Molecular epidemiology, drug susceptibility and economic aspects of tuberculosis in mubende district, Uganda

<div><p>Background</p><p>Tuberculosis (TB) remains a global public health problem whose effects have major impact in developing countries like Uganda. This study aimed at investigating genotypic characteristics and drug resistance profiles of <i>Mycobacterium tuberculosis</i> isolated from suspected TB patients. Furthermore, risk factors and economic burdens that could affect the current control strategies were studied.</p><p>Methods</p><p>TB suspected patients were examined in a cross-sectional study at the Mubende regional referral hospital between February and July 2011. A questionnaire was administered to each patient to obtain information associated with TB prevalence. Isolates of <i>M. tuberculosis</i> recovered during sampling were examined for drug resistance to first line anti-TB drugs using the BACTEC-MGIT960^TMsystem. All isolates were further characterized using deletion analysis, spoligotyping and MIRU-VNTR analysis. Data were analyzed using different software; MIRU-VNTR <i>plus</i>, SITVITWEB, BioNumerics and multivariable regression models.</p><p>Results</p><p><i>M. tuberculosis</i> was isolated from 74 out of 344 patients, 48 of these were co-infected with HIV. Results from the questionnaire showed that previously treated TB, co-infection with HIV, cigarette smoking, and overcrowding were risk factors associated with TB, while high medical related transport bills were identified as an economic burden. Out of the 67 isolates that gave interpretable results, 23 different spoligopatterns were detected, nine of which were novel patterns. T2 with the sub types Uganda-I and Uganda-II was the most predominant lineage detected. Antibiotic resistance was detected in 19% and multidrug resistance was detected in 3% of the isolates.</p><p>Conclusion</p><p>The study detected <i>M. tuberculosis</i> from 21% of examined TB patients, 62% of whom were also HIV positive. There is a heterogeneous pool of genotypes that circulate in this area, with the T2 lineage being the most predominant. High medical related transport bills and drug resistance could undermine the usefulness of the current TB strategic interventions.</p></div

A scoping review of foot-and-mouth disease risk, based on spatial and spatio-temporal analysis of outbreaks in endemic settings

International audienc

A pre-post study of behavioural determinants and practice change in Ugandan Clinical Officers

The data for this research was collected as part of a training course delivered by the Greater Manchester Critical Care Skills Institute in Gulu, Uganda. Travel, accommodation and associated costs were funded by Greater Manchester Critical Care Skills Institute. Members of the training team collected data and their time both in delivering the course and collecting data was unfunded i.e., voluntary (MJJ, RmC, HS, AS, SC, SW). Data collection was supported by other self-funded volunteers (HP, SR). Research design, data analysis and write up was conducted by unfunded volunteers (all authors). There was no formal role for the funding body in the study design, data collection, analysis or write up. However, authors of the paper are active members of the Greater Manchester Critical Care Skills Institute (AS, MJJ, RMc, HS, SC, SW).Peer reviewedPublisher PD

Exploring drivers of self-treatment with antibiotics in three agricultural communities of northern Tanzania

Background: Antimicrobial resistance (AMR) poses a significant global health threat, particularly in low- and middle-income countries (LMICs). Self-treatment with antibiotics, the practice of using antibiotics without professional guidance, is often considered an important contributor to the emergence and spread of AMR. Method: This study investigated the drivers of self-treatment in three common types of agricultural communities in northern Tanzania. The research employed a comprehensive array of methods, including cross-sectional surveys (n = 790), interviews (n = 30) and observations (n = 178) targeting both antibiotic (human and animal) providers and users (patients and farmers). Qualitative interview data were analysed using a coding and association matrix, while descriptive analyses were performed on survey and observation data. Results: Self-treatment with antibiotics was highly prevalent in all communities. Between 41.0% (self-reported) and 60.3% (observed) of human antibiotics were obtained without a prescription and we observed that veterinary antibiotics were regularly purchased in retail shops without referral by a professional. Structural deficiencies in the healthcare system drove this practice: limited access to healthcare facilities, medication stockouts and prolonged waiting times were identified as key factors. The absence of safety nets like insurance schemes further contributed to self-medication. Retail shops offered a convenient and cost-effective alternative when antibiotics were inaccessible or unaffordable. Notably, informal networks comprising treatment vendors, friends or neighbours, as well as personal experiences played a crucial role in guiding individuals in their self-treatment decisions by providing advice on treatment choice and modalities. Conclusions: Addressing self-treatment requires a multi-faceted approach. Improving the availability and accessibility of antibiotics, enhancing healthcare services and involving retail vendors in antibiotic stewardship are essential. Structural issues like access to diagnostics and medicines must be tackled, alongside reducing barriers and incentivising individuals to use professional healthcare services. Training retail vendors to sell specific first-line antibiotics over the counter with guidance on appropriate usage should be considered. Such bottom-up interventions will enable sustainable promotion of responsible antibiotic use, mitigating AMR emergence and securing a healthier future for all

