Seasonal Malaria Research Articles

Development of a new wealth index for South Sudan: association between household wealth and malaria prevention practices in the context of seasonal malaria chemoprevention in Northern Bahr el Ghazal, South Sudan

BackgroundThe World Health Organization recommends seasonal malaria chemoprevention (SMC) using sulfadoxine-pyrimethamine and amodiaquine (SPAQ) to prevent malaria among children aged 3–59 months in regions with marked seasonality of malaria transmission. Socioeconomic disparities in household malaria prevention within the SMC context remain uncharacterized. This study aimed to construct a household wealth index and examine its association with SMC implementation, children malaria infection, and malaria prevention practices in South Sudan. MethodsWe utilized data from repeated cross-sectional household surveys conducted in Aweil County in 2022, involving 2767 households. The survey included asset-based questions tailored to the local context. We constructed a 12-item wealth score scale based on asset ownership using Mokken scale analysis and calculated weighted scores using multiple correspondence analysis to obtain wealth index quintiles. Survey-weighted logistic regressions were performed to assess the association of household wealth index quintiles with SMC implementation, children malaria infection, and malaria prevention practices. ResultsThe constructed 12-item wealth scale demonstrated strong internal consistency (Cronbach’s alpha = 0.72). However, households in the lower wealth quintiles (1st quintile) had lower odds of ownership of mosquito nets compared with those in the 3rd quintile [odds ratio (OR) = 0.12, 95% confidence interval (CI): 0.05–0.26, P < 0.001)]. Households in the highest wealth quintile (5th quintile) had higher odds of access to alternative malaria prevention tools (e.g., repellents) compared with the 3rd quintile (OR = 2.75, 95% CI: 1.30–5.83, P = 0.010). However, household wealth was not significantly associated with SMC implementation (household visits by SMC boma distributors, child receipt of Day 1 SPAQ, and caregiver SMC knowledge) or malaria infection outcomes within SMC context.ConclusionsThe new wealth index tailored to South Sudan is a useful tool for assessing socioeconomic health determinants. While household access to SMC showed a low degree of wealth-associated disparities, reflecting the equitable coverage of the door-to-door SMC delivery model, significant inequities remain in household access to other malaria prevention practices, such as mosquito nets. These findings imply the need for strategies to enhance equity in distributing essential malaria prevention resources.Graphical

A survey of indoor and outdoor Anopheles density, species composition and circumsporozoite rate of malaria vectors on the Bijagós Archipelago, Guinea-Bissau

BackgroundThe malaria-endemic Bijagós Archipelago is situated 50 km off the coast of mainland Guinea-Bissau. It is a seasonal malaria transmission setting, with insecticide-treated bed nets as its primary control strategy. Little is known about the vector diversity and behaviour across the Archipelago.MethodsIn 2019, a survey took place on 16 of the inhabited islands across the Archipelago. Adult mosquitoes were collected using odour-baited outdoor light traps and indoor light traps at houses selected at random. Larval surveys were conducted for each village sampled. Anopheles adults caught were morphologically identified and a sub-sample was analysed to identify species within the Anopheles gambiae complex using RFLP-PCR. Sporozoite positivity was detected within a sub-sample by CSP-ELISA.ResultsAnopheles gambiae sensu lato was present on all islands sampled. Anopheles density varied between islands, with densities ranging from 0.0 to 98.7 per trapping night from indoor traps and 0.1–165.2 per trapping night from outdoor traps. Anopheles melas was the most commonly observed species, accounting for 85.2% of all Anopheles caught from both indoor and outdoor light traps. A high level of hybridization between An. gambiae sensu stricto and Anopheles coluzzii was seen on some islands across the Archipelago. The overall sporozoite rate was 0.86% (0.2% for indoor traps; 1.4% for outdoor traps).ConclusionsSpecies within An. gambiae s.l. are the primary vectors on the Bijagós. Anopheles melas may contribute to transmission throughout the year in the Bijagós. The vector species composition, abundance and infection rates uncovered in this study are useful for informing tailored, effective vector control programme in the Bijagos.

Malaria Parasitemia after Mass Distribution of Azithromycin to Prevent Child Mortality in Burkina Faso: Results from a Cluster Randomized Trial.

