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Background: Retrospective and descriptive molecular epidemiology studies have shown that Mycobacterium tuberculosis whole genome sequencing can identify outbreaks and disease transmission events with higher resolution than conventional epidemiological investigations. Those studies have strengthened our understanding of genomic polymorphisms correlating with person-to-person transmission and helped resolve putative transmission clusters. To date, systematic genomic surveillance programs implemented for M. tuberculosis were only implemented in low-incidence settings. The purpose of this study is to determine whether there is an impact of routine M. tuberculosis whole genome sequencing on tuberculosis case detection in a high-incidence setting., Methods: A cluster randomized controlled trial will be performed. Forty-eight rural village groups (or Fokontany) in the Vohibato district of Madagascar will be randomized to one of three interventions arms. Arm 1 (standard of care) involves healthcare facility-based passive case detection with smear microscopy testing. Arm 2 (best practice) consists of active case finding and Xpert MTB/RIF Ultra PCR testing followed by household contact investigations. Arm 3 (novel intervention) includes the same interventions as arm 2, with addition of sputum culture and M. tuberculosis whole genome sequencing for all newly diagnosed cases. In arm 3, molecular suggested putative outbreaks are investigated, and additional TB suspects are appropriately tested. The intervention observational period will be 2 years. The primary outcome will be the number of detected cases/100,000/year in each arm after 1 year of intervention., Discussion: This study is designed to determine whether there is an impact of prospective whole genome sequencing-based molecular typing on tuberculosis case detection in high-incidence settings. Investigating potential outbreaks and focusing active case finding in spatiotemporal settings where disease transmission is suggested by genomic typing is hypothesized to improve case detection in rural communities., Trial Registration: ClinicalTrials.gov NCT05406453 . Retrospectively registered on June 6, 2022., (© 2024. The Author(s).)

Background: Quality surveillance data used to build tuberculosis (TB) transmission models are frequently unavailable and may overlook community intrinsic dynamics that impact TB transmission. Social network analysis (SNA) generates data on hyperlocal social-demographic structures that contribute to disease transmission., Methods: We collected social contact data in five villages and built SNA-informed village-specific stochastic TB transmission models in remote Madagascar. A name-generator approach was used to elicit individual contact networks. Recruitment included confirmed TB patients, followed by snowball sampling of named contacts. Egocentric network data were aggregated into village-level networks. Network- and individual-level characteristics determining contact formation and structure were identified by fitting an exponential random graph model (ERGM), which formed the basis of the contact structure and model dynamics. Models were calibrated and used to evaluate WHO-recommended interventions and community resiliency to foreign TB introduction., Results: Inter- and intra-village SNA showed variable degrees of interconnectivity, with transitivity (individual clustering) values of 0.16, 0.29, and 0.43. Active case finding and treatment yielded 67%-79% reduction in active TB disease prevalence and a 75% reduction in TB mortality in all village networks. Following hypothetical TB elimination and without specific interventions, networks A and B showed resilience to both active and latent TB reintroduction, while Network C, the village network with the highest transitivity, lacked resiliency to reintroduction and generated a TB prevalence of 2% and a TB mortality rate of 7.3% after introduction of one new contagious infection post hypothetical elimination., Conclusion: In remote Madagascar, SNA-informed models suggest that WHO-recommended interventions reduce TB disease (active TB) prevalence and mortality while TB infection (latent TB) burden remains high. Communities' resiliency to TB introduction decreases as their interconnectivity increases. "Top down" population level TB models would most likely miss this difference between small communities. SNA bridges large-scale population-based and hyper focused community-level TB modeling., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: In Madagascar, the