Genomic malaria surveillance of antenatal care users detects reduced transmission following elimination interventions in Mozambique.

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.

Genomic malaria surveillance of antenatal care users detects reduced transmission following elimination interventions in Mozambique.

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 compared the genetic structure of parasite populations sampled from 289 first ANC attendees and 93 children from the community in Mozambique between 2015 and 2019. Samples were 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, were consistent between the two populations. In an area targeted for elimination, intra-host genetic diversity declined in both populations (p=0.002-0.007), while for the ANC population, population genetic diversity was also lower (p=0.0004), and genetic relatedness between infections were 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.

Burden and risk factors of snakebite in Mopeia, Mozambique: Leveraging larger malaria trials to generate data of this neglected tropical disease.

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.

Alternative approaches for creating a wealth index: the case of Mozambique.

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.

Burden and risk factors of snakebite in Mopeia, Mozambique: Leveraging larger malaria trials to generate data of this neglected tropical disease

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.

Detecting temporal and spatial malaria patterns from first antenatal care visits.

Pregnant women attending first antenatal care (ANC) visits represent a promising malaria surveillance target in Sub-Saharan Africa. We assessed the spatio-temporal relationship between malaria trends at ANC (n = 6471) and in children in the community (n = 3933) and at health facilities (n = 15,467) in southern Mozambique (2016-2019). ANC P. falciparum rates detected by quantitative polymerase chain reaction mirrored rates in children, regardless of gravidity and HIV status (Pearson correlation coefficient [PCC] > 0.8, χ²<1.1), with a 2-3 months lag. Only at rapid diagnostic test detection limits at moderate-to-high transmission, did multigravidae show lower rates than children (PCC = 0.61, 95%CI[-0.12-0.94]). Seroprevalence against the pregnancy-specific antigen VAR2CSA reflected declining malaria trends (PCC = 0.74, 95%CI[0.24-0.77]). 60% (9/15) of hotspots detected from health facility data (n = 6662) using a novel hotspot detector, EpiFRIenDs, were also identified with ANC data (n = 3616). Taken together, we show that ANC-based malaria surveillance offers contemporary information on temporal trends and geographic distribution of malaria burden in the community.

BOHEMIA a cluster randomized trial to assess the impact of an endectocide-based one health approach to malaria in Mozambique: baseline demographics and key malaria indicators.

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.

BOHEMIA a cluster randomized trial to assess the impact of an endectocide-based one health approach to malaria in Mozambique: baseline demographics and key malaria indicators

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.

Detecting temporal and spatial malaria patterns from first antenatal care visits.

Pregnant women attending first antenatal care (ANC) visits represent a promising malaria surveillance target in Sub-Saharan Africa. Here we assessed the spatio-temporal relationship between malaria at ANC (n=6,471), in children at the community(n=9,362) and at health facilities (n=15,467) in southern Mozambique (2016-2019). ANC P. falciparum rates detected by quantitative polymerase chain reaction mirrored rates in children, regardless of gravidity and HIV status (Pearson correlation coefficient [PCC]>0.8, χ²<1.1), with a 2-3 months lag. Only at rapid diagnostic test detection limits at moderate-to-high transmission, multigravidae showed lower rates than children (PCC=0.61, 95%CI[-0.12-0.94]). Seroprevalence against the pregnancy-specific antigen VAR2CSA reflected declining malaria trends (PCC=0.74, 95%CI[0.24-0.77]). 80% (12/15) of hotspots detected from health facility data using a novel hotspot detector, EpiFRIenDs, were also identified with ANC data. The results show that ANC-based malaria surveillance offers contemporary information on temporal trends and the geographic distribution of malaria burden in the community.

Field performance of ultrasensitive and conventional malaria rapid diagnostic tests in southern Mozambique.

BACKGROUND: An ultrasensitive malaria rapid diagnostic test (RDT) was recently developed for the improved detection of low-density Plasmodium falciparum infections. This study aimed to compare the diagnostic performance of the PfHRP2-based Abbott Malaria Ag P. falciparum ultrasensitive RDT (uRDT) to that of the conventional SD-Bioline Malaria Ag P. falciparum RDT (cRDT) when performed under field conditions. METHODS: Finger-prick blood samples were collected from adults and children in two cross-sectional surveys in May of 2017 in southern Mozambique. Using real-time quantitative PCR (RT-qPCR) as the reference method, the age-specific diagnostic performance indicators of the cRDT and uRDT were compared. The presence of histidine-rich protein 2 (HRP2) and Plasmodium lactate dehydrogenase (pLDH) antigens was evaluated in a subset from dried blood spots by a quantitative antigen assay. pfhrp2 and pfhrp3 gene deletions were assessed in samples positive by RT-qPCR and negative by both RDTs. RESULTS: Among the 4,396 participants with complete test results, the sensitivity of uRDTs (68.2; 95% CI 60.8 to 74.9) was marginally better than that of cRDTs (61.5; 95% CI 53.9 to 68.6) (p-value = 0.004), while the specificities were similar (uRDT: 99.0 [95% CI 98.6 to 99.2], cRDT: 99.2 [95% CI 98.9 to 99.4], p-value = 0.02). While the performance of both RDTs was lowest in ≥ 15-year-olds, driven by the higher prevalence of low parasite density infections in this group, the sensitivity of uRDTs was significantly higher in this age group (54.9, 95% CI 40.3 to 68.9) compared to the sensitivity of cRDTs (39.2, 95% CI 25.8 to 53.9) (p-value = 0.008). Both RDTs detected P. falciparum infections at similar geometric mean parasite densities (112.9  parasites/µL for uRDTs and 145.5 parasites/µL for cRDTs). The presence of HRP2 antigen was similar among false positive (FP) samples of both tests (80.5% among uRDT-FPs and 84.4% among cRDT-FPs). Only one false negative sample was detected with a partial pfhrp2 deletion. CONCLUSION: This study showed that the uRDTs developed by Abbott do not substantially outperform SD-Bioline Pf malaria RDTs in the community and are still not comparable to molecular methods to detect P. falciparum infections in this study setting.