The twice-yearly mass distribution of azithromycin to children aged 1-59 months reduces all-cause child mortality. It has been suggested in some studies that mass azithromycin distributions may reduce malaria mortality and parasitemia; however, these studies have been conducted in the absence of seasonal malaria chemoprevention (SMC). Here, we evaluate malaria parasitemia in a cluster randomized trial of azithromycin versus a placebo in Burkina Faso, where SMC was being administered. Thin and thick smears were taken from a random sample of 15 children per cluster in 40 clusters that had been receiving twice-yearly azithromycin or a placebo for 36 months (six distributions). We found no evidence of a difference in malaria parasitemia between children in the azithromycin and placebo clusters (mean difference -6% prevalence; 95% CI -17% to 6%; P = 0.33). These results suggest that reductions in malaria parasitemia may not be a major contributor to the effect of azithromycin on child mortality in settings in which SMC is administered.

Molecular analysis supports at least two putative species within Anopheles pseudopunctipennis s.l. on the American mainland.

Anopheles (Anopheles) pseudopunctipennis, involved in seasonal malaria transmission in the Andean foothills and American coastal areas, was previously proposed as a species complex based on cross-mating experiments and population genetic analyses. In this work, a fragment of the mitochondrial gene cytochrome c oxidase subunit I or COI barcode region, and the nuclear second internal transcribed spacer (ITS2) were analysed in Colombian An. pseudopunctipennis s.l. specimens; the obtained sequences were compared to publicly available data using phylogeny and distance-based species delimitation approaches. Assemble Species by Automatic Partitioning (ASAP) and coalescent-based approaches provided strong evidence of at least two putative species on the American mainland, here designated as the North-Central and Southern lineages. The North-Central lineage is primarily found in southern/southwestern United States, Central America (Mexico and Honduras) and northwestern Colombia, while the Southern lineage is mainly detected in the Colombian Pacific and Argentina; there were some co-occurrences of these lineages in the Colombian regions. The definition of these putative species is crucial for understanding their bionomy, ecology and potential role in malaria transmission. Further research, including a more comprehensive sampling and population genetic analysis, is needed to fully elucidate their evolutionary history and demographic dynamics.

Integrating mobility, travel survey, and malaria case data to understand drivers of malaria importation to Zanzibar, 2022–2023

Background.Zanzibar has achieved historic reductions in malaria incidence, but high connectivity to mainland Tanzania and imported cases continue to pose a challenge to “last mile” malaria elimination.Methods.To understand factors driving malaria importation, we collected travel histories and demographics of malaria cases presenting to 94 health facilities across Zanzibar’s main island, Unguja, from 2022–2023. We also used two other sources of mobility data—self-reported travel at the outbound Dar es Salaam ferry terminal and Meta Data for Good colocation and movement distribution—to examine movement patterns between Unguja and mainland Tanzania. We integrated these with CHIRPS rainfall data to explore the seasonality of human movement and travel-associated malaria risk.Results.Among 1,155 malaria cases with recent travel to mainland Tanzania, travel to Tanga (21%), Dar es Salaam (20%), and Morogoro (15%) were most common. Nearly half of travelers had spent over 14 nights away from home; the majority were visiting family. While mainlanders made up two-thirds of ferry travelers, 28% of Unguja malaria cases reported primary residence on the mainland; these were young adult males working in farming as well as children under age 5. Long-distance travel off the island decreased during the rainy seasons, while rainfall in mainland destinations correlated with imported malaria cases. With different biases, colocation and ferry data reflected the proportion of cases imported from different malaria risk regions on the mainland.Discussion.Movement flows and seasonal rainfall patterns drive imported malaria in predictable ways that can be harnessed to target high-risk travelers for intervention.

Anti-sporozoite monoclonal antibody for malaria prevention: secondary efficacy outcome of a phase 2 randomized trial.