multidrug-resistant tuberculosis (MDR-TB) surveillance programme was launched in late 2012 wherein previously treated TB cases and symptomatic MDR-TB contacts (hereafter called presumptive MDR-TB cases) undergo drug susceptibility testing. This retrospective review had per aim to provide an update on the national MDR-TB epidemiology, assess and enhance programmatic performance and assess Madagascar's MDR-TB cascade of care., Methods: For 2012-2017, national TB control programme notification, clinical management data and reference laboratory data were gathered. The development and coverage of the surveillance programme, the MDR-TB epidemiology and programmatic performance indicators were assessed using descriptive, logistic and spatial statistical analyses. Data for 2017 was further used to map Madagascar's TB and MDR-TB cascade of care., Results: The geographical coverage and diagnostic and referral capacities of the MDR-TB surveillance programme were gradually expanded whereas regional variations persist with regard to coverage, referral rates and sample referral delays. Overall, the rate of MDR-TB among presumptive MDR-TB cases remained relatively stable, ranging between 3.9% in 2013 and 4.4% in 2017. Most MDR-TB patients were lost in the second gap of the cascade pertaining to MDR-TB cases reaching diagnostic centres but failing to be accurately diagnosed (59.0%). This poor success in diagnosis of MDR-TB is due to both the current use of low-sensitivity smear microscopy as a first-line diagnostic assay for TB and the limited access to any form of drug susceptibility testing. Presumptive MDR-TB patients' sample referral took a mean delay of 28 days before testing. Seventy-five percent of diagnosed MDR-TB patients were appropriately initiated on treatment, and 33% reached long-term recurrence-free survival., Conclusions: An expansion of the coverage and strengthening of MDR-TB diagnostic and management capacities are indicated across all regions of Madagascar. With current limitations, the surveillance programme data is likely to underestimate the true MDR-TB burden in the country and an updated national MDR-TB prevalence survey is warranted. In absence of multiple drivers of an MDR-TB epidemic, including high MDR-TB rates, high HIV infection rates and inter-country migration, Madagascar is in a favourable starting position for MDR-TB control and elimination.

Background: Tuberculosis rapid molecular assays, including GeneXpert MTB/RIF® and Loopamp MTBC Detection Kit®, are highly sensitive and specific. Such performance does not automatically translate in improved disease control and highly depends on their use, local epidemiology and the diagnostic algorithms they're implemented within. We evaluate the performance of both assays and assess their impact on additional cases notification when implemented within WHO recommended tuberculosis diagnostic algorithms in Madagascar., Methods: Five hundred forty eight presumptive pulmonary tuberculosis patients were prospectively recruited between November 2013 and December 2014 in Antananarivo, Madagascar, a high TB incidence sub-Saharan African urban setting. Both molecular assays were evaluated as first line or add-on testing following negative smear microscopy. Based on locally defined assay performance characteristics we measure the impact of both assays and WHO-recommended diagnostic algorithms on additional tuberculosis case notifications., Results: High sensitivity and specificity was confirmed for both GeneXpert MTB/RIF® (86.6% (95% CI 81.1-90.7%) and 97.4% (95% CI 94.9-98.8%)) and Loopamp MTBC Detection Kit® (84.6% (95% CI 78.9-89.0%) and 98.4% (95% CI 96.2-99.4%)). Implementation of GeneXpert MTB/RIF® and Loopamp MTBC Detection Kit® increased tuberculosis diagnostic algorithms sensitivity from 73.6% (95% CI 67.1-79.3%) up to 88.1% (95% CI 82.8-91.9%). This increase was highest when molecular assays were used as add-on testing following negative smear microscopy. As add-on testing, GeneXpert MTB/RIF® and Loopamp MTBC Detection Kit® respectively improved case detection by 23.8 and 21.2% (p < 0.05)., Conclusion: Including GeneXpert MTB/RIF® or Loopamp MTBC Detection Kit® molecular assays for TB detection on sputum samples from presumptive TB cases can significantly increase case notification in TB diagnostic centers. The TB case detection rate is further increased when those tests are use as second-line follow-on testing following negative smear microscopy results. A country wide scale-up and digital integration of molecular-based TB diagnosis assays shows promises for TB control in Madagascar.

