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

Delay in Tuberculosis case detection in Pwani region, Tanzania. a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Delay in Tuberculosis (TB) case detection may worsen the disease and increase TB transmission. It is also a challenge to the National TB and Leprosy control Program (NTLP).</p> <p>Methods</p> <p>We conducted a cross sectional study in four out of six districts in Pwani region to estimate the extent and factors responsible for delay in TB case detection in Pwani region. Delays were divided into patient, health facility and total delay.</p> <p>Results</p> <p>We enrolled a total of 226 smear positive TB patients. Out of 226 patient's results were available for 206. The majority (66.5%) of the patients were males. Mean age for males and females were 37.3 and 33.7 years respectively. Mean (SD) total delay was 125.5 (98.5) days (median 90). Out of 206 patients, 79 (38.35%) delayed to seek TB health care. Health facility delay was observed among 121 (58.7%) patients.</p> <p>Risk factors for delay was poor knowledge that chest pain may be a TB symptom (OR = 2.9; 95%CI 1.20- 7.03) and the belief that TB is always associated with HIV/AIDS (OR = 2.7; 95%CI 1.39-5.23). Risk for delay was low among patients who first presented to a government health facility (OR = 0.3; 95%CI 0.12- 0.71) and those presenting with chest pain (OR = 0.2; 95%CI 0.10-0.61).</p> <p>Conclusion</p> <p>There is a considerable delay in TB case detection in Pwani mainly contributed by patients. Risk factors for delay include misconception about TB/HIV and poor knowledge of TB symptoms.</p

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

Evaluation of the KEMRI Hep-cell II test kit for detection of hepatitis B surface antigens in Tanzania

Hepatitis B surface antigen (HBsAg) is one of the most important serological markers used to diagnose acute and chronic hepatitis B infection. The objective of the current evaluation was to assess the operational characteristics of the Kenya Medical Research Institute (KEMRI) Hep-cell II against an ELISA Exsym HBsAg in the detection of hepatitis B surface antigens. To evaluate the Hep-cell II test, blood samples were collected from blood donors and processed for detection of HBsAg using Hep-cell II based on the test principle and procedure outlined by the manufacturer. ELISA Axsym HBsAg test was used as golden standard. Of the 400 samples tested, 287 (71.8%) were positive by Hep-cell test and 295 (73.8%) were positive by the ELISA Axsym. Hep-cell test had a sensitivity of 98.6% and specificity of 95.96%. Similar values of sensitivity and specificity of the Hep-cell test were obtained even when Bayesian Analysis Model was applied. The positive and negative predictive values of Hep-cell test were 98.61% and 95.96%, respectively. The positive and negative diagnostic likelihood ratios of Hep-cell test were 24.4% and 0.0145, respectively. In conclusion, the Hep-cell test is useful for detecting hepatitis B virus and the high likelihood ratio observed suggests that it may be useful in blood screening. However, it may be necessary to evaluate for cost-effectiveness and robustness in field conditions before the test is recommended for use

Xpert® MTB/RIF assay testing on stool for the diagnosis of paediatric pulmonary TB in Tanzania.

SETTING: Six health facilities in Dar es Salaam, Tanzania. OBJECTIVE: To evaluate the use of stool specimens in the diagnostic workup of paediatric TB using the Xpert® MTB/RIF assay. DESIGN: Between December 2018 and May 2019, we performed a cross-sectional diagnostic study of children aged between 1 month and 14 years with presumptive TB. A single stool specimen was tested using Xpert. The result was compared with the reference microbiological standard for respiratory or gastric specimens tested using Xpert and/or solid culture. The sensitivity, specificity and predictive values of stool Xpert assay were assessed. RESULTS: A total of 225 children with a median age of 2.17 years (IQR 1.16-5.19) were enrolled; 165/225 (73.3%) were aged <5 years. Of 225 children, 8 (3.6%) were diagnosed with TB as they were culture- or Xpert-positive on sputum/gastric aspirate. The stool Xpert assay showed a sensitivity of 62.5% (95% CI 25-92) and specificity of 100% (95% CI 98-100) against the reference standard. CONCLUSION: Use of the Xpert assay on stool specimens had a moderate sensitivity and high specificity in the diagnosis of pulmonary TB in children. Our data adds to the body of evidence for the use of Xpert assay on stool as a non-respiratory specimen to complement conventional methods used to diagnose the disease

