Malaria infection and anemia status in under-five children from Southern Tanzania where seasonal malaria chemoprevention is being implemented

Background Malaria and anemia remain major public health challenges in Tanzania. Household socioeconomic factors are known to influence these conditions. However, it is not clear how these factors influence malaria transmission and anemia in Masasi and Nanyumbu Districts. This study presents findings on malaria and anemia situation in under-five children and its influencing socioeconomic factors in Masasi and Nanyumbu Districts, surveyed as part of an ongoing seasonal malaria chemoprevention operational study. Methods A community-based cross-sectional survey was conducted between August and September 2020. Finger-prick blood samples collected from children aged 3–59 months were used to test for malaria infection using malaria rapid diagnostic test (mRDT), thick smears for determination of asexual and sexual parasitemia, and thin smear for parasite speciation. Hemoglobin concentration was measured using a HemoCue spectrophotometer. A structured questionnaire was used to collect household socioeconomic information from parents/caregivers of screened children. The prevalence of malaria was the primary outcome. Chi-square tests, t-tests, and logistic regression models were used appropriately. Results Overall mRDT-based malaria prevalence was 15.9% (373/2340), and was significantly higher in Nanyumbu (23.7% (167/705) than Masasi District (12.6% (206/1635), p<0.001. Location (Nanyumbu), no formal education, household number of people, household number of under-fives, not having a bed net, thatched roof, open/partially open eave, sand/soil floor, and low socioeconomic status were major risks for malaria infection. Some 53.9% (1196/2218) children had anemia, and the majority were in Nanyumbu (63.5% (458/705), p<0.001. Location (Nanyumbu), mRDT positive, not owning a bed net, not sleeping under bed net, open/partially open eave, thatched window, sex of the child, and age of the child were major risk factors for anemia. Conclusion Prevalence of malaria and anemia was high and was strongly associated with household socioeconomic factors. Improving household socioeconomic status is expected to reduce the prevalence of the conditions in the area.

Evaluation of pilot implementation of seasonal malaria chemoprevention on morbidity in young children in Northern Sahelian Ghana

Background In Sahelian Africa, the risk of malaria increases with the arrival of the rains, particularly in young children. Following successful trials, the World Health Organization (WHO) recommended the use of seasonal malaria chemoprevention (SMC) in areas with seasonal peak in malaria cases. This study evaluated the pilot implementation of SMC in Northern Ghana. Methods Fourteen communities each serving as clusters were selected randomly from Lawra District of Upper West Region as intervention area and West Mamprusi District in the Northern Region as the non-intervention area. The intervention was undertaken by the National Malaria Control Programme in collaboration with regional health directorates using sulfadoxine-pyrimethamine plus amodiaquine and standard WHO protocols. Before and after surveys for malaria parasitaemia and haemoglobin levels as well as monitoring for malaria morbidity and mortality were undertaken. Results At the end of the intervention, participant retention was 92.9% (697/731) and 89.5% (634/708) in the intervention and the non-intervention areas, respectively. The proportion of children with asexual parasites reduced by 19% (p = 0.000) in the intervention and increased by 12% (p = 0.000) in the non-intervention area. Incidence rates of severe malaria were 10 and 20 per 1000 person-years follow up in the intervention and comparison areas, respectively with P.E of 45% (p = 0.62). For mild malaria, it was 220 and 170 per 1000 person-years in intervention and comparison area, respectively with PE of - 25% (p = 0.31). The proportion of children with anaemia defined as Hb< 11.0 g/dl reduced from 14.2% (52.8–38.6%) in the intervention area as compared to an increase of 8.1% (54.5% to 62.6) the non-intervention arm, Mean Hb reduced by 0. 24 g/dl (p = 0.000) in the non-intervention area and increased of 0.39 g/dl (p = 000) in the intervention area. Conclusions The feasibility and effectiveness of SMC introduction in Northern Ghana was demonstrated as evidenced by high study retention, reduction in malaria parasitaemia and anaemia during the wet season.