Background: Large projects in the extractive industry sector can affect people's health and wellbeing. In low- and middle-income countries (LMICs), women's health is of particular concern in such contexts due to potential educational and economic disadvantages, vulnerability to transactional sex and unsafe sex practices. At the same time, community health interventions and development initiatives present opportunities for women's and maternal health., Methods: Within the frame of the health impact assessment (HIA) of the Trident copper mining project in Zambia, two health surveys were conducted (baseline in 2011 and follow-up in 2015) in order to monitor health and health-related indicators. Emphasis was placed on women residing in the mining area and, for comparison, in settings not impacted by the project., Results: All measured indicators improved over time, regardless of whether communities were affected by the project or not. Additionally, the percentage of mothers giving birth in a health facility, the percentage of women who acknowledge that HIV cannot be transmitted by witchcraft or other supernatural means and the percentage of women having ever tested for HIV showed a significant increase in the impacted sites but not in the comparison communities. In 2015, better health, behavioural and knowledge outcomes in women were associated with employment by the project (or a sub-contractor thereof), migration background, increased wealth and higher educational attainment., Conclusions: Our study reveals that natural resource development projects can positively impact women's health, particularly if health risks are adequately anticipated and managed. Hence, the conduct of a comprehensive HIA should be a requirement at the feasibility stage of any large infrastructure project, particularly in LMICs. Continued monitoring of health outcomes and wider determinants of health after the initial assessment is crucial to judge the project's influence on health and for reducing inequalities over time.

Background: To avoid or mitigate potential project-related adverse health effects, the Trident copper project in Kalumbila, northwestern Zambia, commissioned a health impact assessment. HIV was identified a priority health issue based on the local vulnerability to HIV transmission and experience from other mining projects in Africa. Hence, an HIV/AIDS management plan was developed, including community and workplace interventions, with HIV testing and counselling (HTC) being one of the key components. We present trends in HTC data over a 4-year period., Methods: In 13 communities affected by the Trident project, HTC was implemented from 2012 onwards, using rapid diagnostic tests, accompanied by pre- and post-test counselling through trained personnel. In addition, HTC was initiated in the project workforce in 2013, coinciding with the launch of the mine development. HTC uptake and HIV positivity rates were assessed in the study population and linked to demographic factors using regression analysis., Results: In total, 11,638 community members and 5564 workers have taken up HTC with an increase over time. The HIV positivity rate in the community was 3.0% in 2012 and 3.4% in 2015, while positivity rate in the workforce was 5.2% in 2013 and 4.3% in 2015. Females showed a significantly higher odds of having a positive test result than males (odds ratio (OR) = 1.96, 95% confidence interval (CI): 1.55-2.50 among women in the community and OR = 2.90, 95% CI: 1.74-4.84 among women in the workforce). HTC users in the 35-49 years age group were most affected by HIV, with an average positivity rate of 6.6% in the community sample and 7.9% in the workforce sample. These study groups had 4.50 and 4.95 higher odds of being positive, respectively, compared to their younger counterparts (15-24 years)., Conclusions: While HTC uptake increased five-fold in the community and almost three-fold in the workplace, the HIV positivity rates were insignificantly higher in 2015 compared to 2012. Our data can be used alongside other surveillance data to track HIV transmission in this specific context. Guided by the health impact assessment, the HIV prevention and control programme was readily adapted to the current setting through the identification of socioeconomic and environmental determinants of health.

