESIGN: The Trial of Vitamins-4 (ToV4) is an individually randomized, double-blind, placebo-controlled trial of vitamin D3 (cholecalciferol) supplementation conducted among 4000 HIV-infected adults with low vitamin D levels [25-hydroxyvitamin D (25(OH)D) <30 ng/mL] initiating ART in Dar es Salaam, Tanzania. The two primary aims of the trial are to determine the effect of a vitamin D3 supplementation regimen on incidence of (1) mortality and (2) pulmonary TB as compared to a matching placebo regimen. The primary safety outcome of the study is incident hypercalcemia. The investigational vitamin D3 regimen consists of oral supplements containing 50,000 IU vitamin D3 taken under direct observation at randomization and once a week for 3 weeks (four doses) followed by daily oral supplements containing 2000 IU vitamin D3 taken at home from the fourth week until trial discharge at 1 year post ART initiation. Trial participants are followed up at weekly clinic visits during the first month of ART and at monthly clinic visits thereafter until trial discharge at 1 year post ART initiation. Secondary aims of the trial are to examine the effect of the vitamin D3 regimen on CD4 T cell reconstitution, incidence of non-TB comorbidities, body mass index (BMI), depression and anxiety, physical activity, bone health, and immunologic biomarkers. DISCUSSION: The ToV4 will provide causal evidence on the effect of vitamin D3 supplementation on incidence of pulmonary TB and mortality among HIV-infected Tanzanian adults initiating ART. The trial will also give insight to whether vitamin D3 supplementation trials for the prevention of pulmonary TB should be pursued in HIV-uninfected populations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01798680 . Registered on 21 February 2013.

Tuberculosis associated mortality in a prospective cohort in Sub Saharan Africa: Association with HIV and antiretroviral therapy.

OBJECTIVE: Nine out of ten tuberculosis deaths occur in tuberculosis-burdened countries, particularly Sub Saharan Africa. In these setting mortality has not been fully described. We describe the magnitude and pattern of TB mortality in Tanzania. METHODS: A multicenter prospective cohort study was conducted among HIV infected and uninfected pulmonary tuberculosis patients from time of anti-TB treatment initiation to completion. Patients were censored at the time of treatment completion, or at their last visit for those who did not complete TB treatment. Kaplan-Meier curves were used to estimate time to death; cox proportional hazards model was used to examine risk factors for mortality. RESULTS: A total of 58 deaths out of 1696 patients (3.4%) occurred, two thirds (n=39) during the first two months of treatment. Compared to HIV un-infected TB patients, mortality risk for TB/HIV co-infected patients was least when antiretroviral therapy (ART) was initiated after 14 days of anti-TB (RR=3.55; 95% CI: 1.44, 8.73 p<0.0001) and highest when ART was initiated 90 days or less prior to anti-TB and within the first 14 days of anti-TB therapy (RR=10; 95% CI: 3.28, 30.54; p<0.0001). CONCLUSION: Meticulously planned and supervised antiretroviral therapy reduces mortality among TB/HIV patients. Among patients with TB/HIV naïve of ART, withholding ART until the third week of anti-tuberculosis therapy will likely reduce TB mortality in Tanzania. Patients on ART and later develop tuberculosis should be closely monitored.