A multiphase program for malaria elimination in southern Mozambique (the Magude project): A before-after study.

BACKGROUND: Malaria eradication remains the long-term vision of the World Health Organization (WHO). However, whether malaria elimination is feasible in areas of stable transmission in sub-Saharan Africa with currently available tools remains a subject of debate. This study aimed to evaluate a multiphased malaria elimination project to interrupt Plasmodium falciparum malaria transmission in a rural district of southern Mozambique. METHODS AND FINDINGS: A before-after study was conducted between 2015 and 2018 in the district of Magude, with 48,448 residents living in 10,965 households. Building on an enhanced surveillance system, two rounds of mass drug administrations (MDAs) per year over two years (phase I, August 2015-2017), followed by one year of reactive focal mass drug administrations (rfMDAs) (phase II, September 2017-June 2018) were deployed with annual indoor residual spraying (IRS), programmatically distributed long-lasting insecticidal nets (LLINs), and standard case management. The four MDA rounds covered 58%-72% of the population, and annual IRS reported coverage was >70%. Yearly parasite surveys and routine surveillance data were used to monitor the primary outcomes of the study-malaria prevalence and incidence-at baseline and annually since the onset of the project. Parasite prevalence by rapid diagnostic test (RDT) declined from 9.1% (95% confidence interval [CI] 7.0-11.8) in May 2015 to 2.6% (95% CI 2.0-3.4), representing a 71.3% (95% CI 71.1-71.4, p < 0.001) reduction after phase I, and to 1.4% (95% CI 0.9-2.2) after phase II. This represented an 84.7% (95% CI 81.4-87.4, p < 0.001) overall reduction in all-age prevalence. Case incidence fell from 195 to 75 cases per 1,000 during phase I (61.5% reduction) and to 67 per 1,000 during phase II (65.6% overall reduction). Interrupted time series (ITS) analysis was used to estimate the level and trend change in malaria cases associated with the set of project interventions and the number of cases averted. Phase I interventions were associated with a significant immediate reduction in cases of 69.1% (95% CI 57.5-77.6, p < 0.001). Phase II interventions were not associated with a level or trend change. An estimated 76.7% of expected cases were averted throughout the project (38,369 cases averted of 50,005 expected). One malaria-associated inpatient death was observed during the study period. There were 277 mild adverse events (AEs) recorded through the passive pharmacovigilance system during the four MDA rounds. One serious adverse event (SAE) that resulted in death was potentially related to the drug. The study was limited by the incomplete coverage of interventions, the quality of the routine and cross-sectional data collected, and the restricted accuracy of ITS analysis with a short pre-intervention period. CONCLUSION: In this study, we observed that the interventions deployed during the Magude project fell short of interrupting P. falciparum transmission with the coverages achieved. While new tools and strategies may be required to eventually achieve malaria elimination in stable transmission areas of sub-Saharan Africa, this project showed that innovative mixes of interventions can achieve large reductions in disease burden, a necessary step in the pathway towards elimination. TRIAL REGISTRATION: ClinicalTrials.gov NCT02914145.

A multiphase program for malaria elimination in southern Mozambique (the Magude project): A before-after study