Background: Operational/implementation research (OR/IR) is a key activity to improve disease control programme performance. We assessed the extent to which malaria and tuberculosis (TB) grants from the Global Fund to Fight AIDS, Tuberculosis and Malaria ("Global Fund") include support for OR/IR, and discuss the implications of the current Global Fund operating mechanisms for OR/IR support., Methods: The situation analysis focussed on malaria and TB, while HIV was excluded. Stakeholder interviews were conducted at the Global Fund secretariat and in six purposefully selected high disease burden countries, namely the Democratic Republic of the Congo, Ethiopia, India, Indonesia, Myanmar and Zimbabwe. Interviewed in-country stakeholders included the relevant disease control programme managers, project implementation partners, representatives from international organisations with a stake in global health, academic and governmental research institutions, and other relevant individuals such as members of the country coordination mechanism. Additionally, documentation of grants and OR/IR obtained from the Global Fund was reviewed., Results: The Global Fund provides substantial resources for malaria and TB surveys, and supports OR/IR if such support is requested and the application is well justified. We observed considerable variations from one country to another and between programmes with regards to need, demand, absorption capacity and funding for OR/IR related to malaria and TB. Important determinants for the extent of such funding are the involvement of national research coordination bodies, established research agendas and priorities, human and technical research capacity, and involvement of relevant stakeholders in concept note development. Efforts to disseminate OR/IR findings were generally weak, and the Global Fund does not maintain a central OR/IR database. When faced with a need to choose between procurement of commodities for disease control and supporting research, countries tend to seek research funding from other donors. The Global Fund is expected to issue more specific guidance on the conditions under which it supports OR/IR, and to adapt administrative procedures to facilitate research., Conclusions: The importance of OR/IR for optimising disease control programmes is generally accepted but countries vary in their capacity to demand and implement studies. Countries expect guidance on OR/IR from the Global Fund. Administrative procedures specifically related to the budget planning should be modified to facilitate ad-hoc OR/IR funding. More generally, several countries expressed a need to strengthen capacity for planning, negotiating and implementing research.

Background: Multiple factors determine children's nutritional status, including energy and nutrient intake, recurrent infectious diseases, access (or lack thereof) to clean water and improved sanitation, and hygiene practices, among others. The "Vegetables go to School: improving nutrition through agricultural diversification" (VgtS) project implements an integrated school garden programme in five countries, including Burkina Faso. The aim of this study was to determine the prevalence of undernutrition and its risk factors among schoolchildren in Burkina Faso before the start of the project., Methods: In February 2015, a cross-sectional survey was carried out among 455 randomly selected children, aged 8-14 years, in eight schools in the Plateau Central and Centre-Ouest regions of Burkina Faso. Nutritional status was determined by anthropometric assessment. Helminth and intestinal protozoa infections were assessed using the Kato-Katz and a formalin-ether concentration method. A urine filtration technique was used to identify Schistosoma haematobium eggs. Prevalence of anaemia was determined by measuring haemoglobin levels in finger-prick blood samples. Questionnaires were administered to children to determine their knowledge of nutrition and health and their related attitudes and practices (KAP). Questionnaires were also administered to the children's caregivers to identify basic household socio-demographic and economic characteristics, and water, sanitation and hygiene (WASH) conditions. To determine the factors associated with schoolchildren's nutritional status, mixed logistic regression models were used. Differences and associations were considered statistically significant if P-values were below 0.05., Results: Complete datasets were available for 385 children. The prevalence of undernutrition, stunting and thinness were 35.1%, 29.4% and 11.2%, respectively. The multivariable analysis revealed that undernutrition was associated with older age (i.e. 12-14 years compared to <12 years; adjusted odds ratio (aOR) = 3.45, 95% confidence interval (CI) 2.12-5.62, P < 0.001), multiple pathogenic parasitic infections (aOR = 1.87, 95% CI 1.02-3.43, P = 0.044) and with moderate and severe anaemia in children (aOR = 2.52, 95% CI 1.25-5.08, P = 0.010)., Conclusions: We found high prevalence of undernutrition among the children surveyed in the two study regions of Burkina Faso. We further observed that undernutrition, anaemia and parasitic infections were strongly associated. In view of these findings, concerted efforts are needed to address undernutrition and associated risk factors among school-aged children. As part of the VgtS project, WASH, health education and nutritional interventions will be implemented with the goal to improve children's health., Trial Registration: ISRCTN17968589 (date assigned: 17 July 2015).

