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Sulfadoxine-pyrimethamine plus amodiaquine is delivered to children aged 3–59 months as seasonal malaria chemoprevention (SMC) in areas where transmission is highly seasonal such as Chad and other Sahelian countries. Although clinical trials show a 75% reduction in malaria cases, evidence of SMC’s impact at scale remains limited. Using data from the Chadian National Health Management Information System, we analyzed associations between SMC implementation during July–October and monthly district-level malaria incidence (suspected and confirmed outpatient cases) among children aged 0–59 months at health facilities in 23 health districts with SMC implementation during 2013–2018. Generalized additive models were fitted with separate cyclic cubic spline terms for each district to adjust for seasonality in cases. SMC implementation in Chad was associated, compared with no implementation, with lower monthly counts of both suspected (rate ratio [RR]: 0.82, 95% CI: 0.72–0.94. P = 0.006) and confirmed malaria cases (RR: 0.81, 95% CI: 0.71–0.93, P = 0.003), representing around 20% reduction in malaria incidence. Sensitivity analyses showed effect sizes of up to 28% after modifying model assumptions. Caution should be exercised in interpreting our findings, which may not be comparable with other studies, and may over- or underestimate impact of SMC; not all malaria cases present at health facilities, not all suspected cases are tested, and not all facilities report cases consistently. This study’s approach presents a solution for employing readily available routine data to evaluate the impact of health interventions at scale without extensive covariate data. Further efforts are needed to improve the quality of routine data in Chad and elsewhere.

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.This prospective surveillance study seeks to generateThe 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.NCT05306067.

BackgroundIn 2012, the WHO issued a policy recommendation for the use of seasonal malaria chemoprevention (SMC) to children 3–59 months in areas of highly seasonal malaria transmission. Clinical trials have found SMC to prevent around 75% of clinical malaria. Impact under routine programmatic conditions has been assessed during research studies but there is a need to identify sustainable methods to monitor impact using routinely collected data.MethodsData from Demographic Health Surveys were merged with rainfall, geographical and programme data in Burkina Faso (2010, 2014, 2017) and Nigeria (2010, 2015, 2018) to assess impact of SMC. We conducted mixed-effects logistic regression to predict presence of malaria infection in children aged 6–59 months (rapid diagnostic test (RDT) and microscopy, separately).ResultsWe found strong evidence that SMC administration decreases odds of malaria measured by RDT during SMC programmes, after controlling for seasonal factors, age, sex, net use and other variables (Burkina Faso OR 0.28, 95% CI 0.21 to 0.37, pConclusionsImpact of SMC can be detected in reduced prevalence of malaria from data collected through household surveys if conducted during SMC administration or within 2 months afterwards. Such evidence could contribute to broader evaluation of impact of SMC programmes.

In urban settings in malaria-endemic countries, malaria incidence is not well characterized and assumed to be typically very low and consisting largely of imported infections. In such contexts, surveillance systems should adapt to ensure that data are of sufficient spatial and temporal resolution to inform appropriate programmatic interventions. The aim of this research was to 1) assess spatial and temporal trends in reported malaria cases in Maputo City, Mozambique, using an expanded case notification form and 2) to determine how malaria surveillance can be optimized to characterize the local epidemiological context, which can then be used to inform targeted entomological investigations and guide implementation of localized malaria responses. This study took place in all six health facilities of KaMavota District in Maputo City, Mozambique. A questionnaire was administered to all confirmed cases from November 2019 to August 2021. Households of cases were retrospectively geolocated using local landmarks as reference. Overall, 2,380 malaria cases were reported, with the majority being uncomplicated (97.7%) and a median age of 21 years; 70.8% of cases had reported traveling outside the city in the past month with nine reporting traveling internationally. Maps of the 1,314 malaria cases that were geolocated showed distinct spatial patterns. The expanded case notification form enables a more granular overview of the malaria epidemiology in Maputo City; the geolocation data clearly show the areas where endemic transmission is likely, thus informing where resources should be prioritized. As urbanization is rapidly increasing in malaria endemic areas, identifying systems and key variables to collect ensures an operational way to characterize urban malaria through optimization of routine data to inform decision-making.

BACKGROUND Seasonal 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 global malaria cases, and malaria represents one out first four causes of death in the country. Based on recommendations in the Malaria Strategic Plan, Malaria Consortium, in partnership with the Mozambican National Malaria Control Program (NMCP), initiated a phased SMC implementation study in the northern province of Nampula. It is as a two-year implementation study, with the first phase, conducted in 2020-2021, focusing on the feasibility and acceptability of SMC and the second phase on demonstrating impact. This paper describes phase 2 of the implementation study. OBJECTIVE Thsi study aims to test the feasibility, effectiveness and chemopreventive efficacy of SMC with SPAQ in a province of Mozambique, Nampula, where malaria transmission is highly seasonal. METHODS This 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: a cluster randomized control trial (cRCT) to establish confirmed malaria cases, a prospective cohort to determine whether SPAQ provides 28 days of protection from infection, and whether drug concentrations and/or resistance influence the duration of protection, a resistance markers study in children aged 3–59 months to describe changes in resistance marker prevalence over time. Finally, a process evaluation will determine feasibility and acceptability of SMC. RESULTS Ethical approval was granted by Comité Nacional de Bioética para a Saùde (CNBS) of MoH of Mozambique (Ref: 803/CNBS/21) and by Research Ethics Committee of the Hospital Clinic of Barcelona (Ref: HCB/2021/0944). Data collection begins in mid-January 2022, and data analysis is expected to be completed by August 2022. CONCLUSIONS This 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 the Sahel. The chemoprevention efficacy cohort study is a unique opportunity to better understand SMC drug efficacy in this new SMC environment. CLINICALTRIAL The trial has been registered on clinicaltrials.gov (Ref: NCT05186363).