Effectiveness and Community Acceptance of Extending Seasonal Malaria Chemoprevention to Children 5 to 14 Years of Age in Dangassa, Mali

Seasonal malaria chemoprevention (SMC) was adopted in Mali in 2012 for preventing malaria in children younger than 5 years. Although this strategy has been highly effective in reducing childhood malaria, an uptick in malaria occurrence has occurred in children 5 to 15 years of age. This study aimed to investigate the feasibility of providing SMC to older children. A cohort of 350 children age 5 to 14 years were monitored during the 2019 transmission season in Dangassa, Mali. The intervention group received five monthly rounds of sulfadoxine–pyrimethamine plus amodiaquine, whereas the control group consisted of untreated children. Community acceptance for extending SMC was assessed during the final round. Logistic regression models were applied to compare the risk of Plasmodium falciparum malaria infection, anemia, and fever between the intervention and control groups. Kaplan-Meier survival analyses were used to compare the time to P. falciparum parasitemia infection between the groups. The community acceptance rate was 96.5% (139 of 144). Significant declines were observed in the prevalence of P. falciparum parasitemia (adjusted odds ratio, 0.22; 95% CI, 0.11–0.42) and anemia (adjusted odds ratio, 0.15; 95% CI, 0.07–0.28) in the intervention group compared with the control group. The cumulative incidence of P. falciparum infections was significantly greater (75.4%, 104 of 138) in the control group compared with the intervention group (40.7%, 61 of 143, P = 0.001). This study reveals that expanding SMC to older children is likely feasible, has high community acceptance, and is in reducing uncomplicated malaria and anemia in older children.

Co-implementing Vitamin A supplementation with Seasonal Malaria Chemoprevention in Sokoto State, Nigeria: a feasibility and acceptability study

Background Bi-annual high dose vitamin A supplements administered to children aged 6-59 months can significantly reduce child mortality, but vitamin A supplementation (VAS) coverage is low in Nigeria. The World Health Organization recommends that VAS be integrated into other public health programmes which are aimed at improving child survival. Seasonal malaria chemoprevention (SMC) provides a ready platform for VAS integration to improve health outcomes. Methods A mixed methods study design was used to assess the feasibility and acceptability of co-implementing VAS with SMC in one local government area of Sokoto state in northern Nigeria. Existing SMC implementation tools and job aids were revised and community drug distributors, experienced in SMC delivery, were trained on the determination of VAS eligibility, administration of the correct doses and identification of adverse drug reactions. SMC and VAS were delivered using a door-to-door approach. VAS and SMC coverage were calculated and the outcome of the integration was assessed using questionnaires administered to 188 and 197 households at baseline and endline respectively. The Bowen framework was used to assess feasibility through focus group discussions and key informant interviews; thematic analysis was carried out on the qualitative data. Results At endline, the proportion of children who received at least one dose of VAS in the last six months increased significantly from 2–59% (p<0.001). There were no adverse effects on the coverage of SMC delivery with 70% eligible children reached at baseline, increasing to 76% (p=0.412) at endline. There was no significant change (p=0.264) in the quality of SMC, measured by proportion of children receiving their first dose as directly observed treatment (DOT), at endline (68%) compared to baseline (54%). Study findings demonstrated acceptability among caregivers, community drug distributors, State and National healthcare officials. Conclusion This study showed that it is feasible and acceptable to integrate VAS with SMC delivery in areas of high seasonal malaria transmission such as northern Nigeria, where SMC campaigns are implemented. SMC-VAS integrated campaign can significantly increase vitamin A coverage but more research is required to demonstrate the feasibility of this integration in different settings and on a larger scale.

Prevalence of malaria in an area receiving seasonal malaria chemoprevention in Niger

