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Abstract Background Malaria remains the leading cause of mortality and morbidity in young children in sub-Saharan Africa. To prevent malaria in children living in moderate-to-high malaria transmission areas, the World Health Organization has recommended perennial malaria chemoprevention (PMC). Prior to piloting PMC implementation in southern Togo, a household survey was conducted to estimate malaria infection prevalence in children under 2 years of age (U2). Methods A cross-sectional community-based household survey was conducted in the Haho district in the Togo Plateaux region. A three-stage random sampling method was used to select study participants aged 10–23 months whose caretakers gave informed consent. The prevalence of Plasmodium infection, defined as a positive rapid diagnostic test (RDT), was estimated with 95% confidence interval (CI). Clinical malaria was defined as having a positive RDT plus fever (≥ 37.5 °C) or history of fever in the last 24 h. Mixed-effects logistic regression models were used to assess the child’s, caretaker’s, and household’s factors associated with malaria infection. Results A total of 685 children were included in the survey conducted January–February in 2022 (dry season). Median age was 17 months (interquartile range: 13–21). About 80% of the children slept under a bed net the night before the interview. Malaria infection prevalence was 32.1% (95% CI 27.7–37.0) with significant area variation (cluster range: 0.0–73.3). Prevalence of clinical malaria was 15.4% (95% CI 12.2–19.2). Children whose caretakers were animist (aOR: 1.71, 95% CI 1.19–2.46) and those living in mother-headed households (aOR: 2.39, 95% CI 1.43–3.99) were more likely to have a positive RDT. Living more than 5 km away from the nearest health facility (aOR: 1.60, 95% CI 1.04–2.44) and presence of two or more under-5-years children in the household (aOR: 1.44, 95% CI 1.01–2.07) were also associated with increased risk of infection. Conclusion One-third of the children U2 who participated in this survey had malaria infection, thus PMC could be a promising strategy to reduce malaria burden in young children in Plateaux region. Reinforcement of outreach services and targeting the poorest households should be prioritized to reduce the inequity in malaria prevention in children exposed to the infection.

Abstract Background The importation of parasites across borders remains a threat to malaria elimination. The Southern African Development Community Malaria Elimination Eight (E8) established 39 border health facilities on 5 key international borders between high and low-burden countries. These clinics aimed to improve access to prevention, diagnosis, and treatment of malaria for residents in border areas and for mobile and migrant populations who frequently cross borders. Studies were conducted in each of the four high-burden E8 countries (Angola, Mozambique, Zambia, and Zimbabwe) to evaluate malaria services in border areas. Methods Cross-sectional surveys were conducted within 30 km of recently established E8 Border Health Posts. Structured questionnaires were administered to randomly selected respondents to assess malaria-related knowledge and behavior, access to malaria prevention, diagnosis and treatment of malaria, and risk factors for malaria associated with local and cross-border travel. Results Results showed that most providers followed appropriate guidelines performing blood tests when individuals presented with fever, and that nearly all those who reported a positive blood test received medication. Lack of access to health care due to distance, cost or mistrust of the provider was rare. A minority of respondents reported not receiving timely diagnosis either because they did not seek help, or because they were not offered a blood test when presenting with fever. There was a high level of correct knowledge of causes, symptoms, and prevention of malaria. A majority, of border residents had access to primary prevention against malaria through either long-lasting insecticidal nets (LLINs) or indoor residual spraying (IRS). Cross border travel was common with travellers reporting sleeping outside without protection against malaria. Conclusions The study demonstrated the importance of border health facilities in providing access to malaria services. Prevention needs to be improved for people who travel and sleep outdoors. Community health workers can play a key role in providing access to information, testing and treating malaria.

Abstract 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 (

Abstract Mozambique is one of the four African countries which account for over half of all malaria deaths worldwide, yet little is known about the parasite genetic structure in that country. We performed P. falciparum amplicon and whole genome sequencing on 2251 malaria-infected blood samples collected in 2015 and 2018 in seven provinces of Mozambique to genotype antimalarial resistance markers and interrogate parasite population structure using genome-wide microhaplotyes. Here we show that the only resistance-associated markers observed at frequencies above 5% were pfmdr1-184F (59%), pfdhfr-51I/59 R/108 N (99%) and pfdhps-437G/540E (89%). The frequency of pfdhfr/pfdhps quintuple mutants associated with sulfadoxine-pyrimethamine resistance increased from 80% in 2015 to 89% in 2018 (p