Background In many endemic areas, Plasmodium vivax malaria is predominantly a disease of young adults and children. International recommendations for radical cure recommend fixed target doses of 0.25 or 0.5 mg/kg/day of primaquine for 14 days in glucose-6-phosphate dehydrogenase normal patients of all ages. However, for many anti-malarial drugs, including primaquine, there is evidence that children have lower exposures than adults for the same weight-adjusted dose. The aim of the study was to develop 14-day weight-based and age-based primaquine regimens against high-frequency relapsing tropical P. vivax. Methods The recommended adult target dose of 0.5 mg/kg/day (30 mg in a 60 kg patient) is highly efficacious against tropical P. vivax and was assumed to produce optimal drug exposure. Primaquine doses were calculated using allometric scaling to derive a weight-based primaquine regimen over a weight range from 5 to 100 kg. Growth curves were constructed from an anthropometric database of 53,467 individuals from the Greater Mekong Subregion (GMS) to define weight-for-age relationships. The median age associated with each weight was used to derive an age-based dosing regimen from the weight-based regimen. Results The proposed weight-based regimen has 5 dosing bands: (i) 5–7 kg, 5 mg, resulting in 0.71–1.0 mg/kg/day; (ii) 8–16 kg, 7.5 mg, 0.47–0.94 mg/kg/day; (iii) 17–40 kg, 15 mg, 0.38–0.88 mg/kg/day; (iv) 41–80 kg, 30 mg, 0.37–0.73 mg/kg/day; and (v) 81–100 kg, 45 mg, 0.45–0.56 mg/kg/day. The corresponding age-based regimen had 4 dosing bands: 6–11 months, 5 mg, 0.43–1.0 mg/kg/day; (ii) 1–5 years, 7.5 mg, 0.35–1.25 mg/kg/day; (iii) 6–14 years, 15 mg, 0.30–1.36 mg/kg/day; and (iv) ≥ 15 years, 30 mg, 0.35–1.07 mg/kg/day. Conclusion The proposed weight-based regimen showed less variability around the primaquine dose within each dosing band compared to the age-based regimen and is preferred. Increased dose accuracy could be achieved by additional dosing bands for both regimens. The age-based regimen might not be applicable to regions outside the GMS, which must be based on local anthropometric data. Pharmacokinetic data in small children are needed urgently to inform the proposed regimens.

Background Remaining Plasmodium falciparum cases in Cambodia are concentrated in forested border areas and in remote populations who are hard to reach through passive case detection. A key approach to reach these populations is active case detection by mobile malaria workers (MMWs). However, this is operationally challenging because of changing movement patterns of the target population moving into less accessible areas. From January 2018 to December 2020, a tailored package of active case detection approaches was implemented in forested border areas of three provinces in north-eastern Cambodia to reach remote populations and support the elimination of falciparum malaria. Methods Key elements of this project were to tailor approaches to local populations, use responsive monitoring systems, maintain operational flexibility, build strong relationships with local communities, and implement close supervision practices. MMWs were recruited from local communities. Proactive case detection approaches included mobile malaria posts positioned at frequented locations around and within forests, and locally informed outreach activities targeting more remote locations. Reactive case detection was conducted among co-travellers of confirmed cases. Testing for malaria was conducted independent of fever symptoms. Routine monitoring of programmatic data informed tactical adaptations, while supervision exercises ensured service quality. Results Despite operational challenges, service delivery sites were able to maintain consistently high testing rates throughout the implementation period, with each of 45 sites testing a monthly average of 64 (SD 6) people in 2020. In 2020, project MMWs detected only 32 P. falciparum cases. Over the project period, the P. falciparum/P. vivax ratio steadily inversed. Including data from neighbouring health centres and village malaria workers, 45% (80,988/180,732) of all people tested and 39% (1280/3243) of P. falciparum cases detected in the area can be attributed to project MMWs. Remaining challenges of the last elimination phase include maintaining intensified elimination efforts, addressing the issue of detecting low parasitaemia cases and shifting focus to P. vivax malaria. Conclusions Reaching remote populations through active case detection should remain a key strategy to eliminate P. falciparum malaria. This case study presented a successful approach combining tailored proactive and reactive strategies that could be transferred to similar settings in other areas of the Greater Mekong Subregion.