CIS43LS is a long-acting monoclonal antibody specific for the Plasmodium falciparum circumsporozoite protein expressed on sporozoites. We previously reported that CIS43LS is protective against P. falciparum infection as detected by thick blood smear (TBS; primary endpoint) in a phase 2 double-blind randomized trial involving 330 healthy Malian adults receiving placebo or a single intravenous infusion of 10 mg kg-1 or 40 mg kg-1 of CIS43LS (1:1:1). At enrollment, all participants received artemether-lumefantrine to clear possible P. falciparum infection. Although TBS examination is the standard assay to assess efficacy in malaria vaccines trials in endemic areas, it has poor analytical sensitivity; therefore, it remained unknown whether CIS43LS had achieved sterile protection against infection. Here we report the prespecified secondary efficacy endpoint that used a Plasmodium 18S rRNA quantitative reverse transcription-PCR (qRT-PCR) assay that is ~2,000-fold more sensitive than TBS. We analyzed 5,015 dried blood spots collected before CIS43LS or placebo administration and biweekly thereafter over a 6-month malaria season. At 6 months, efficacy of CIS43LS against qRT-PCR-detected infection assessed in a time-to-event analysis was 87.4% for 40 mg kg-1 (adjusted 95% confidence interval (CI), 79.5-92.3; P < 0.001) and 77.0% for 10 mg kg-1 (adjusted 95% CI, 65.0-84.0; P < 0.001) versus placebo. A post hoc analysis with a gametocyte mRNA-specific qRT-PCR assay showed 6-month efficacy against gametocytemia of 87.7% for 40 mg kg-1 (adjusted 95% CI, 75.6-93.8; P < 0.001) and 73.0% for 10 mg kg-1 (adjusted 95% CI, 54.0-84.0; P < 0.001), versus placebo. These data indicate that a single dose of anti-sporozoite monoclonal antibodies can achieve durable, sterile protection against P. falciparum infection, underscoring their potential to reduce malaria disease burden and transmission. ClinicalTrials.gov identifier: NCT04329104 .

Performances of Malaria PfHRP2 and the Combined PfHRP2/pLDH Based Rapid Diagnostic Tests among Children Under Five Years of Age in a High Seasonal Malaria Transmission Area in Burkina Faso

PurposeDespite countrywide seasonal malaria chemoprevention (SMC) in Burkina Faso, malaria remains high among under-five year children during peak transmission season, questioning about SMC effectiveness and diagnostic tools accuracy.MethodsThis study assessed the performance of SD-Bioline malaria rapid diagnostic test (RDT) P.f® (PfHRP2) alongside combined SD-Bioline malaria RDT P.f® (HRP2/pLDH) and light microscopy (LM) against varATS quantitative polymerase chain reaction (qPCR) as reference, among SMC-aged children in high seasonal malaria transmission setting in Burkina Faso. A two-year longitudinal study (March 2019-March 2021) conducted in Nanoro health district screened 995 suspected malaria cases. Diagnostic performances of PfHRP2-based RDT and LM were assessed in all cases, while both RDTs were evaluated in a subgroup of 401.ResultsMalaria proportion was 79.9% (795/995), 88.7% (883/995) and 73.6% (732/995) by varATS qPCR, PfHRP2-based RDT and LM respectively. PfHRP2-based RDT and the LM showed similar accuracy [85.3% (95%CI: 83.0-87.5) and 84.6% (95%CI: 82.2–86.8), respectively], but differed in specificity [41.5% (95%CI: 34.6–48.7) versus 77.5% (95%CI: 71.1–83.1), p < 0.001]. Specificity of PfHRP2-based RDT further declined during the high transmission season compared to the low [27.1% (95%CI: 19.0-36.6) versus 58.1% (95%CI: 47.4–68.2), p < 0.001]. In the subgroup, PfHRP2/pLDH-based RDT showed higher specificity than PfHRP2-based RDT during both high [42.3% (95%CI: 28.7–56.8) versus 17.3% (95%CI: 8.2–30.3), p < 0.001] and low transmission seasons [84.0% (95%CI: 63.9–95.5) versus 60.0% (95%CI: 38.7–78.9), p < 0.001]. Moreover, LM substantially agreed with PfHRP2/pLDH-based RDT (Kappa = 0.71), but moderately with PfHRP2-based RDT (Kappa = 0.46).ConclusionFindings suggest revising of malaria RDT recommendations, promoting PfHRP2/pLDH-based RDTs to improve malarial and non-malarial fevers management in SMC-aged children.