Background Malaria transmission is highly seasonal in Niger. Despite the introduction of seasonal malaria chemoprevention (SMC) in the Magaria District, malaria incidence remains high, and the epidemiology of malaria in the community is not well-understood. Methods Four cross-sectional, household-based malaria prevalence surveys were performed in the Magaria District of Niger between October 2016 and February 2018. Two occurred during the peak malaria season and two during the low malaria season. Individuals in each of three age strata (3–59 months, 5–9 years, and 10 years and above) were sampled in randomly-selected households. Capillary blood was collected by fingerprick, thick and thin blood films were examined. Microscopy was performed at Epicentre, Maradi, Niger, with external quality control. The target sample size was 396 households during the high-season surveys and 266 households during the low-season surveys. Results Prevalence of parasitaemia was highest in children aged 5–9 years during all four surveys, ranging between 53.6% (95%CI 48.8–63.6) in February 2018 and 73.2% (66.2–79.2) in September 2017. Prevalence of parasitaemia among children aged 3–59 months ranged between 39.6% (33.2–46.4) in February 2018 and 51.9% (45.1–58.6) in October 2016. Parasite density was highest in children aged 3–59 months during all four surveys, and was higher in high season surveys than in low season surveys among all participants. The prevalence of gametocytaemia in children aged 3–59 months ranged between 9.9% (6.5–14.8) in February 2018 and 19.3% (14.6–25.2) in October 2016. The prevalence of gametocytaemia in children aged 5–9 years ranged between 6.3% (3.5–11.1) in February 2018 and 18.5% (12.7–26.1) in October 2016. Conclusions Asymptomatic malaria infection is highly prevalent in this area, even during the season with low incidence of clinical malaria. The high prevalence of parasitaemia in children aged 5–9 years warrants considering their inclusion in SMC programmes in this context.

Modeled Impact of Seasonal Malaria Chemoprevention on District-Level Suspected and Confirmed Malaria Cases in Chad Based on Routine Clinical Data (2013–2018)

Sulfadoxine-pyrimethamine plus amodiaquine to children aged 3–59 months is delivered 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.

Co-implementing Vitamin A supplementation with Seasonal Malaria Chemoprevention in Sokoto State, Nigeria: a feasibility and acceptability study

BackgroundBi-annual high dose vitamin A supplements administered to children aged 6-59 months can significantly reduce child mortality, but vitamin A supplementation (VAS) coverage is low in Nigeria. The World Health Organization recommends that VAS be integrated into other public health programmes which are aimed at improving child survival. Seasonal malaria chemoprevention (SMC) provides a ready platform for VAS integration to improve health outcomes.MethodsA mixed methods study design was used to assess the feasibility and acceptability of co-implementing VAS with SMC in one local government area of Sokoto state in northern Nigeria. Existing SMC implementation tools and job aids were revised and community drug distributors, experienced in SMC delivery, were trained on the determination of VAS eligibility, administration of the correct doses and identification of adverse drug reactions. SMC and VAS were delivered using a door-to-door approach. VAS and SMC coverage were calculated and the outcome of the integration was assessed using questionnaires administered to 188 and 197 households at baseline and endline respectively. The Bowen framework was used to assess feasibility through focus group discussions and key informant interviews; thematic analysis was carried out on the qualitative data. ResultsAt endline, the proportion of children who received at least one dose of VAS in the last six months increased significantly from 2% to 59% (p<0.001). There were no adverse effects on the coverage of SMC delivery with 70% eligible children reached at baseline, increasing to 76% (p=0.412) at endline. There was no significant change (p=0.264) in the quality of SMC, measured by proportion of children receiving their first dose as directly observed treatment (DOT), at endline (68%) compared to baseline (54%). Study findings demonstrated acceptability among caregivers, community drug distributors, State and National healthcare officials. ConclusionThis study showed that it is feasible and acceptable to integrate VAS with SMC delivery in areas of high seasonal malaria transmission such as northern Nigeria, where SMC campaigns are implemented. SMC-VAS integrated campaign can significantly increase vitamin A coverage but more research is required to demonstrate the feasibility of this integration in different settings and on a larger scale.