Background Malaria 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. Objective This 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. Methods This 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. Results Ethical 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. Conclusions This 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

Malaria incidence in Myanmar has significantly reduced over recent years, however, completeness and timeliness of incidence data remain a challenge. The first ever nationwide malaria infection and seroprevalence survey was conducted in Myanmar in 2015 to better understand malaria epidemiology and highlight gaps in Annual Parasite Index (API) data. The survey was a cross-sectional two-stage stratified cluster-randomised household survey conducted from July-October 2015. Blood samples were collected from household members for ultra-sensitive PCR and serology testing for P. falciparum and P. vivax. Data was gathered on demography and a priori risk factors of participants. Data was analysed nationally and within each of four domains defined by API data. Prevalence and seroprevalence of malaria were 0.74% and 16.01% nationwide, respectively. Prevalent infection was primarily asymptomatic P. vivax, while P. falciparum was predominant in serology. There was large heterogeneity between villages and by domain. At the township level, API showed moderate correlation with P. falciparum seroprevalence. Risk factors for infection included socioeconomic status, domain, and household ownership of nets. Three K13 P. falciparum mutants were found in highly prevalent villages. There results highlight high heterogeneity of both P. falciparum and P. vivax transmission between villages, accentuated by a large hidden reservoir of asymptomatic P. vivax infection not captured by incidence data, and representing challenges for malaria elimination. Village-level surveillance and stratification to guide interventions to suit local context and targeting of transmission foci with evidence of drug resistance would aid elimination efforts.

Healthcare workers (HCWs) are at the frontline of the Coronavirus Disease 2019 (COVID-19) pandemic response, yet there is a paucity of literature on their knowledge, attitudes and practices (KAP) in relation to the pandemic. Community Health Workers (CHWs) in Mozambique are known locally as agentes polivalentes elementares (APEs). While technical guidance surrounding COVID-19 is available to support APEs, communicating this information has been challenging due to restrictions on travel, face-to-face group meetings and training, imposed from May to August 2020. A digital health platform, upSCALE, that already supports 1,213 APEs and 299 supervisors across three provinces, is being used to support APEs on effective COVID-19 management by delivering COVID-19 sensitive SMS messages, training modules and a COVID-19 KAP survey. The KAP survey, conducted from June 2020 to August 2020, consisted of 10 questions. Of 1,065 active upSCALE APEs, 28% completed the survey. Results indicate that only a small proportion of APEs listed the correct COVID-19 symptoms, transmission routes and appropriate prevention measures (n = (25%), n = (16%) and n = (39%), respectively) specifically included in national health education materials. Misconceptions were mainly related to transmission routes, high risk individuals and asymptomatic patients. 84% said they followed all government prevention guidelines. The results from the KAP survey were used to support the rapid development and deployment of targeted COVID-19 awareness and education materials for the APEs. A follow-up KAP survey is planned for November 2020. Adapting the existing upSCALE platform enabled a better understanding, in real time, of the KAP of APEs around COVID-19 management. Subsequently, supporting delivery of tailored messages and education, vital for ensuring a successful COVID-19 response.

Background Seasonal malaria chemoprevention (SMC) using sulfadoxine-pyrimethamine and amodiaquine is an efficacious intervention for protection of children against Plasmodium falciparum malaria during the rainy season. In response to the global COVID-19 pandemic, Malaria Consortium adapted its SMC delivery model to ensure safety of distributors, data collectors and beneficiaries. We conducted a SMC monitoring survey in July 2020 in the states of Bauchi, Jigawa, Kano, Katsina, Sokoto and Yobe, with questions on COVID-19 prevention behaviours and symptoms, and belief in misinformation. We investigated the associations between receipt of information on COVID-19 by different sources, including from SMC distributors, and these three outcomes using logistic generalised estimating equations. We also considered moderation of effectiveness of message delivery by SMC distributors and adherence to use of face coverings. Results We obtained a representative sample of 40,157 caregivers of eligible children aged 3–59 months, of which 36,914 (91.92%) reported knowledge of COVID-19. The weighted proportions of respondents who correctly identified COVID-19 prevention behaviours and symptoms, and who reported belief in COVID-19 misinformation, were 80.52% (95% confidence interval [95% CI] 80.02–81.00), 81.72% (95% CI 81.23–82.20) and 22.90% (95% CI 22.24–23.57). Receipt of information on COVID-19 from SMC distributors during the campaign was significantly associated with higher odds of caregiver knowledge of COVID-19 prevention behaviours (odds ratio [OR] 1.78, 95% CI 1.64–1.94, p < 0.001) and symptoms (OR 1.74, 95% CI 1.59–1.90, p < 0.001) and lower odds of belief in COVID-19 misinformation (OR 0.92, 95% CI 0.85–1.00, p = 0.038). The associations between message delivery by SMC distributors and the three outcomes were moderated by their adherence to face covering use. Receipt of information by other sources used to deliver government public health messages, including radio and health facility workers, was also associated with knowledge of COVID-19. Conclusions Malaria Consortium’s SMC programme was successfully adapted in the context of COVID-19 and was a conduit for high-quality public health messages. Standard SMC monitoring and evaluation activities can be adapted to gather evidence on emerging public health issues such as the global COVID-19 pandemic.