Isolation of non-tuberculous mycobacteria from pastoral ecosystems of Uganda: Public Health significance

<p>Abstract</p> <p>Background</p> <p>The importance of non-tuberculous mycobacteria (NTM) infections in humans and animals in sub-Saharan Africa at the human-environment-livestock-wildlife interface has recently received increased attention. NTM are environmental opportunistic pathogens of humans and animals. Recent studies in pastoral ecosystems of Uganda detected NTM in humans with cervical lymphadenitis and cattle with lesions compatible with bovine tuberculosis. However, little is known about the source of these mycobacteria in Uganda. The aim of this study was to isolate and identify NTM in the environment of pastoral communities in Uganda, as well as assess the potential risk factors and the public health significance of NTM in these ecosystems.</p> <p>Method</p> <p>A total of 310 samples (soil, water and faecal from cattle and pigs) were examined for mycobacteria. Isolates were identified by the INNO-Lipa test and by 16S rDNA sequencing. Additionally, a questionnaire survey involving 231 pastoralists was conducted during sample collection. Data were analysed using descriptive statistics followed by a multivariable logistic regression analysis.</p> <p>Results</p> <p>Forty-eight isolates of NTM were detected; 25.3% of soil samples, 11.8% of water and 9.1% from animal faecal samples contained mycobacteria. Soils around water sources were the most contaminated with NTM (29.8%). Of these samples, <it>M. fortuitum-peregrinum </it>complex, <it>M. avium </it>complex, <it>M. gordonae</it>, and <it>M. nonchromogenicum </it>were the most frequently detected mycobacteria. Drinking untreated compared to treated water (OR = 33), use of valley dam versus stream water for drinking and other domestic use (OR = 20), sharing of water sources with wild primates compared to antelopes (OR = 4.6), sharing of water sources with domestic animals (OR = 5.3), and close contact with cattle or other domestic animals (OR = 13.8) were the most plausible risk factors for humans to come in contact with NTM in the environment.</p> <p>Conclusions</p> <p>The study detected a wide range of potentially pathogenic NTM from the environment around the pastoral communities in Uganda. Drinking untreated water and living in close contact with cattle or other domestic animals may be risk factors associated with the possibility of humans and animals acquiring NTM infections from these ecosystems.</p

Impact of COVID-19 on healthcare programs in Zimbabwe: a mixed methods study

Abstract Background The COVID-19 pandemic disrupted healthcare services. Understanding similar epidemic-related disruptions on a broader scope in our local setting is critical for the effective planning of essential services. The study determined the impact of Coronavirus disease(COVID-19) on healthcare programs in Zimbabwe. Methods A mixed-methods study compared healthcare service delivery trends from the Ministry of Health and Child Care before, during and post the pandemic. It employed two methods of data collection: Key informant interviews (KII) and secondary data analysis from the Zimbabwe District Health Information Systems 2 (DHIS2). Purposive sampling obtained key informants for interviews whilst 18 healthcare service indicators were identified from the national database. Statistical analysis consisted of an interrupted time series analysis of those indicators preceded by visualization to appreciate trend change. An inductive approach was used to code and identify basic themes which were then triangulated against DHIS2 findings. Results The study revealed that COVID-19 had a negative impact on health service delivery; increasing disruptions of critical healthcare services, maternal and child health, reproductive health issues, and other specialist services were prominent. The rise in maternal and child mortality cases and caesarean sections could be directly linked to the decline in service delivery during the pandemic. Mitigation strategies that were introduced during the pandemic included the use of community-based services, outreach services, capacity building, and de-congestion of public services. Conclusions The pandemic disrupted healthcare delivery, causing service usage to decline due to lockdowns. Response strategies included community services, capacity building, and stakeholder engagement. Future readiness requires epidemic plans, enhanced resources, a multisectoral approach, workforce training, and public education