Risk of Plasmodium falciparum infection in south-west Burkina Faso - potential impact of expanding eligibility for seasonal malaria chemoprevention

Background Burkina Faso has one of the highest malaria burdens in sub-Saharan Africa despite the mass deployment of insecticide-treated nets (ITNs) and use of seasonal malaria chemoprevention (SMC) in children aged up to 5 years. Identification of risk factors for Plasmodium falciparum infection in rural Burkina Faso could help to identify and target malaria control measures. Methods A cross-sectional survey of 1,199 children and adults was conducted during the peak malaria transmission season in south-west Burkina Faso in 2017. Logistic regression was used to identify risk factors for microscopically confirmed P. falciparum infection. A malaria transmission dynamic model was used to determine the impact on malaria cases averted of administering SMC to children aged 5–15 year old. Results P. falciparum prevalence was 32.8% in the study population. Children aged 5 to < 10 years old were at 3.74 times the odds (95% CI = 2.68–5.22, p < 0.001) and children aged 10 to 15 years old at 3.14 times the odds (95% CI = 1.20–8.21, p = 0.02) of P. falciparum infection compared to children aged less than 5 years old. Administration of SMC to children aged up to 10 years is predicted to avert an additional 57 malaria cases per 1000 population per year (9.4% reduction) and administration to children aged up to 15 years would avert an additional 89 malaria cases per 1000 population per year (14.6% reduction) in the Cascades Region, assuming coverage of pyrethroid-piperonyl butoxide ITNs. Conclusion Malaria infections were high in all age strata, although highest in children aged 5 to 15 years, despite roll out of core malaria control interventions. Given the burden of infection in school-age children, extension of the eligibility criteria for SMC could help reduce the burden of malaria in Burkina Faso and other countries in the region.

Effectiveness of seasonal malaria chemoprevention (SMC) treatments when SMC is implemented at scale: Case–control studies in 5 countries

Background Seasonal malaria chemoprevention (SMC) has shown high protective efficacy against clinical malaria and severe malaria in a series of clinical trials. We evaluated the effectiveness of SMC treatments against clinical malaria when delivered at scale through national malaria control programmes in 2015 and 2016. Methods and findings Case–control studies were carried out in Mali and The Gambia in 2015, and in Burkina Faso, Chad, Mali, Nigeria, and The Gambia in 2016. Children aged 3–59 months presenting at selected health facilities with microscopically confirmed clinical malaria were recruited as cases. Two controls per case were recruited concurrently (on or shortly after the day the case was detected) from the neighbourhood in which the case lived. The primary exposure was the time since the most recent course of SMC treatment, determined from SMC recipient cards, caregiver recall, and administrative records. Conditional logistic regression was used to estimate the odds ratio (OR) associated with receipt of SMC within the previous 28 days, and SMC 29 to 42 days ago, compared with no SMC in the past 42 days. These ORs, which are equivalent to incidence rate ratios, were used to calculate the percentage reduction in clinical malaria incidence in the corresponding time periods. Results from individual countries were pooled in a random-effects meta-analysis. In total, 2,126 cases and 4,252 controls were included in the analysis. Across the 7 studies, the mean age ranged from 1.7 to 2.4 years and from 2.1 to 2.8 years among controls and cases, respectively; 42.2%–50.9% and 38.9%–46.9% of controls and cases, respectively, were male. In all 7 individual case–control studies, a high degree of personal protection from SMC against clinical malaria was observed, ranging from 73% in Mali in 2016 to 98% in Mali in 2015. The overall OR for SMC within 28 days was 0.12 (95% CI: 0.06, 0.21; p < 0.001), indicating a protective effectiveness of 88% (95% CI: 79%, 94%). Effectiveness against clinical malaria for SMC 29–42 days ago was 61% (95% CI: 47%, 72%). Similar results were obtained when the analysis was restricted to cases with parasite density in excess of 5,000 parasites per microlitre: Protective effectiveness 90% (95% CI: 79%, 96%; P<0.001), and 59% (95% CI: 34%, 74%; P<0.001) for SMC 0–28 days and 29–42 days ago, respectively. Potential limitations include the possibility of residual confounding due to an association between exposure to malaria and access to SMC, or differences in access to SMC between patients attending a clinic and community controls; however, neighbourhood matching of cases and controls, and covariate adjustment, attempted to control for these aspects, and the observed decline in protection over time, consistent with expected trends, argues against a major bias from these sources. Conclusions SMC administered as part of routine national malaria control activities provided a very high level of personal protection against clinical malaria over 28 days post-treatment, similar to the efficacy observed in clinical trials. The case–control design used in this study can be used at intervals to ensure SMC treatments remain effective.