Improving treatment outcomes for patients with pulmonary tuberculosis in Tanzania : host and pathogen factors

Tuberculosis (TB) causes more than 1.2 million deaths each year globally. Yet, survivors of tuberculosis are left with long term sequelae of chronic inflammatory responses with consequent reduced quality of life. Biomarkers of monitoring tuberculosis disease activity, clinical response and mortality might assist in reducing mortality and ultimately in improving quality of life post tuberculosis disease. The general aim of the thesis was to describe mortality among patients treated for a first episode of tuberculosis in Tanzania in relation to selected known pathogen related predictors of poor tuberculosis outcomes, namely HIV and anti-tuberculosis drug resistance. We also explored the role of cytokines as part of the host immune response, in relation to mortality and in modulating lung damage. In Paper I: We show an overall mortality of 3.4 – 9.3% among patients treated for tuberculosis in Tanzania, and that TB/HIV patients were at a higher risk of death compared to TB mono-infected patients. The best benefits of antiretroviral therapy (ART) in reducing mortality for TB/HIV co-infected patients occurred when ART was initiated after 14 days of anti-tuberculosis therapy (ATT). We also observed (Paper II) that among 861 patients with tuberculosis, those with isoniazid resistance without concomitant rifampicin resistance had an increased risk of unsuccessful treatment outcome (death or treatment failure or loss from follow up - combined). In Paper III, we observed that patients who exhibited, in cell-based assays, higher interferon gamma (IFN-γ) responses against cytomegalovirus (CMV), Epstein Barr virus (EBV) or Mycobacterium tuberculosis ESAT-6 antigens at the time of TB diagnosis had a survival benefit following treatment for TB. However, IFN- γ responses to some viral antigens (H5N1 and HSV-1) as well as other mycobacterial antigens (Ag85A, Rv2958c, Rv0447c) were not significantly different between patients who survived and those who died. In Paper IV, we observed very high levels of interleukin 6 (IL-6) in serum from 234 patients with pulmonary tuberculosis, as compared to levels of IL-6 in serum from seven healthy controls. Other cytokines (IFN-γ, TNF-α, IL-2, IL-10, IL-17A and IL-21) were also analyzed at the time of TB diagnosis. Unlike with the other cytokines which returned to pretreatment levels or below following ATT, IL-6 levels at end of ATT were significantly higher than their corresponding pre-treatment levels. In addition, we also found that higher IL-6 levels at TB diagnosis correlated with survival of patients with pulmonary tuberculosis, as well as with severe lung injury, defined by chest x-ray score more than 80 at diagnosis. In conclusion, between 3 and 9 out of 100 Tanzanian patients treated for first time tuberculosis will die during treatment. Well planned ART, appropriate clinical monitoring and timely addressing of background isoniazid resistance are essential to improve treatment outcomes. While anti CMV and EBV immune responses may serve to stratify mortality risk, adjunct therapy with IL-6 may serve as a possible target in reducing lung damage and consequently aid to improve quality of life following Mycobacterium tuberculosis disease in the future

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

Background: Reports on a 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 the Hospital Information Management System as well as from patients’ charts. Data extracted included diagnosis at discharge, the reason for admission and thereafter assessed admission trends over the decade. We summarised the data as frequency and percentages. We compared proportions using the Chi-squared test, P 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 \u3c .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 occurred 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 a 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

Anemia at the Initiation of Tuberculosis Therapy Is Associated with Delayed Sputum Conversion among Pulmonary Tuberculosis Patients in Dar-es-Salaam, Tanzania.