Abstract Background Intermittent Preventive Treatment of malaria in infants (IPTi) is a malaria control strategy consisting of the administration of an anti-malarial drug alongside routine immunizations. So far, this is being implemented nationwide in Sierra Leone only. IPTi has been renamed as Perennial Malaria Chemoprevention -PMC-, accounting for its recently recommended expansion into the second year of life. Before starting a pilot implementation on PMC, the currently implemented strategy and malaria prevalence were assessed in young children in selected areas of Sierra Leone. Methods A cross-sectional, community-based, multi-stage cluster household survey was conducted from November to December 2021 in selected districts of the Northern and northwestern provinces of Sierra Leone among 10–23 months old children, whose caretakers gave written informed consent to participate in the survey. Coverage of IPTi and malaria prevalence—assessed with rapid diagnostic tests—were calculated using percentages and 95% confidence intervals weighted for the sampling design and adjusted for non-response within clusters. Factors associated with RDT + and iPTi coverage were also assessed. Results A total of 720 children were recruited. Coverage of three IPTi doses was 50.57% (368/707; 95% CI 45.38–55.75), while prevalence of malaria infection was 28.19% (95% CI 24.81–31.84). Most children had received IPTi1 (80.26%, 574/707; 95% CI 75.30–84.44), and IPTi2 (80.09%, 577/707; 95% CI 76.30–83.40) and over half of the children also received IPTi3 (57.72%, 420/707; 95% CI 53.20–62.11). The uptake of each IPTi dose was lower than that of the vaccines administered at the same timepoint at all contacts. Conclusion In Sierra Leone, half of the children received the three recommended doses of IPTi indicating an increase in its uptake compared to previous data of just a third of children receiving the intervention. However, efforts need to be made in improving IPTi coverage, especially in the planned expansion of the strategy into the second year of life following recent WHO guidelines.

Abstract 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.

BackgroundSnakebite 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.MethodsThis 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.FindingsWe 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.ConclusionsThis 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.

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.

Estimating the effectiveness of malaria vector control interventions has typically relied on resource-intensive cluster randomised trials. Here, the authors estimate changes in malaria prevalence using entomological data from experimental hut trials, which may provide an alternative route to approval of interventions in some situations.

Introduction Pregnant women are currently considered a vulnerable population to SARS-CoV-2 infection, with increased risk of severe COVID-19, preterm birth and maternal mortality. There is, however, a paucity of data on the burden of maternal SARS-CoV-2 infection in sub-Saharan countries. The objective of this study is to determine the prevalence and health effects of maternal SARS-CoV-2 infection in selected sites from Gabon and Mozambique.Methods and analysis MA-CoV (MAternal CoVid) is an observational, multicentre prospective cohort study where 1000 pregnant women (500 per country) will be enrolled at the antenatal clinic visits. Participants will undergo monthly follow-up at each antenatal care visit, delivery and postpartum visit. The primary study outcome is the prevalence of SARS-CoV-2 infection during pregnancy. The clinical presentation of COVID-19 in pregnancy will also be characterised, and incidence of infection during pregnancy will be evaluated, as well as the risk factors of maternal and neonatal morbidity and mortality associated with SARS-CoV-2 infection and the risk of mother to child transmission of SARS-CoV-2. SARS-CoV-2 infection screening will be performed through PCR diagnosis.Ethics and dissemination The protocol was reviewed and approved by the Comité National d’Éthique pour la Recherche au Gabon, Comité Nacional de Bioética para Saúde de Moçambique and the Ethics Committee of the Hospital Clinic of Barcelona (Spain). Project results will be presented to all stakeholders and published in open access journals.Trial registration number NCT05303168.

Abstract Background Impact evaluation of most water, sanitation and hygiene (WASH) interventions in health are user-centered. However, recent research discussed WASH herd protection – community WASH coverage could protect neighboring households. We evaluated the effect of water and sanitation used in the household and by household neighbors in children’s morbidity and mortality using recorded health data. Methods We conducted a retrospective cohort including 61,333 children from a district in Mozambique during 2012–2015. We obtained water and sanitation household data and morbidity data from Manhiça Health Research Centre surveillance system. To evaluate herd protection, we estimated the density of household neighbors with improved facilities using a Kernel Density Estimator. We fitted negative binomial adjusted regression models to assess the minimum children-based incidence rates for every morbidity indicator, and Cox regression models for mortality. Results Household use of unimproved water and sanitation displayed a higher rate of outpatient visit, diarrhea, malaria, and anemia. Households with unimproved water and sanitation surrounded by neighbors with improved water and sanitation high coverage were associated with a lower rate of outpatient visit, malaria, anemia, and malnutrition. Conclusion Household and neighbors’ access to improve water and sanitation can affect children’s health. Accounting for household WASH and herd protection in interventions’ evaluation could foster stakeholders’ investment and improve WASH related diseases control. Graphical Abstract Distribution of main water and sanitation facilities used during study period.

