Impact of Human Immunodeficiency Virus Infection on the Outcome of Treatment and Survival of Tuberculosis Patients in Mwanza, Tanzania.

Little is known about the outcome of tuberculosis (TB) treatment and subsequent survival of human immunodeficiency virus (HIV) infected patients treated under routine programme conditions in a developing country. We followed a cohort of HIV-positive and HIV-negative tuberculosis patients during therapy and assessed their vital and tuberculosis status 3 years after completion of treatment in Mwanza, Tanzania. Newly diagnosed and relapse tuberculosis cases consecutively registered over a 6-month period were enrolled into an epidemiological study of TB/HIV. Treatment outcome was based on information in tuberculosis treatment registers. Patients surviving treatment were assessed 3 years later by personal interview. Cause of death was determined by verbal autopsy. Of 561 patients enrolled into the study, 505 patients alive at completion of treatment were eligible for assessment at 3 years. Except for mortality, HIV infection was not statistically associated with differing treatment outcomes. At time of follow-up, the overall mortality was 19% and was associated with HIV infection (hazard ratio [hr] 3.7, 95% confidence interval [CI] 2.6-5.2) and age 35 years and over (hr 1.5, 95% CI 1.02-2.1), but not with type of tuberculosis, gender, or initial drug resistance. By life table analysis, probability of survival at 4 years was 35% for HIV-positive patients compared to 90% for HIV-negative patients. Although no relapse cases were diagnosed, verbal autopsy suggested equivalent low rates of relapse in both groups. These results demonstrate the effectiveness of the current approach to the treatment of tuberculosis patients regardless of HIV status. However, HIV-related mortality remains high both during and following completion of treatment, and further studies are needed to determine if this mortality might be reduced by simple interventions which are feasible in developing countries.\u

Dynamic ploidy changes drive fluconazole resistance in human cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM) causes an estimated 180,000 deaths annually, predominantly in sub-Saharan Africa, where most patients receive fluconazole (FLC) monotherapy. While relapse after FLC monotherapy with resistant strains is frequently observed, the mechanisms and impact of emergence of FLC resistance in human CM are poorly understood. Heteroresistance (HetR) - a resistant subpopulation within a susceptible strain - is a recently described phenomenon in Cryptococcus neoformans (Cn) and Cryptococcus gattii (Cg), the significance of which has not previously been studied in humans. METHODS: A cohort of 20 patients with HIV-associated CM in Tanzania was prospectively observed during therapy with either FLC monotherapy or in combination with flucytosine (5FC). Total and resistant subpopulations of Cryptococcus spp. were quantified directly from patient cerebrospinal fluid (CSF). Stored isolates underwent whole genome sequencing and phenotypic characterization. RESULTS: Heteroresistance was detectable in Cryptococcus spp. in the CSF of all patients at baseline (i.e., prior to initiation of therapy). During FLC monotherapy, the proportion of resistant colonies in the CSF increased during the first 2 weeks of treatment. In contrast, no resistant subpopulation was detectable in CSF by day 14 in those receiving a combination of FLC and 5FC. Genomic analysis revealed high rates of aneuploidy in heteroresistant colonies as well as in relapse isolates, with chromosome 1 (Chr1) disomy predominating. This is apparently due to the presence on Chr1 of ERG11, which is the FLC drug target, and AFR1, which encodes a drug efflux pump. In vitro efflux levels positively correlated with the level of heteroresistance. CONCLUSION: Our findings demonstrate for what we believe is the first time the presence and emergence of aneuploidy-driven FLC heteroresistance in human CM, association of efflux levels with heteroresistance, and the successful suppression of heteroresistance with 5FC/FLC combination therapy. FUNDING: This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z and the Daniel Turnberg Travel Fellowship

Red meat consumption and its association with hypertension and hyperlipidaemia among adult Maasai pastoralists of Ngorongoro Conservation Area, Tanzania