Estimating the potential malaria morbidity and mortality avertable by the US President's Malaria Initiative in 2025: a geospatial modelling analysis.

Estimating the potential malaria morbidity and mortality avertable by the US President's Malaria Initiative in 2025: a geospatial modelling analysis.

Effect of mass drug administration on malaria incidence in southeast Senegal during 2020-22: a two-arm, open-label, cluster-randomised controlled trial.

Effect of mass drug administration on malaria incidence in southeast Senegal during 2020-22: a two-arm, open-label, cluster-randomised controlled trial.

Intense rainfalls and floods reshape malaria transmission in Niger.

Intense rainfalls and floods reshape malaria transmission in Niger.

Study of the coverage and the impact of the chemoprevention of seasonal malaria in Niger from 2013 to 2022: systematic review

Purpose Malaria remains a public health problem in Niger, especially among children under the age of five. To combat this scourge, since 2012, the World Health Organization (WHO) has recommended seasonal malaria chemoprevention (SMC), a strategy based on the administration of sulfadoxine-pyrimethamine and amodiaquine (SP-AQ) during the period of high transmission. This systematic review assesses the coverage, efficacy, and challenges of SMC in Niger between 2013 and 2022, analyzing its impact on malaria morbidity and mortality. Materials and methods The PRISMA guidelines were used to ensure a rigorous and comprehensive recording of the systematic review process. Through searches in five different databases, articles were imported into Zotero software, then transferred to the Covidence application, where data processing was carried out. The selected articles were independently evaluated by two reviewers. These included studies that assessed coverage, malaria incidence, and the impact of SMC. Studies published in French and English were included. Data extraction from the included studies was performed, and a quality assessment was conducted, including an evaluation of the risk of bias. Results Among the six studies, three assessed SMC coverage in all eight regions of Niger while also evaluating side effects. They showed high overall coverage but low coverage in some areas. Another study examined the impact in terms of the incidence of complicated malaria, malaria-related hospitalization, and mortality. Another publication revealed that antibody responses against the blood and pre-erythrocytic stages of P. falciparum were higher in the area where SMC was implemented. Conclusions This study demonstrates that SMC has a significant impact on reducing malaria incidence. Although there is high overall coverage, variations exist, particularly in hard-to-reach areas. Few adverse events were reported. However, very few studies are available, highlighting the need for additional research in Niger to better understand this strategy.

RDT performance through high-throughput bead-based antigen detection during malaria school survey in Senegal.

Rapid Diagnostic Tests (RDTs) remain the frontline tool for malaria diagnosis, but their performance in detecting low-density infections is variable and poorly characterized at the population level. This study aimed to evaluate the diagnostic performance of HRP2-based RDTs by integrating high-throughput bead-based HRP2 quantification into school-based malaria surveys. A cross-sectional study was conducted in three Senegalese districts (Diourbel, Tambacounda, and Kédougou), enrolling 3,748 school-aged children. All participants were tested using RDTs, and dried blood spots were analyzed with a multiplex bead-based HRP2 assay. A Gaussian mixture model was used to classify HRP2 positivity, and logistic regression assessed the relationship between HRP2 concentration and RDT outcome. The overall RDT positivity rate was 7.2%, with marked heterogeneity across districts (Diourbel: 3.0%, Kédougou: 15.9%, Tambacounda: 7.6%). HRP2 concentration was the strongest predictor of RDT positivity (aOR: 14.55 per log10 increase, 95% CI: 11.14-19.00). RDT limits of detection (LOD95) varied significantly: 3.9 ng/mL in Tambacounda, 121.2 ng/mL in Kédougou, and 204.3 ng/mL in Diourbel. RDTs remain a useful surveillance tool, particularly in moderate- to high-transmission settings. However, reduced sensitivity at lower antigen concentrations in hypo-endemic areas highlights the value of complementary high-sensitivity assays for elimination-focused strategies. Future research should explore the application of these integrated diagnostic approaches in regions without seasonal malaria chemoprophylaxis intervention.

