High levels of Plasmodium falciparum rosetting in all clinical forms of severe malaria in African children

Plasmodium falciparum rosetting (the spontaneous binding of infected erythrocytes to uninfected erythrocytes) is a well-recognized parasite virulence factor. However, it is currently unclear whether rosetting is associated with all clinical forms of severe malaria, or only with specific syndromes such as cerebral malaria. We investigated the relationship between rosetting and clinical malaria in 209 Malian children enrolled in a case-control study of severe malaria. Rosetting was significantly higher in parasite isolates from severe malaria cases compared with non-severe hyperparasitemia and uncomplicated malaria controls (F(2,117) = 8.15, P < 0.001). Analysis of sub-categories of severe malaria (unrousable coma, severe anemia, non-comatose neurological impairment, repeated seizures or a small heterogeneous group with signs of renal failure or jaundice) showed high levels of rosetting in all sub-categories, and no statistically significant differences in rosetting between sub-categories (F(4,67) = 1.28, P = 0.28). Thus rosetting may contribute to the pathogenesis of all severe malaria syndromes in African children, and interventions to disrupt rosetting could be potential adjunctive therapies for all forms of severe malaria in Africa

Platelet-mediated clumping of Plasmodium falciparum infected erythrocytes is associated with high parasitemia but not severe clinical manifestations of malaria in African children

Platelet-mediated clumping of Plasmodium falciparum infected erythrocytes is an adhesive phenotype commonly found in field isolates that has previously been associated with severe malaria. Here, clumping was assessed in 131 isolates from Malian children. The clumping phenotype was seen in 6% (n=51) of uncomplicated malaria, 24% (n=51) of severe malaria, and 45% (n=29) of high parasitemia non-severe malaria isolates. Multivariate analysis indicated that clumping was strongly positively associated with parasitemia (F(1,122)=24.1, p<0.001) but not with disease category (F(2,122)=1.8, p=0.17). Therefore platelet-mediated clumping in Malian P. falciparum isolates is primarily associated with high parasitemia and not with severe clinical manifestations of malaria

Low multiplication rates of African Plasmodium falciparum isolates and lack of association of multiplication rate and red blood cell selectivity with malaria virulence

Two potential malaria virulence factors, parasite multiplication rate (PMR) and red blood cell selectivity (measured as selectivity index [SI]), were assessed in Plasmodium falciparum clinical isolates from Mali and Kenya. At both sites, PMRs were low (Kenya median = 2.2, n = 33; Mali median = 2.6, n = 61) and did not differ significantly between uncomplicated and severe malaria cases. Malian isolates from hyperparasitemic patients had significantly lower PMRs (median = 1.8, n = 19) than other Malian isolates (uncomplicated malaria median = 3.1, n = 23; severe malaria median = 2.8, n = 19; P = 0.03, by Kruskal-Wallis test). Selective invasion occurred at both sites (Kenya geometric mean SI = 1.9, n = 98; Mali geometric mean SI = 1.6, n = 104), and there was no significant association between the SI and malaria severity. Therefore, in contrast to previous results from Thailand, we found no association of PMR and SI with malaria severity in African children. This raises the possibility of differences in the mechanisms of malaria virulence between sub-Saharan Africa and Asia

First Detection of Leishmania major DNA in Sergentomyia (Spelaeomyia) darlingi from Cutaneous Leishmaniasis Foci in Mali

Leishmania major complex is the main causative agent of zoonotic cutaneous leishmaniasis (ZCL) in the Old World. Phlebotomus papatasi and Phlebotomus duboscqi are recognized vectors of L. major complex in Northern and Southern Sahara, respectively. In Mali, ZCL due to L. major is an emerging public health problem, with several cases reported from different parts of the country. The main objective of the present study was to identify the vectors of Leishmania major in the Bandiagara area, in Mali. Methodology/Principal Findings: An entomological survey was carried out in the ZCL foci of Bandiagara area. Sandflies were collected using CDC miniature light traps and sticky papers. In the field, live female Phlebotomine sandflies were identified and examined for the presence of promastigotes. The remaining sandflies were identified morphologically and tested for Leishmania by PCR in the ITS2 gene. The source of blood meal of the engorged females was determined using the cyt-b sequence. Out of the 3,259 collected sandflies, 1,324 were identified morphologically, and consisted of 20 species, of which four belonged to the genus Phlebotomus and 16 to the genus Sergentomyia. Leishmania major DNA was detected by PCR in 7 of the 446 females (1.6%), specifically 2 out of 115 Phlebotomus duboscqi specimens, and 5 from 198 Sergentomyia darlingi specimens. Human DNA was detected in one blood-fed female S. darlingi positive for L. major DNA. Conclusion: Our data suggest the possible involvement of P. duboscqi and potentially S. darlingi in the transmission of ZCL in Mali

Natural immunity to malaria preferentially targets the endothelial protein C receptor-binding regions of PfEMP1s

