Systematic assessment of clinical and bacteriological markers for tuberculosis reveals discordance and inaccuracy of symptom-based diagnosis for treatment response monitoring

This work was supported by Commonwealth PhD studentship award to Dr Bariki Mtafya (Award number: TZS-2016-718) at University of St Andrews and European and Developing Countries Clinical Trials Partnership through TWENDE project (grant number; TWENDE-EDCTP-CSA-2014-283) and PanACEA II (grant number; 97118-PanACEA-TRIA.2015.1102) awarded to Professor Stephen Gillespie and Dr Wilber Sabiiti at the University of St Andrews, UK.Background : Clinical symptoms are the benchmark of tuberculosis (TB) diagnosis and monitoring of treatment response but is not clear how they relate to TB bacteriology, particularly the novel tuberculosis Molecular Bacterial Load Assay (TB-MBLA). Methods : Presumptive cases were bacteriologically confirmed for TB and assessed for symptom and bacteriological resolution using smear microscopy (SM), culture and TB-MBLA over 6-month treatment course. Kaplan Meier and Kappa statistics were used to test relationship between symptom- and bacteriological-positivity. Results : A cohort of 46 bacteriologically confirmed TB cases were analysed for treatment response over a six-month treatment course. Pre-treatment symptom and bacteriological positivity concurred in over 70% of the cases. This agreement was lost in over 50% of cases whose chest pain, night sweat, and loss of appetite had resolved by week 2 of treatment. Cough resolved at a 3.2% rate weekly and was 0.3% slower than the combined bacteriological (average of MGIT and TB-MBLA positivity) resolution rate, 3.5% per week. Drop in TB-MBLA positivity reflected fall in bacillary load, 5.7±1.3- at baseline to 0.30±1.0- log10 eCFU/mL at month 6, and closer to cough resolution than other bacteriological measures, accounting for the only one bacteriologically positive case out of seven still coughing at month 6. Low baseline bacillary load patients were more likely to be bacteriologically negative, HR 5.6, p=0.003 and, HR 3.2, p=0.014 by month-2 and 6 of treatment respectively. Conclusion : The probability of clinical symptoms reflecting bacteriological positivity weakens as patient progresses on anti-TB therapy, making symptom-based diagnosis a less reliable marker of treatment response.Publisher PDFPeer reviewe

Molecular bacterial load assay (MBLA) concurs with culture on the NaOH-induced Mycobacterium tuberculosis loss of viability

This work was supported by the commonwealth studentship award for Bariki Mtafya at University of St Andrews in UK and European and Developing Countries Clinical Trials Partnership (EDCTP) through TWENDE and PanACEA II grants.Effective methods to detect viable Mycobacterium tuberculosis (Mtb), the main causative agent of tuberculosis (TB) are urgently needed. To date, cultivation of Mtb is the gold standard which depends on initial sample processing with N-Acetyl-L-Cysteine/Sodium hydroxide (NALC/NaOH), chemicals that compromise Mtb viability and, consequently the performance of downstream tests. We applied culture and the novel Molecular bacterial load assay (MBLA) to measure the loss of Mtb viability following NALC/NaOH treatment of Mtb H37Rv pure culture and clinical sputa from pulmonary TB patients. Compared to untreated controls, NALC/NaOH treatment of Mtb, reduced MBLA detectable bacillary load (estimated colony forming units/milliliter (eCFU/mL) by 0.66±0.21log10- at 23°C (P=0.018) and 0.72±0.08log10- at 30°C (P=0.013). Likewise, NALC/NaOH treatment reduced viable count on solid culture by 0.84±0.02log10- at 23°C (P<0.001) and 0.85±0.01log10- CFU/mL at 30°C (P<0.001) respectively. The reduction in viable count was reflected by a corresponding increase in time to positivity of MGIT liquid culture, 1.2 days at 23°C (P<0.001), and 1.1 days at 30°C (P<0.001). This NaOH-induced Mtb viability loss was replicated in clinical sputum samples, with bacterial load dropping by 0.65±0.17log10 from 5.36±0.24log10- to 4.71±0.16log10- eCFU/mL for untreated and treated sputa respectively. Applying the Bowness et al model, revealed that the treated MGIT time to culture positivity of 142hrs was equivalent to 4.86±0.28log10CFU, consistent with MBLA-measured bacterial load. Our study confirms the contribution of NALC/NaOH treatment to loss of viable bacterial count. Tests that obviate the need of decontamination may offer alternative option for accurate detection of viable Mtb and treatment response monitoring.PostprintPeer reviewe