“I heard at home. The leader came by to inform”. The role of community leaders and community distributors in promoting uptake of seasonal malaria chemoprevention in Nampula Province, Mozambique: a qualitative study

BackgroundSeasonal malaria chemoprevention (SMC) is a highly effective intervention to prevent malaria in children, in high transmission areas that have seasonal peaks. Since 2020, SMC with sulfadoxine -pyrimethamine plus amodiaquine (SPAQ) has been implemented in northern Mozambique. During SMC campaigns community leaders are involved in the sensitisation and mobilisation of households prior to the start of the SMC round. This qualitative study explores perceptions among caregivers and other stakeholders of the importance of community leader and community distributor engagement for enhancing community knowledge, acceptance and uptake of SMC.MethodsA qualitative study, consisting of focus group discussions (FGDs) and key informant interviews (KIIs), was conducted in four districts of Nampula province in northern Mozambique during two SMC campaign rounds. Focus group discussions were conducted with caregivers whose children received SMC, and implementers involved in delivering SMC. Key informant interviews were conducted with stakeholders actively involved in SMC implementation at national, provincial, and district levels. Participants were identified through purposive sampling. All FGDs and KIIs were conducted in Portuguese or Emakhuwa. Data were coded and thematically analysed using MAXQDA2022.ResultsBetween April 2021 and June 2022, KIIs were conducted with community leaders (n = 11) and stakeholders at national (n = 8), province (n = 8) and district level (n = 4). Focus group discussions (FGDs) (n = 42) were conducted with caregivers (n = 152), community distributors (n = 70), community distributors’ supervisors (n = 23) and health workers (n = 30). Findings showed there was unanimous recognition among caregivers, community distributors, and key stakeholders, of the critical role community engagement played during the SMC campaign. Caregivers reported obtaining information about SMC from local leaders, and that community distributors provided additional information and helped to build trust, and reduced anxiety and distrust towards the medication. Community leaders’ participation during community distributors household visits was also reported to promote participant recruitment, fostering a sense of intervention ownership. Stakeholders believed that the active involvement of community leaders helped prevent misinformation about the SMC campaign.ConclusionInvolving community leaders in the mobilisation and distribution of interventions, such as SMC, helps to facilitate active participation from the community and result in greater acceptability and community uptake.

Seasonal malaria chemoprevention in northern Mozambique: a cost-effectiveness analysis

Abstract Background Malaria is endemic in Mozambique and one of the leading causes of death in children under 5 years old. In 2020 the country adopted the WHO-recommended seasonal malaria chemoprevention (SMC) strategy and delivered the intervention in all 23 districts of Nampula province between January and April 2023. The aim of this study is to estimate the cost-effectiveness of SMC in Nampula, Mozambique. Methods Financial cost of implementing SMC were estimated from a limited health care provider perspective for the year 2023 in US$. Data on resource use of the SMC implementation was assessed from Malaria Consortium records. The number of eligible and treated children was collected from surveys after cycle 4. The number of malaria cases, deaths and Disability Adjusted Life-Years (DALYs) averted were estimated based on data from Global Burden of Disease 2019, Malaria Indicator Survey 2018, and National Malaria Control Programme. Incremental cost-effectiveness ratios (ICERs) were estimated, and sensitivity analyses were used to test the robustness of the ICERs. Results The total financial cost of SMC implementation in Nampula province in 2023 was estimated to be $7,871,361.72. The study estimated a cost per targeted child of $6.05 and a cost per child who received full 3-day course of sulfadoxine-pyrimethamine in combination with amodiaquine (SPAQ) of $7.92. Furthermore, the cost per household with eligible children visited by a community distributor was $7.65; the cost per child who received day 1 SPAQ was $7.85 and the cost per child who received day 1 SPAQ by community distributor adhering to directly observed treatment was $8.50. In addition, the estimated cost was $93.50 per malaria case averted, $3286.59 per malaria death averted, and $130.16 per DALY averted. The ICERs were robust to a variety of alternative assumptions on costs and benefit estimates. Finally, $1,726,189.63 could have been saved if no ineligible children (60–119 months old) were treated through the programme. Conclusions In line with existing evidence from other African countries, SMC is found to be cost-effective in Mozambique. SMC is a beneficial prevention strategy to improve under-five health in the country, at a relatively low-cost.

