The role of trust in the implementation and uptake of COVID-19 response measures: a qualitative study of health professionals' experiences in Tanzania.

BACKGROUND: Even though trust is placed at the central point in ensuring proper functioning of the health systems, studies remain scant on how it affects both the implementation and uptake of COVID-19 response measures in low- and middle-income countries such as Tanzania. This study, therefore, explored the role of trust in the implementation and uptake of recommended COVID-19 response measures including vaccines from the perspective of health professionals in Tanzania. METHODS: This cross-sectional qualitative study was implemented in four of Tanzania's thirty-one regions. Qualitative data was collected through 26 in-depth interviews held with regional and district disease outbreak response teams, district cold chain co-ordinators and health facility in-charges. In addition, five focus group discussions and seven group interviews were conducted with healthcare workers from the lower-level health facilities. Thematic analysis was conducted and applied the trust constructs. RESULTS: Interpersonal trust and health system trust emerged as two major themes in the study. Interpersonal trust was reported to stem from lack of transparency that instigated fear, worries, and confusion regarding the implementation and uptake of the recommended response measures. The distrust was mainly between health professionals in health facilities and those assigned to isolation centres as well as between patients and community members. On the other hand, the health system trust was shaped by mixed feelings regarding COVID-19 vaccine national decisions, and conflicting messages from national officials, politicians and religious leaders on COVID-19 responses, safety, and effectiveness of the vaccines. Questions surrounding the short duration of clinical trials, indeterminate post-vaccination protection duration, impotence-linked beliefs, freemasonry notion and unclear vaccinated cards information are other reported contributory factors to mistrust in the health system. However, after a comprehensive health education and experience in COVID-19 vaccination administration most professionals affirmed the effectiveness of the vaccines in limiting infections and its severe consequences. CONCLUSION: Participants indicated limited trust at both interpersonal and health system levels aggravated by lack of transparency, unclear and conflicting messages on COVID-19 infections and response measures. Enforced transparency on pandemics alongside standardised messages from the reliable sources is crucial in enhancing trust in implementation and uptake of the recommended response measures.

Health care workers' self-perceived infection risk and COVID-19 vaccine uptake: A mixed methods study.

Vaccination is the most cost-effective way of preventing Coronavirus Disease 2019 (COVID-19) although there was a considerable delay in its institution in Tanzania. This study assessed health care workers' (HCWs) self-perceived infection risk and uptake of COVID-19 vaccines. A concurrent embedded, mixed methods design was utilized to collect data among HCWs in seven Tanzanian regions. Quantitative data was collected using a validated, pre-piloted, interviewer administered questionnaire whereas in-depth interviews (IDIs) and focus group discussions (FGDs) gathered qualitative data. Descriptive analyses were performed while chi-square test and logistic regression were used to test for associations across categories. Thematic analysis was used to analyze the qualitative data. A total of 1,368 HCWs responded to the quantitative tool, 26 participated in the IDIs and 74 in FGDs. About half of the HCW (53.6%) reported to have been vaccinated and three quarters (75.5%) self-perceived to be at a high risk of acquiring COVID-19 infection. High perceived infection risk was associated with increased COVID-19 vaccine uptake (OR 1.535). Participants perceived that the nature of their work and the working environment in the health facilities increased their infection risk. Limited availability and use of personal protective equipment (PPE) was reported to elevate the perceived infection risks. Participants in the oldest age group and from low and mid-level health care facilities had higher proportions with a high-risk perception of acquiring COVID-19 infection. Only about half of the HCWs reported to be vaccinated albeit the majority recounted higher perception of risk to contracting COVID-19 due to their working environment, including limited availability and use of PPE. Efforts to address heightened perceived-risks should include improving the working environment, availability of PPE and continue updating HCWs on the benefits of COVID-19 vaccine to limit their infection risks and consequent transmission to their patients and public.

Mentorship of young researchers in resource-limited settings: experiences of the mentees from selected health sciences Universities in Tanzania.