Community engagement for the Voluntary Medical Male Circumcision (VMMC) program: an analysis of key stakeholder roles to promote a sustainable program in Zambia [version 2; peer review: 1 approved, 2 approved with reservations]

Background: Within the Voluntary Medical Male Circumcision (VMMC) programme, community engagement has been central in facilitating the acceptance of VMMC, especially in non-circumcising communities. We used the case of the development of community engagement plans for sustainability of VMMC in Zambia to illustrate diversity of stakeholders, their power, roles, and strategies in community engagement. Methods: Data were collected using document review, in-depth interviews (n=35) and focus group discussions (n=35) with community stakeholders, health workers, health centre committees, counsellors, teachers, community volunteers and parents/caregivers. Data were analysed using thematic analysis. The analysis was guided by the power and interest model. Results: Differences were noted between the rural and urban sites in terms of power/influence and interest rating of community stakeholders who could be involved in the sustainability phase of the VMMC response in Zambia. For example, in the urban setting, neighbourhood health committees (NHCs), health workers, leaders of clubs, community health workers (CHWs), radio, television and social media platforms were ranked highest. From this list, social media and television platforms were not highly ranked in rural areas. Some stakeholders had more sources of power than others. Forms or sources of power included technical expertise, local authority, financial resources, collective action (action through schools, churches, media platforms, other community spaces), and relational power.   Key roles and strategies included strengthening and broadening local coordination systems, enhancing community involvement, promoting community-led monitoring and evaluation, through the use of locally recognised communication spaces and channels, facilitating ownership of VMMC, and improving local accountability processes in VMMC activities. Conclusions: By consulting with the most relevant stakeholders, and considering community needs in programme development, the VMMC programme may be able to leverage the community structures and systems to reduce long term demand generation costs for VMMC and increase the acceptability and frequency of male circumcision

Challenges and innovations brought about by the Covid-19 pandemic regarding medical and pharmacy education especially in Africa and implications for the future

Background: Multiple measures introduced early to restrict COVID-19 have dramatically impacted the teaching of medical and pharmacy students, exacerbated by the lack of infrastructure and experience with e-learning at the start of the pandemic. In addition, the costs and reliability of the Internet across Africa pose challenges alongside undertaking clinical teaching and practical programmes. Consequently, there is a need to understand the many challenges and how these were addressed, given increasingly complex patients, to provide future direction. Method: An exploratory study was conducted among senior-level medical and pharmacy educators across Africa, addressing four key questions, including the challenges resulting from the pandemic and how these were dealt with. Results: Staff and student members faced multiple challenges initially, including adapting to online learning. In addition, concerns with the lack of equipment (especially among disadvantaged students), the costs of Internet bundles, and how to conduct practicals and clinical teaching. Multiple activities were undertaken to address these challenges. These included training sessions, developing innovative approaches to teaching, and seeking ways to reduce Internet costs. Robust approaches to practicals, clinical teaching, and assessments have been developed. Conclusions: Appreciable difficulties to teaching arising from the pandemic are being addressed across Africa. Research is ongoing to improve education and assessments

Estimating the basic reproduction number for the 2015 bubonic plague outbreak in Nyimba district of Eastern Zambia.

BackgroundPlague is a re-emerging flea-borne infectious disease of global importance and in recent years, Zambia has periodically experienced increased incidence of outbreaks of this disease. However, there are currently no studies in the country that provide a quantitative assessment of the ability of the disease to spread during these outbreaks. This limits our understanding of the epidemiology of the disease especially for planning and implementing quantifiable and cost-effective control measures. To fill this gap, the basic reproduction number, R0, for bubonic plague was estimated in this study, using data from the 2015 Nyimba district outbreak, in the Eastern province of Zambia. R0 is the average number of secondary infections arising from a single infectious individual during their infectious period in an entirely susceptible population.Methodology/principal findingsSecondary epidemic data for the most recent 2015 Nyimba district bubonic plague outbreak in Zambia was analyzed. R0 was estimated as a function of the average epidemic doubling time based on the initial exponential growth rate of the outbreak and the average infectious period for bubonic plague. R0 was estimated to range between 1.5599 [95% CI: 1.382-1.7378] and 1.9332 [95% CI: 1.6366-2.2297], with average of 1.7465 [95% CI: 1.5093-1.9838]. Further, an SIR deterministic mathematical model was derived for this infection and this estimated R0 to be between 1.4 to 1.5, which was within the range estimated above.Conclusions/significanceThis estimated R0 for bubonic plague is an indication that each bubonic plague case can typically give rise to almost two new cases during these outbreaks. This R0 estimate can now be used to quantitatively analyze and plan measurable interventions against future plague outbreaks in Zambia

Health beliefs and health seeking behavior towards lymphatic filariasis morbidity management and disability prevention services in Luangwa District, Zambia: Community and provider perspectives.