Healthcare workers (HCWs) are at the frontline of the Coronavirus Disease 2019 (COVID-19) pandemic response, yet there is a paucity of literature on their knowledge, attitudes and practices (KAP) in relation to the pandemic. Community Health Workers (CHWs) in Mozambique are known locally as agentes polivalentes elementares (APEs). While technical guidance surrounding COVID-19 is available to support APEs, communicating this information has been challenging due to restrictions on travel, face-to-face group meetings and training, imposed from May to August 2020. A digital health platform, upSCALE, that already supports 1,213 APEs and 299 supervisors across three provinces, is being used to support APEs on effective COVID-19 management by delivering COVID-19 sensitive SMS messages, training modules and a COVID-19 KAP survey.The KAP survey, conducted from June 2020 to August 2020, consisted of 10 questions. Of 1,065 active upSCALE APEs, 28 percent completed the survey. Results indicate that only a small proportion of APEs listed the correct COVID-19 symptoms, transmission routes and appropriate prevention measures (25 percent, 16 percent and 39 percent, respectively) specifically included in national health education materials. Misconceptions were mainly related to transmission routes, high risk individuals and asymptomatic patients. 84 percent said they followed all government prevention guidelines. The results from the KAP survey were used to support the rapid development and deployment of targeted COVID-19 awareness and education materials for the APEs. SMS messages were continually adjusted based on the KAP survey results and a series of seven COVID-19 training modules were developed and disseminated. A follow-up KAP survey is planned for November 2020.Adapting the existing upSCALE platform enabled a better understanding, in real time, of the KAP of APEs around COVID-19 management. Subsequently, supported improved delivery of tailored messages and education, vital for ensuring a successful COVID-19 response.

Background The radical cure of Plasmodium vivax and P. ovale requires treatment with primaquine or tafenoquine to clear dormant liver stages. Either drug can induce haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, necessitating screening. The reference diagnostic method for G6PD activity is ultraviolet (UV) spectrophotometry; however, a universal G6PD activity threshold above which these drugs can be safely administered is not yet defined. Our study aimed to quantify assay-based variation in G6PD spectrophotometry and to explore the diagnostic implications of applying a universal threshold. Methods and findings Individual-level data were pooled from studies that used G6PD spectrophotometry. Studies were identified via PubMed search (25 April 2018) and unpublished contributions from contacted authors (PROSPERO: CRD42019121414). Studies were excluded if they assessed only individuals with known haematological conditions, were family studies, or had insufficient details. Studies of malaria patients were included but analysed separately. Included studies were assessed for risk of bias using an adapted form of the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Repeatability and intra- and interlaboratory variability in G6PD activity measurements were compared between studies and pooled across the dataset. A universal threshold for G6PD deficiency was derived, and its diagnostic performance was compared to site-specific thresholds. Study participants (n = 15,811) were aged between 0 and 86 years, and 44.4% (7,083) were women. Median (range) activity of G6PD normal (G6PDn) control samples was 10.0 U/g Hb (6.3–14.0) for the Trinity assay and 8.3 U/g Hb (6.8–15.6) for the Randox assay. G6PD activity distributions varied significantly between studies. For the 13 studies that used the Trinity assay, the adjusted male median (AMM; a standardised metric of 100% G6PD activity) varied from 5.7 to 12.6 U/g Hb (p < 0.001). Assay precision varied between laboratories, as assessed by variance in control measurements (from 0.1 to 1.5 U/g Hb; p < 0.001) and study-wise mean coefficient of variation (CV) of replicate measures (from 1.6% to 14.9%; p < 0.001). A universal threshold of 100% G6PD activity was defined as 9.4 U/g Hb, yielding diagnostic thresholds of 6.6 U/g Hb (70% activity) and 2.8 U/g Hb (30% activity). These thresholds diagnosed individuals with less than 30% G6PD activity with study-wise sensitivity from 89% (95% CI: 81%–94%) to 100% (95% CI: 96%–100%) and specificity from 96% (95% CI: 89%–99%) to 100% (100%–100%). However, when considering intermediate deficiency (, Daniel Pfeffer and coauthors report on the assessment of glucose-6-phosphate dehydrogenase activity, which is required for safe use of some malaria treatments., Author summary Why was this study done? Complete cure of vivax malaria, the most geographically widespread malaria species, requires the use of 8-aminoquinoline drugs to clear dormant liver stages of the parasite (‘radical cure’); however, these drugs can cause severe haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Ultraviolet (UV) spectrophotometry is used as the reference test to measure G6PD activity, for validating new point-of-care diagnostics, and to determine population-specific definitions of G6PD deficiency. Currently, there is no universal threshold to define G6PD deficiency, and each laboratory must invest time and resources to derive site- and laboratory-specific definitions of G6PD deficiency. What did the researchers do and find? We pooled measurements of G6PD activity from studies conducted across different countries and laboratories worldwide. We assessed the comparability of spectrophotometry results between these laboratories to see whether a universal definition and diagnostic cutoff for G6PD deficiency could be determined. There was substantial variation in the performance and absolute measurements of spectrophotometry conducted in different laboratories, hindering the definition of a universal cutoff for G6PD deficiency. What do these findings mean? These findings highlight the importance of quality-control measures to minimise the influence of laboratory procedures on observed measurements. The data suggest that while a robust universal, assay-specific G6PD activity cutoff value can be established for diagnosis of severe G6PD deficiency (