INTRODUCTION: Mentorship is an essential component of research capacity building for young researchers in the health sciences. The mentorship environment in resource-limited settings is gradually improving. This article describes mentees' experiences in a mentorship program for junior academicians amid the COVID-19 pandemic in Tanzania. METHODS: This is a survey study that examined the experiences of mentees who participated in a mentorship program developed as part of the Transforming Health Education in Tanzania (THET) project. The THET project was funded by the US National Institutes of Health (NIH) under a consortium of three partnering academic institutions in Tanzania and two collaborating US-based institutions. Senior faculty members of respective academic institutions were designated as mentors of junior faculty. Quarterly reports submitted by mentees for the first four years of the mentorship program from 2018 to 2022 were used as data sources. RESULTS: The mentorship program included a total of 12 mentees equally selected from each of the three health training institutions in Tanzania. The majority (7/12) of the mentees in the program were males. All mentees had a master's degree, and the majorities (8/12) were members of Schools/Faculties of Medicine. Most mentors (9/10) were from Tanzania's three partnering health training institutions. All mentors had an academic rank of senior lecturer or professor. Despite the onset of the COVID-19 pandemic, the regular weekly meetings between mentors and mentees were not affected. By the fourth year of the mentorship program, more than three-quarters of mentees had published research related to the mentorship program in a peer-reviewed journal, over half had enrolled in Ph.D. studies, and half had applied for and won competitive grant awards. Almost all mentees reported being satisfied with the mentorship program and their achievements. CONCLUSION: The mentorship program enhanced the skills and experiences of the mentees as evidenced by the quality of their research outputs and their dissemination of research findings. The mentorship program encouraged mentees to further their education and enhanced other skills such as grant writing. These results support the initiation of similar mentorship programs in other institutions to expand their capacity in biomedical, social, and clinical research, especially in resource-limited settings, such as Sub-Saharan Africa.

Confidence in COVID-19 vaccine effectiveness and safety and its effect on vaccine uptake in Tanzania: A community-based cross-sectional study.

COVID-19 is a major public health threat associated with increased disease burden, mortality, and economic loss to countries and communities. Safe and efficacious COVID-19 vaccines are key in halting and reversing the pandemic. Low confidence in vaccines has been one of the factors leading to hesitancy. We aimed to assess the COVID-19 vaccine confidence (safety and effectiveness), associated factors, and its effects on vaccine uptake among general community members in Tanzania. This was a community-based cross-sectional survey conducted from December 2021 to April 2022 in six regions of Tanzania mainland and two regions in Zanzibar. Participants were interviewed using an electronic questionnaire. Multiple logistic regression models estimated odds ratios (ORs) and 95% confidence interval (CI) for factors associated with vaccine confidence. All analyses were performed using SPSS version 25.0. The study enrolled 3470 general Tanzanian community members; their mean age was 40.3 (standard deviation ±14.9) years, and 34% were males. The proportion of COVID-19 vaccine confidence was 54.6%. Geographical region, residence area, COVID-19 disease risk perception, and good knowledge of COVID-19 vaccines were significantly associated with COVID-19 vaccine confidence. Confidence in COVID-19 vaccines was associated with over three times higher odds of vaccine uptake. Confidence in COVID-19 vaccines was low in Tanzania. Innovative community engagement strategies and region-specific interventions are needed to improve comprehensive knowledge and address community perceptions and attitudes toward COVID-19 vaccines.

COVID-19 Vaccine Uptake and Associated Factors in Sub-Saharan Africa: Evidence from a Community-Based Survey in Tanzania.

