A social network analysis model approach to understand tuberculosis transmission in remote rural Madagascar.

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.

Multidrug-resistant tuberculosis surveillance and cascade of care in Madagascar: a five-year (2012-2017) retrospective study.

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.

Performance and impact of GeneXpert MTB/RIF® and Loopamp MTBC Detection Kit® assays on tuberculosis case detection in Madagascar.

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.

Selected indicators and determinants of women's health in the vicinity of a copper mine development in northwestern Zambia.

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.

Operational and implementation research within Global Fund to Fight AIDS, Tuberculosis and Malaria grants: a situation analysis in six countries.

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.

The epidemiology of malaria and anaemia in the Bonikro mining area, central Côte d'Ivoire.

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.

Concordance of targeted and whole genome sequencing for Mycobacterium tuberculosis genotypic drug susceptibility testing.

Targeted Next Generation Sequencing (tNGS) and Whole Genome Sequencing (WGS) are increasingly used for genotypic drug susceptibility testing (gDST) of Mycobacterium tuberculosis. Thirty-two multi-drugs resistant and 40 drug susceptible isolates from Madagascar were tested with Deeplex® Myc-TB and WGS using the Mykrobe analysis pipeline. Sixty-four of 72 (89 %) yielded concordant categorical gDST results for drugs tested by both assays. Mykrobe didn't detect pncA K96T, pncA Q141P, pncA H51P, pncA H82R, rrs C517T and rpsL K43R mutations, which were identified as minority variants in corresponding isolates by tNGS. One discrepancy (rrs C517T) was associated with insufficient sequencing depth on WGS. Deeplex® Myc-TB didn't detect inhA G-154A which isn't covered by the assay's amplification targets. Despite those targets being included in the Deeplex® Myc-TB assay, a pncA T47A and a deletion in gid were not identified in one isolate respectively. The evaluated WGS and tNGS gDST assays show high but imperfect concordance.

Exploring the Impact of Mining on Community Health and Health Service Delivery: Perceptions of Key Informants Involved in Gold Mining Communities in Burkina Faso.

Sub-Saharan Africa is rich in natural resources but also faces widespread poverty. The United Nations' Sustainable Development Goals brought increased attention to resource extraction projects, emphasizing their development potential in extraction regions. While mining companies are required to conduct environmental impact assessments, their effect on the project-affected communities' health mostly lacks systematic management, and their consideration of community perspectives is insufficient. Between March and May 2019, qualitative research was conducted at three industrial gold mines in Burkina Faso. Thirty-six participants, including community leaders, healthcare providers, and mining officials, were interviewed through key informant interviews about their perceptions on the impacts of mining operations on health, health determinants, and health service delivery. Disparities in perceptions were a key focus of the analysis. Mining officials reported mainly positive effects, while healthcare providers and community leaders described enhancing and adverse health impacts without clear trends observed regarding the extent of the impacts on health determinants. The perception of predominantly positive health impacts by mining officials represents a potential risk for insufficient acknowledgement of stakeholders' concerns and mining-related effects on community health in affected populations. Overall, this study enhances comprehension of the complex interplay between mining operations and health, emphasizing the need for comprehensive assessments, stakeholder involvement, and sustainable practices to mitigate negative impacts and promote the well-being of mining communities.

Current Global Health Impact Assessment Practice.

Health impact assessment (HIA) practice has expanded across the world, since it was established more than two decades ago. This paper presents a snapshot of current global HIA practice based on the findings of an online questionnaire survey. HIA practitioners from all world regions were invited to participate. A total of 122 HIA practitioners from 29 countries completed the survey, following a broad international outreach effort. The large variety in the types of HIAs conducted, and the application of HIA in various fields reported by respondents, demonstrates that HIA practice has evolved over the past two decades. Although differences in the use of HIA were reported across world regions, an overall increasing trend in global HIA practice can be observed. In order to sustain this upward trend, efforts are needed to address the main barriers in the utilisation of HIA. The establishment of new national and international HIA teaching and training offerings seems to be an obvious strategy to pursue along with the strengthening of policies and legal frameworks that specify the circumstances, under which HIA is required, and to what extent.

Latent tuberculosis infection prevalence in rural Madagascar.

BACKGROUND: Understanding latent Mycobacterium tuberculosis infection (LTBI) prevalence is crucial for the design of TB control strategies. There are no data on LTBI in rural Madagascar. METHODS: Tuberculin skin tests were performed in 98 adults aged >15 y in five rural villages in the Ifanadiana district, Madagascar. RESULTS: Of adults, 78.6% were positive for LTBI, ranging between 28.6% and 95.0% among villages. The majority (65.3%) showed an induration reaction of >15 mm. CONCLUSIONS: LTBI prevalence is high in rural Madagascar. Long-term TB control strategies including LTBI testing and treatment must account for high and heterogeneous prevalence in remote, underdeveloped areas.

