Effect of routine seasonal malaria chemoprevention on malaria trends in children under 5 years in Dangassa, Mali.

BACKGROUND: Seasonal malaria chemoprevention (SMC) is a new strategy to prevent malaria in children under 5 years old. It has been recommended by the World Health Organization since 2012 in malaria-endemic areas with seasonal transmission. This study aimed to assess the changes in malaria indicators through two consecutive years of SMC routine implementation in children under 5 years old in Dangassa, where malaria is endemic with a long and high transmission season. METHODS: From 2012 to 2016, a cohort study was conducted in Dangassa village. The study team based in the village followed all malaria clinical cases in children under 5 years old at the community health centre. During the study, SMC was routinely implemented in collaboration with the National Malaria Control Programme. The Cox regression model was used in order to compare malaria risk during the study. RESULTS: The Cox regression model showed a significant reduction in malaria clinical incidence, both in 2015 (HR = 0.27 (0.18-0.40), 95% CI) and in 2016 (HR = 0.23 (0.15-0.35), 95% CI) of SMC implementation compared to October 2013. Gametocyte and fever prevalence was lower between September and October during SMC implementation (2015 and 2016) compared to the same period before SMC implementation (2013-2014). A slight increase of malaria incidence was observed in December at the end of SMC implementation. CONCLUSION: SMC has significantly reduced both malaria incidence and gametocyte prevalence and improved haemoglobin levels in children under 5 years old after 2 years of routine implementation.

The Plasmodium falciparum-specific human memory B cell compartment expands gradually with repeated malaria infections.

Immunity to Plasmodium falciparum (Pf) malaria is only acquired after years of repeated infections and wanes rapidly without ongoing parasite exposure. Antibodies are central to malaria immunity, yet little is known about the B-cell biology that underlies the inefficient acquisition of Pf-specific humoral immunity. This year-long prospective study in Mali of 185 individuals aged 2 to 25 years shows that Pf-specific memory B-cells and antibodies are acquired gradually in a stepwise fashion over years of repeated Pf exposure. Both Pf-specific memory B cells and antibody titers increased after acute malaria and then, after six months of decreased Pf exposure, contracted to a point slightly higher than pre-infection levels. This inefficient, stepwise expansion of both the Pf-specific memory B-cell and long-lived antibody compartments depends on Pf exposure rather than age, based on the comparator response to tetanus vaccination that was efficient and stable. These observations lend new insights into the cellular basis of the delayed acquisition of malaria immunity.

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.

Hemoglobin variants shape the distribution of malaria parasites in human populations and their transmission potential.

Hemoglobin variants C and S protect against severe malaria but their influence on parameters not directly linked to disease severity such as gametocyte carriage and infection chronicity is less well understood. To assess whether these infection-related phenotypes depend on the host hemoglobin genotype, we followed 500 Malian individuals over 1-2 years and determined their parasitological status during monthly visits and incidental clinical episodes. While adults heterozygous for hemoglobin S mutation were less often parasitemic compared to AA adults (odds ratio [OR] 0.50 95% confidence interval [CI] 0.31-0.79, P = 0.003), schoolchildren (but not toddlers or adults) with AC genotype carried parasites, including gametocytes, more often than their AA counterparts (OR 3.01 95% CI 1.38-6.57, P = 0.006). AC children were also likelier to be parasite-positive during the dry season, suggesting longer infections, and were more infectious in mosquito skin feeding assays than AA children. Notably, AC school-aged children, who comprise ~5% of the population, harbor a third of infections with patent gametocytes between May and August, when transmission transitions from very low to intense. These findings indicate that schoolchildren with hemoglobin C mutation might contribute disproportionately to the seasonal malaria resurgence in parts of West Africa where the HbC variant is common.

[Reference values of neonatal erythrocyte and leukocyte count in Bamako, Mali]. / Valeurs de Référence érythrocytaires et leucocytaires chez le Nouveau-né à Bamako, Mali.