COVID-19 is a major public health threat associated with the increased global burden of infectious diseases, mortality, and enormous economic loss to countries and communities. Safe and efficacious COVID-19 vaccines are crucial in halting the pandemic. We assessed the COVID-19 vaccine uptake and associated factors among community members from eight regions in Tanzania. The interviewer-administered questionnaire collected data. Multiple logistic regression models determined the factors associated with vaccine uptake. The median age of 3470 respondents was 37 years (interquartile range of 29-50 years) and 66% of them were females. Only 18% of them had received the COVID-19 vaccine, ranging from 8% in Dar es Salaam to 37% in Simiyu regions. A third (34%) of those vaccinated people did not know which vaccine they were given. Significantly higher rates of COVID-19 vaccine uptake were among the respondents aged 30+ years, males, and with a history of COVID-19 infection. Unfavorable perceptions about vaccine safety and efficacy lowered the rates of vaccine uptake. Setting-specific interventions and innovations are critical to improving vaccine uptake, given the observed differences between regions. Efforts are needed to increase vaccine uptake among women and younger people aged less than 30 years. Knowledge-based interventions should enhance the understanding of the available vaccines, benefits, target groups, and availability.

Serial T-SPOT.TB responses in Tanzanian adolescents: Transient, persistent and irregular conversions.

BACKGROUND: Prospective studies of interferon-gamma release assays (IGRA) on healthy subjects in tuberculosis-endemic regions have not examined the long-term variability of serial assays. This issue is relevant to the interpretation of tuberculosis (TB) vaccine trials based on prevention of infection. METHODS: T-SPOT.TB assays were performed manually on healthy adolescents during a tuberculosis vaccine trial in Tanzania at 5 intervals over 3 years. Assay results were defined as negative, positive, borderline or invalid. Subsequently, microtiter plates were analyzed by an automated reader to obtain quantitative counts of spot forming cells (SFCs) for the present analysis. RESULTS: 3387 T-SPOT.TB samples were analyzed from 928 adolescents; manual and automated assay results were 97% concordant. Based on the quantitative results 143 (15%) participants were prevalent IGRA-positives at baseline, were ineligible for further study. Among the remaining IGRA-negative participants, the annual rate of IGRA conversion was 2·9%. Among 43 IGRA converters with repeat assays 12 (28%) were persistent converters, 16 (37%) were transient converters, and 15 (35%) comprised a new category defined as irregular converters (≥2 different subsequent results). ESAT-6 and CFP-10 responses were higher in prevalent than incident positives: 53 vs 36 for CFP-10 (p < 0·007); 44 vs 34 for ESAT-6 (p = 0·12). CONCLUSIONS: Definitions of IGRA conversion, reversion, and persistence depend critically on the frequency of testing. Multiple shifts in categories among adolescents in a TB-endemic country may represent multiple infections, variable host responses in subclinical infection, or assay variation. These findings should to be considered in the design and interpretation of TB vaccine trials based on prevention of infection. Household contact studies could determine whether even transient IGRA conversion might represent exposure to an active case of M. tuberculosis disease.

Adherence to Antiretroviral Therapy by Medication Possession Ratio and Virological Suppression among Adolescents and Young Adults Living with HIV in Dar es Salaam, Tanzania.

Background: Adherence to antiretroviral therapy (ART) is a strong determinant of virological suppression. We aimed to determine the magnitude of adherence as measured by medication possession ratio (MPR) and virological suppression with its predictors among adolescents and young adults (AYA) living with HIV on ART in Tanzania. Methods: This retrospective cohort study was conducted using archived data from HIV care and treatment centers in Dar es Salaam, Tanzania between 2015 and 2019. The logistic regression model assessed predictors for adherence and virological suppression. Results: Data of 5750 AYA living with HIV were analysed. The majority were females: 4748 (82.6%). About 63% had good adherence with MPR ≥ 85% at one year post ART initiation. Independent predictors of ART adherence were male sex (aOR = 1.3, 95% CI 1.1−1.5), CD4 > 500 cells/mm3 (aOR = 0.7, 95% CI: 0.6−0.9), WHO stage III (aOR = 1.6, 95% CI 1.3−1.9), enrollment in 2019 (aOR = 1.5, 95% CI 1.2−1.9), and virological suppression (aOR = 2.0, 95% CI 1.6−2.9). Using an Efavirenz- and a Nevirapine-based combination was associated with reduced odds of ART adherence (aOR = 0.3, 95% CI 0.1−0.8) and (aOR = 0.2, 95% CI 0.1−0.6), respectively. Predictors of virological suppression were MPR ≥ 85% (aOR = 2.0, 95% CI 1.6−2.4); CD4 > 500 cells/mm3 (aOR = 2.4, 95% CI 1.7−3.4), and once-daily dosing (aOR = 2.0, 95% CI 1.3−2.5). Conclusion: Adherence to ART among AYA living with HIV is suboptimal. Sex, year of enrollment, ART drug combination used, and immunological status at ART initiation are important predictors of adherence to ART and virological suppression.