BackgroundSeasonal malaria chemoprevention (SMC) is a highly effective community-based intervention to prevent malaria infections in areas where the malaria burden is high and transmission occurs mainly during the rainy season. In Africa, so far, SMC has been implemented in the Sahel region. Mozambique contributes 4% of the global malaria cases, and malaria is responsible for one-quarter of all deaths in the country. Based on recommendations in the Malaria Strategic Plan, the Malaria Consortium, in partnership with the National Malaria Control Programme in Mozambique, initiated a phased SMC implementation study in the northern province of Nampula. The first phase of this 2-year implementation study was conducted in 2020-2021 and focused on the feasibility and acceptability of SMC. The second phase will focus on demonstrating impact. This paper describes phase 2 of the implementation study. ObjectiveSpecific objectives include the following: (1) to determine the effectiveness of SMC in terms of its reduction in incidence of malaria infection among children aged 3 to 59 months; (2) to determine the chemoprevention efficacy of sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ) when used for SMC in Nampula Province, Mozambique, and the extent to which efficacy is impacted by drug resistance and drug concentrations; (3) to investigate the presence and change in SP+AQ– and piperaquine-resistance markers over time as a result of SMC implementation; and (4) to understand the impact of the SMC implementation model, determining the process and acceptability outcomes for the intervention. MethodsThis type 2, hybrid, effectiveness-implementation study uses a convergent mixed methods approach. SMC will be implemented in four monthly cycles between December 2021 and March 2022 in four districts of Nampula Province. Phase 2 will include four components: (1) a cluster randomized controlled trial to establish confirmed malaria cases, (2) a prospective cohort to determine the chemoprevention efficacy of the antimalarials used for SMC and whether drug concentrations or resistance influence the duration of protection, (3) a resistance marker study in children aged 3 to 59 months to describe changes in resistance marker prevalence over time, and (4) a process evaluation to determine feasibility and acceptability of SMC. ResultsData collection began in mid-January 2022, and data analysis is expected to be completed by October 2022. ConclusionsThis is the first effectiveness trial of SMC implemented in Mozambique. The findings from this trial will be crucial to policy change and program expansion to other suitable geographies outside of the Sahel. The chemoprevention efficacy cohort study is a unique opportunity to better understand SMC drug efficacy in this new SMC environment. Trial RegistrationClinicalTrials.gov NCT05186363; https://clinicaltrials.gov/ct2/show/NCT05186363 International Registered Report Identifier (IRRID)DERR1-10.2196/36403

Introduction Genomic data constitute a valuable adjunct to routine surveillance that can guide programmatic decisions to reduce the burden of infectious diseases. However, genomic capacities remain low in Africa. This study aims to operationalise a functional malaria molecular surveillance system in Mozambique for guiding malaria control and elimination.Methods and analyses This prospective surveillance study seeks to generate Plasmodium falciparum genetic data to (1) monitor molecular markers of drug resistance and deletions in rapid diagnostic test targets; (2) characterise transmission sources in low transmission settings and (3) quantify transmission levels and the effectiveness of antimalarial interventions. The study will take place across 19 districts in nine provinces (Maputo city, Maputo, Gaza, Inhambane, Niassa, Manica, Nampula, Zambézia and Sofala) which span a range of transmission strata, geographies and malaria intervention types. Dried blood spot samples and rapid diagnostic tests will be collected across the study districts in 2022 and 2023 through a combination of dense (all malaria clinical cases) and targeted (a selection of malaria clinical cases) sampling. Pregnant women attending their first antenatal care visit will also be included to assess their value for molecular surveillance. We will use a multiplex amplicon-based next-generation sequencing approach targeting informative single nucleotide polymorphisms, gene deletions and microhaplotypes. Genetic data will be incorporated into epidemiological and transmission models to identify the most informative relationship between genetic features, sources of malaria transmission and programmatic effectiveness of new malaria interventions. Strategic genomic information will be ultimately integrated into the national malaria information and surveillance system to improve the use of the genetic information for programmatic decision-making.Ethics and dissemination The protocol was reviewed and approved by the institutional (CISM) and national ethics committees of Mozambique (Comité Nacional de Bioética para Saúde) and Spain (Hospital Clinic of Barcelona). Project results will be presented to all stakeholders and published in open-access journals.Trial registration number NCT05306067.

Abstract Background Insecticide-treated net (ITN) use is crucial for preventing malaria infection. Despite significant improvements in ITN access and use over the past two decades, many malaria-endemic countries in sub-Saharan Africa have not yet reached global targets for universal coverage of ITNs. To reduce the gaps in ITN use, it is important to understand the factors associated with ITN use. The goal of this analysis was to determine the factors associated with ITN use in Manica District, Mozambique. Methods A cross-sectional community-based survey was conducted from October to November 2019. Households were randomly selected, and all members of selected households were eligible to participate. Data on socio-demographic characteristics, housing construction and the ownership, use and characteristics of ITNs were collected using structured questionnaires. Factors independently associated with ITN use were identified using generalized estimating equations multivariate logistic regression. Results Of the 302 households surveyed, 209 (69.2%) owned at least one ITN and 176 (58.3%) had one ITN for every two household members. The multivariate analysis indicated that the odds of ITN use was significantly lower among individuals in households with 3 or more members. However, the odds of ITN use was significantly higher among older age groups, poorer households, and as the number of ITNs in a household increased. Conclusions The findings of this analysis highlight the need for behaviour change communication strategies targeting young people and ITN distribution campaigns targeting larger households to increase ITN ownership, thereby improving ITN use in Manica District.