Summary Background Seasonal malaria chemoprevention (SMC) aims to prevent malaria in children during the high malaria transmission season. The Achieving Catalytic Expansion of SMC in the Sahel (ACCESS-SMC) project sought to remove barriers to the scale-up of SMC in seven countries in 2015 and 2016. We evaluated the project, including coverage, effectiveness of the intervention, safety, feasibility, drug resistance, and cost-effectiveness. Methods For this observational study, we collected data on the delivery, effectiveness, safety, influence on drug resistance, costs of delivery, impact on malaria incidence and mortality, and cost-effectiveness of SMC, during its administration for 4 months each year (2015 and 2016) to children younger than 5 years, in Burkina Faso, Chad, The Gambia, Guinea, Mali, Niger, and Nigeria. SMC was administered monthly by community health workers who visited door-to-door. Drug administration was monitored via tally sheets and via household cluster-sample coverage surveys. Pharmacovigilance was based on targeted spontaneous reporting and monitoring systems were strengthened. Molecular markers of resistance to sulfadoxine–pyrimethamine and amodiaquine in the general population before and 2 years after SMC introduction was assessed from community surveys. Effectiveness of monthly SMC treatments was measured in case-control studies that compared receipt of SMC between patients with confirmed malaria and neighbourhood-matched community controls eligible to receive SMC. Impact on incidence and mortality was assessed from confirmed outpatient cases, hospital admissions, and deaths associated with malaria, as reported in national health management information systems in Burkina Faso and The Gambia, and from data from selected outpatient facilities (all countries). Provider costs of SMC were estimated from financial costs, costs of health-care staff time, and volunteer opportunity costs, and cost-effectiveness ratios were calculated as the total cost of SMC in each country divided by the predicted number of cases averted. Findings 12 467 933 monthly SMC treatments were administered in 2015 to a target population of 3 650 455 children, and 25 117 480 were administered in 2016 to a target population of 7 551 491. In 2015, among eligible children, mean coverage per month was 76·4% (95% CI 74·0–78·8), and 54·5% children (95% CI 50·4–58·7) received all four treatments. Similar coverage was achieved in 2016 (74·8% [72·2–77·3] treated per month and 53·0% [48·5–57·4] treated four times). In 779 individual case safety reports over 2015–16, 36 serious adverse drug reactions were reported (one child with rash, two with fever, 31 with gastrointestinal disorders, one with extrapyramidal syndrome, and one with Quincke's oedema). No cases of severe skin reactions (Stevens-Johnson or Lyell syndrome) were reported. SMC treatment was associated with a protective effectiveness of 88·2% (95% CI 78·7–93·4) over 28 days in case-control studies (2185 cases of confirmed malaria and 4370 controls). In Burkina Faso and The Gambia, implementation of SMC was associated with reductions in the number of malaria deaths in hospital during the high transmission period, of 42·4% (95% CI 5·9 to 64·7) in Burkina Faso and 56·6% (28·9 to 73·5) in The Gambia. Over 2015–16, the estimated reduction in confirmed malaria cases at outpatient clinics during the high transmission period in the seven countries ranged from 25·5% (95% CI 6·1 to 40·9) in Nigeria to 55·2% (42·0 to 65·3) in The Gambia. Molecular markers of resistance occurred at low frequencies. In individuals aged 10–30 years without SMC, the combined mutations associated with resistance to amodiaquine (pfcrt CVIET haplotype and pfmdr1 mutations [86Tyr and 184Tyr]) had a prevalence of 0·7% (95% CI 0·4–1·2) in 2016 and 0·4% (0·1–0·8) in 2018 (prevalence ratio 0·5 [95% CI 0·2–1·2]), and the quintuple mutation associated with resistance to sulfadoxine–pyrimethamine (triple mutation in pfdhfr and pfdhps mutations [437Gly and 540Glu]) had a prevalence of 0·2% (0·1–0·5) in 2016 and 1·0% (0·6–1·6) in 2018 (prevalence ratio 4·8 [1·7–13·7]). The weighted average economic cost of administering four monthly SMC treatments was US$3·63 per child. Interpretation SMC at scale was effective in preventing morbidity and mortality from malaria. Serious adverse reactions were rarely reported. Coverage varied, with some areas consistently achieving high levels via door-to-door campaigns. Markers of resistance to sulfadoxine–pyrimethamine and amodiaquine remained uncommon, but with some selection for resistance to sulfadoxine–pyrimethamine, and the situation needs to be carefully monitored. These findings should support efforts to ensure high levels of SMC coverage in west and central Africa. Funding Unitaid.

Strengthening the surveillance component is key toward achieving country-wide malaria elimination in Cambodia. A Web-based upgraded malaria information system (MIS) was deemed to essentially act as the central component for surveillance strengthening. New functionality (eg, data visualization) and operational (eg, data quality) attributes of the system received particular attention. However, building from the lessons learned in previous systems' developments, other aspects unique to Cambodia were considered to be equally important; for instance, feasibility issues, particularly at the field level (eg, user acceptability at various health levels), and sustainability needs (eg, long-term system flexibility). The Cambodian process of identifying the essential changes and critical attributes for this new information system can provide a model for other countries at various stages of the disease control and elimination continuum. Sharing these experiences not only facilitates the establishment of "best practices" but also accelerates global and regional malaria elimination efforts. In this article, Cambodia's experience in developing and upgrading its MIS to remain responsive to country-specific needs demonstrates the necessity for considering functionality, operationalization, feasibility, and sustainability of an information system in the context of malaria elimination.