Background: Red meat is an important dietary source of protein and other essential nutrients. Its high intake has been associated with an increased risk of cardiovascular morbidity and mortality, including hypertension (HTN) and hyperlipidaemia (HLP). Despite being physically active, the Maasai at Ngorongoro Conservation Area (NCA) depend heavily on animals' products as their staple food with fewer intakes of vegetables or fruits due to restriction from carrying out agricultural activities within the NCA. This study aimed at determining the prevalence of HTN and HLP and their association with red meat consumption among adult Maasai of NCA. Methods: A community-based cross-sectional study was conducted in October 2018 using multistage sampling technique. Eight hundred and ninety-four (894) participants enrolled from seven villages in three wards within NCA Data were collected using a modified WHO NCDs-STEPS tool. Anthropometric measurements, blood pressure (BP) measurements, and blood samples for glucose and cholesterol tests were obtained from the study participants. Crude and adjusted prevalence ratio (PR) for factors associated with HTN and HLP were estimated using Ordinal and Bayesian logistic regression models, respectively. Results: The prevalence of HLP was 23.7 percent. The levels were higher among males than were among the females (29.0% vs. 20.1%, p = 0.002). The prevalence of HTN and pre-HTN (elevated BP) were 9.8 and 37.0 percent, respectively. Both HTN and elevated BP were higher among males than were among females (hypertensive [10.9% vs. 9.0%]; elevated BP [44.0% vs. 32.1%], p<0.001). The prevalence of HLP was significantly associated with level II (PR = 1.56, 95%CrI: 1.10–2.09) and level III (PR = 1.64, 95%CrI: 1.08–2.41) of red meat consumption as opposed to level I. Conclusion: The prevalence of hyperlipidaemia and elevated BP were high among NCA Maasai. We found a significant association between red meat consumption and hyperlipidaemia. Further follow-up studies are warranted to establish a temporal relationship between red meat consumption and both conditions

Perceptions of tuberculosis and treatment seeking behaviour in Ilala and Kinondoni Municipalities in Tanzania

This study was carried out in Ilala and Kinondoni Municipalities in Tanzania to explore the perceptions of Tuberculosis (TB), and treatment seeking behaviour, among patients attending healthcare facilities. The study was conducted in four randomly selected health facilities providing directly observed treatment (DOT). Exit interviews were administered to 69 randomly selected TB patients. The mean age of the respondents was 33.2 years (range= 11-72 years). Forty-six (66.7%) of the patients had primary school education. Fifty-nine (84.1%) patients had good knowledge on the transmission of TB. Majority (75%) of the respondents were of the opinion that the incidence of TB was on the increase and this was mainly associated with HIV/AIDS epidemic. All respondents knew that TB was a curable disease if one complies with the treatment. Sixty-four (60%) respondents had good knowledge on the correct duration of tuberculosis treatment. The median duration before seeking treatment from a health facility was 1.5 months. The majority of the patients 47 (68%) visited public health facilities for treatment as their fi rst action. Overall, 83.8% (57/68) respondents said females comply better with treatment than male patients. The majority of the respondents lived within a walking distance to a healthcare facility. Only 18.8% (13/69) had to spend an average of US$ 0.2-0.3 as travel costs to the healthcare facility. Most of the respondents (57.8%) said they were well attended by service providers. Half (21/42) and 59.3% (16/27) of the males and females, respectively, mentioned good patient-service provider relationship as an important reason for satisfaction of the service (&#967;2 =0.57, df=1, P>0.005). Twenty-nine (42%) of respondents were of the opinion that female TB patients conformed better to treatment than males and a similar number thought that both of them equally conformed to treatment. Findings from this study indicate that a large population in urban settings are aware that health facilities play a major role in TB treatment. In conclusion, there is a need to further explore how this information could potentially be used to enhance early seeking of appropriate services among TB patients in the era of rapid urbanization. Strategies in the control of TB and other diseases should focus on advocacy in seeking appropriate care. Keywords: tuberculosis, perceptions, gender, treatment, behaviour, Tanzania Tanzania Journal of Health Research Vol. 10 (2) 2008: pp. 89-9