Abstract Background As malaria cases increase in some of the highest burden countries, more strategic deployment of new and proven interventions must be evaluated to meet global malaria reduction goals. Methods The cost and cost-effectiveness of indoor residual spraying (IRS) with pirimiphos-methyl (Actellic®300 CS) were assessed in a high transmission district (Mopeia) with high access to pyrethroid insecticide-treated nets (ITNs), compared to ITNs alone. The major mosquito vectors in the area were susceptible to primiphos-methyl, but resistant to pyrethoids. A decision analysis approach was followed to conduct deterministic and probabilistic sensitivity analyses in a theoretical cohort of 10,000 children under five years of age (U5) and 10,000 individuals of all ages, separately. Model parameters and distributions were based on prospectively collected cost and epidemiological data from a cluster-randomized control trial and a literature review. The primary analysis used health facility-malaria incidence, while community cohort incidence and cross-sectional prevalence rates were used in sensitivity analyses. Lifetime costs, malaria cases, deaths and disability-adjusted life-years (DALYs) were calculated to determine the incremental costs per DALY averted through IRS. Results The average IRS cost per person protected was US$8.26 and 51% of the cost was insecticide. IRS averted 46,609 (95% CI 46,570–46,646) uncomplicated and 242 (95% CI 241–243) severe lifetime cases in a theoretical children U5 cohort, yielding an incremental cost-effectiveness ratio (ICER) of US$400 (95% CI 399–402) per DALY averted. In the all-age cohort, the ICER was higher: US$1,860 (95% CI 1,852–1,868) per DALY averted. Deterministic and probabilistic results were consistent. When adding the community protective effect of IRS, the cost per person protected decreased (US$7.06) and IRS was highly cost-effective in children U5 (ICER = US$312) and cost-effective in individuals of all ages (ICER = US$1,431), compared to ITNs alone. Conclusion This study provides robust evidence that IRS with pirimiphos-methyl can be cost-effective in high transmission regions with high pyrethroid ITN coverage where the major vector is susceptible to pirimiphos-methyl but resistant to pyrethroids. The finding that insecticide cost is the main driver of IRS costs highlights the need to reduce the insecticide price without jeopardizing effectiveness. Trial registration: ClinicalTrials.gov identifier NCT02910934 (Registered 22 September 2016). https://clinicaltrials.gov/ct2/show/NCT02910934?term=NCT02910934&draw=2&rank=1

Abstract Background Attaining the goal of reducing the global malaria burden is threatened by recent setbacks in maintaining the effectiveness of vector control interventions partly due to the emergence of pyrethroid resistant vectors. One potential strategy to address these setbacks could be combining indoor residual spraying (IRS) with non-pyrethroids and standard insecticide-treated nets (ITNs). This study aimed to provide evidence on the incremental epidemiological benefit of using third-generation IRS product in a highly endemic area with high ITN ownership. Methods A cluster-randomized, open-label, parallel-arms, superiority trial was conducted in the Mopeia district in Zambezia, Mozambique from 2016 to 2018. The district had received mass distribution of alphacypermethrin ITNs two years before the trial and again mid-way. 86 clusters were defined, stratified and randomized to receive or not receive IRS with pirimiphos-methyl (Actellic®300 CS). Efficacy of adding IRS was assessed through malaria incidence in a cohort of children under five followed prospectively for two years, enhanced passive surveillance at health facilities and by community health workers, and yearly cross-sectional surveys at the peak of the transmission season. Findings A total of 1536 children were enrolled in the cohort. Children in the IRS arm experienced 4,801 cases (incidence rate of 3,532 per 10,000 children-month at risk) versus 5,758 cases in the no-IRS arm (incidence rate of 4,297 per 10,000 children-month at risk), resulting in a crude risk reduction of 18% and an incidence risk ratio of 0.82 (95% CI 0.79–0.86, p-value