Predictors of mortality among adolescents and young adults living with HIV on antiretroviral therapy in Dar es Salaam, Tanzania: a retrospective cohort study.

INTRODUCTION: Global AIDS-related deaths have declined by only 10% among adolescents since its peak in 2003. This is disproportionately low compared to a decline of 74% among children aged 0-9 years old. We determined the magnitude of, and predictors of mortality among adolescents and young adults living with HIV on antiretroviral therapy (ART) in Dar-es-Salaam, Tanzania. METHODS: A retrospective cohort study was conducted among adolescents (aged 10-19) and young adults (aged 20-24) living with HIV and enrolled in care and treatment centres in Dar es Salaam, Tanzania between January 2015 and December 2019. Data were analysed using STATA version 16. Cumulative hazard curves were used to estimate and illustrate 1-year mortality. Predictors for mortality were assessed by the Fine and Gray competing risk regression model. Sub-hazard ratios (SHR) and 95% confidence intervals (95% CI) were then reported. RESULTS: A total of 15,874 young people living with HIV were included: 4916 (31.3%) were adolescents and 10,913 (68.7%) were young adults. A total of 3843 (77.5%) adolescents and 9517 (87.2%) young adults were female. Deaths occurred in 2.3% (114/4961) of adolescents and 1.2% (135/10,913) of young adults (p < 0.001). Over a follow-up of 9292 person-years, the mortality rate was 3.8 per 100 person years [95% CI 3.2-4.6/100 person-years] among adolescents and 2.1 per 100 person-years among young adults [95% CI 1.8-2.5/100 person-years]. Independent predictors of mortality among adolescents were male sex (adjusted (SHR) aSHR = 1.90, 95% CI: 1.3-2.8), CD4 count < 200 cells/mm3 (aSHR = 2.7, 95% CI: 1.4-5.0) and attending a private health facility (aSHR = 1.7, 95% CI: 1.1-2.5). Predictors of mortality among young adults were CD4 count < 200 cells/mm3 (aSHR = 2.8, 95% CI 1.7-4.5), being underweight (aSHR = 2.1, 95% CI: 1.4-3.3) and using nevirapine-based therapy (aHR = 8.3, 95% CI: 3.5-19.5). CONCLUSIONS: The mortality rate for persons living with HIV and on ART in Tanzania was significantly higher in adolescents than young adults. Age- and sex-specific risk factors identify targets for intervention to reduce mortality among affected adolescents and young adults.

Cervical cancer in Northern Tanzania-What do women living with HIV know.