Community Health Impacts of the Trident Copper Mine Project in Northwestern Zambia: Results from Repeated Cross-Sectional Surveys.

The application of a health impact assessment (HIA) for a large-scale copper mining project in rural Zambia triggered the long-term monitoring and evaluation of determinants of health and health outcomes in communities living in proximity to the mine. Three consecutive cross-sectional surveys were conducted at intervals of four years; thus, at baseline (2011), four (2015) and eight (2019) years into the project's development. Using the same field and laboratory procedures, the surveys allowed for determining changes in health indicators at the household level, in young children (<5 years), school attendees (9-14 years) and women (15-49 years). Results were compared between communities considered impacted by the project and communities outside the project area (comparison communities). The prevalence of Plasmodium falciparum infection increased in both the impacted and comparison communities between 2011 and 2019 but remained consistently lower in the impacted communities. Stunting in children < 5 years and the prevalence of intestinal parasite infections in children aged 9-14 years mostly decreased. In women of reproductive age, selected health indicators (i.e., anaemia, syphilis, underweight and place of delivery) either remained stable or improved. Impacted communities generally showed better health outcomes than comparison communities, suggesting that the health interventions implemented by the project as a consequence of the HIA have mitigated potential negative effects and enhanced positive effects. Caution is indicated to avoid promotion of health inequalities within and beyond the project area.

Drones and digital adherence monitoring for community-based tuberculosis control in remote Madagascar: A cost-effectiveness analysis.

BACKGROUND: Continuing tuberculosis control with current approaches is unlikely to reach the World Health Organization's objective to eliminate TB by 2035. Innovative interventions such as unmanned aerial vehicles (or drones) and digital adherence monitoring technologies have the potential to enhance patient-centric quality tuberculosis care and help challenged National Tuberculosis Programs leapfrog over the impediments of conventional Directly Observed Therapy (DOTS) implementation. A bundle of innovative interventions referred to for its delivery technology as the Drone Observed Therapy System (DrOTS) was implemented in remote Madagascar. Given the potentially increased cost these interventions represent for health systems, a cost-effectiveness analysis was indicated. METHODS: A decision analysis model was created to calculate the incremental cost-effectiveness of the DrOTS strategy compared to DOTS, the standard of care, in a study population of 200,000 inhabitants in rural Madagascar with tuberculosis disease prevalence of 250/100,000. A mixed top-down and bottom-up costing approach was used to identify costs associated with both models, and net costs were calculated accounting for resulting TB treatment costs. Net cost per disability-adjusted life years averted was calculated. Sensitivity analyses were performed for key input variables to identify main drivers of health and cost outcomes, and cost-effectiveness. FINDINGS: Net cost per TB patient identified within DOTS and DrOTS were, respectively, $282 and $1,172. The incremental cost per additional TB patient diagnosed in DrOTS was $2,631 and the incremental cost-effectiveness ratio of DrOTS compared to DOTS was $177 per DALY averted. Analyses suggest that integrating drones with interventions ensuring highly sensitive laboratory testing and high treatment adherence optimizes cost-effectiveness. CONCLUSION: Innovative technology packages including drones, digital adherence monitoring technologies, and molecular diagnostics for TB case finding and retention within the cascade of care can be cost effective. Their integration with other interventions within health systems may further lower costs and support access to universal health coverage.

Kankanet: An artificial neural network-based object detection smartphone application and mobile microscope as a point-of-care diagnostic aid for soil-transmitted helminthiases.

BACKGROUND: Endemic areas for soil-transmitted helminthiases often lack the tools and trained personnel necessary for point-of-care diagnosis. This study pilots the use of smartphone microscopy and an artificial neural network-based (ANN) object detection application named Kankanet to address those two needs. METHODOLOGY/PRINCIPAL FINDINGS: A smartphone was equipped with a USB Video Class (UVC) microscope attachment and Kankanet, which was trained to recognize eggs of Ascaris lumbricoides, Trichuris trichiura, and hookworm using a dataset of 2,078 images. It was evaluated for interpretive accuracy based on 185 new images. Fecal samples were processed using Kato-Katz (KK), spontaneous sedimentation technique in tube (SSTT), and Merthiolate-Iodine-Formaldehyde (MIF) techniques. UVC imaging and ANN interpretation of these slides was compared to parasitologist interpretation of standard microscopy.Relative to a gold standard defined as any positive result from parasitologist reading of KK, SSTT, and MIF preparations through standard microscopy, parasitologists reading UVC imaging of SSTT achieved a comparable sensitivity (82.9%) and specificity (97.1%) in A. lumbricoides to standard KK interpretation (97.0% sensitivity, 96.0% specificity). The UVC could not accurately image T. trichiura or hookworm. Though Kankanet interpretation was not quite as sensitive as parasitologist interpretation, it still achieved high sensitivity for A. lumbricoides and hookworm (69.6% and 71.4%, respectively). Kankanet showed high sensitivity for T. trichiura in microscope images (100.0%), but low in UVC images (50.0%). CONCLUSIONS/SIGNIFICANCE: The UVC achieved comparable sensitivity to standard microscopy with only A. lumbricoides. With further improvement of image resolution and magnification, UVC shows promise as a point-of-care imaging tool. In addition to smartphone microscopy, ANN-based object detection can be developed as a diagnostic aid. Though trained with a limited dataset, Kankanet accurately interprets both standard microscope and low-quality UVC images. Kankanet may achieve sensitivity comparable to parasitologists with continued expansion of the image database and improvement of machine learning technology.

Perceptions of drones, digital adherence monitoring technologies and educational videos for tuberculosis control in remote Madagascar: a mixed-method study protocol.

INTRODUCTION: Poor road and communication infrastructure pose major challenges to tuberculosis (TB) control in many regions of the world. TB surveillance and patient support often fall to community health workers (CHWs) who may lack the time or knowledge needed for this work. To meet the End TB Strategy goal of reducing TB incidence by 90% by 2035, the WHO calls for intensified research and innovation including the rapid uptake of new tools, interventions and strategies. Technologies that 'leapfrog' infrastructure challenges and support CHWs in TB control responsibilities have the potential to dramatically change TB outcomes in remote regions. Such technologies may strengthen TB control activities within challenged national tuberculosis treatment and control programmes (NTPs), and be adapted to address other public health challenges. The deployment of innovative technologies needs to be differentially adapted to context-specific factors. The Drone Observed Therapy System (DrOTS) project was launched in Madagascar in 2017 and integrates a bundle of innovative technologies including drones, digital adherence monitoring technology and mobile device-based educational videos to support TB control. METHODS AND ANALYSIS: This mixed-methods study gathers and analyses cultural perceptions of the DrOTS project among key stakeholders: patients, community members, CHWs, village chiefs and NTP-DrOTS mobile health teams. Data from questionnaires, semistructured interviews, focus group discussions (FGD) and ethnographic observation gathered from June 2018 to June 2019 are thematically analysed and compared to identify patterns and singularities in how DrOTS stakeholders perceive and interact with DrOTS technologies, its enrolment processes, objectives and team. ETHICS AND DISSEMINATION: Ethics approval was obtained from the National Bioethics Research Committee of Madagascar and Stony Brook University institutional review board. Study results will be submitted for peer-reviewed publication. In Madagascar, results will be presented in person to Ministry and other Malagasy decision-makers through the Institut Pasteur de Madagascar. PATIENT AND PUBLIC INVOLVEMENT: This study is designed to foreground the voices of patients and potential patients in the DrOTS programme. CHW participants in this study also supported the design of study information sessions and recruitment strategies. One member of the mobile health team provided detailed input on the wording and content of FGD and interview guides. Study findings will be presented via a report in French and Malagasy to CHW, mobile health team and other village-level participants who have email/internet access.

Bi-directional drones to strengthen healthcare provision: experiences and lessons from Madagascar, Malawi and Senegal.

Drones are increasingly being used globally for the support of healthcare programmes. Madagascar, Malawi and Senegal are among a group of early adopters piloting the use of bi-directional transport drones for health systems in sub-Saharan Africa. This article presents the experiences as well as the strengths, weaknesses, opportunities and threats (SWOT analysis) of these country projects. Methods for addressing regulatory, feasibility, acceptability, and monitoring and evaluation issues are presented to guide future implementations. Main recommendations for governments, implementers, drone providers and funders include (1) developing more reliable technologies, (2) thorough vetting of drone providers' capabilities during the selection process, (3) using and strengthening local capacity, (4) building in-country markets and businesses to maintain drone operations locally, (5) coordinating efforts among all stakeholders under government leadership, (6) implementing and identifying funding for long-term projects beyond pilots, and (7) evaluating impacts via standardised indicators. Sharing experiences and evidence from ongoing projects is needed to advance the use of drones for healthcare.

A cluster of multidrug-resistant Mycobacterium tuberculosis among patients arriving in Europe from the Horn of Africa: a molecular epidemiological study.

BACKGROUND: The risk of tuberculosis outbreaks among people fleeing hardship for refuge in Europe is heightened. We describe the cross-border European response to an outbreak of multidrug-resistant tuberculosis among patients from the Horn of Africa and Sudan. METHODS: On April 29 and May 30, 2016, the Swiss and German National Mycobacterial Reference Laboratories independently triggered an outbreak investigation after four patients were diagnosed with multidrug-resistant tuberculosis. In this molecular epidemiological study, we prospectively defined outbreak cases with 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) profiles; phenotypic resistance to isoniazid, rifampicin, ethambutol, pyrazinamide, and capreomycin; and corresponding drug resistance mutations. We whole-genome sequenced all Mycobacterium tuberculosis isolates and clustered them using a threshold of five single nucleotide polymorphisms (SNPs). We collated epidemiological data from host countries from the European Centre for Disease Prevention and Control. FINDINGS: Between Feb 12, 2016, and April 19, 2017, 29 patients were diagnosed with multidrug-resistant tuberculosis in seven European countries. All originated from the Horn of Africa or Sudan, with all isolates two SNPs or fewer apart. 22 (76%) patients reported their travel routes, with clear spatiotemporal overlap between routes. We identified a further 29 MIRU-VNTR-linked cases from the Horn of Africa that predated the outbreak, but all were more than five SNPs from the outbreak. However all 58 isolates shared a capreomycin resistance-associated tlyA mutation. INTERPRETATION: Our data suggest that source cases are linked to an M tuberculosis clone circulating in northern Somalia or Djibouti and that transmission probably occurred en route before arrival in Europe. We hypothesise that the shared mutation of tlyA is a drug resistance mutation and phylogenetic marker, the first of its kind in M tuberculosis sensu stricto. FUNDING: The Swiss Federal Office of Public Health, the University of Zurich, the Wellcome Trust, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), the Medical Research Council, BELTA-TBnet, the European Union, the German Center for Infection Research, and Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG).

Experience and lessons from health impact assessment guiding prevention and control of HIV/AIDS in a copper mine project, northwestern Zambia.

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.

School Children's Intestinal Parasite and Nutritional Status One Year after Complementary School Garden, Nutrition, Water, Sanitation, and Hygiene Interventions in Burkina Faso.

The potential health benefits of combined agricultural, nutrition, water, sanitation, and hygiene (WASH) interventions are poorly understood. We aimed to determine whether complementary school garden, nutrition, and WASH interventions reduce intestinal parasites and improve school children's nutritional status in two regions of Burkina Faso. A cluster-randomized controlled trial was conducted in the Plateau Central and Center-Ouest regions of Burkina Faso. A total of 360 randomly selected children, aged 8-15 years, had complete baseline and end-line survey data. Mixed regression models were used to assess the impact of the interventions, controlling for baseline characteristics. The prevalence of intestinal parasitic infections decreased both in intervention and control schools, but the decrease was significantly higher in the intervention schools related to the control schools (odds ratio [OR] of the intervention effect = 0.2, 95% confidence interval [CI] = 0.1-0.5). Indices of undernutrition did not decrease at end-line in intervention schools. Safe handwashing practices before eating and the use of latrines at schools were significantly higher in the intervention schools than in the control schools at end-line (OR = 6.9, 95% CI = 1.4-34.4, and OR = 14.9, 95% CI = 1.4-153.9, respectively). Parameters of water quality remained unchanged. A combination of agricultural, nutritional, and WASH-related interventions embedded in the social-ecological systems and delivered through the school platform improved several child health outcomes, including intestinal parasitic infections and some WASH-related behaviors. Sustained interventions with stronger household and community-based components are, however, needed to improve school children's health in the long-term.

Prevalence and risk factors of undernutrition among schoolchildren in the Plateau Central and Centre-Ouest regions of Burkina Faso.

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).

Monitoring of Selected Health Indicators in Children Living in a Copper Mine Development Area in Northwestern Zambia.

The epidemiology of malaria, anaemia and malnutrition in children is potentially altered in mining development areas. In a copper extraction project in northwestern Zambia, a health impact assessment (HIA) was commissioned to predict, manage and monitor health impacts. Two cross-sectional surveys were conducted: at baseline prior to project development (2011) and at four years into development (2015). Prevalence of Plasmodium falciparum, anaemia and stunting were assessed in under-five-year-old children, while hookworm infection was assessed in children aged 9-14 years in communities impacted and comparison communities not impacted by the project. P. falciparum prevalence was significantly higher in 2015 compared to 2011 in both impacted and comparison communities (odds ratio (OR) = 2.51 and OR = 6.97, respectively). Stunting was significantly lower in 2015 in impacted communities only (OR = 0.63). Anaemia was slightly lower in 2015 compared to baseline in both impacted and comparison communities. Resettlement due to the project and migration background (i.e., moving into the area within the past five years) were generally associated with better health outcomes in 2015. We conclude that repeated cross-sectional surveys to monitor health in communities impacted by projects should become an integral part of HIA to deepen the understanding of changing patterns of health and support implementation of setting-specific public health measures.