Pulmonary tuberculosis and anemia are both prevalent in Tanzania. There is limited and inconsistent literature on the association between anemia and sputum conversion following tuberculosis treatment. Newly diagnosed sputum smear positive pulmonary tuberculosis patients aged ≥15 years initiating on standard anti tuberculosis therapy were recruited from 14 of 54 tuberculosis clinics in Dar es Salaam. Patients were receiving medication according to the recommended short course Directly Observed Therapy (DOT) strategy and were followed up prospectively until completion of treatment (six months). Patients were evaluated before initiation of TB treatment by performing the following; clinical history, physical examination, complete blood counts, serum biochemistry and sputum microscopy. Sputum smears were re-examined at two months of anti-tuberculosis therapy for presence of acid fast bacilli. Anemia was defined as hemoglobin <13 g/dl (males) or <12 g/dl (females). Log-binomial regression was used to assess the association between anemia and sputum conversion at two months. Of the 1245 patients included in the study, 86% were anemic and 7% were sputum smear positive at two months of anti-tuberculosis therapy. Anemic patients were three times more likely to have sputum positive smear as compared to non-anemic patients at two months (RR = 3.05; 95% CI 1.11-8.40) p = 0.03. The risk for sputum positive smear results increased with severity of anemia (P for trend <0.01). Baseline anemia is associated with increased risk for persistent positive sputum smears at two months of tuberculosis treatment. Future studies should evaluate the mechanisms for TB-associated anemia as well as the role of intervention for anemia among TB patients

Multi Drug and Other Forms of Drug Resistant Tuberculosis Are Uncommon among Treatment Naïve Tuberculosis Patients in Tanzania

Background: Surveillance and effective management of drug resistance is important to sustaining tuberculosis (TB) control efforts. We aimed to determine resistance rates to first line anti tuberculosis drugs and to describe factors associated with the resistance to any of the first line anti tuberculosis drugs in Dar es Salaam Tanzania. Materials Newly diagnosed, TB patients with neither history of tuberculosis treatment nor isoniazid prophylaxis were included into the study. Sputum specimens were cultured on either mycobacteria growth indicator tube 960 (MGIT 960) or Lowenstein Jenstein (LJ) medium supplemented with either glycerol (GLJ) or pyruvate (PLJ). Drug susceptibility for isoniazid, rifampicin, streptomycin and ethambutol was determined by either Lowenstein–Jensen (LJ) medium or mycobacteria growth indicator tube 960 (MGIT 960). Results: A total of 933 newly diagnosed TB patients, were included into the study. Multi drug resistance (MDR) tuberculosis was detected among 2 (0.2%) patients. Resistance to any of the four tested drugs was detected among 54 (5.8%) patients. Mono-resistance to isoniazid, rifampicin, streptomycin and ethambutol were 21(2.3%), 3 (0.3%), 13 (1.4%), 9 (1.0%) respectively. Conclusion: Primary resistance to first line anti tuberculosis drugs is still low in this setting. Continued vigilance including periodic national surveillance of anti-tuberculosis resistance is recommended

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

Hepatitis A, B and C viral co-infections among HIV-infected adults presenting for care and treatment at Muhimbili National Hospital in Dar es Salaam, Tanzania

<p>Abstract</p> <p>Background</p> <p>Tanzania is currently scaling-up access to anti-retro viral therapy (ART) to reach as many eligible persons as possible. Hepatitis viral co-infections are known to influence progression, management as well as outcome of HIV infection. However, information is scarce regarding the prevalence and predictors of viral hepatitis co-infection among HIV-infected individuals presenting at the HIV care and treatment clinics in the country.</p> <p>Methods</p> <p>A cross-sectional study conducted between April and September 2006 enrolled 260 HIV-1 infected, HAART naïve patients aged ≥18 years presenting at the HIV care and treatment clinic (CTC) of the Muhimbili National Hospital (MNH). The evaluation included clinical assessment and determination of CD4+ T-lymphocyte count, serum transaminases and serology for Hepatitis A, B and C markers by ELISA.</p> <p>Results</p> <p>The prevalence of anti HAV IgM, HBsAg, anti-HBc IgM and anti-HCV IgG antibodies were 3.1%, 17.3%, 2.3% and 18.1%, respectively. Dual co-infection with HBV and HCV occurred in 10 individuals (3.9%), while that of HAV and HBV was detected in two subjects (0.8%). None of the patients had all the three hepatitis viruses. Most patients (81.1%) with hepatitis co-infection neither had specific clinical features nor raised serum transaminases. History of blood transfusion and jaundice were independent predictors for HBsAg and anti-HBc IgM positivity, respectively.</p> <p>Conclusion</p> <p>There is high prevalence of markers for hepatitis B and C infections among HIV infected patients seeking care and treatment at MNH. Clinical features and a raise in serum alanine aminotransferase were of limited predictive values for the viral co-infections. Efforts to scale up HAART should also address co-infections with Hepatitis B and C viruses.</p

