Modulation of innate immune responses at birth by prenatal malaria exposure and association with malaria risk during the first year of life.

BACKGROUND: Factors driving inter-individual differences in immune responses upon different types of prenatal malaria exposure (PME) and subsequent risk of malaria in infancy remain poorly understood. In this study, we examined the impact of four types of PME (i.e., maternal peripheral infection and placental acute, chronic, and past infections) on both spontaneous and toll-like receptors (TLRs)-mediated cytokine production in cord blood and how these innate immune responses modulate the risk of malaria during the first year of life. METHODS: We conducted a birth cohort study of 313 mother-child pairs nested within the COSMIC clinical trial (NCT01941264), which was assessing malaria preventive interventions during pregnancy in Burkina Faso. Malaria infections during pregnancy and infants' clinical malaria episodes detected during the first year of life were recorded. Supernatant concentrations of 30 cytokines, chemokines, and growth factors induced by stimulation of cord blood with agonists of TLRs 3, 7/8, and 9 were measured by quantitative suspension array technology. Crude concentrations and ratios of TLR-mediated cytokine responses relative to background control were analyzed. RESULTS: Spontaneous production of innate immune biomarkers was significantly reduced in cord blood of infants exposed to malaria, with variation among PME groups, as compared to those from the non-exposed control group. However, following TLR7/8 stimulation, which showed higher induction of cytokines/chemokines/growth factors than TLRs 3 and 9, cord blood cells of infants with evidence of past placental malaria were hyper-responsive in comparison to those of infants not-exposed. In addition, certain biomarkers, which levels were significantly modified depending on the PME category, were independent predictors of either malaria risk (GM-CSF TLR7/8 crude) or protection (IL-12 TLR7/8 ratio and IP-10 TLR3 crude, IL-1RA TLR7/8 ratio) during the first year of life. CONCLUSIONS: These findings indicate that past placental malaria has a profound effect on fetal immune system and that the differential alterations of innate immune responses by PME categories might drive heterogeneity between individuals to clinical malaria susceptibility during the first year of life

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Home-Based Practices Of Complementary Foods Improvement Are Associated With Better Height-For-Age Z Score In Rural Burkina Faso

Repositioning nutrition is central to development. Childcare practices, which include feeding practices, appear in the conceptual framework of malnutrition. The objective of this study was to analyze the nutritional status of young children in relation to feeding practices. This cross-sectional, community-based study was conducted in the rural district of Kongoussi (Burkina Faso). Three hundred ninety nine children (95% of expected 420 children: 30 clusters of 14 children), 6-23 months of age, were recruited by "probability proportionate-tosize" cluster sampling. Items related to the early and current breastfeeding patterns and the mode of complementary feeding were recorded by interview of the mothers. Fortified cereals were defined as home-based improved flours by mixing "soumbala," fishmeal, toasted groundnut, or several of these local foods with cereal. Soumbala is a fermented product from the African bean tree used both as a condiment and as a meat substitute in soups, because it is rich in protein and micronutrients. The height-for-age Z-score (HAZ) and weight-for-height Z-score (WHZ) were computed using height and weight measurements. Adjusted mean HAZ and WHZ were derived from multiple linear regression models and compared using analysis of variance (ANOVA) and post hoc t-test with Bonferroni correction. The prevalence of wasting was 26.3% (95% CI: 21.5% - 30.5%). The mean WHZ (± standard deviation) was –1.39 (± 1.14). The WHZ was associated with the children’s age and the mother’s nutritional status. The prevalence of stunting was 35.8% (95% CI: 29.4% - 41.1%). The mean HAZ was –1.68 (± 1.15). After adjustment for children, mothers and household characteristics, and for current and past breastfeeding patterns, the HAZ remained associated with the mode of complementary feeding among children 12-23 months of age (p=0.018), but not among children 6-11 months of age (p=0.136). Among children 12-23 months of age, the adjusted mean HAZ (standard error) was –1.33 (0.63), -1.61 (0.30), and –2.11 (0.32) for children using fortified cereals, unfortified cereals, or no complementary feeding, respectively (p=0.018). These results underline the high frequency of malnutrition in the rural district of Kongoussi, and the great need for nutritional intervention. The prevention of growth impairment in this area could be based on home fortification of complementary foods using locally available foods; this is more sustainable. Thorough research is needed to specify and standardize the procedures of utilisation of the available foods in the prevention of growth impairment

Home-based practices of complementary foods improvement are associated with better height-for-age Z score in 12-23 months-old children from a rural district of Burkina Faso.