Background: Malaria eradication remains the long-term vision of the World Health Organization (WHO). However, whether malaria elimination is feasible in areas of stable transmission in sub-Saharan Africa with currently available tools remains a subject of debate. This study aimed to evaluate a multiphased malaria elimination project to interrupt Plasmodium falciparum malaria transmission in a rural district of southern Mozambique. Methods and findings: A before-after study was conducted between 2015 and 2018 in the district of Magude, with 48,448 residents living in 10,965 households. Building on an enhanced surveillance system, two rounds of mass drug administrations (MDAs) per year over two years (phase I, August 2015-2017), followed by one year of reactive focal mass drug administrations (rfMDAs) (phase II, September 2017-June 2018) were deployed with annual indoor residual spraying (IRS), programmatically distributed long-lasting insecticidal nets (LLINs), and standard case management. The four MDA rounds covered 58%-72% of the population, and annual IRS reported coverage was >70%. Yearly parasite surveys and routine surveillance data were used to monitor the primary outcomes of the study-malaria prevalence and incidence-at baseline and annually since the onset of the project. Parasite prevalence by rapid diagnostic test (RDT) declined from 9.1% (95% confidence interval [CI] 7.0-11.8) in May 2015 to 2.6% (95% CI 2.0-3.4), representing a 71.3% (95% CI 71.1-71.4, p < 0.001) reduction after phase I, and to 1.4% (95% CI 0.9-2.2) after phase II. This represented an 84.7% (95% CI 81.4-87.4, p < 0.001) overall reduction in all-age prevalence. Case incidence fell from 195 to 75 cases per 1,000 during phase I (61.5% reduction) and to 67 per 1,000 during phase II (65.6% overall reduction). Interrupted time series (ITS) analysis was used to estimate the level and trend change in malaria cases associated with the set of project interventions and the number of cases averted. Phase I interventions were associated with a significant immediate reduction in cases of 69.1% (95% CI 57.5-77.6, p < 0.001). Phase II interventions were not associated with a level or trend change. An estimated 76.7% of expected cases were averted throughout the project (38,369 cases averted of 50,005 expected). One malaria-associated inpatient death was observed during the study period. There were 277 mild adverse events (AEs) recorded through the passive pharmacovigilance system during the four MDA rounds. One serious adverse event (SAE) that resulted in death was potentially related to the drug. The study was limited by the incomplete coverage of interventions, the quality of the routine and cross-sectional data collected, and the restricted accuracy of ITS analysis with a short...

Moving towards malaria elimination in southern Mozambique: Cost and cost-effectiveness of mass drug administration combined with intensified malaria control.

BACKGROUND: As new combinations of interventions aiming at interrupting malaria transmission are under evaluation, understanding the associated economic costs and benefits is critical for decision-making. This study assessed the economic cost and cost-effectiveness of the Magude project, a malaria elimination initiative implemented in a district in southern Mozambique (i.e. Magude) between August 2015-June 2018. This project piloted a combination of two mass drug administration (MDA) rounds per year for two consecutive years, annual rounds of universal indoor residual spraying (IRS) and a strengthened surveillance and response system on the back of universal long-lasting insecticide treated net (LLIN) coverage and routine case management implemented by the National Malaria Control Program (NMCP). Although local transmission was not interrupted, the project achieved large reductions in the burden of malaria in the target district. METHODS: We collected weekly economic data, estimated costs from the project implementer perspective and assessed the incremental cost-effectiveness ratio (ICER) associated with the Magude project as compared to routine malaria control activities, the counterfactual. We estimated disability-adjusted life years (DALYs) for malaria cases and deaths and assessed the variation of the ICER over time to capture the marginal costs and effectiveness associated with subsequent phases of project implementation. We used deterministic and probabilistic sensitivity analyses to account for uncertainty and built an alternative scenario by assuming the implementation of the interventions from a governmental perspective. Economic costs are provided in constant US$2015. RESULTS: After three years, the Magude project averted a total of 3,171 DALYs at an incremental cost of $2.89 million and an average yearly cost of $20.7 per targeted person. At an average cost of $19.4 per person treated per MDA round, the social mobilization and distribution of door-to-door MDA contributed to 53% of overall resources employed, with personnel and logistics being the main cost drivers. The ICER improved over time as a result of decreasing costs and improved effectiveness. The overall ICER was $987 (CI95% 968-1,006) per DALY averted, which is below the standard cost-effectiveness (CE) threshold of $1,404/DALY averted, three times the gross domestic product (GDP) per capita of Mozambique, but above the threshold of interventions considered highly cost-effective (one time the GDP per capita or $468/DALY averted) and above the recently suggested thresholds based on the health opportunity cost ($537 purchasing power parity/ DALY averted). A significantly lower ICER was obtained in the implementation scenario from a governmental perspective ($441/DALY averted). CONCLUSION: Despite the initial high costs and volume of resources associated with its implementation, MDA in combination with other existing malaria control interventions, can be a cost-effective strategy to drastically reduce transmission in areas of low to moderate transmission in sub-Saharan Africa. However, further studies are needed to understand the capacity of the health system and financial affordability to scale up such strategies at regional or national level.

Moving towards malaria elimination in southern Mozambique: Cost and cost-effectiveness of mass drug administration combined with intensified malaria control

As new combinations of interventions aiming at interrupting malaria transmission are under evaluation, understanding the associated economic costs and benefits is critical for decision-making. This study assessed the economic cost and cost-effectiveness of the Magude project, a malaria elimination initiative implemented in a district in southern Mozambique (i.e. Magude) between August 2015­June 2018. This project piloted a combination of two mass drug administration (MDA) rounds per year for two consecutive years, annual rounds of universal indoor residual spraying (IRS) and a strengthened surveillance and response system on the back of universal long-lasting insecticide treated net (LLIN) coverage and routine case management implemented by the National Malaria Control Program (NMCP). Although local transmission was not interrupted, the project achieved large reductions in the burden of malaria in the target district.

Demographic and health community-based surveys to inform a malaria elimination project in Magude district, southern Mozambique.

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.