Rigorous evidence of "what works" to improve health care is in demand, but methods for the development of interventions have not been scrutinized in the same ways as methods for evaluation. This article presents and examines intervention development processes of eight malaria health care interventions in East and West Africa. A case study approach was used to draw out experiences and insights from multidisciplinary teams who undertook to design and evaluate these studies. Four steps appeared necessary for intervention design: (1) definition of scope, with reference to evaluation possibilities; (2) research to inform design, including evidence and theory reviews and empirical formative research; (3) intervention design, including consideration and selection of approaches and development of activities and materials; and (4) refining and finalizing the intervention, incorporating piloting and pretesting. Alongside these steps, projects produced theories, explicitly or implicitly, about (1) intended pathways of change and (2) how their intervention would be implemented.The work required to design interventions that meet and contribute to current standards of evidence should not be underestimated. Furthermore, the process should be recognized not only as technical but as the result of micro and macro social, political, and economic contexts, which should be acknowledged and documented in order to infer generalizability. Reporting of interventions should go beyond descriptions of final intervention components or techniques to encompass the development process. The role that evaluation possibilities play in intervention design should be brought to the fore in debates over health care improvement.

Background In Cambodia, behaviour change communication (BCC) represents an integral component of malaria efforts aimed at fighting artemisinin resistant parasites and achieving elimination. The multi-pronged BCC interventions include interpersonal communication through village health volunteers (VHVs) and village malaria workers (VMWs), broadcasting malaria prevention, diagnosis and treatment messages via TV, radio and mobile broadcasting units (MBUs), distributing information education and communication (IEC) materials and introducing mobile malaria workers (MMWs) in endemic villages. Methods This was a cross sectional household survey using a stratified multi-stage cluster sampling approach, conducted in December 2012. A stratified multi-stage cluster sampling approach was used; 30 villages were selected (15 in each stratum) and a total of 774 households were interviewed. This survey aimed to assess the potential added effect of ‘intense’ BCC interventions in three Western provinces. Conducted 2 years after start of these efforts, ‘non-intense’ BCC (niBBC) interventions (e.g., radio or TV) were compared to “intense” BCC (iBBC) implemented through a set of interpersonal communication strategies such as VMWs, VHVs, mobile broadcasting units and listener viewer clubs. Results In both groups, the knowledge of the mode of malaria transmission was high (96.9 vs 97.2 %; p = 0.83), as well as of fever as a symptom (91.5 vs 93.5 %; p = 0.38). Knowledge of local risk factors, such as staying in the forest (39.7 vs 30.7 %; p = 0.17) or the farm (7.1 vs 5.1 %; p = 0.40) was low in both groups. Few respondents in either group knew that they must get tested if they suspected malaria (0.3 vs 0.1; p = 0.69). However, iBBC increased the discussions about malaria in the family (51.7 vs 35.8 %; p = 0.002) and reported prompt access to treatment in case of fever (77.1 vs 59.4 %; p

International audience; The Cambodian National Strategic Plan for Elimination of Malaria aims to move step by step toward elimination of malaria across Cambodia with an initial focus on Plasmodium falciparum malaria before achieving elimination of all forms of malaria, including Plasmodium vivax in 2025. The emergence of artemisinin-resistant P. falciparum in western Cambodia over the last decade has drawn global attention to support the ultimate goal of P. falciparum elimination, whereas the control of P. vivax lags much behind, making the 2025 target gradually less achievable unless greater attention is given to P. vivax elimination in the country. The following review presents in detail the past and current situation regarding P. vivax malaria, activities of the National Malaria Control Program, and interventional measures applied. Constraints and obstacles that can jeopardize our efforts to eliminate this parasite species are discussed.

OBJECTIVE: To estimate the direct burden of malaria among children younger than 5 years in sub-Saharan Africa (SSA) for the year 2000, as part of a wider initiative on burden estimates. METHODS: A systematic literature review was undertaken in June 2003. Severe malaria outcomes (cerebral malaria, severe malarial anaemia and respiratory distress) and non-severe malaria data were abstracted separately, together with information on the characteristics of each study and its population. Population characteristics were also collated at a national level. A meta-regression model was used to predict the incidence of malaria fevers at a national level. For severe outcomes, results were presented as median rates as data were too sparse for modelling. RESULTS: For the year 2000, an estimated 545,000 (uncertainty interval: 105,000-1,750,000) children under the age of 5 in SSA experienced an episode of severe malaria for which they were admitted to hospital. A total of 24,000 (interquartile range: 12,000-37,000) suffered from persistent neurological deficits as a result of cerebral malaria. The number of malaria fevers associated with high parasite density in under-5s in SSA in 2000 was estimated as 115,750,000 (uncertainty interval: 91,243,000-257,957,000). CONCLUSION: Our study predicts a lower burden than previous estimates of under-5 malaria morbidity in SSA. As there is a lack of suitable data to enable comprehensive estimates of annual malaria incidence, we describe the information needed to improve the validity of future estimates.