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

A cross-sectional study of factors associated with dog ownership in Tanzania

Background: Mass vaccination of owned domestic dogs is crucial for the control of rabies in sub-Saharan Africa. Knowledge of the proportion of households which own dogs, and of the factors associated with dog ownership, is important for the planning and implementation of rabies awareness and dog vaccination programmes, and for the promotion of responsible dog ownership. This paper reports the results of a cross-sectional study of dog ownership by households in urban and rural communities in the United Republic of Tanzania. Results: Fourteen percent (202) of 1,471 households surveyed were identified as dog-owning, with an average of 2.4 dogs per dog-owning household. The percentage of dog-owning households was highest in inland rural areas (24%) and lowest in coastal urban communities (7%). The overall human: dog ratio was 14: 1. Multivariable logistic regression revealed that households which owned cattle, sheep or goats were much more likely to own dogs than households with no livestock. Muslim households were less likely to own dogs than Christian households, although this effect of religion was not seen among livestock-owning households. Households were more likely to own a dog if the head of the household was male; if they owned a cat; or if they owned poultry. Dog ownership was also broadly associated with larger, wealthier households. Conclusion: The human: dog ratios in Tanzania are similar to those reported elsewhere in sub-Saharan Africa, although cultural and geographic variation is evident. Estimation of the number of owned dogs, and identification of household predictors of dog ownership, will enable targeted planning of rabies control effort

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

Detection of pulmonary tuberculosis among patients with cough attending outpatient departments in Dar Es Salaam, Tanzania: does duration of cough matter?

According to WHO estimates, tuberculosis case detection rate in Tanzania is less than 50% and this poses a major challenge to control tuberculosis in the country. Currently, one of the defining criteria for suspecting tuberculosis is cough for two weeks or more. We wanted to find out whether the prevalence of tuberculosis was different in patients who reported cough for two weeks or more, compared to patients with cough for less than two weeks. We conducted a cross sectional study in six health facilities in Dar es Salaam, between September and October 2007. All patients aged five years and above with cough were screened for pulmonary tuberculosis (PTB) by smear microscopy. Patients were divided into two groups, those who coughed for less than two weeks (<2 wks) and those who coughed for two weeks or more (> or = 2 wks). A total of 65,530 patients attended outpatients department (OPD). Out of these, 2274 (3.5%) patients reported cough. Among patients who reported cough, 2214 (97.4%) remembered their cough duration. One thousand nine hundred and seventy three patients (89.1%) coughed for >/= 2 wks as compared to 241 (10.9%) patients who coughed for <2 wks. Of those who coughed for two weeks or more, 250 (12.7%) had smear positive PTB, and of those who had coughed for less than two weeks, 21 (8.7%) had smear positive PTB. There was no statistically significant difference in prevalence of smear positive tuberculosis among the two groups (Pearson Chi-Square 3.2; p = 0.074). Detection of smear positive PTB among patients who coughed for less than two weeks was as high as for those who coughed for two weeks or more

Improving treatment outcomes for MDR-TB - Novel host-directed therapies and personalised medicine of the future

Multidrug-resistant TB (MDR-TB) is a major threat to global health security. In 2017, only 50% of patients with MDR-TB who received WHO-recommended treatment were cured. Most MDR-TB patients who recover continue to suffer from functional disability due to long-term lung damage. Whilst new MDR-TB treatment regimens are becoming available, conventional drug therapies need to be complemented with host-directed therapies (HDTs) to reduce tissue damage and improve functional treatment outcomes. This viewpoint highlights recent data on biomarkers, immune cells, circulating effector molecules and genetics which could be utilised for developing personalised HDTs. Novel technologies currently used for cancer therapy which could facilitate in-depth understanding of host genetics and the microbiome in patients with MDR-TB are discussed. Against this background, personalised cell-based HDTs for adjunct MDR-TB treatment to improve clinical outcomes are proposed as a possibility for complementing standard therapy and other HDT agents. Insights into the molecular biology of the mechanisms of action of cellular HDTs may also aid to devise non-cell-based therapies targeting defined inflammatory pathway(s) in Mtb-driven immunopathology