Reference values for blood cell count are not established at birth in Mali. This study aimed to determine reference values for erythrocyte and leukocyte at birth in Bamako. Blood was collected from the umbilical cord immediately following its clamping and studied for complete blood cell count in 481 newborns with a birth weight > 2500g, Apgar score ≤ 7 at 5 or 10 minutes, without abnormal hemoglobin mutations and whose mothers were willing in Bamako, Mali. Other than the median and mean values, 2.5 and 97.5 percentiles were calculated. The findings suggest that the normal reference values following a timely clamping of the umbilical cord were (mean ± 1SD and range): RBC = 4,00 ± 0,46.1012/L (3,13 - 4,89), Hb = 14,12 ± 1,49 g/dL (11,20 - 17,00), Hct = 40,27 ± 4,71% (31,62 - 50,18), MCV = 101 ± 5 fl (91 - 112), MCHC = 35,37 ± 2,16 pg/cellule (30,70 - 39,59), MCH = 35,06 ± 0,93 g/dL (33,40 - 36,90), RDW = 17,79 ± 7,33% (15,50 - 20,39), Reticulocytes (109/L) = 133,081 ± 29,95 (66,62 - 200,86), GB (109/L) = 13,24 ± 7,23 (7,20 - 23,70), PMN (109/L) = 7,16 ± 4,70 (3,07 - 14,22), PME (109/L) = 0,28 ± 0,26 (0 - 0,98), PMB(109/L) = 0,05 ± 0,09 (0 - 0,31), Lymphocytes (109/L) = 4,49 ± 2,45 (1,96 - 9,42), Monocytes (109/L) = 1,06 ± 0,73 (0,21 - 2,54), myelocytes = 1.43 ± 1.51%, erythroblasts = 4.52 ± 7.83%. It should be noted that male babies had a lower neutrophil count than female newborns. By taking into account these results when interpreting the blood cell count in Malian newborn infants, costly misdiagnoses should be considerably decreased in a population struggling with low incomes.

Les valeurs de référence de l'hémogramme ne sont pas établies à la naissance au Mali. Cette étude détermine les valeurs de référence érythrocytaires et leucocytaires du nouveau-né à Bamako. Le sang du cordon ombilical a été prélevé après clampage sans délai et étudié pour les paramètres érythrocytaires et leucocytaires chez 481 nouveau-nés à terme avec un poids de naissance > 2500g, un score d'Apgar ≥ 7 à 5 ou 10 minutes, sans mutant de l'hémoglobine et dont les mamans étaient consentantes, à Bamako, Mali. Outre les valeurs médianes et moyennes, les percentiles 2,5 et 97,5 ont été calculés. Les valeurs considérées comme normes de référence locales après un clampage sans délai du cordon ombilical (moyenne ± 1SD et extrêmes) sont : GR = 4,00 ± 0,46.1012/L (3,13 ­ 4,89), Hb = 14,12 ± 1,49 g/dL (11,20 ­ 17,00), Ht = 40,27 ± 4,71% (31,62 ­ 50,18), VGM = 101 ± 5 fl (91 ­ 112), TCMH = 35,37 ± 2,16 pg/cellule (30,70 ­ 39,59), CCMH = 35,06 ± 0,93 g/dL (33,40 ­ 36,90), IDR = 17,79 ± 7,33% (15,50 ­ 20,39), Réticulocytes (109/L) = 133,081 ± 29,95 (66,62 ­ 200,86), GB (109/L) = 13,24 ± 7,23 (7,20 ­ 23,70), PNN (109/L) = 7,16 ± 4,70 (3,07 ­ 14,22), PE (109/L) = 0,28 ± 0,26 (0 ­ 0,98), PB (109/L) = 0,05 ± 0,09 (0 ­ 0,31), Lymphocytes (109/L) = 4,49 ± 2,45 (1,96 ­ 9,42), Monocytes (109/L) = 1,06 ± 0,73 (0,21 ­ 2,54), myélocytes = 1,43 ± 1,51%, érythroblastes = 4,52 ± 7,83%. A noter un taux des polynucléaires neutrophiles plus bas chez le garçon que chez la fille. Ces valeurs diffèrent de celles rapportées pour d'autres populations. La prise en compte de ces résultats dans l'interprétation de l'hémogramme du nouveau-né au Mali, devrait éviter des erreurs de diagnostic et des explorations par excès chez une population à faibles revenues.

The TLR9 agonist CpG fails to enhance the acquisition of Plasmodium falciparum-specific memory B cells in semi-immune adults in Mali.

Antibodies play a key role in controlling blood stage malaria infections, and an effective blood stage malaria vaccine will likely require that it induce vaccine-specific memory B cells (MBCs). Our previous studies showed that the addition of the TLR9 agonist CpG to Plasmodium falciparum protein subunit vaccines greatly increased their efficacy in inducing MBCs in nonimmune U.S. volunteers. Here we show that in contrast the same CpG-containing malaria vaccine did not enhance the acquisition of MBCs in semi-immune adults living in Mali. Understanding the molecular basis of this apparent refractoriness to TLR9 agonist will be of significant interest in vaccine design.