Repositioning nutrition is central to development. Childcare practices, which include feeding practices, appear in the conceptual framework of malnutrition. The objective of this study was to analyze the nutritional status of young children in relation to feeding practices. This cross-sectional, community-based study was conducted in the rural district of Kongoussi (Burkina Faso). Three hundred ninety nine children (95% of expected 420 children: 30 clusters of 14 children), 6-23 months of age, were recruited by “probability proportionate-tosize” cluster sampling. Items related to the early and current breastfeeding patterns and the mode of complementary feeding were recorded by interview of the mothers. Fortified cereals were defined as home-based improved flours by mixing “soumbala,” fishmeal, toasted groundnut, or several of these local foods with cereal. Soumbala is a fermented product from the African bean tree used both as a condiment and as a meat substitute in soups, because it is rich in protein and micronutrients. The height-for-age Z-score (HAZ) and weight-for-height Z-score (WHZ) were computed using height and weight measurements. Adjusted mean HAZ and WHZ were derived from multiple linear regression models and compared using analysis of variance (ANOVA) and post hoc t-test with Bonferroni correction. The prevalence of wasting was 26.3% (95% CI: 21.5% - 30.5%). The mean WHZ (± standard deviation) was –1.39 (± 1.14). The WHZ was associated with the children's age and the mother's nutritional status. The prevalence of stunting was 35.8% (95% CI: 29.4% - 41.1%). The mean HAZ was –1.68 (± 1.15). After adjustment for children, mothers and household characteristics, and for current and past breastfeeding patterns, the HAZ remained associated with the mode of complementary feeding among children 12-23 months of age (p=0.018), but not among children 6-11 months of age (p=0.136). Among children 12-23 months of age, the adjusted mean HAZ (standard error) was –1.33 (0.63), -1.61 (0.30), and –2.11 (0.32) for children using fortified cereals, unfortified cereals, or no complementary feeding, respectively (p=0.018). These results underline the high frequency of malnutrition in the rural district of Kongoussi, and the great need for nutritional intervention. The prevention of growth impairment in this area could be based on home fortification of complementary foods using locally available foods; this is more sustainable. Thorough research is needed to specify and standardize the procedures of utilisation of the available foods in the prevention of growth impairment. Keywords: Fortification, Cereals, Stunting, Children, BurkinaAJFAND Vol. 8 (2) 2008 pp. 204-21

Selection of drug resistance-mediating Plasmodium falciparum genetic polymorphisms by seasonal malaria chemoprevention in Burkina Faso.

Seasonal malaria chemoprevention (SMC), with regular use of amodiaquine plus sulfadoxine-pyrimethamine (AQ/SP) during the transmission season, is now a standard malaria control measure in the Sahel subregion of Africa. Another strategy under study is SMC with dihydroartemisinin plus piperaquine (DP). Plasmodium falciparum single nucleotide polymorphisms (SNPs) in P. falciparum crt (pfcrt), pfmdr1, pfdhfr, and pfdhps are associated with decreased response to aminoquinoline and antifolate antimalarials and are selected by use of these drugs. To characterize selection by SMC of key polymorphisms, we assessed 13 SNPs in P. falciparum isolated from children aged 3 to 59 months living in southwestern Burkina Faso and randomized to receive monthly DP or AQ/SP for 3 months in 2009. We compared SNP prevalence before the onset of SMC and 1 month after the third treatment in P. falciparum PCR-positive samples from 120 randomly selected children from each treatment arm and an additional 120 randomly selected children from a control group that did not receive SMC. The prevalence of relevant mutations was increased after SMC with AQ/SP. Significant selection was seen for pfcrt 76T (68.5% to 83.0%, P = 0.04), pfdhfr 59R (54.8% to 83.3%, P = 0.0002), and pfdhfr 108N (55.0% to 87.2%, P = 0.0001), with trends toward selection of pfmdr1 86Y, pfdhfr 51I, and pfdhps 437G. After SMC with DP, only borderline selection of wild-type pfmdr1 D1246 (mutant; 7.7% to 0%, P = 0.05) was seen. In contrast to AQ/SP, SMC with DP did not clearly select for known resistance-mediating polymorphisms. SMC with AQ/SP, but not DP, may hasten the development of resistance to components of this regimen. (This study has been registered at ClinicalTrials.gov under registration no. NCT00941785.)

Selection of drug resistance-mediating Plasmodium falciparum genetic polymorphisms by seasonal malaria chemoprevention in Burkina Faso.

Seasonal malaria chemoprevention (SMC), with regular use of amodiaquine plus sulfadoxine-pyrimethamine (AQ/SP) during the transmission season, is now a standard malaria control measure in the Sahel subregion of Africa. Another strategy under study is SMC with dihydroartemisinin plus piperaquine (DP). Plasmodium falciparum single nucleotide polymorphisms (SNPs) in P. falciparum crt (pfcrt), pfmdr1, pfdhfr, and pfdhps are associated with decreased response to aminoquinoline and antifolate antimalarials and are selected by use of these drugs. To characterize selection by SMC of key polymorphisms, we assessed 13 SNPs in P. falciparum isolated from children aged 3 to 59 months living in southwestern Burkina Faso and randomized to receive monthly DP or AQ/SP for 3 months in 2009. We compared SNP prevalence before the onset of SMC and 1 month after the third treatment in P. falciparum PCR-positive samples from 120 randomly selected children from each treatment arm and an additional 120 randomly selected children from a control group that did not receive SMC. The prevalence of relevant mutations was increased after SMC with AQ/SP. Significant selection was seen for pfcrt 76T (68.5% to 83.0%, P = 0.04), pfdhfr 59R (54.8% to 83.3%, P = 0.0002), and pfdhfr 108N (55.0% to 87.2%, P = 0.0001), with trends toward selection of pfmdr1 86Y, pfdhfr 51I, and pfdhps 437G. After SMC with DP, only borderline selection of wild-type pfmdr1 D1246 (mutant; 7.7% to 0%, P = 0.05) was seen. In contrast to AQ/SP, SMC with DP did not clearly select for known resistance-mediating polymorphisms. SMC with AQ/SP, but not DP, may hasten the development of resistance to components of this regimen. (This study has been registered at ClinicalTrials.gov under registration no. NCT00941785.)