Micronutrient Powders Combined With Malaria Chemoprevention to Improve Anaemia and Cognitive Function in Early Childhood in Mali: A Cluster-Randomised Trial.

A cluster-randomised controlled trial was conducted in 60 communities in southern Mali to evaluate the impact of micronutrient powders (MNP) combined with seasonal malaria chemoprevention (SMC) on anaemia (primary endpoint), Plasmodium infection, stunting and cognitive function in children < 5 years. The 60 communities were randomly allocated to the intervention or control arm, and cross-sectional biomedical and cognitive surveys were conducted after 1 and 3 years in a random sample of 3 and 5 years olds (1052 and 1081 children, respectively). All children aged 3-59 m in intervention and control communities received two rounds of SMC each year during the peak malaria season, and in intervention communities, all children aged 6-59 m additionally received 4 months of daily MNP after the peak malaria season. Despite a high baseline prevalence of anaemia and good fidelity to intervention, this trial found no evidence of impact on study outcomes. The prevalence of anaemia was similar in both arms for both age groups after 1 and 3 years of intervention-after 3 years, the prevalence of anaemia amongst 3-year olds was 57.6% in the intervention arm versus 60.1% in the control group (p = 0.352). For 5-year olds, it was 51.3% and 53.0%, respectively (p = 0.607). No effect was observed on stunting or cognitive function either.

Supporting evidence-based decisions about the geographic and demographic extensions of seasonal malaria chemoprevention in Benin: A modelling study.

Seasonal malaria chemoprevention (SMC) has been implemented yearly in northern Benin since 2019 to reduce the malaria burden in children under 5 years of age. Its geographic scope was progressively extended until in 2022 two different extensions of SMC were considered: either demographic - children aged 5-10 in the currently targeted departments would also receive SMC, or geographic to children under 5 in new eligible departments to the south. As SMC had neither been implemented in the areas nor in the age groups suggested for expansion, modelling was used to compare the likely impact of both extensions. The model OpenMalaria was calibrated to represent the history of malaria interventions and transmission risk in administrative units of Benin. Currently planned future interventions and two scenarios for SMC extensions were simulated to inform where impact would be the highest. The model predicted that between 2024 and 2026 the geographic extension of SMC would avert at least four times more severe malaria cases and five times more direct malaria deaths per targeted child than the demographic extension. Indeed, most severe cases are concentrated in children under 5 in all departments of interest, as malaria burden remains high in this region. Numbers of severe cases averted per targeted child were similar between health zones eligible for geographic extension. The main limitations of this work are global model parameters due to lack of country-specific data on efficacy of interventions or development of immunity. SMC coverage was assumed to be uniform across rounds, zones, and age groups. Due to the high malaria burden in northern and central Benin, the geographic extension would be more impactful than the demographic extension both in absolute number of severe cases averted and per child protected, and has started to be implemented in 2024. Health zones were prioritised by availability of community health workers to deliver SMC. Mathematical modelling was a supportive tool to understand the relative impact of the different proposed SMC extensions and contributed to the decision-making process. Its integration significantly enhanced the utilisation of data for decision-making purposes. Rather than being used for forecasting, the model provided qualitative guidance that complemented other types of evidence.

Mathematical modeling of malaria vaccination with seasonality and immune feedback.

Malaria is one of the deadliest infectious diseases globally, claiming hundreds of thousands of lives each year. The disease presents substantial heterogeneity among the population, with approximately two-thirds of fatalities occurring in children under five years old. Immunity to malaria develops through repeated exposure and plays a crucial role in disease dynamics. Seasonal environmental fluctuations, such as changes in temperature and rainfall, lead to temporal heterogeneity and further complicate transmission dynamics and the utility of intervention strategies. We employ an age-structured partial differential equation model to characterize seasonal malaria transmission and assess vaccination strategies that vary by timing and duration. Our model integrates vector-host epidemiological dynamics across different age groups and nonlinear feedback between transmission and immunity. We calibrate the model to year-round and seasonal malaria settings and conduct extensive sensitivity analyses for both scenarios to systematically assess which assumptions lead to the most uncertainty. We use time-varying sensitivity indices to identify critical disease parameters during low and high transmission seasons. We further investigate the impact of vaccination and its implementation in the seasonal malaria settings. When implementing a three-dose primary vaccination series, seasonally targeted campaigns can prevent significantly more cases per vaccination than constant year-long programs in regions with strong seasonal variation in transmission. In such scenarios, the optimal vaccination interval aligns with the peak in infected mosquito abundance and precedes the peak in malaria transmission. In contrast, seasonal booster programs may provide limited advantages over year-long vaccination. Additionally, while increasing annual vaccination counts can reduce overall disease incidence, it yields marginal improvements in cases prevented per vaccination.