BackgroundMorbidity management and disability prevention (MMDP) services are essential for the management of chronic stages of lymphatic filariasis (LF) infection. However, there is limited information on health beliefs and health seeking behavior towards MMDP services for LF in endemic regions of Zambia. This study sought to document health beliefs and health seeking behavior towards MMDP services for LF in Luangwa District, Zambia.MethodsThis was an exploratory qualitative study conducted with community members including LF patients, community health workers and healthcare providers. Data was collected through a series of four focus group discussions stratified by sex and 26 in-depth interviews. Data was analyzed by thematic analysis using NVivo software.ResultsThe perceived causes of the chronic manifestations of LF included; contact with animal faeces, use of traditional herbal aphrodisiacs (mutoto), witchcraft and sexual contact with women who were menstruating or had miscarried. LF patients opted to visit traditional healers before going to health facilities. Hydrocele patients were afraid of hydrocelectomies as they were thought to cause infertility or death. Very few community members were able to identify any home and facility-based care strategies for lymphoedema. Health system and cultural barriers to seeking healthcare included; long distances to the health facilities, lack of awareness of existing MMDP services, perceived costs of accessing MMDP services, gender and social norms, and fear of stigmatization.ConclusionHealth seeking behavior for LF in the district is mainly driven by negative beliefs about the causes of the disease and lack of awareness of available MMDP services and homecare strategies. Lymphatic filariasis programs should promote strategies that seek to empower patients and community members with the required information to access and use the MMDP services at the health facilities, as well as adhere to self-care practices in their households

Mental health disorders among medical students during the COVID-19 pandemic in the area with no mandatory lockdown: a multicenter survey in Tanzania

Abstract The COVID-19 pandemic brought about a major public health concern worldwide. It forced many countries to enforce lockdowns, leading to the closure of higher learning institutions. The abrupt shift in the lifestyle of students had a profound impact on their mental health. This study aims to determine the prevalence and factors associated with mental health conditions among university students in Tanzania during the COVID-19 pandemic. A sample of 425 students from six medical universities and colleges in Tanzania completed an online survey and was included in the analysis. The questionnaire consisted of validated Depression, Anxiety and Stress Scale—21 Items (DASS-21) questions (Cronbach’s alpha = 0.92) assessing the presence of mental health symptoms: depression, anxiety, and stress. Multivariable logistic regression models were fitted to explain the factors associated with mental health conditions. A P-value < 0.05 was considered statistically significant in all inferential analyses. The median age (interquartile range) of the participants was 24 (22–26). The prevalence of mental health conditions was 28.94%, 54.12%, and 15.06% for depression, anxiety, and stress, respectively, while the prevalence of having any mental health condition was 58.59%. In an adjusted regression model, being in the fourth and fifth years of study and living with a spouse were significantly associated with increased odds of depression: AOR = 5.99 (1.31–27.47), AOR = 5.52 (1.18–25.81), and AOR = 1.84 (1.08–3.15), respectively. Moreover, studying in private universities and living with a spouse were significantly associated with an increased likelihood of anxiety: AOR = 2.35 (1.72–2.76), and AOR = 2.32 (1.20–4.50), respectively. The likelihood of stress was only among participants studying in private universities; AOR = 2.90 (1.60–5.27). The study revealed alarmingly high rates of mental health conditions among medical students in Tanzania during the COVID-19 pandemic. The findings suggest the need for regular checkups for medical students regarding their mental health status. Additionally, it recommends that the government and other stakeholders establish mental health services within the universities for the effective prevention of the rising burden of mental health problems among universities in Tanzania and other countries with similar settings

Corrigendum to “A practical approach to render tuberculosis samples safe for application of tuberculosis molecular bacterial load assay in clinical settings without a biosafety level 3 laboratory” [Tuberculosis 138 (2023) 102275 1-5] (Tuberculosis (2023) 138, (S1472979222001123), (10.1016/j.tube.2022.102275))

The authors regret to insert a corrigendum text in Table 1 of the published manuscript. This text corrects a typo error of TB-MBLA bacterial load (Mean ± SD/mL) of the un-diluted sputum (100) published as 2.26E+0 ± 1.41E+03 to 2.26E+05 ± 1.41E+03. This typo error misleads the message of the paper and data presented in Table 1. The authors would like to apologise for any inconvenience caused.</p

Datasets.

Data collected and reported in the manuscript. (ZIP)</p

Disease status and morbidity management practices among hydrocele patients in Luangwa District.

Disease status and morbidity management practices among hydrocele patients in Luangwa District.</p