Abstract Background Neglected tropical diseases (NTDs) affect more than one billion people living in vulnerable conditions. In spite of initiatives recently contributing to fill NTDs gaps on national and local prevalence and distribution, more epidemiological data are still needed for effective control and elimination interventions. Main text Mozambique is considered one of the countries with highest NTDs burden although available data is scarce. This study aims to conduct a systematic review on published available data about the burden and distribution of the different NTDs across Mozambique since January 1950 until December 2018. We identified manuscripts from electronic databases (Pubmed, EmBase and Global Health) and paper publications and grey literature from Mozambique Ministry of Health. Manuscripts fulfilling inclusion criteria were: cross-sectional studies, ecological studies, cohorts, reports, systematic reviews, and narrative reviews capturing epidemiological information of endemic NTDs in Mozambique. Case-control studies, letters to editor, case reports and case series of imported cases were excluded. A total of 466 manuscripts were initially identified and 98 were finally included after the revision following PRISMA guidelines. Eleven NTDs were reported in Mozambique during the study span. Northern provinces (Nampula, Cabo Delgado, Niassa, Tete and Zambezia) and Maputo province had the higher number of NTDs detected. Every disease had their own report profile: while schistosomiasis have been continuously reported since 1952 until nowadays, onchocerciasis and cysticercosis last available data is from 2007 and Echinococcosis have never been evaluated in the country. Thus, both space and time gaps on NTDs epidemiology have been identified. Conclusions This review assembles NTDs burden and distribution in Mozambique. Thus, contributes to the understanding of NTDs epidemiology in Mozambique and highlights knowledge gaps. Hence, the study provides key elements to progress towards the control and interruption of transmission of these diseases in the country.

Introduction Malaria infection during pregnancy is an important driver of maternal and neonatal health especially among HIV-infected women. Intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine–pyrimethamine is recommended for malaria prevention in HIV-uninfected women, but it is contraindicated in those HIV-infected on cotrimoxazole prophylaxis (CTXp) due to potential adverse effects. Dihydroartemisinin–piperaquine (DHA–PPQ) has been shown to improve antimalarial protection, constituting a promising IPTp candidate. This trial’s objective is to determine if monthly 3-day IPTp courses of DHA–PPQ added to daily CTXp are safe and superior to CTXp alone in decreasing the proportion of peripheral malaria parasitaemia at the end of pregnancy.Methods and analysis This is a multicentre, two-arm, placebo-controlled, individually randomised trial in HIV-infected pregnant women receiving CTXp and antiretroviral treatment. A total of 664 women will be enrolled at the first antenatal care clinic visit in sites from Gabon and Mozambique. Participants will receive an insecticide-treated net, and they will be administered monthly IPTp with DHA-PPQ or placebo (1:1 ratio) as directly observed therapy from the second trimester of pregnancy. Primary study outcome is the prevalence of maternal parasitaemia at delivery. Secondary outcomes include prevalence of malaria-related maternal and infant outcomes and proportion of adverse perinatal outcomes. Participants will be followed until 6 weeks after the end of pregnancy and their infants until 1 year of age to also evaluate the impact of DHA–PPQ on mother-to-child transmission of HIV. The analysis will be done in the intention to treat and according to protocol cohorts, adjusted by gravidity, country, seasonality and other variables associated with malaria.Ethics and dissemination The protocol was reviewed and approved by the institutional and national ethics committees of Gabon and Mozambique and the Hospital Clinic of Barcelona. Project results will be presented to all stakeholders and published in open-access journals.Trial registration number NCT03671109.

BackgroundMalaria is a significant cause of morbidity and mortality in children aged under 5 years in Mozambique. The World Health Organization recommends seasonal malaria chemoprevention (SMC), the administration of four monthly courses of sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ), to children aged 3-59 months during rainy season. However, as resistance to SP is widespread in East and Southern Africa, SMC has so far only been implemented across the Sahel in West Africa. ObjectiveThis protocol describes the first phase of a pilot project that aims to assess the protective effect of SP and AQ when used for SMC and investigate the levels of molecular markers of resistance of Plasmodium falciparum to antimalarial medicines in the study districts. In addition, it is important to understand whether SMC is a feasible and acceptable intervention in the context of Nampula Province, Mozambique. MethodsThis study will adopt a hybrid effectiveness-implementation design to conduct a mixed methods evaluation with six objectives: a molecular marker study, a nonrandomized controlled trial, an analysis of reported malaria morbidity indicators, a documentation exercise of the contextual SMC adaptation, an acceptability and feasibility assessment, and a coverage and quality assessment. ResultsEthical approval for this study was granted by the Mozambican Ministry of Health National Bioethics Committee on September 15, 2020. Data collection began in October 2020, and data analysis is expected to be completed by August 2021. ConclusionsThis research will make a unique contribution to our understanding of whether the combination of SP and AQ, when used for SMC, can confer a protective effect against malaria in children aged 3-59 months in a region where malaria transmission is seasonal and SP resistance is expected to be high. If the project is successful, subsequent phases are expected to provide a more comprehensive assessment of the effectiveness and sustainability of SMCs. International Registered Report Identifier (IRRID)DERR1-10.2196/27855