Factors associated with malaria among 3 to 59 months old children in Boromo and Gaoua Health Districts, Burkina, 2020

Introduction: Every 75 seconds, a child under the age of 5 years dies of malaria throughout the world. Burkina Faso is ravaged by malaria and has responded to the disease by implementing several strategies including Seasonal Malaria Chemoprevention (SMC). In order to make available baseline data for the study on the efficacy of supervised 3 doses SMC distribution, this study was intended to identify malaria-associated factors in children from 0 to 59 months old in the two health districts. Methods: This is an analytical cross-sectional study, a first step of a quasi-experimental study that was conducted in Boromo and Gaoua. Data were collected outside of SMC campaigns. A logistic regression calculated the odds ratios with a level of ɑ= 0.05. Results: Age groups of 11-23 months (aOR =2.08, 95% CI = [2.02- 2.38]), 24-59 months (aOR= 2.28, 95% CI = [2.11-2.71], P&lt;0.0001); past history of fever (aOR=92.43 95% CI = [37.98-224.92]), p&lt;0.0001; ≥5km distance from village to healthcare center (aOR=4.71, 95% CI = [1.43, 15.45] , p=0.01), sleeping under a long-lasting insecticide-treated net during the last night (aOR= 0.49, 95% CI =[0.28-0.69], P=&lt;0.0001) were associated with malaria. Conclusion: Several strategies to respond better to malaria should be implemented in these two districts in order to eliminate malaria. These should target the parents of children whose age is at least one year, living far from healthcare centers, and focus on the use of insecticide-treated nets and the need to send every child with a fever to a healthcare centre.

The role of Seasonal Malaria Chemoprevention in the effect of Azithromycin on Child Mortality: A Secondary Analysis of the CHAT Cluster Randomized Clinical Trial.

Mass treatment with azithromycin (AZ) and administration of seasonal malaria chemoprevention (SMC) are both effective in reducing mortality among children under 5. However, it is not clear whether the benefit of AZ for mortality varies in the presence of routine SMC administration. The objective of this study was to examine whether the effect of mass AZ distribution on all-cause mortality among children less than 5 years of age varies with SMC administration season or SMC coverage. This was a secondary analysis of the Community Health with Azithromycin Trial (CHAT), a cluster randomized placebo-controlled trial of 341 communities in the Nouna District of Burkina Faso. Communities randomized to intervention received treatment with twice yearly mass AZ while control communities receive placebo. All communities received SMC as standard-of-care. SMC administration and coverage data were provided from National Malaria Control Program. SMC administration season was defined as the period during and immediately following SMC (July-December) versus the months of no SMC (January-June). SMC coverage was assessed as proportion of the population covered and by whether it was below or above a threshold of 80%. We used Poisson regression models with person-time at risk used as an offset and robust standard error to analyze mortality rates by treatment group and SMC subgroups and assessed interaction on both the multiplicative and additive scales. Mortality was higher in SMC seasons for both arms, with a mortality rate of 10.3 per 1,000 person-years (95% CI: 9.0 to 11.6) in SMC seasons and 7.9 (95% CI: 6.9 to 9.0) in non-SMC seasons. Compared to placebo, the mortality rate in AZ clusters was 0.77 (95% CI: 0.60 to 0.98) during SMC season, while it was 0.89 (95% CI: 0.68 to 1.15) during the non-SMC seasons. The effect of AZ compared to placebo in clusters with <80% SMC coverage was 0.73 95%CI (0.56 to 0.96) and in clusters with ≥80% SMC coverage, it was 1.0 95%CI (0.59 to 1.69). The interaction between AZ and SMC season or coverage was not statistically significant on the additive or multiplicative scales. While our findings did not reach statistical significance, they raise the question of whether prioritizing MDA AZ during high transmission periods or in regions with low SMC coverage could be beneficial. Further research is needed to determine if targeting these periods or areas could lead to greater reductions in child mortality. ClinicalTrials.gov Identifier: NCT03676764.