BACKGROUND: The relationships between human population movement (HPM) and health are a concern at global level. In the case of malaria, those links are crucial in relation to the spread of drug resistant parasites and to the elimination of malaria in the Greater Mekong sub-Region (GMS) and beyond. The mobile and migrant populations (MMP) who are involved in forest related activities are both at high risk of being infected with malaria and at risk of receiving late and sub-standard treatment due to poor access to health services. In Cambodia, in 2012, the National Malaria Control Programme (NMCP) identified, as a key objective, the development of a specific strategy for MMPs in order to address these challenges. A population movement framework (PMF) for malaria was developed and operationalized in order to contribute to this strategy. METHODS: A review of the published and unpublished literature was conducted. Based on a synthesis of the results, information was presented and discussed with experienced researchers and programme managers in the Cambodian NMCP and led to the development and refinement of a PMF for malaria. The framework was "tested" for face and content validity with national experts through a workshop approach. RESULTS: In the literature, HPM has been described using various spatial and temporal dimensions both in the context of the spread of anti-malarial drug resistance, and in the context of malaria elimination and previous classifications have categorized MMPs in Cambodia and the GMS through using a number of different criteria. Building on these previous models, the PMF was developed and then refined and populated with in-depth information relevant to Cambodia collected from social science research and field experiences in Cambodia. The framework comprises of the PMF itself, MMP activity profiles and a Malaria Risk Index which is a summation of three related indices: a vulnerability index, an exposure index and an access index which allow a qualitative ranking of malaria risk in the MMP population. Application of currently available data to the framework illustrates that the highest risk population are those highly mobile populations engaged in forest work. CONCLUSION: This paper describes the process of defining MMPs in Cambodia, identifying the different activities and related risks to appropriately target and tailor interventions to the highest risk groups. The framework has been used to develop more targeted behaviour change and outreach interventions for MMPs in Cambodia and its utility and effectiveness will be evaluated as part of those interventions.

BackgroundUser-friendly, accurate, point-of-care rapid tests to detect glucose-6-phosphate dehydrogenase deficiency (G6PDd) are urgently needed at peripheral level to safely recommend primaquine for malaria elimination.MethodsThe CareStart G6PD RDT (AccessBio, New Jersey, USA), a novel rapid diagnostic test and the most commonly used test, the fluorescent spot test (FST) were assessed against the quantitatively measured G6PD enzyme activity for detecting G6PDd. Subjects were healthy males and non-pregnant females aged 18 years or older residing in six villages in Pailin Province, western Cambodia.FindingsOf the 938 subjects recruited, 74 (7.9%) were severe and moderately severe G6PD deficient (enzyme activity ConclusionsThe CareStart G6PD RDT reliably detected moderate and severe G6PD deficient individuals (enzyme activity

Summary Background Valid information about cause-specific child mortality and morbidity is an essential foundation for national and international health policy. We undertook a systematic review to investigate the geographical dispersion of and time trends in publication for policy-relevant information about children's health and to assess associations between the availability of reliable data and poverty. Methods We identified data available on Jan 1, 2001, and published since 1980, for the major causes of morbidity and mortality in young children. Studies with relevant data were assessed against a set of inclusion criteria to identify those likely to provide unbiased estimates of the burden of childhood disease in the community. Findings Only 308 information units from more than 17 000 papers identified were regarded as possible unbiased sources for estimates of childhood disease burden. The geographical distribution of these information units revealed a pattern of small well-researched populations surrounded by large areas with little available information. No reliable population-based data were identified from many of the world's poorest countries, which account for about a third of all deaths of children worldwide. The number of new studies diminished over the last 10 years investigated. Interpretation The number of population-based studies yielding estimates of burden of childhood disease from less developed countries was low. The decreasing trend over time suggests reductions in research investment in this sphere. Data are especially sparse from the world's least developed countries with the highest child mortality. Guidelines are needed for the conduct of burden-of-disease studies together with an international research policy that gives increased emphasis to global equity and coverage so that knowledge can be generated from all regions of the world.

International audience; BACKGROUND:Human population movement across country borders presents a real challenge for malaria control and elimination efforts in Cambodia and its neighbouring countries. To quantify Plasmodium infection among the border-crossing population, including asymptomatic and artemisinin resistant (AR) parasites, three official border crossing points, one from each of Cambodia's borders with Thailand, Laos and Vietnam, were selected for sampling.METHODS AND FINDINGS:A total of 3206 participants (of 4110 approached) were recruited as they crossed the border, tested for malaria and interviewed. By real-time polymerase chain reaction (RT-PCR), 5.4% of all screened individuals were found to harbour Plasmodium parasites. The proportion was highest at the Laos border (11.5%). Overall there were 97 P. vivax (55.7%), 55 P. falciparum (31.6%), two P. malariae (1.1%) and 20 mixed infections (11.5%). Of identified infections, only 20% were febrile at the time of screening. Of the 24 P. falciparum samples where a further PCR was possible to assess AR, 15 (62.5%) had mutations in the K13 propeller domain gene, all from participants at the Laos border point. Malaria rapid diagnostic test (RDT) pLDH/HRP-2 identified a positivity rate of 3.2% overall and sensitivity compared to RT-PCR was very low (43.1%). Main individual risk factors for infection included sex, fever, being a forest-goer, poor knowledge of malaria prevention methods and previous malaria infection. Occupation, day of the week and time of crossing (morning vs. afternoon) also appeared to play an important role in predicting positive cases.CONCLUSIONS:This study offers a novel approach to identify asymptomatic infections and monitor AR parasite flow among mobile and migrant populations crossing the borders. Similar screening activities are recommended to identify other hot borders and characterise potential hot spots of AR. Targeted "customised" interventions and surveillance activities should be implemented in these sites to accelerate elimination efforts in the region.