Abstract Background Malaria remains a leading cause of morbidity and mortality in Mozambique. Increased investments in malaria control have reduced the burden, but few studies have estimated the costs of malaria in the country. This paper estimates the economic costs associated with malaria care to households and to the health system in the high burden district of Mopeia in central Mozambique. Methods Malaria care-seeking and morbidity costs were routinely collected among 1373 households with at least one child enrolled in an active case detection (ACD) cohort in Mopeia, and through cross-sectional surveys with 824 families in 2017 and 805 families in 2018. Household costs included direct medical expenses, transportation and opportunity costs of the time lost due to illness. Structured questionnaires were used to estimate the health system costs associated with malaria care in all 13 district health facilities. Cost estimations followed an ingredient-based approach with a top-down allocation approach for health system expenses. Results Among participants in cross-sectional studies, households sought care for nine severe malaria cases requiring hospital admission and for 679 uncomplicated malaria cases. Median household costs associated with uncomplicated malaria among individuals of all ages were US$ 3.46 (IQR US$ 0.07–22.41) and US$ 81.08 (IQR US$ 39.34–88.38) per severe case. Median household costs were lower among children under five (ACD cohort): US$ 1.63 (IQR US$ 0.00–7.79) per uncomplicated case and US$ 64.90 (IQR US$ 49.76–80.96) per severe case. Opportunity costs were the main source of household costs. Median health system costs associated with malaria among patients of all ages were US$ 4.34 (IQR US$ 4.32–4.35) per uncomplicated case and US$ 26.56 (IQR US$ 18.03–44.09) per severe case. Considering household and health system costs, the overall cost of malaria care to society was US$ 7.80 per uncomplicated case and US$ 107.64 per severe case, representing an economic malaria burden of US$ 332,286.24 (IQR US$ 186,355.84–1,091,212.90) per year only in Mopeia. Conclusions Despite the provision of free malaria services, households in Mopeia incur significant direct and indirect costs associated with the disease. Furthermore, the high malaria cost on the Mozambican health system underscores the need to strengthen malaria prevention to reduce the high burden and improve productivity in the region.

Abstract Background Plasmodium falciparum drug resistance surveillance is key to successful disease control and eradication. Contemporary methods that only allow determination of prevalence of resistance are expensive, time consuming and require ethical considerations. A newer method involving Next Generation Sequencing (NGS) permits obtaining frequency of resistance while allowing to detect minority variants in mixed infections. Here, NGS was tested for P. falciparum resistance marker detection in mosquito samples as a feasible and suitable alternative for molecular resistance surveillance. Anopheles funestus were collected in southern Mozambique using CDC light traps and manual collections. DNA was extracted from either whole mosquito, head-thorax and abdomen separately or pools of five mosquitoes. These samples were screened for P. falciparum and if positive for k13, pfcrt, pfmdr1, pfdhps and pfdhfr mutations related to anti-malarial drug resistance with Sanger sequencing and NGS. Results Among the 846 samples screened for P. falciparum, 122 were positive by 18S ssrDNA qPCR with an infection rate of 23.6%. No mutations were observed for k13 and pfcrt72-76 and almost zero for pfmdr86, but quintuple pfdhfr/pfdhps mutations were near fixation and about half of the isolates contained the pfmdr184F polymorphism. Similar allele frequencies of resistance markers were estimated with NGS in comparison with the prevalence of markers obtained with the gold standard Sanger sequencing. Conclusions Pooled deep sequencing of P. falciparum isolates extracted from mosquitoes is a promising, efficient and cost-effective method to quantify allele frequencies at population level which allows to detect known and unknown markers of resistance in single and mixed infections in a timelier manner. Using mosquitoes as sentinel group and focusing on allele frequency opposed to prevalence, permits active surveillance across a more homogeneous geographical range.

Objectives A Demographic and Health Platform was established in Magude in 2015, prior to the deployment of a project aiming to evaluate the feasibility of malaria elimination in southern Mozambique, named the Magude project. This platform aimed to inform the design, implementation and evaluation of the Magude project, through the identification of households and population; and the collection of demographic, health and malaria information.Setting Magude is a rural district of southern Mozambique which borders South Africa. It has nine peripheral health facilities and one referral health centre with an inpatient ward.Intervention A baseline census enumerated and geolocated all the households, and their resident and non-resident members, collecting demographic and socio-economic information, and data on the coverage and usage of malaria control tools. Inpatient and outpatient data during the 5 years (2010 to 2014) before the survey were obtained from the district health authorities. The demographic platform was updated in 2016.Results The baseline census conducted in 2015 reported 48 448 (92.1%) residents and 4133 (7.9%) non-residents, and 10 965 households. Magude’s population is predominantly young, half of the population has no formal education and the main economic activities are agriculture and fishing. Houses are mainly built with traditional non-durable materials and have poor sanitation facilities. Between 2010 and 2014, malaria was the most common cause of all-age inpatient discharges (representing 20% to 40% of all discharges), followed by HIV (12% to 22%) and anaemia (12% to 15%). In early 2015, all-age bed-net usage was between 21.8% and 27.1% and the reported coverage of indoor residual spraying varied across the district between 30.7% and 79%.Conclusion This study revealed that Magude has limited socio-economic conditions, poor access to healthcare services and low coverage of malaria vector control interventions. Thus, Magude represented an area where it is most pressing to demonstrate the feasibility of malaria elimination.Trial registration number NCT02914145; Pre-results.