Safety and immunogenicity of H1/IC31®, an adjuvanted TB subunit vaccine, in HIV-infected adults with CD4+ lymphocyte counts greater than 350 cells/mm3: a phase II, multi-centre, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Novel tuberculosis vaccines should be safe, immunogenic, and effective in various population groups, including HIV-infected individuals. In this phase II multi-centre, double-blind, placebo-controlled trial, the safety and immunogenicity of the novel H1/IC31 vaccine, a fusion protein of Ag85B-ESAT-6 (H1) formulated with the adjuvant IC31, was evaluated in HIV-infected adults. METHODS: HIV-infected adults with CD4+ T cell counts >350/mm3 and without evidence of active tuberculosis were enrolled and followed until day 182. H1/IC31 vaccine or placebo was randomly allocated in a 5:1 ratio. The vaccine was administered intramuscularly at day 0 and 56. Safety assessment was based on medical history, clinical examinations, and blood and urine testing. Immunogenicity was determined by a short-term whole blood intracellular cytokine staining assay. RESULTS: 47 of the 48 randomised participants completed both vaccinations. In total, 459 mild or moderate and 2 severe adverse events were reported. There were three serious adverse events in two vaccinees classified as not related to the investigational product. Local injection site reactions were more common in H1/IC31 versus placebo recipients (65.0% vs. 12.5%, p = 0.015). Solicited systemic and unsolicited adverse events were similar by study arm. The baseline CD4+ T cell count and HIV viral load were similar by study arm and remained constant over time. The H1/IC31 vaccine induced a persistent Th1-immune response with predominately TNF-α and IL-2 co-expressing CD4+ T cells, as well as polyfunctional IFN-γ, TNF-α and IL-2 expressing CD4+ T cells. CONCLUSION: H1/IC31 was well tolerated and safe in HIV-infected adults with a CD4+ Lymphocyte count greater than 350 cells/mm3. The vaccine did not have an effect on CD4+ T cell count or HIV-1 viral load. H1/IC31 induced a specific and durable Th1 immune response. TRIAL REGISTRATION: Pan African Clinical Trials Registry (PACTR) PACTR201105000289276

Strengthening integration of chronic care in Africa: protocol for the qualitative process evaluation of integrated HIV, diabetes and hypertension care in a cluster randomised controlled trial in Tanzania and Uganda.

INTRODUCTION: In sub-Saharan Africa, the burden of non-communicable diseases (NCDs), particularly diabetes mellitus (DM) and hypertension, has increased rapidly in recent years, although HIV infection remains a leading cause of death among young-middle-aged adults. Health service coverage for NCDs remains very low in contrast to HIV, despite the increasing prevalence of comorbidity of NCDs with HIV. There is an urgent need to expand healthcare capacity to provide integrated services to address these chronic conditions. METHODS AND ANALYSIS: This protocol describes procedures for a qualitative process evaluation of INTE-AFRICA, a cluster randomised trial comparing integrated health service provision for HIV infection, DM and hypertension, to the current stand-alone vertical care. Interviews, focus group discussions and observations of consultations and other care processes in two clinics (in Tanzania, Uganda) will be used to explore the experiences of stakeholders. These stakeholders will include health service users, policy-makers, healthcare providers, community leaders and members, researchers, non-governmental and international organisations. The exploration will be carried out during the implementation of the project, alongside an understanding of the impact of broader structural and contextual factors. ETHICS AND DISSEMINATION: Ethical approval was granted by the Liverpool School of Tropical Medicine (UK), the National Institute of Medical Research (Tanzania) and TASO Research Ethics Committee (Uganda) in 2020. The evaluation will provide the opportunity to document the implementation of integration over several timepoints (6, 12 and 18 months) and refine integrated service provision prior to scale up. This synergistic approach to evaluate, understand and respond will support service integration and inform monitoring, policy and practice development efforts to involve and educate communities in Tanzania and Uganda. It will create a model of care and a platform of good practices and lessons learnt for other countries implementing integrated and decentralised community health services. TRIAL REGISTRATION NUMBER: ISRCTN43896688; Pre-results

Quantifying Risk Factors for Human Brucellosis in Rural Northern Tanzania

Brucellosis is a zoonosis of veterinary, public health and economic significance in most developing countries. Human brucellosis is a severely debilitating disease that requires prolonged treatment with a combination of antibiotics. The disease can result in permanent and disabling sequel, and results in considerable medical expenses in addition to loss of income due to loss of working hours. A study was conducted in Northern Tanzania to determine the risk factors for transmission of brucellosis to humans in Tanzania. This was a matched case-control study. Any patient with a positive result by a competitive ELISA (c-ELISA) test for brucellosis, and presenting to selected hospitals with at least two clinical features suggestive of brucellosis such as headache, recurrent or continuous fever, sweating, joint pain, joint swelling, general body malaise or backache, was defined as a case. For every case in a district, a corresponding control was traced and matched by sex using multistage cluster sampling. Other criteria for inclusion as a control included a negative c-ELISA test result and that the matched individual would present to hospital if falls sick. Multivariable analysis showed that brucellosis was associated with assisted parturition during abortion in cattle, sheep or goat. It was shown that individuals living in close proximity to other households had a higher risk of brucellosis. People who were of Christian religion were found to have a higher risk of brucellosis compared to other religions. The study concludes that assisting an aborting animal, proximity to neighborhoods, and Christianity were associated with brucellosis infection. There was no association between human brucellosis and Human Immunodeficiency Virus (HIV) serostatus. Protecting humans against contact with fluids and tissues during assisted parturition of livestock may be an important means of reducing the risk of transferring brucellosis from livestock to humans. These can be achieved through health education to the communities where brucellosis is common