Seasonal malaria chemoprevention, previously known as intermittent preventive treatment in children, is highly effective in areas with a short malaria transmission season. Here we assess seasonality in malaria incidence data and define a predictor of seasonality based on rainfall. We then use spatial rainfall, malaria endemicity and population data to identify areas likely to have highly seasonal malaria incidence, and estimate the population at risk and malaria burden in areas where seasonal malaria chemoprevention would be appropriate. We estimate that in areas suitable for seasonal malaria chemoprevention, there are 39 million children under 5 years of age, who experience 33.7 million malaria episodes and 152,000 childhood deaths from malaria each year. The majority of this burden occurs in the Sahelian or sub-Sahelian regions of Africa. Our data suggest that seasonal malaria chemoprevention has the potential to avert several million malaria cases and tens of thousands of childhood deaths each year if successfully delivered to the populations at risk., Seasonal malaria chemoprevention can lower the incidence of malaria in areas where transmission is highly periodical. Combining data on rainfall, population and malaria endemicity, Cairns et al. identify geographical areas in sub-Saharan Africa where this intervention is likely to be effective and cost-effective.

Novel malaria monitoring and evaluation (M&E) tools are urgently needed to complement the current “gold standard” Malaria Indicator Surveys (MIS). Rapid up scaling of malaria control efforts is resulting in substantial reductions in malaria burden across sub-Saharan Africa. As transmission goes down, timely, accurate, sub-national, and district level burden estimates are needed to guide increasingly targeted control efforts in remaining hotspot areas. To test a novel district level M&E tool, we have conducted a continuous (“rolling”) MIS (rMIS) since May 2010 covering 50 villages in Chikhwawa district in southern Malawi, essentially adapting an existing cross-sectional evaluation tool into a continuous monitoring tool. Here, we report on our experience after completing the first full year of monthly data collection focusing on the methods, operational aspects, and estimated costs of rMIS in a programmatic setting. The potential applicability of this promising M&E approach for district-level program managers and control efforts is discussed.

To estimate the direct burden of malaria among children younger than 5 years in sub-Saharan Africa (SSA) for the year 2000, as part of a wider initiative on burden estimates.A systematic literature review was undertaken in June 2003. Severe malaria outcomes (cerebral malaria, severe malarial anaemia and respiratory distress) and non-severe malaria data were abstracted separately, together with information on the characteristics of each study and its population. Population characteristics were also collated at a national level. A meta-regression model was used to predict the incidence of malaria fevers at a national level. For severe outcomes, results were presented as median rates as data were too sparse for modelling.For the year 2000, an estimated 545,000 (uncertainty interval: 105,000-1,750,000) children under the age of 5 in SSA experienced an episode of severe malaria for which they were admitted to hospital. A total of 24,000 (interquartile range: 12,000-37,000) suffered from persistent neurological deficits as a result of cerebral malaria. The number of malaria fevers associated with high parasite density in under-5s in SSA in 2000 was estimated as 115,750,000 (uncertainty interval: 91,243,000-257,957,000).Our study predicts a lower burden than previous estimates of under-5 malaria morbidity in SSA. As there is a lack of suitable data to enable comprehensive estimates of annual malaria incidence, we describe the information needed to improve the validity of future estimates.

Background Households in malaria endemic countries experience considerable costs in accessing formal health facilities because of childhood malaria. The Ministry of Health in Malawi has defined certain villages as hard-to-reach on the basis of either their distance from health facilities or inaccessibility. Some of these villages have been assigned a community health worker, responsible for referring febrile children to a health facility. Health facility utilization and household costs of attending a health facility were compared between individuals living near the district hospital and those in hard-to-reach villages. Methods Two cross-sectional household surveys were conducted in the Chikhwawa district of Malawi; one during each of the wet and dry seasons. Half the participating villages were located near the hospital, the others were in areas defined as hard-to-reach. Data were collected on attendance to formal health facilities and economic costs incurred due to recent childhood febrile illness. Results Those living in hard-to-reach villages were less likely to attend a formal health facility compared to those living near the hospital (Dry season: OR 0.35, 95%CI0.18-0.67; Wet season: OR 0.46, 95%CI0.27-0.80). Analyses including community health workers (CHW) as a source of formal health-care decreased the strength of this relationship, and suggested that consulting a CHW may reduce attendance at health facilities, even if indicated. Although those in hard-to-reach villages were still less likely to attend in both the dry (OR 0.53, 95%CI 0.25-1.11) and wet (OR 0.60, 95%CI 0.37-0.98) seasons. Household costs for those who attended a health facility were greater for those in HTR villages (Dry: USD5.24; Wet: USD5.60) than for those living near the district hospital (Dry: USD3.45; Wet: USD4.46). Conclusion Those living in hard-to-reach areas were less likely to attend a health facility for a childhood febrile event and experienced greater associated household costs. Consulting CHWs was infrequent, but appeared to reduce attendance at a health facility, even when indicated. Health service planners must consider geographic and financial barriers to accessing public health facilities in designing appropriate interventions.