Abstract Background Malaria programmes use Plasmodium falciparum histidine-rich protein-2 (PfHRP2) based rapid diagnostic tests (RDTs) for malaria diagnosis. The deletion of this target antigen could potentially lead to misdiagnosis, delayed treatment and continuation of active transmission. Methods Plasmodium falciparum isolates (n = 1162) collected in Southern Mozambique were assessed by RDTs, microscopy and/or 18SrRNA qPCR. pfhrp2 and pfhrp3 deletions were investigated in isolates from individuals who were negative by RDT but positive by microscopy and/or qPCR (n = 69) using gene-specific PCRs, with kelch13 PCR as the parasite DNA control. Results Lack of pfhrp2 PCR amplification was observed in one of the 69 isolates subjected to molecular analysis [1.45% (95% CI 0.3–7.8%)]. Conclusions The low prevalence of pfhrp2 deletions suggests that RDTs will detect the vast majority of the P. falciparum infections. Nevertheless, active surveillance for changing deletion frequencies is required.

Abstract Recent reports regarding the re-emergence of parasite sensitivity to chloroquine call for a new consideration of this drug as an interesting complementary tool in malaria elimination efforts, given its good safety profile and long half-life. A randomized (2:1), single-blind, placebo-controlled trial was conducted in Manhiça, Mozambique, to assess the in-vivo efficacy of chloroquine to clear plasmodium falciparum (Pf) asymptomatic infections. Primary study endpoint was the rate of adequate and parasitological response (ACPR) to therapy on day 28 (PCR-corrected). Day 0 isolates were analyzed to assess the presence of the PfCRT-76T CQ resistance marker. A total of 52 and 27 male adults were included in the CQ and Placebo group respectively. PCR-corrected ACPR was significantly higher in the CQ arm 89.4% (95%CI 80–98%) compared to the placebo (p

Abstract After publication of the article [1], it has been brought to our attention that two of the authors have had their names spelt incorrectly in the original publication. The eighth author should be “N. Regina Rabinovich” but was previously spelt as “N. Regina Rabinovitch”. The tenth author should be “Francisco Saute” but was previously spelt as “Franciso Saute”. The original version of this article has now been revised to include these corrections.

BACKGROUND: Maternal mortality is a major health problem concentrated in resource-poor regions. Accurate data on its causes using rigorous methods is lacking, but is essential to guide policy-makers and health professionals to reduce this intolerable burden. The aim of this study was to accurately describe the causes of maternal death in order to contribute to its reduction, in one of the regions of the world with the highest maternal mortality ratios. METHODS AND FINDINGS: We conducted a prospective study between October 2002 and December 2004 on the causes of maternal death in a tertiary-level referral hospital in Maputo, Mozambique, using complete autopsies with histological examination. HIV detection was done by virologic and serologic tests, and malaria was diagnosed by histological and parasitological examination. During 26 mo there were 179 maternal deaths, of which 139 (77.6%) had a complete autopsy and formed the basis of this analysis. Of those with test results, 65 women (52.8%) were HIV-positive. Obstetric complications accounted for 38.2% of deaths; haemorrhage was the most frequent cause (16.6%). Nonobstetric conditions accounted for 56.1% of deaths; HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis were the most common causes (12.9%, 12.2%, 10.1% and 7.2% respectively). Mycobacterial infection was found in 12 (8.6%) maternal deaths. CONCLUSIONS: In this tertiary hospital in Mozambique, infectious diseases accounted for at least half of all maternal deaths, even though effective treatment is available for the four leading causes, HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and pyogenic meningitis. These observations highlight the need to implement effective and available prevention tools, such as intermittent preventive treatment and insecticide-treated bed-nets for malaria, antiretroviral drugs for HIV/AIDS, or vaccines and effective antibiotics for pneumococcal and meningococcal diseases. Deaths due to obstetric causes represent a failure of health-care systems and require urgent improvement.

Summary: Difference-in-differences (DID) is a key tool for causal impact evaluation but faces challenges when applied to sensitive data restricted by privacy regulations. Obtaining consent can shrink sample sizes and reduce statistical power, limiting the analysis’s effectiveness. Federated learning addresses these issues by sharing aggregated statistics rather than individual data, though advanced federated DID software is limited. We developed a federated version of the Callaway and Sant’Anna difference-in-differences (CSDID), integrated into the DataSHIELD platform, adhering to stringent privacy protocols. Our approach reproduces key estimates and standard errors while preserving confidentiality. Using simulated and real-world data from a malaria intervention in Mozambique, we demonstrate that federated estimates increase sample sizes, reduce estimation uncertainty, and enable analyses when data owners cannot share treated or untreated group data. Our work contributes to facilitating the evaluation of policy interventions or treatments across centers and borders.