Symptoms and functional limitations related to respiratory health and carbon monoxide poisoning in Tanzania: a cross sectional study

BACKGROUND: The burden of chronic respiratory symptoms and respiratory functional limitations is underestimated in Africa. Few data are available on carbon monoxide (CO) poisoning in sub-Saharan Africa and existing data is derived from CO in ambient air, but not from biomarkers in the blood. METHODS: Data from the Tanzanian Lung Health study, a cross-sectional study on lung health among outpatients and visitors to an urban as well as a rural hospital in Tanzania, was analyzed to describe respiratory symptoms and functional limitations. Saturation of peripheral blood with carbon monoxide (SpCO) was measured transcutaneously and non-invasively in participants using a modified pulse oxymeter indicative of CO poisoning. Univariate and multivariate analysis was performed. RESULTS: Nine hundred and ninety-seven participants were included in the analysis, the median age of participants was 46 years (49% male). 38% of participants reported some degree of chronic shortness of breath and 26% felt limited in their daily activities or at work by this symptom. The median SpCO was 7% (IQR 4-13, range 2-31%) among all participants without active smoking status (N = 808). Participants cooking with gas or electricity had the lowest SpCO (median 5%), followed by participants cooking with charcoal (median 7%). Cooking with wood, particularly using a stove, resulted in highest SpCO (median 11.5%). Participants from households where cooking takes place in a separate room had the lowest SpCO as compared to cooking outside or cooking in a shared room inside (6% vs. 9% vs.10.5%, p < 0.01). Sex or the activity of cooking itself was not associated with a difference in SpCO. Multivariate analysis confirmed cooking in a separate room (as compared to cooking outside) and living in a rural vs. urban setting as protective factors against high SpCO. CONCLUSION: The findings demonstrate a high burden of chronic respiratory symptoms which also cause socioeconomic impact. High levels of SpCO indicate a relevant burden of carbon monoxide poisoning in the local population. The level of CO in the blood is more dependent on shared exposure to sources of CO with the type of housing and type of cooking fuel as most relevant factors, and less on person-individual risk factors or activities

Management of chronic conditions in resource limited settings: multi stakeholders’ perception and experiences with receiving and providing integrated HIV, diabetes and hypertension services in Tanzania

Background: The rising prevalence of non-communicable diseases (NCDs) alongside the continuing high burden of HIV poses a serious challenge to middle- and low-income countries’ healthcare systems. Pilot studies of integrated models of service delivery for HIV, hypertension and diabetes have demonstrated that they are feasible and acceptable among patients and care providers. This study assessed multi-stakeholders’ perspectives of the delivery and receipt of integrated care in Tanzania. Methods: A qualitative process evaluation was conducted in Dar es Salaam region of Tanzania where the integrated service delivery model was implemented from July to November 2021. In-depth interviews were held with seven key informants at the national, regional and district levels, eight healthcare providers, two researchers working at the integrated clinic and forty patients benefiting from integrated services at a large hospital. Three focus group discussions were held with community leaders and residents of the hospital’s catchment area, and clinic level observations were conducted. Thematic analysis was conducted followed by the use of Bronfenbrenner’s ecological model to identify factors pertinent to sustaining and scaling up of the integrated model. Results: Participants of the study at all levels were aware of the increased prevalence of NCDs specifically for hypertension and diabetes and were concerned about the trend of increasing co-morbid conditions among people living with HIV (PLHIV). The integrated service delivery model was positively perceived by stakeholders because of its multiple benefits for both patients and the healthcare system. These include stigma and discrimination reduction, improved quality of care, efficient use of limited resources, cost and time saving, reduced duplication of services and fostering of early detection for undiagnosed conditions. The organisation of the clinic was critical in increased satisfaction. Several challenges were observed, which included costs for NCD services relative to free care for HIV and inconsistent availability of NCD medications. Conclusion: Stakeholders reported numerous benefits of the integrated service delivery model that are fundamental in improving the health of many Tanzanians living with NCDs and HIV. These benefits highlight the need for policy and decision-makers to sustain and expand the integrated service delivery model as a solution to many challenges facing the health system especially at the primary care level

Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA lineage (remarkable by absence of spacers 2 and 3, and represented by SIT126) which seems to be specific to Tanzania. However, further genotyping information would be needed to confirm this specificity