Working conditions and public health risks in slaughterhouses in western Kenya

Background: Inadequate facilities and hygiene at slaughterhouses can result in contamination of meat and occupational hazards to workers. The objectives of this study were to assess current conditions in slaughterhouses in western Kenya and the knowledge, and practices of the slaughterhouse workers toward hygiene and sanitation. Methods: Between February and October 2012 all consenting slaughterhouses in the study area were recruited. A standardised questionnaire relating to facilities and practices in the slaughterhouse was administered to the foreperson at each site. A second questionnaire was used to capture individual slaughterhouse workers’ knowledge, practices and recent health events. Results: A total of 738 slaughterhouse workers from 142 slaughterhouses completed questionnaires. Many slaughterhouses had poor infrastructure, 65% (95% CI 63–67%) had a roof, cement floor and walls, 60% (95% CI 57–62%) had a toilet and 20% (95% CI 18–22%) had hand-washing facilities. The meat inspector visited 90% (95% CI 92–95%) of slaughterhouses but antemortem inspection was practiced at only 7% (95% CI 6–8%). Nine percent (95% CI 7–10%) of slaughterhouses slaughtered sick animals. Only half of workers wore personal protective clothing - 53% (95% CI 51–55%) wore protective coats and 49% (95% CI 46–51%) wore rubber boots. Knowledge of zoonotic disease was low with only 31% (95% CI 29–33%) of workers aware that disease could be transmitted from animals. Conclusions: The current working conditions in slaughterhouses in western Kenya are not in line with the recommendations of the Meat Control Act of Kenya. Current facilities and practices may increase occupational exposure to disease or injury and contaminated meat may enter the consumer market. The findings of this study could enable the development of appropriate interventions to minimise public health risks. Initially, improvements need to be made to facilities and practices to improve worker safety and reduce the risk of food contamination. Simultaneously, training programmes should target workers and inspectors to improve awareness of the risks. In addition, education of health care workers should highlight the increased risks of injury and disease in slaughterhouse workers. Finally, enhanced surveillance, targeting slaughterhouse workers could be used to detect disease outbreaks. This “One Health” approach to disease surveillance is likely to benefit workers, producers and consumers

Comparing one dose of HPV vaccine in girls aged 9-14 years in Tanzania (DoRIS) with one dose of HPV vaccine in historical cohorts: an immunobridging analysis of a randomised controlled trial