Abstract Background The Magude Project assessed the feasibility of eliminating malaria in Magude district, a low transmission setting in southern Mozambique, using a package of interventions, including long-lasting insecticidal nets (LLINs). As the efficacy of LLINs depends in part on their physical integrity, this metric was quantified for Olyset® Nets post mass-distribution, in addition to net use, care and handling practices and other risk factors associated with net physical integrity. Methods Nets were collected during a cross-sectional net evaluation, nine months after the Magude project commenced, which was 2 years after the nets were distributed by the National Malaria Control Programme (NMCP). The physical integrity of the nets was assessed by counting and sizing the holes at different positions on each net. A structured questionnaire was administered to assess how the selected net was used and treated (care, wash and repair). Net bio-efficacy was assessed following the standard World Health Organization (WHO) cone bioassay procedures. Results Out of the 170 Olyset® Nets included in the analysis, 63.5% had been used the night before. The main reason for not using a net was the notion that there were no mosquitoes present. The average number of people using each net was 1.79. Two thirds of the nets had only been washed once or twice since distribution. Most nets (80.9%) were holed and 18% were torn, but none of the risk factors were significantly associated with net integrity, except for presence of mice in the household. Less than half of the participants noticed holes in holed nets, and of those only 38.6% attempted to repair those. None of the six nets that were tested for bio-efficacy passed the WHO threshold of 80% mosquito mortality. Conclusion Overall the majority of Olyset® Nets were in serviceable condition two years post-distribution, but their insecticidal effect may have been lost. This study—together with previous evidence on suboptimal access to and use of LLINs in Magude district—highlights that LLINs as an intervention could have been optimized during the Magude project to achieve maximum intervention impact.

Abstract Routine sampling of pregnant women at first antenatal care (ANC) visits could make Plasmodium falciparum genomic surveillance more cost-efficient and convenient in sub-Saharan Africa. We compare the genetic structure of parasite populations sampled from 289 first ANC users and 93 children from the community in Mozambique between 2015 and 2019. Samples are amplicon sequenced targeting 165 microhaplotypes and 15 drug resistance genes. Metrics of genetic diversity and relatedness, as well as the prevalence of drug resistance markers, are consistent between the two populations. In an area targeted for elimination, intra-host genetic diversity declines in both populations (p = 0.002-0.007), while for the ANC population, population genetic diversity is also lower (p = 0.0004), and genetic relatedness between infections is higher (p = 0.002) than control areas, indicating a recent reduction in the parasite population size. These results highlight the added value of genomic surveillance at ANC clinics to inform about changes in transmission beyond epidemiological data.

Abstract Background Different anopheline species (even within a species group/complex) can differ in their feeding and resting behaviours, which impact both malaria transmission patterns as well as the efficacy of vector control interventions. While morphological identification of sampled specimens is an important first step towards understanding species diversity and abundance, misidentification can result in the implementation of less effective vector control measures, and consequently smaller reductions in the number of local malaria cases. Focusing on southern Mozambique, a malaria pre-elimination area where malaria remains persistent, the aims of this preliminary study were to use molecular identification (CO1 and ITS2 barcoding) to (1) validate the results from the morphological identification (with a particular focus on Anopheles pharoensis and Anopheles squamosus), and (2) have a closer look at the Anopheles coustani group (which includes Anopheles tenebrosus and Anopheles ziemanni). Methods Female anopheline mosquitoes (n = 81) were identified morphologically and subsequently sequenced at the ribosomal DNA internal transcribed spacer region 2 (ITS2) and/or cytochrome oxidase subunit 1 (CO1) loci towards species determination. Results Out of the 62 specimens that were identified morphologically to species, 4 (6.5%) were misidentified. Regarding the An. coustani group, morphological identification showed that several members are present in southern Mozambique, including An. coustani sensu lato (s.l.), An. ziemanni and An. tenebrosus. However, based on both ITS2 and CO1 sequences, the exact species remains unknown for the latter two members until voucher sequences are available for comparison. Conclusion The reason(s) for morphological misidentification of anopheline mosquitoes need to be mitigated. This is usually related to both the capacity (i.e. training) of the microscopist to identify anopheline species, and the information provided in the dichotomous identification key. As the An. coustani complex contributes to (residual) malaria transmission in sub-Saharan Africa, it may play a role in the observed persistent malaria in southern Mozambique. A better baseline characterizing of the local anophelines species diversity and behaviours will allow us to improve entomological surveillance strategies, better understand the impact of vector control on each local vector species, and identify new approaches to target those vector species.