Background: Cervical cancer (CC) is more prevalent in women living with human immunodeficiency virus (HIV) infection compared to the general population. The magnitude is high among all countries burdened with HIV-Tanzania is no exception. Despite the unprecedented risk, women living with HIV (WLHIV) may not be aware of the risk and might have unfounded beliefs thereof. This study aimed to determine the knowledge, awareness, and beliefs on CC screening among WLHIV attending a clinic at the Kilimanjaro Christian Medical Centre (KCMC) in Northern Tanzania. Methods: This hospital-based cross-sectional study was conducted among 327 WLHIV attending care and treatment clinic (CTC) at KCMC. A pre-tested questionnaire was used to collect quantitative data. Both descriptive and regression methods were used to determine CC knowledge, awareness, and beliefs as well as factors associated with knowledge of CC among WLHIV using SPSS version 23. Results: Participants' mean age was 46 ± 10.4 years. Although just half (54.7%) of WLHIV had insufficient knowledge of CC, the majority of the participants (83.5%) were able to recognize at least three risk factors, but with limited understanding of symptoms and prevention. The majority held positive beliefs on CC and screening practices. Factors associated with good knowledge of CC included being married (AOR: 3.66, 95% CI: 1.84-7.28), having used ART for at least 2 years (AOR: 4.08, 95% CI: 1.36-12.21), and having previously screened for CC (AOR: 1.62, 95% CI: 1.01-2.59). Conclusion: WLHIV attending care and treatment center had insufficient knowledge about CC screening. To further improve screening and treatment for CC, at both facility and community levels, targeted awareness and education campaigns are warranted.

DAR-901 vaccine for the prevention of infection with Mycobacterium tuberculosis among BCG-immunized adolescents in Tanzania: A randomized controlled, double-blind phase 2b trial.

BACKGROUND: SRL172 prevented disease due to Mycobacterium tuberculosis in a Phase 3 trial. DAR-901 represents a scalable manufacturing process for SRL172. We sought to determine if DAR-901 would prevent infection with M. tuberculosis among BCG-primed adolescents age 13-15 years in Tanzania. METHODS: Adolescents with a negative T- SPOT.TBR interferon gamma release assay (IGRA) were randomized 1:1 to three intradermal injections of DAR-901 or saline placebo at 0, 2 and 4 months. Repeat IGRAs were performed at 2 months, and at 1, 2, and 3 years. The primary efficacy outcome was time to new TB infection (IGRA conversion to positive); the secondary outcome was time to persistent TB infection (IGRA conversion with repeat positive IGRA). RESULTS: Among 936 participants screened 667 were eligible and randomized to their first dose of vaccine or placebo (safety cohort). At 2 months, 625 participants remained IGRA-negative and were scheduled for the additional two doses (efficacy cohort). DAR-901 was safe and well-tolerated. One DAR-901 recipient developed a vaccine site abscess. Neither the primary nor secondary endpoints differed between the two treatment arms (p = 0.90 and p = 0.20, respectively). DAR-901 IGRA converters had median responses to ESAT-6 of 50.1 spot-forming cells (SFCs) vs. 19.6 SFCs in placebo IGRA converters (p = 0.03). CONCLUSIONS: A three-dose series of 1 mg DAR-901 was safe and well-tolerated but did not prevent initial or persistent IGRA conversion. DAR-901 recipients with IGRA conversion demonstrated enhanced immune responses to ESAT-6. Since protection against disease may require different immunologic responses than protection against infection a trial of DAR-901 to prevent TB disease is warranted. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov as NCT02712424.

The potential of CBC-derived ratios (monocyte-to-lymphocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte) to predict or diagnose incident TB infection in Tanzanian adolescents.