Safety and efficacy of the blood-stage malaria vaccine RH5.1/Matrix-M in Burkina Faso: interim results of a double-blind, randomised, controlled, phase 2b trial in children.

Two pre-erythrocytic vaccines (R21/Matrix-M and RTS,S/AS01) are now approved for Plasmodium falciparum malaria. However, neither induces blood-stage immunity against parasites that break through from the liver. RH5.1/Matrix-M, a blood-stage P falciparum malaria vaccine candidate, was highly immunogenic in Tanzanian adults and children. We therefore assessed the safety and efficacy of RH5.1/Matrix-M in Burkinabe children. In this double-blind, randomised, controlled, phase 2b trial, RH5.1/Matrix-M was given to children aged 5-17 months in Nanoro, Burkina Faso, a seasonal malaria transmission setting. Children received either three intramuscular vaccinations with 10 μg RH5.1 protein with 50 μg Matrix-M adjuvant or three doses of rabies control vaccine, Rabivax-S, given either in a delayed third-dose (0, 1, and 5 month) regimen (first cohort) or a 0, 1, and 2 month regimen (second cohort). Vaccinations were completed part way through the malaria season. Children were randomly assigned 2:1 within each cohort to receive RH5.1/Matrix-M or Rabivax-S. Participants were assigned according to a random allocation list generated by an independent statistician using block randomisation with variable block sizes. Participants, their families, and the study teams were masked to group allocation; only pharmacists who prepared the vaccines were unmasked. Vaccine safety, immunogenicity, and efficacy were evaluated. The coprimary outcomes assessed were: first, the safety and reactogenicity of RH5.1/Matrix-M; and second, the protective efficacy of RH5.1/Matrix-M against clinical malaria (measured as time to first episode of clinical malaria, using a Cox regression model) from 14 days to 6 months after the third vaccination in the per-protocol sample. This ongoing trial is registered with ClinicalTrials.gov (NCT05790889). From April 6 to 13 and July 3 to 7, 2023, 412 children aged 5-17 months were screened, and 51 were excluded. A total of 361 children were enrolled in this study. In the first cohort, 119 were assigned to the RH5.1/Matrix-M delayed third-dose group, and 62 to the equivalent rabies control group. The second cohort included 120 children in the monthly RH5.1/Matrix-M group and 60 in the equivalent rabies control group. The final vaccination was administered to all groups from Sept 4 to 21, 2023. RH5.1/Matrix-M in both cohorts had a favourable safety profile and was well tolerated. Most adverse events were mild, with the most common being local swelling and fever. No serious adverse events were reported. Comparing the RH5.1/Matrix-M delayed third-dose regimen with the pooled control groups resulted in a vaccine efficacy of 55% (95% CI 20 to 75%; p=0·0071). The same analysis showed a vaccine efficacy of 40% (-3 to 65%; p=0·066) when comparing the monthly regimen with the pooled control groups. Participants vaccinated with RH5.1/Matrix-M in both cohorts showed high concentrations of anti-RH5.1 serum IgG antibodies 14 days after the third vaccination, and the purified IgG showed high levels of in vitro growth inhibition activity against P falciparum; these responses were higher in patients who received the RH5.1/Matrix-M vaccine delayed third-dose regimen, as opposed to monthly regimen (growth inhibition activity 79·0% [SD 14·3] vs 74·2% [SD 15·9]; p=0·016). RH5.1/Matrix-M appears safe and highly immunogenic in African children and shows promising efficacy against clinical malaria when given in a delayed third-dose regimen. This trial is ongoing to further monitor efficacy over time. The European and Developing Countries Clinical Trials Partnership, the UK Medical Research Council, the National Institute for Health and Care Research Oxford Biomedical Research Centre, the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, the US Agency for International Development, and the Wellcome Trust.