Examining oral pre-exposure prophylaxis (PrEP) literacy among participants in an HIV vaccine trial preparedness cohort study

Background: PrEP literacy is influenced by many factors including the types of information available and how it is interpreted. The level of PrEP literacy may influence acceptability and uptake. Methods: We conducted 25 in-depth interviews in a HIV vaccine trial preparedness cohort study. We explored what participants knew about PrEP, sources of PrEP knowledge and how much they know about PrEP. We used the framework approach to generate themes for analysis guided by the Social Ecological Model and examined levels of PrEP literacy using the individual and interpersonal constructs of the SEM. Results: We found that PrEP awareness is strongly influenced by external factors such as social media and how much participants know about HIV treatment and prevention in the local community. However, while participants highlighted the importance of the internet/social media as a source of information about PrEP they talked of low PrEP literacy in their communities. Participants indicated that their own knowledge came as a result of joining the HIV vaccine trial preparedness study. However, some expressed doubts about the effectiveness of the drug and worried about side effects. Participants commented that at the community level PrEP was associated with being sexually active, because it was used to prevent the sexual transmission of HIV. As a result, some participants commented that one could feel judged by the health workers for asking for PrEP at health facilities in the community. Conclusion: The information collected in this study provided an understanding of the different layers of influence around individuals that are important to address to improve PrEP acceptability and uptake. Our findings can inform strategies to address the barriers to PrEP uptake, particularly at structural and community levels. Trial registration: https://clinicaltrials.gov/ct2/show/NCT0406688

Viral suppression and mortality among HIV infected adults initiated Anti-Retroviral Therapy at Temeke Regional hospital: Programmatic achievements and Opportunities for improvement

Background: Despite the fact that HIV disease has greater impact in the Sub-Saharan Africa (SSA) region, treatment outcomes are scarcely reported at implementation level. Programmatic data present real life implementation challenges of public health importance which should inform policies. This study was conducted to describe mortality, viral suppression and document challenges at secondary facility HIV clinic in Temeke, Dar es Salaam Tanzania.Methods: Hospital-based retrospective cohort study was conducted among HIV patients initiated on ART between May and November 2016 at Temeke Hospital, Dar es Salaam, Tanzania. Data was collected from HIV database between May and November 2017. Mortality was reported as proportion while viral suppression was defined as HIV-RNA below 50 copies per ml.Results: A total of 747 PLHIV were eligible and were included in the study. Out of these, forty (5.4) patients died. Good adherence to Antiretroviral therapy was seen in 70% of PLHV only. Of the 419 participants with HIV viral load measurements, viral suppression was achieved in 318 (75.9%) patients. Viral suppression is more likely for patients with CD4+ T lymphocyte count greater than 200 cells/μL. There was high attrition rate from the clinic, more than one-third 35.2% of those initiated ART were still attending the clinic at one year.Conclusion: HIV viral suppression and adherence to ART at Temeke HIV CTC are still sub-optimal. Good tracking, enhanced adherence as well as early diagnosis and treatment might improve viral suppression at one year. High attrition from the clinic may need careful examination. Keywords: Viral suppression, HIV, SSA, treatment failure, AIDS, Tanzani

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

Abstract 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