BACKGROUND: Ratios of different immune cell populations (i.e., monocyte-to-lymphocyte, neutrophil-to-lymphocyte, and platelet-to-lymphocyte ratios) have been studied as a means of predicting future tuberculosis (TB) disease risk or to assist in the diagnosis of incident TB disease. No studies to-date, however, have evaluated the potential of these ratios to predict or assist in the diagnosis of incident TB infection - the first step in the natural history of TB disease. METHODS: In this prospective study, we evaluated the complete blood count (CBC)-derived metrics of monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) as predictors of future TB infection risk or aids in the diagnosis of TB infection among 145 Tanzanian adolescents enrolled in the DAR-901 vaccine trial, using paired CBCs and interferon-gamma release assays (IGRAs) obtained at 0, 60 and 720 days after study enrollment. RESULTS: At baseline, there were no significant differences between study participants who remained persistently IGRA negative throughout the study period and those who subsequently converted to IGRA positive with respect to MLR (0.18 vs 0.17, p = 0.10), NLR (0.88 vs 1.02, p = 0.08), or PLR (115 vs 120, p = 0.28). Similarly, no significant differences were noted with respect to MLR, NLR, and PLR between IGRA converters and time-matched negative controls at the time of IGRA conversion. With respect to other blood cell measures, however, there were modest but significant differences between IGRA negatives and IGRA converters with respect to red blood cell count (4.8 vs 4.6 ×  106 cells/mcL, p = 0.008), hemoglobin (12.6 vs 12.3 g/dL, p = 0.01), and hematocrit (38.8 vs 37.8%, p = 0.005). CONCLUSIONS: In contrast to prior studies that have suggested that the ratios of different immune cell populations are associated with development of TB disease, our present findings do not demonstrate an association between these ratios and the development of TB infection. However, decreased red blood cell measures were associated with the subsequent development of TB infection, suggesting either that dysregulation of iron metabolism may play a role in TB pathogenesis or that following TB infection, iron dysregulation may precede IGRA positivity. TRIAL REGISTRATION: Clinicaltrials.gov NCT02712424 . Date of registration: March 14, 2016.

How do community advisory boards fulfil their ethical role in HIV clinical trials? A protocol for a systematic review of qualitative evidence.

INTRODUCTION: Community advisory boards (CABs) continue to gain wide use and acceptance in global health research including in HIV clinical trials. They provide means through which community concerns regarding the trial can be considered by the research team, and provide an important platform of communication between the researchers and the community about study goals. Therefore, this systematic review protocol will guide the review of qualitative evidence on the ethical roles of CABs in HIV clinical trials based on the three fundamental ethical principles: respect for the person, beneficence and justice. METHODS AND ANALYSIS: This systematic review of qualitative evidence will involve searching four medical databases: PubMed, ScienceDirect, CINAHL and Cochrane Library. Additionally, other relevant evidence will be obtained through hand searching and grey literature. Searches will be limited to studies published in the English language from 1989 (the year that CABs were first established in HIV clinical trials) to 2019. Articles searched will be screened by two independent authors based on inclusion and exclusion criteria. Included articles will be appraised for quality using the Critical Appraisal Skills Programme checklist and followed by qualitative data extraction. Findings will be analysed based on the meta-aggregative approach with the aid of EPPI-Reviewer 4 web-based software. ETHICS AND DISSEMINATION: Ethical approval does not apply to this review. Data will be disseminated through scientific conferences and peer-reviewed journals to inform policies and stake-holders about the ethical role of CABs. PROSPERO REGISTRATION NUMBER: CRD42019133787.

Medical management of acute loss of vision in tuberculous meningitis: A case report.

Blindness and vision impairment are unpredictable complications of tuberculous meningitis (TBM) that are often unrecognized in the acute stages of illness due to inability to assess vision in patients with depressed levels of consciousness or confusion. We present a patient with definite TBM confirmed by positive Xpert MTB/RIF assay of cerebrospinal fluid (CSF) who developed binocular blindness two weeks after diagnosis and initiation of standard anti-tuberculosis treatment (ATT). Ophthalmological exam demonstrated complete bilateral abducens nerve palsies, impaired pupillary responses to light, normal optic discs, and visual acuity of hand motion only in each eye. Brain CT showed progressive enlargement of the third and lateral ventricles. We managed the patient medically with dexamethasone, acetazolamide, and substitution of moxifloxacin for ethambutol. Serial brain CTs confirmed gradual resolution of hydrocephalus. The patient had complete neurological recovery at six months except for residual blindness in the right eye. Visual acuity in the left eye recovered to normal (20/20). The assessment and management of vision impairment in TBM is discussed.