BACKGROUND: Human papillomavirus (HPV) vaccines are given as a two-dose schedule in children aged 9-14 years, or as three doses in older individuals. We compared antibody responses after one dose of HPV vaccine in the Dose Reduction Immunobridging and Safety Study (DoRIS), a randomised trial of different HPV vaccine schedules in Tanzania, to those from two observational HPV vaccine trials that found high efficacy of one dose up to 11 years against HPV16 and HPV18 (Costa Rica Vaccine Trial [CVT] and Institutional Agency for Research on Cancer [IARC] India trial). METHODS: In this immunobridging analysis of an open-label randomised controlled trial, girls were recruited from 54 government schools in Mwanza, Tanzania, into the DoRIS trial. Girls were eligible if they were aged 9-14 years, healthy, and HIV negative. Participants were randomly assigned (1:1:1:1:1:1), using permutated block sizes of 12, 18, and 24, to one, two, or three doses of the 2-valent vaccine (Cervarix, GSK Biologicals, Rixensart, Belgium) or the 9-valent vaccine (Gardasil 9, Sanofi Pasteur MSD, Lyon, France). For this immunobridging analysis, the primary objective was to compare geometric mean concentrations (GMCs) at 24 months after one dose in the per-protocol population compared with in historical cohorts: the one-dose 2-valent vaccine group in DoRIS was compared with recipients of the 2-valent vaccine Cervarix from CVT and the one-dose 9-valent vaccine group in DoRIS was compared with recipients of the 4-valent vaccine Gardasil (Merck Sharp & Dohme, Whitehouse Station, NJ, USA) from the IARC India trial. Samples were tested together with virus-like particle ELISA for HPV16 and HPV18 IgG antibodies. Non-inferiority of GMC ratios (DoRIS trial vs historical cohort) was predefined as when the lower bound of the 95% CI was greater than 0·50. This study is registered with ClinicalTrials.gov, NCT02834637. FINDINGS: Between Feb 23, 2017, and Jan 6, 2018, we screened 1002 girls for eligibility, of whom 930 were enrolled into DoRIS and 155 each were assigned to one dose, two doses, or three doses of 2-valent vaccine, or one dose, two doses, or three doses of 9-valent vaccine. 154 (99%) participants in the one-dose 2-valent vaccine group (median age 10 years [IQR 9-12]) and 152 (98%) in the one-dose 9-valent vaccine group (median age 10 years [IQR 9-12]) were vaccinated and attended the 24 month visit, and so were included in the analysis. 115 one-dose recipients from the CVT (median age 21 years [19-23]) and 139 one-dose recipients from the IARC India trial (median age 14 years [13-16]) were included in the analysis. At 24 months after vaccination, GMCs for HPV16 IgG antibodies were 22·9 international units (IU) per mL (95% CI 19·9-26·4; n=148) for the DoRIS 2-valent vaccine group versus 17·7 IU/mL (13·9-22·5; n=97) for the CVT (GMC ratio 1·30 [95% CI 1·00-1·68]) and 13·7 IU/mL (11·9-15·8; n=145) for the DoRIS 9-valent vaccine group versus 6·7 IU/mL (5·5-8·2; n=131) for the IARC India trial (GMC ratio 2·05 [1·61-2·61]). GMCs for HPV18 IgG antibodies were 9·9 IU/mL (95% CI 8·5-11·5: n=141) for the DoRIS 2-valent vaccine group versus 8·0 IU/mL (6·4-10·0; n=97) for the CVT trial (GMC ratio 1·23 [95% CI 0·95-1·60]) and 5·7 IU/mL (4·9-6·8; n=136) for the DoRIS 9-valent vaccine group versus 2·2 IU/mL (1·9-2·7; n=129) for the IARC India trial (GMC ratio 2·12 [1·59-2·83]). Non-inferiority of antibody GMCs was met for each vaccine for both HPV16 and HPV18. INTERPRETATION: One dose of HPV vaccine in young girls might provide sufficient protection against persistent HPV infection. A one-dose schedule would reduce costs, simplify vaccine delivery, and expand access to the vaccine. FUNDING: UK Department for International Development/UK Medical Research Council/Wellcome Trust Joint Global Health Trials Scheme, The Bill & Melinda Gates Foundation, and the US National Cancer Institute. TRANSLATION: For the KiSwahili translation of the abstract see Supplementary Materials section

Characterization of Non-Tuberculous Mycobacterium from Humans and Water in an Agro pastoral area in Zambia

Abstract Background The non-tuberculous mycobacteria include those mycobacterium species that are not members of the Mycobacterium tuberculosis complex, the causative agent of pulmonary tuberculosis and Mycobacterium leprae. In Zambia, Non-tuberculous Mycobacteria are gaining recognition as pathogens of public health significance. However, there is scanty information on the isolation and speciation of these organisms for better patient management, consequently reducing the burden of these infections. Given the above information, the thrust of this study was to isolate and characterize NTM from humans and water in Namwala district of Zambia. Method This was a cross-sectional study were 153 individuals with suspected TB were sampled from four health facilities in Namwala district, sputum samples were also collected. Additionally, 149 water samples were collected from different water drinking sources such as Tap water, Borehole water, rivers, wells and streams. Standard TB culture methods were employed to isolate Non-tuberculous Mycobacteria and later 16S–23S internal transcribed spacer region Sequencing was employed to characterize NTM. Results Seven (7, 4.6%) NTM species were identified from humans with M. arupense (3, 42.9%) being the most common organism, while twenty three (23, 15.4%) NTM were identified from water with the common species being Mycobacterium gordonae (5, 21.7%). Mycobacterium avium and Mycobacterium fortuitum were both identified from human and water samples. Conclusion This study has shown the isolation of NTM species from humans and water. The isolation of NTM from drinking water sources could signify a public health risk to humans

Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches