Background:Ivermectin is a widely used antiparasitic drug with over 5.9 billion treatments distributed through global programs by 2025, yet its safety during early pregnancy remains uncertain. Early animal studies suggested teratogenicity at doses several-fold higher than the ones used in humans. Inadvertent exposures during mass drug administration campaigns have not shown clear increase in risk of harms. We aim to describe the effect of inadvertent ivermectin exposure during the periconception period on the risk of adverse pregnancy outcomes. Methods:The BOHEMIA trials were open-label, assessor-blinded, cluster-randomized, controlled studies conducted in Mozambique and Kenya to assess the effect of three monthly rounds of 400 mcg/kg of ivermectin mass drug administration versus 400 mg fixed dose of albendazole on malaria transmission. The first implementation took place between mid-March and mid-June 2022 in Mopeia (Mozambique) and the second implementation occurred between October 2023 and December 2023 in Kwale (Kenya). A nested observational prospective cohort sub-study was conducted alongside the main trial to evaluate the safety of drug exposure around the time of conception. This sub-study included women aged 13-49 years who became pregnant between two weeks before and the four weeks following exposure to either ivermectin or albendazole and were excluded from further treatment and monitored monthly until the end of pregnancy. The primary study outcome was incidence of pregnancy outcomes, considering a positive pregnancy outcome all live births without any detectable major congenital anomalies, and adverse pregnancy outcomes defined as a composite of miscarriages, stillbirths, and congenital anomalies. The trial was registered on clinicaltrials.gov (NCT04966702) and on the Pan African Clinical Trial Registry (PACTR202106695877303). Findings:A total of 238 pregnant participants were enrolled in Mozambique and Kenya, 129/238 (54%) were potentially exposed to ivermectin and 109/238 (46%) to albendazole. Adverse pregnancy outcomes occurred in 24/105 (22.9%) women exposed to ivermectin and 15/77 (19.5%) women exposed to albendazole. Among the women with evaluable pregnancy outcomes, the odds of adverse pregnancy outcomes for ivermectin versus albendazole (OR = 1.22, 95% CI 0.59-2.50, p = 0.582) did not differ significantly between treatment arms. Interpretation:Among women exposed to ivermectin or albendazole between two weeks pre-conception and the first four weeks of pregnancy, this study found broad confidence intervals do not exclude a clinically meaningful difference in either direction. It does however add meaningful data to a small cumulative evidence base on inadvertent ivermectin exposure in early pregnancy, even if the number of exposures documented to date remains too small to support policy or regulatory conclusions. Funding:Unitaid.

BackgroundThe Lihir Islands of Papua New Guinea, located in an area with high burden of malaria and hosting a large mining operation, offer a unique opportunity to study transmission. There, we investigated human and vector factors influencing malaria transmission.MethodsIn 2019, a cross-sectional study was conducted on 2,914 individuals assessing malaria prevalence through rapid diagnostic tests (RDT), microscopy, and quantitative PCR (qPCR). A logistic regression analysis identified infection-associated factors. Anopheles species distribution, biting behaviours, and sporozoite carriage were assessed through human landing catches and larval surveys.ResultsOverall malaria prevalence (any species) was 3.6% by RDT, 4.5% by microscopy, and 15.0% by qPCR. P. vivax accounted for 37.1% of infections, P. falciparum for 34.6%, P. malariae for 3.0%, P. ovale 0.2%, and mixed infections for 24.5%. Prevalence (qPCR) varied across geographic areas, from 8.5% in the mine-impacted zone (MIZ) to 27.0% in the non-MIZ. Other factors independently associated with infection risk included cohabiting with an infected individual (aOR = 1.94, 95%CI: 1.56-2.42), and residing in traditional housing (aOR = 1.65, 95%CI: 1.21-2.25). Children had double the infection risk compared to adults, and the use of long-lasting insecticidal-treated nets did not decrease risk of infection. An. punctulatus was the major vector in one of the four geographical areas; while An. farauti was predominant in the rest of them, both with an early biting behaviour but with different biting intensities by geographical area. Entomological inoculation rates ranged from 26.9 (95%CI: 12.3-45.2) infective bites per person-year in the MIZ to 441.3 (95%CI: 315.7-572.1) in the non-MIZ.ConclusionsMalaria transmission and infection was lower in the MIZ compared to other areas. Measures focusing on at-risk groups, including vector-control and transmission interruption methods, could be taken into account by the mine and the healthcare authorities to reduce malaria burden outside the MIZ.

BACKGROUND:Ivermectin is an endectocide effective against scabies that is under evaluation as a malaria vector control tool. During the BOHEMIA malaria trial, we did a substudy with the aim of assessing the efficacy of ivermectin mass drug administration (MDA) against scabies. METHODS:The BOHEMIA trial was an open-label, assessor-masked, cluster-randomised trial done in a malaria and scabies co-endemic community in Mozambique. Clusters were randomised (1:1:1) to receive a single dose of either ivermectin 400 μg/kg to all eligible humans, 400 μg/kg to humans and 200 μg/kg to eligible livestock, or 400 mg albendazole in humans only (control) for 3 consecutive months. In this scabies substudy, 39 clusters were randomly selected from the main trial. The primary endpoint was scabies prevalence at 3 months. Secondary endpoints were scabies prevalence in directly exposed participants (those who took the study drug) at 1, 2, and 3 months, and indirectly exposed children younger than 5 years (who were living in clusters but did not take the study drug) at 3 and 6 months. An intention-to-treat analysis was done by use of a logistic regression model with a generalised estimating equation approach. This study is registered with ClinicalTrials.gov, NCT04966702, and on the Pan African Clinical Trial Registry, PACTR202106695877303, and is complete. FINDINGS:Recruitment started on March 15, 2022 and was completed on July 6, 2022. Of 40 524 participants from 100 clusters accessed in the BOHEMIA trial, 1951 participants were enrolled from 39 clusters (13 per group) in the scabies substudy. Scabies prevalence in the ivermectin group was lower after 3 months (2·11%, 95% CI 1·21-3·41) than at baseline (8·10%, 6·36-9·85), whereas it did not change in the albendazole group (13·71%, 10·81-17·05, at 3 months vs 12·30%, 9·43-15·17, at baseline). The odds of having scabies was lower in pooled ivermectin clusters than in albendazole clusters after 3 months (adjusted odds ratio [aOR] 0·18, 95% CI 0·07-0·45, p=0·0002). This effect was observed both in directly exposed participants who took ivermectin after 1 month (aOR 0·27, 95% CI 0·11-0·66, p=0·0023), 2 months (0·18, 0·07-0·47, p=0·0006), and 3 months (0·16, 0·06-0·45, p=0·0004), and in indirectly exposed children after 3 months (0·17, 0·05-0·58, p=0·0048) and 6 months (0·21, 0·06-0·72, p=0·013). There were two severe adverse events; both were deaths in the ivermectin group that were not considered related to the study drug. No safety signal was detected. INTERPRETATION:Ivermectin MDA designed for malaria might have significant benefits against scabies. In addition to directly exposed participants, our results also suggested an effect in indirectly exposed participants, which might reflect a community benefit. FUNDING:Unitaid.

Malaria presents a disproportionate threat to pregnant women, making access to malaria prevention tools crucial for controlling the disease in this vulnerable population. This prospective descriptive study targeted women of reproductive age (13–49 years old) living in the Mopeia district, a high malaria endemic area in Zambezia province, Mozambique. As part of the BOHEMIA cluster randomized trial, the study included a simplified and full census to collect data on socio-demographic, socio-economic and household factors, health status, and malaria prevention tools from the target population. Data from 7,099 women of reproductive age living in the BOHEMIA clinical trial study area was collected, including 497 (7.0

Headlice are prevalent worldwide, with a higher burden in rural, lower-middle income settings. They can cause intense itchiness, discomfort, and secondary bacterial infections with potentially serious consequences. Ivermectin is efficacious against headlice, and is also being evaluated as a malaria vector control tool. In this study, we explored risk factors for headlice, and assessed the efficacy of ivermectin mass drug administration (MDA) designed for malaria against headlice. We conducted an open-label, assessor-blind, cluster-randomized controlled trial in Mopeia, Mozambique. A single dose of ivermectin was given monthly to eligible humans or humans and livestock (humans: 400 μg/kg, livestock: 1

Background:Endectocides are a novel vector control tool that reduce the survival and fertility of blood sucking arthropods that feed upon treated humans or animals. Ivermectin mass drug administration is under evaluation as a complementary strategy for malaria vector control. The BOHEMIA consortium conducted two cluster-randomized trials, one in Mozambique, reported here and one in Kenya, reported elsewhere. Methods:The trial was conducted in Mopeia, a highly endemic district in Zambezia province, with perennial transmission and over 70% coverage of both indoor residual spraying and long-lasting insecticidal nets. As per protocol, we planned to randomise 53 clusters per arm (1:1:1), to receive either (a) single 400 mcg/kg dose of ivermectin to all eligible humans, once a month for three months, (b) the same ivermectin treatment to eligible humans plus injectable ivermectin (1% solution) to all eligible pigs (300 mcg/kg) and cattle (200 mcg/kg) in the cluster once a month for three months or (c) albendazole (400 mg), to serve as control, to eligible humans, following the same schedule. The primary efficacy outcome was malaria incidence of infections determined by RDT in a cohort of children under five years that was followed monthly for six months starting with the first mass drug administration round. Dual HRP-2 and pLDH rapid diagnostic tests were used in an attempt to discriminate incident infections. The rate of adverse events was captured in all treated individuals. The analysis was done using generalized estimating equations following intention-to-treat. Findings:Before the start of mass drug administration, the study site experience floods caused by the Gombe cyclone, resulting in severe logistical constrains and the loss of 57 clusters. We present a complete case analysis of the remaining clusters. The study ran between march 17 and October 18, 2022. Overall, a total of 22,724 participants from a reduced number of 100 clusters were enrolled. Six months after the first treatment round, the malaria infection incidence was comparable between all three arms with adjusted incidence rate ratio values of 0.99 (95% CI, 0.86-1.14, P > 0.9) and 1.05 (95% CI, 0.87-1.27, P = 0.6) between the human-only and control group and the human and livestock and control group respectively. The rate of severe adverse events per 10,000 treatments was not significantly different between the combined ivermectin arms and the control (IRR = 1.29; 95% CI 0.62-2.68). Interpretation:This trial did not meet implementation goals due to operational challenges including low coverage, displaced populations and delayed start of drug distribution which render the efficacy data inconclusive. However, important aspects regarding the action of endectocides at community level which could be key for implementation are described. Additionally, valuable data regarding safety were collected (ClinicalTrials.gov number, NCT04966702). Funding:The study was funded and supported by Unitaid under the "BOHEMIA" grant.

BACKGROUND:Malaria control and elimination is threatened by the spread of insecticide resistance and behavioral adaptation of vectors. Whether mass administration of ivermectin, a broad-spectrum antiparasitic drug that also kills mosquitoes feeding on treated persons, can reduce malaria transmission is unclear. METHODS:We conducted a cluster-randomized trial in Kwale, a county in coastal Kenya in which malaria is highly endemic and coverage and use of insecticide-treated nets are high. Clusters of household areas were randomly assigned in a 1:1 ratio to receive mass administration of ivermectin (400 μg per kilogram of body weight) or albendazole (400 mg, active control) once a month for 3 consecutive months at the beginning of the "short rains" season. Children 5 to 15 years of age were tested for malaria infection monthly for 6 months after the first round of treatment. The two primary outcomes were the cumulative incidence of malaria infection (assessed among children 5 to 15 years of age) and of adverse events (assessed among all eligible participants). Analyses were performed with generalized estimating equations in accordance with the intention-to-treat principle. RESULTS:A total of 84 clusters comprising 28,932 eligible participants underwent randomization. The baseline characteristics of the participants were similar in the trial groups. Six months after the first round of treatment, the incidence of malaria infection was 2.20 per child-year at risk in the ivermectin group and 2.66 per child-year at risk in the albendazole group; the adjusted incidence rate ratio (ivermectin vs. albendazole) was 0.74 (95% confidence interval [CI], 0.58 to 0.95, P = 0.02). The incidence of serious adverse events per 100 treatments did not differ significantly between the trial groups (incidence rate ratio, 0.63; 95% CI, 0.21 to 1.91). CONCLUSIONS:Among children 5 to 15 years of age who were living in an area with high coverage and use of bed nets, ivermectin, administered once a month for 3 consecutive months, resulted in a 26% lower incidence of malaria infection than albendazole. No safety concerns were identified. (Funded by Unitaid; BOHEMIA ClinicalTrials.gov number, NCT04966702; Pan African Clinical Trial Registry number, PACTR202106695877303.).

BACKGROUND:Vertical transmission of Trypanosoma cruzi represents approximately 20% of new Chagas disease cases. Early detection and treatment for women of childbearing age and newborns is a public health priority, but the lack of a simple and reliable diagnostic test remains a major barrier. We aimed to evaluate the performance of a point-of-care loop-mediated isothermal amplification (LAMP) assay for the detection of T cruzi. METHODS:In this proof-of-concept study, we coupled a low-cost 3D printer repurposed for sample preparation and amplification (PrintrLab) to the Eiken T cruzi-LAMP prototype to detect vertically transmitted T cruzi, which we compared with standardised PCR and with the gold-standard algorithm (microscopy at birth and 2 months and serological study several months later). We screened pregnant women from two hospitals in the Bolivian Gran Chaco province, and those who were seropositive for T cruzi were offered the opportunity for their newborns to be enrolled in the study. Newborns were tested by microscopy, LAMP, and PCR at birth and 2 months, and by serology at 8 months. FINDINGS:Between April 23 and Nov 17, 2018, 986 mothers were screened, among whom 276 were seropositive for T cruzi (28·0% prevalence, 95% CI 25·6-31·2). In total, 224 infants born to 221 seropositive mothers completed 8 months of follow-up. Congenital transmission was detected in nine of the 224 newborns (4·0% prevalence, 1·9-7·5) by direct microscopy observation, and 14 more cases were diagnosed serologically (6·3%, 3·6-10·3), accounting for an overall vertical transmission rate of 10·3% (6·6-15·0; 23 of 224). All microscopy-positive newborns were positive by PrintrLab-LAMP and by PCR, while these techniques respectively detected four and five extra positive cases among the remaining 215 microscopy-negative newborns. INTERPRETATION:The PrintrLab-LAMP yielded a higher sensitivity than microscopy-based analysis. Considering the simpler use and expected lower cost of LAMP compared with PCR, our findings encourage its evaluation in a larger study over a wider geographical area. FUNDING:Inter-American Development Bank.

Background:Migrants are disproportionately affected by several infectious diseases differing the risk within migrant groups. This study aimed to estimate the prevalence of six chronic infections in asymptomatic migrants attended at primary care or specialized units where health assessments are offered. Methods:A multicentric cross-sectional study was conducted to estimate the prevalence of human immunodeficiency virus (HIV), hepatitis B and C virus, Strongyloides stercoralis, Schistosoma spp., and Trypanosoma cruzi infections in the migrant population who participated in a screening programme implemented at six primary health care centres, and two infectious diseases outpatient clinics in Catalonia, Spain. Results:Of the 314 recruited migrants, 284 (90.4 %) were tested for at least one infection. The prevalence of the infections was as follows: 1.8 % for HIV, 1.8 % for chronic hepatitis B virus, 14.1 % for previous exposure to a hepatitis B virus infection, 0.4 % for hepatitis C virus infection, 2.6 % for S.stercoralis infection, and 7.0 % for T.cruzi infection. No cases infected with Schistosoma spp. were reported. A higher prevalence of HIV, hepatitis B and C virus was observed in Sub-Saharan Africans, whereas a higher prevalence of S.stercoralis and T.cruzi infections was reported in migrants from Latin-America and the Caribbean. Conclusion:Findings suggest a high burden of the studied infections, including parasitic infections, in the migrant population with variations within migrant groups based on areas of birth.

Objectives: We aimed to evaluate the epidemiology of seven infections (Chagas disease, strongyloidiasis, schistosomiasis, human immunodeficiency virus, hepatitis B and C virus, and active tuberculosis) in migrant populations attended at primary care facilities in Catalonia, Spain. Methods: This is a cross sectional study conducted from March to December 2018 at eight primary care centres in Catalonia, Spain where health professionals were recommended to systematically screen multiple infections in migrants considering the endemicity of the pathogens in their country of birth. Routine health data were retrospectively extracted from electronic health records of the primary care centres. The proportion of cases among individuals tested for each infection was estimated with its 95% confident interval (CI). Mixed-effects logistics regression models were conducted to assess any possible association between the exposure variables and the primary outcome. Results: Out of the 15,780 migrants that attended primary care centres, 2410 individuals were tested for at least one infection. Of the 508 (21.1%) migrants diagnosed with at least one condition, a higher proportion originated from Sub-Saharan Africa (207, 40.7%), followed by South-East Europe (117, 23.0%) and Latin-America (88, 17.3%; p value <0.001). The proportion of migrants diagnosed with Chagas disease was 5/122 (4.1%, 95%CI 0.5-7.7), for strongyloidiasis 56/409 (13.7%, 95%CI 10.3-17.0) and for schistosomiasis 2/101 (2.0%, 95%CI 0.0-4.7) with very few cases tested. The estimated proportion for human immunodeficiency virus was 67/1176 (5.7%, 95%CI 4.4-7.0); 377/1478 (25.5%, 95%CI 23.3-27.7) for hepatitis B virus, with 108/1478 (7.3%, 95%CI 6.0-8.6) of them presenting an active infection, while 31/1433 (2.2%, 95%CI 1.4-2.9) were diagnosed with hepatitis C virus. One case of active tuberculosis was diagnosed after testing 172 migrant patients (0.6%, 95%CI 0.0-1.7). Conclusions: We estimated a high proportion of the studied infections in migrants from endemic areas. Country-specific estimations of the burden of infections in migrants are fundamental for the implementation of preventive interventions.

IntroductionISMiHealth is a clinical decision support system, integrated as a software tool in the electronic health record system of primary care, that aims to improve the screening performance on infectious diseases and female genital mutilation (FGM) in migrants. The aim of this study is to assess the health impact of the tool and to perform a process evaluation of its feasibility and acceptability when implemented in primary care in Catalonia (Spain).Methods and analysisThis study is a cluster randomised control trial where 35 primary care centres in Catalonia, Spain will be allocated into one of the two groups: intervention and control. The health professionals in the intervention centres will receive prompts, through the ISMiHealth software, with screening recommendations for infectious diseases and FGM targeting the migrant population based on an individualised risk assessment. Health professionals of the control centres will follow the current routine practice.A difference in differences analysis of the diagnostic rates for all aggregated infections and each individual condition between the intervention and control centres will be performed. Mixed-effects logistic regression models will be carried out to identify associations between the screening coverage and predictor factors. In addition, a process evaluation will be carried out using mixed methodology.Ethics and disseminationThe study protocol has been approved by the institutional review boards at Hospital Clínic (16 June 2022, HCB/2022/0363), Clinical Research Ethics Committee of the Primary Care Research Institute IDIAPJGol (22 June 2022, 22/113-P) and the Almería Research Ethics Committee (27 July 2022, EMC/apg). The study will follow the tenets of the Declaration of Helsinki and Good Clinical Practice. All researchers and associates signed a collaboration agreement in which they undertake to abide by good clinical practice standards.Findings will be disseminated in peer-reviewed journals and communications to congresses.Trial registration numberNCT05868005.

Background Headlice are prevalent worldwide, with a higher burden in rural, lower-middle income settings. They can cause intense itchiness, discomfort, and secondary bacterial infections with potentially serious consequences. Ivermectin is known to be efficacious against headlice, and is also currently being evaluated as a malaria vector control tool. In this study, we explored risk factors for headlice, and assessed the efficacy of ivermectin mass drug administration designed for malaria against headlice. Methods We conducted an open-label, assessor-blind, cluster-randomized controlled trial in Mopeia, Mozambique. A single dose of ivermectin was given monthly to eligible humans or humans and livestock (humans: 400 ug/kg, livestock: 1% injectable 200 ug/kg) in 3 consecutive months during the rainy season. The control group received albendazole (humans only). 39 clusters (13 per arm) were randomly selected for the nested assessment of headlice prevalence. 1,341 treated participants were followed up at, 1, 2 and 3 months and 382 untreated (ineligible) participants at 3 and 6 months after baseline. Headlice diagnosis was determined by examination of the scalp. Logistic regression was used to identify risk factors for headlice at baseline, and to estimate the treatment effect at each time point. This study is registered with ClinicalTrials.gov (NCT04966702). Results The baseline prevalence of headlice was 11%. Risk factors included living with a household member with head itch, being female, and living with poor water and sanitation facilities. The treated population receiving ivermectin had significantly lower odds of having headlice at 3 months compared to those receiving albendazole (aOR 0.22 95%CI 0.05–0.89). There was no indirect effect on headlice among ineligible children. Conclusion In a highly endemic setting, mass drug administration with ivermectin significantly reduces headlice infestation prevalence among those who receive the drug for three sequential months. The lack of effect among untreated, ineligible children implies that additional interventions would be needed to interrupt local transmission.

INTRODUCTION:The wealth index is widely used as a proxy for a household's socioeconomic position (SEP) and living standard. This work constructs a wealth index for the Mopeia district in Mozambique using data collected in year 2021 under the BOHEMIA (Broad One Health Endectocide-based Malaria Intervention in Africa) project.METHODS:We evaluate the performance of three alternative approaches against the Demographic and Health Survey (DHS) method based wealth index: feature selection principal components analysis (PCA), sparse PCA and robust PCA. The internal coherence between four wealth indices is investigated through statistical testing. Validation and an evaluation of the stability of the wealth index are performed with additional household income data from the BOHEMIA Health Economics Survey and the 2018 Malaria Indicator Survey data in Mozambique.RESULTS:The Spearman's rank correlation between wealth index ventiles from four methods is over 0.98, indicating a high consistency in results across methods. Wealth rankings and households' income show a strong concordance with the area under the curve value of ~0.7 in the receiver operating characteristic analysis. The agreement between the alternative wealth indices and the DHS wealth index demonstrates the stability in rankings from the alternative methods.CONCLUSIONS:This study creates a wealth index for Mopeia, Mozambique, and shows that DHS method based wealth index is an appropriate proxy for the SEP in low-income regions. However, this research recommends feature selection PCA over the DHS method since it uses fewer asset indicators and constructs a high-quality wealth index.

Background Many geographical areas of sub-Saharan Africa, especially in rural settings, lack complete and up-to-date demographic data, posing a challenge for implementation and evaluation of public health interventions and carrying out large-scale health research. A demographic survey was completed in Mopeia district, located in the Zambezia province in Mozambique, to inform the Broad One Health Endectocide-based Malaria Intervention in Africa (BOHEMIA) cluster randomized clinical trial, which tested ivermectin mass drug administration to humans and/or livestock as a potential novel strategy to decrease malaria transmission. Methods The demographic survey was a prospective descriptive study, which collected data of all the households in the district that accepted to participate. Households were mapped through geolocation and identified with a unique identification number. Basic demographic data of the household members was collected and each person received a permanent identification number for the study. Results 25,550 households were mapped and underwent the demographic survey, and 131,818 individuals were registered in the district . The average household size was 5 members and 76.9% of households identified a male household head. Housing conditions are often substandard with low access to improved water systems and electricity. The reported coverage of malaria interventions was 71.1% for indoor residual spraying and 54.1% for universal coverage of long-lasting insecticidal nets. The median age of the population was 15 years old. There were 910 deaths in the previous 12 months reported, and 43.9% were of children less than 5 years of age. Conclusions The study showed that the district had good coverage of vector control tools against malaria but sub-optimal living conditions and poor access to basic services. The majority of households are led by males and Mopeia Sede/Cuacua is the most populated locality in the district. The population of Mopeia is young (< 15 years) and there is a high childhood mortality. The results of this survey were crucial as they provided the household and population profiles and allowed the design and implementation of the cluster randomized clinical trial. Trial registration NCT04966702.

BACKGROUND:Chagas disease, caused by the parasite Trypanosoma cruzi, is a neglected infectious disease that exerts the highest public health burden in the Americas. There are two anti-parasitic drugs approved for its treatment-benznidazole and nifurtimox-but the absence of biomarkers to early assess treatment efficacy hinders patients´ follow-up.METHODOLOGY/PRINCIPAL FINDINGS:We conducted a longitudinal, observational study among a cohort of 106 chronically T. cruzi-infected patients in Cochabamba (Bolivia) who completed the recommended treatment of benznidazole. Participants were followed-up for five years, in which we collected clinical and serological data, including yearly electrocardiograms and optical density readouts from two ELISAs (total and recombinant antigens). Descriptive and statistical analyses were performed to understand trends in data, as well as the relationship between clinical symptoms and serological evolution after treatment. Our results showed that both ELISAs documented average declines up to year three and slight inclines for the following two years. The recorded clinical parameters indicated that most patients did not have any significant changes to their cardiac or digestive symptoms after treatment, at least in the timeframe under investigation, while a small percentage demonstrated either a regression or progression in symptoms. Only one participant met the "cure criterion" of a negative serological readout for both ELISAs by the final year.CONCLUSIONS/SIGNIFICANCE:The study confirms that follow-up of benznidazole-treated T. cruzi-infected patients should be longer than five years to determine, with current tools, if they are cured. In terms of serological evolution, the single use of a total antigen ELISA might be a more reliable measure and suffice to address infection status, at least in the region of Bolivia where the study was done. Additional work is needed to develop a test-of-cure for an early assessment of drugs´ efficacy with the aim of improving case management protocols.

Background Snakebite is a neglected disease that disproportionally affects the rural poor. There is a dearth of evidence regarding incidence and risk factors in snakebite-endemic countries. Without this basic data, it will be impossible to achieve the target of a 50% reduction of snakebite morbidity and mortality by 2030 as set by the World Health Organization. Methods This was a descriptive analysis nested in a 2021 community-based demographic survey of over 70,000 individuals conducted in Mopeia, Mozambique, in preparation for a cluster randomized trial to test an intervention for malaria. We describe the incidence rate, demographics, socioeconomic indicators and outcomes of snakebite in this population. Findings We found the incidence of self-reported snakebite in Mopeia to be 393 bites per 100,000 person-years at risk, with 2% of households affected in the preceding 12 months. Whilst no fatalities were recorded, over 3,000 days of work or school days were lost with an individual household economic impact higher than that of uncomplicated malaria. 1 in 6 of those affected did not fully recover at the time of the study. We found significant relationships between age older than 15, use of firewood for household fuel, and animal possession with snakebite. Conclusions This study exposes higher than expected incidence and burden of snakebite in rural Mozambique. Whilst snakebite elimination in Mozambique seems unattainable today, it remains a preventable disease with manageable sequelae. We have shown that snakebite research is particularly easy to nest in larger studies, making this a practical and cost-effective way of estimating its incidence.

Background Residual malaria transmission is the result of adaptive mosquito behavior that allows malaria vectors to thrive and sustain transmission in the presence of good access to bed nets or insecticide residual spraying. These behaviors include crepuscular and outdoor feeding as well as intermittent feeding upon livestock. Ivermectin is a broadly used antiparasitic drug that kills mosquitoes feeding on a treated subject for a dose-dependent period. Mass drug administration with ivermectin has been proposed as a complementary strategy to reduce malaria transmission. Methods A cluster randomized, parallel arm, superiority trial conducted in two settings with distinct eco-epidemiological conditions in East and Southern Africa. There will be three groups: human intervention, consisting of a dose of ivermectin (400 mcg/kg) administered monthly for 3 months to all the eligible population in the cluster (>15 kg, non-pregnant and no medical contraindication); human and livestock intervention, consisting human treatment as above plus treatment of livestock in the area with a single dose of injectable ivermectin (200 mcg/kg) monthly for 3 months; and controls, consisting of a dose of albendazole (400 mg) monthly for 3 months. The main outcome measure will be malaria incidence in a cohort of children under five living in the core of each cluster followed prospectively with monthly RDTs Discussion The second site for the implementation of this protocol has changed from Tanzania to Kenya. This summary presents the Mozambique-specific protocol while the updated master protocol and the adapted Kenya-specific protocol undergo national approval in Kenya. BOHEMIA will be the first large-scale trial evaluating the impact of ivermectin-only mass drug administration to humans or humans and cattle on local malaria transmission Trial registration ClinicalTrials.gov NCT04966702 . Registered on July 19, 2021. Pan African Clinical Trials Registry PACTR202106695877303.

Background: Migrants in host countries are at risk for the development of mental health conditions. The two aims of the study were to describe routine diagnoses of mental disorders among migrant patients at primary healthcare level and the associated risk factors, and to test the utility of an innovative migrant mental health assessment by evaluating whether the health professionals followed the recommendations proposed by the clinical decision support system (CDSS) tool.Methods: A cross-sectional study was carried out in eight primary care centres (PCCs) in four non-randomly selected health regions of Catalonia, Spain from March to December 2018. Routine health data and mental health diagnoses based on the International Classification of Diseases (10th edition), including mental, behavioural and neuro developmental disorders (F01-F99), symptoms and signs involving emotional state (R45), and sleep disorders (G47), were extracted from the electronic health records. The proportion of mental health conditions was estimated and logistic regression models were used to assess any possible association with mental health disorders. The utility of the mental health assessment was assessed with the proportion of questionnaires performed by health professionals for migrants fulfilling the mental health screening criterion (country of origin with an active conflict in 2017) and the diagnoses given to the screened patients. Results: Of 14,130 migrants that visited any of the PCCs during the study period, 7,358 (52.1 %) were women with a median age of 38.0 years-old. There were 520/14,130 (3.7 %) migrant patients diagnosed with a mental disorder, being more frequent among women (342/7,358; 4.7 %, p-value < 0.001), migrants from Latin-America (177/3,483; 5.1 %, p < 0.001) and those who recently arrived in Spain (170/3,672; 4.6 %, p < 0.001). A lower proportion of mental disorders were reported in migrants coming from conflicted countries in 2017 (116/3,669, 3.2 %, p = 0.053).Out of the 547 mental health diagnoses reported in 520 patients, 69/14,130 (0.5 %) were mood disorders, 346/ 14,130 (2.5 %) anxiety disorders and 127/14,130 (0.9 %) sleeping disorders. Mood disorders were more common in migrants from Eastern Europe (25/2,971; 0.8 %, p < 0.001) and anxiety disorders in migrants from Latin -America (126/3,483; 3.6 %, p < 0.001), while both type of disorders were more often reported in women (p < 0.001).In the adjusted model, women (aOR: 1.5, [95 % CI 1.2-1.8, p < 0.001]), migrants with more than one visit to the health center during the study period (aOR: 4.4, [95 %CI 2.8-6.8, p < 0.001]) and who presented an infectious disease (aOR: 2.1, [95 %CI 1.5-3.1, p < 0.001]) had higher odds of having a mental disorder. Lastly, out of the 1,840 migrants coming from a conflicted country in 2017 who were attended in centres where the CDSS tool was implemented, 29 (1.6 %) had a mental health assessment performed and the tool correctly identified one individual.Conclusions: Mental health is a condition that may be overlooked in migrants at primary healthcare. Interventions at this level of care must be reinforced and adapted to the needs and circumstances of migrants to ensure equity in health services.

BACKGROUND:Trypanosoma cruzi causes Chagas disease (CD), a potentially fatal disease characterized by cardiac disorders and digestive, neurological or mixed alterations. T. cruzi is transmitted to humans by the bite of triatomine vectors; both the parasite and disease are endemic in Latin America and the United States. In the last decades, population migration has changed the classic epidemiology of T. cruzi, contributing to its global spread to traditionally non-endemic countries. Screening is recommended for Latin American populations residing in non-endemic countries. METHODS:The present study analyzes the epidemiological characteristics of 2,820 Latin American individuals who attended the International Health Service (IHS) of the Hospital Clinic de Barcelona between 2002 and 2019. The initial assessment of organ damage among positive cases of T. cruzi infection was analyzed, including the results of electrocardiogram (ECG), echocardiogram, barium enema and esophagogram. RESULTS:Among all the screened individuals attending the clinic, 2,441 (86.6%) were born in Bolivia and 1,993 (70.7%) were female. Of individuals, 1,517 (81.5%) reported previous exposure to the vector, which is a strong risk factor associated with T. cruzi infection; 1,382 individuals were positive for T. cruzi infection. The first evaluation of individuals with confirmed T. cruzi infection, showed 148 (17.1%) individuals with Chagasic cardiomyopathy, the main diagnostic method being an ECG and the right bundle branch block (RBBB) for the most frequent disorder; 16 (10.8%) individuals had a normal ECG and were diagnosed of Chagasic cardiomyopathy by echocardiogram. CONCLUSIONS:We still observe many Latin American individuals who were at risk of T. cruzi infection in highly endemic areas in their countries of origin, and who have not been previously tested for T. cruzi infection. In fact, even in Spain, a country with one of the highest proportion of diagnosis of Latin American populations, T. cruzi infection remains underdiagnosed. The screening of Latin American populations presenting with a similar profile as reported here should be promoted. ECG is considered necessary to assess Chagasic cardiomyopathy in positive individuals, but echocardiograms should also be considered as a diagnostic approach given that it can detect cardiac abnormalities when the ECG is normal.