Background: Unsafe drinking water, unimproved sanitation and lack of hygiene pose health risks, particularly to children in low- and middle-income countries. This study aimed to assess the prevalence and risk factors of intestinal parasitic infections in school-aged children in two regions of Burkina Faso., Methods: A cross-sectional survey was carried out in February 2015 with 385 children aged 8-14 years from eight randomly selected schools in the Plateau Central and Centre-Ouest regions of Burkina Faso. Stool samples were subjected to the Kato-Katz and a formalin-ether concentration method for the diagnosis of helminths and intestinal protozoa infections. Urine samples were examined with a urine filtration technique for Schistosoma haematobium eggs. Water samples from community sources (n = 37), children's households (n = 95) and children's drinking water cups (n = 113) were analysed for contamination with coliform bacteria and faecal streptococci. Data on individual and family-level risk factors were obtained using a questionnaire. Mixed logistic regression models were employed to determine factors associated with intestinal parasitic infections in schoolchildren., Results: Intestinal parasitic infections were highly prevalent; 84.7 % of the children harboured intestinal protozoa, while helminth infections were diagnosed in 10.7 % of the children. We found significantly lower odds of pathogenic intestinal protozoa infection (Entamoeba histolytica/E. dispar and Giardia intestinalis) among children from the Plateau Central, compared to the Centre-Ouest region (P < 0.001). Children from households with "freely roaming domestic animals" (P = 0.008), particularly dogs (P = 0.016) showed higher odds of G. intestinalis, and children reporting exposure to freshwater sources through domestic chores had higher odds of S. haematobium infection compared to children without this water contact activity (P = 0.035). Water quality, household drinking water source and storage did not emerge as significant risk factors for intestinal parasitic infections in children., Conclusions: Intestinal protozoa but not helminths were highly prevalent among schoolchildren in randomly selected schools in two regions of Burkina Faso. Our findings call for specific public health measures tailored to school-aged children and rural communities in this part of Burkina Faso. It will be interesting to assess the effect of water, sanitation and hygiene interventions on the transmission of intestinal parasitic infections., Trial Registration: ISRCTN17968589 (date assigned: 17 July 2015).

Background: The epidemiology of malaria and anaemia is characterized by small-scale spatial and temporal heterogeneity, which might be influenced by human activities, such as mining and related disturbance of the environment. Private sector involvement holds promise to foster public health, including the prevention and control of malaria and anaemia. Here, results from a cross-sectional epidemiological survey, conducted in communities that might potentially be affected by the Bonikro Gold Mine (BGM) in Côte d'Ivoire, are reported., Methods: In December 2012, a cross-sectional survey was carried out in seven communities situated within a 20-km radius of the BGM in central Côte d'Ivoire. Capillary blood samples were obtained from children aged six to 59 months. Samples were subjected to a rapid diagnostic test (RDT) for Plasmodium falciparum detection, whilst haemoglobin (Hb) was measured to determine anaemia. Additionally, mothers were interviewed with a malaria-related knowledge, attitudes and practices questionnaire., Results: A total of 339 children and 235 mothers participated in the surveys. A positive RDT for P. falciparum was found in 69% of the children, whilst 72% of the children were anaemic (Hb <11 g/dl). Plasmodium falciparum infection was significantly associated with anaemia (odds ratio (OR) 7.43, 95% confidence interval (CI) 3.97-13.89), access to a health facility (OR 5.59, 95% CI 1.81-17.32) and age (OR 0.04, 95% CI 0.01-0.12; youngest (six to 11 months) versus oldest (48-59 months) age group). Less than a quarter of mothers knew that malaria is uniquely transmitted by mosquitoes (22.3%, 95% CI 16.8-27.7%). Misconceptions were common; most of the mothers believe that working in the sun can cause malaria., Conclusions: Malaria and anaemia are highly endemic in the surveyed communities around the BGM project area in Côte d'Ivoire. The data presented here provide a rationale for designing setting-specific interventions and can be utilized as a benchmark for longitudinal monitoring of potential project-related impacts due to changes in the social-ecological and health systems.