Antibody responses to variant surface antigens (VSAs) produced by the malaria parasite Plasmodium falciparum may contribute to age-related natural immunity to severe malaria. One VSA family, P. falciparum erythrocyte membrane protein-1 (PfEMP1), includes a subset of proteins that binds endothelial protein C receptor (EPCR) in human hosts and potentially disrupts the regulation of inflammatory responses, which may lead to the development of severe malaria. We probed peptide microarrays containing segments spanning five PfEMP1 EPCR-binding domain variants with sera from 10 Malian adults and 10 children to determine the differences between adult and pediatric immune responses. We defined serorecognized peptides and amino acid residues as those that elicited a significantly higher antibody response than malaria-naïve controls. We aimed to identify regions consistently serorecognized among adults but not among children across PfEMP1 variants, potentially indicating regions that drive the development of immunity to severe malaria. Adult sera consistently demonstrated broader and more intense serologic responses to constitutive PfEMP1 peptides than pediatric sera, including peptides in EPCR-binding domains. Both adults and children serorecognized a significantly higher proportion of EPCR-binding peptides than peptides that do not directly participate in receptor binding, indicating a preferential development of serologic responses at functional residues. Over the course of a single malaria transmission season, pediatric serological responses increased between the start and the peak of the season, but waned as the transmission season ended. IMPORTANCE Severe malaria and death related to malaria disproportionately affect sub-Saharan children under 5 years of age, commonly manifesting as cerebral malaria and/or severe malarial anemia. In contrast, adults in malaria-endemic regions tend to experience asymptomatic or mild disease. Our findings indicate that natural immunity to malaria targets specific regions within the EPCR-binding domain, particularly peptides containing EPCR-binding residues. Epitopes containing these residues may be promising targets for vaccines or therapeutics directed against severe malaria. Our approach provides insight into the development of natural immunity to a binding target linked to severe malaria by characterizing an "adult-like" response as recognizing a proportion of epitopes within the PfEMP1 protein, particularly regions that mediate EPCR binding. This "adult-like" response likely requires multiple years of malaria exposure, as increases in pediatric serologic response over a single malaria transmission season do not appear significant. </p

Leveraging data science and machine learning for urban climate adaptation in two major African cities: a HE 2 AT Center study protocol

Introduction: African cities, particularly Abidjan and Johannesburg, face challenges of rapid urban growth, informality and strained health services, compounded by increasing temperatures due to climate change. This study aims to understand the complexities of heat-related health impacts in these cities. The objectives are: (1) mapping intraurban heat risk and exposure using health, socioeconomic, climate and satellite imagery data; (2) creating a stratified heat–health forecast model to predict adverse health outcomes; and (3) establishing an early warning system for timely heatwave alerts. The ultimate goal is to foster climate-resilient African cities, protecting disproportionately affected populations from heat hazards. Methods and analysis: The research will acquire health-related datasets from eligible adult clinical trials or cohort studies conducted in Johannesburg and Abidjan between 2000 and 2022. Additional data will be collected, including socioeconomic, climate datasets and satellite imagery. These resources will aid in mapping heat hazards and quantifying heat–health exposure, the extent of elevated risk and morbidity. Outcomes will be determined using advanced data analysis methods, including statistical evaluation, machine learning and deep learning techniques. Ethics and dissemination: The study has been approved by the Wits Human Research Ethics Committee (reference no: 220606). Data management will follow approved procedures. The results will be disseminated through workshops, community forums, conferences and publications. Data deposition and curation plans will be established in line with ethical and safety considerations

Protocol of an individual participant data meta-analysis to quantify the impact of high ambient temperatures on maternal and child health in Africa (HE 2 AT IPD)

Introduction: Globally, recognition is growing of the harmful impacts of high ambient temperatures (heat) on health in pregnant women and children. There remain, however, major evidence gaps on the extent to which heat increases the risks for adverse health outcomes, and how this varies between settings. Evidence gaps are especially large in Africa. We will conduct an individual participant data (IPD) meta-analysis to quantify the impacts of heat on maternal and child health in sub-Saharan Africa. A detailed understanding and quantification of linkages between heat, and maternal and child health is essential for developing solutions to this critical research and policy area. Methods and analysis: We will use IPD from existing, large, longitudinal trial and cohort studies, on pregnant women and children from sub-Saharan Africa. We will systematically identify eligible studies through a mapping review, searching data repositories, and suggestions from experts. IPD will be acquired from data repositories, or through collaboration with data providers. Existing satellite imagery, climate reanalysis data, and station-based weather observations will be used to quantify weather and environmental exposures. IPD will be recoded and harmonised before being linked with climate, environmental, and socioeconomic data by location and time. Adopting a one-stage and two-stage meta-analysis method, analytical models such as time-to-event analysis, generalised additive models, and machine learning approaches will be employed to quantify associations between exposure to heat and adverse maternal and child health outcomes. Ethics and dissemination: The study has been approved by ethics committees. There is minimal risk to study participants. Participant privacy is protected through the anonymisation of data for analysis, secure data transfer and restricted access. Findings will be disseminated through conferences, journal publications, related policy and research fora, and data may be shared in accordance with data sharing policies of the National Institutes of Health. PROSPERO registration number: CRD42022346068

Carbone des sols en Afrique

Les sols sont une ressource essentielle à préserver pour la production d’aliments, de fibres, de biomasse, pour la filtration de l’eau, la préservation de la biodiversité et le stockage du carbone. En tant que réservoirs de carbone, les sols sont par ailleurs appelés à jouer un rôle primordial dans la lutte contre l’augmentation de la concentration de gaz à effet de serre. Ils sont ainsi au centre des objectifs de développement durable (ODD) des Nations unies, notamment les ODD 2 « Faim zéro », 13 « Lutte contre le changement climatique », 15 « Vie terrestre », 12 « Consommation et production responsables » ou encore 1 « Pas de pauvreté ». Cet ouvrage présente un état des lieux des sols africains dans toute leur diversité, mais au-delà, il documente les capacités de stockage de carbone selon les types de sols et leurs usages en Afrique. Il propose également des recommandations autour de l’acquisition et de l’interprétation des données, ainsi que des options pour préserver, voire augmenter les stocks de carbone dans les sols. Tous les chercheurs et acteurs du développement impliqués dans les recherches sur le rôle du carbone des sols sont concernés par cette synthèse collective. Fruit d’une collaboration entre chercheurs africains et européens, ce livre insiste sur la nécessité de prendre en compte la grande variété des contextes agricoles et forestiers africains pour améliorer nos connaissances sur les capacités de stockage de carbone des sols et lutter contre le changement climatique

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