Cerebral malaria, a major cause of death during malaria infection, is characterised by the sequestration of infected red blood cells (IRBC) in brain microvessels. Most of the molecules implicated in the adhesion of IRBC on endothelial cells (EC) are already described; however, the structure of the IRBC/EC junction and the impact of this adhesion on the EC are poorly understood. We analysed this interaction using human brain microvascular EC monolayers co-cultured with IRBC. Our study demonstrates the transfer of material from the IRBC to the brain EC plasma membrane in a trogocytosis-like process, followed by a TNF-enhanced IRBC engulfing process. Upon IRBC/EC binding, parasite antigens are transferred to early endosomes in the EC, in a cytoskeleton-dependent process. This is associated with the opening of the intercellular junctions. The transfer of IRBC antigens can thus transform EC into a target for the immune response and contribute to the profound EC alterations, including peri-vascular oedema, associated with cerebral malaria. Cerebral malaria, a major cause of death during malaria infection, is characterised by the sequestration of infected red blood cells (IRBC) in brain microvessels. This study describes the interactions between plasmodium infected red blood cell and human brain endothelial cells. It highlights the activation of a trogocytosis-like mechanism followed by an engulfment of the infected red blood cells by endothelial cells (EC). This transfer concerns up to 20% of the IRBC cocultured with EC. This means that the parasite infected erythrocyte can mimic the leukocytes interaction with endothelial cells. This process is associated with i) a transfer of malaria antigens to the EC which can inappropriately activate the immune system and ii) an opening of the intercellular junctions, which can trigger blood-brain-barrier leakage during cerebral malaria. This transfer of IRBC antigens can thus transform EC into a target for the immune response and contribute to cerebral malaria pathogenesis.

Artemisinin, a thapsigargin-like sesquiterpene has been shown to inhibit the Plasmodium falciparum sarco/endoplasmic reticulum calcium-ATPase PfSERCA. To collect baseline pfserca sequence information before field deployment of Artemisinin-based Combination therapies that may select mutant parasites, we conducted a sequence analysis of 100 isolates from multiple sites in Africa, Asia and South America. Coding sequence diversity was large, with 29 mutated codons, including 32 SNPs (average of one SNP/115 bp), of which 19 were novel mutations. Most SNP detected in this study were clustered within a region in the cytosolic head of the protein. The PfSERCA functional domains were very well conserved, with non synonymous mutations located outside the functional domains, except for the S769N mutation associated in French Guiana with elevated IC₅₀ for artemether. The S769N mutation is located close to the hinge of the headpiece, which in other species modulates calcium affinity and in consequence efficacy of inhibitors, possibly linking calcium homeostasis to drug resistance. Genetic diversity was highest in Senegal, Brazil and French Guiana, and few mutations were identified in Asia. Population genetic analysis was conducted for a partial fragment of the gene encompassing nucleotide coordinates 87-2862 (unambiguous sequence available for 96 isolates). This supported a geographic clustering, with a separation between Old and New World samples and one dominant ancestral haplotype. Genetic drift alone cannot explain the observed polymorphism, suggesting that other evolutionary mechanisms are operating. One possible contributor could be the frequency of haemoglobinopathies that are associated with calcium dysregulation in the erythrocyte.

Low-income cities that are subject to high population pressure and vulnerable to climate events often have a low capacity to continuously deliver safe drinking water. Here we reported the results of a 32-year survey on the temporal dynamics of drinking water quality indicators in the city of Antananarivo. We analyzed the long-term evolution of the quality of the water supplied and characterized the interactions between climatic conditions and the full-scale water supply system. A total of 25,467 water samples were collected every week at different points in the supplied drinking water system. Samples were analyzed for total coliforms (TC), Escherichia coli (EC), intestinal Enterococci (IE), and Spores of Sulphite-Reducing Clostridia (SSRC). Nine-hundred-eighty-one samples that were identified as positive for one or more indicators were unevenly distributed over time. The breakpoint method identified four periods when the time series displayed changes in the level and profile of contamination (i) and the monthly pattern of contamination (ii), with more direct effects of rainfall on the quality of supplied drinking water. The modeling showed significantly different lags among indicators of bacteria occurrence after cumulative rainfall, which range from 4 to 8 weeks. Among the effects of low-income urbanization, a rapid demographic transition and the degradation of urban watersheds have gradually affected the quality of the water supplied and resulted in the more direct effects of rainfall events. We focused on the need to adopt an alternative perspective of drinking water and urban watersheds management.

Infection with Plasmodium berghei is a widely used model of murine malaria and a powerful tool for reverse genetic and pathogenesis studies. However, the efficacy of in vitro reinvasion of erythrocytes is generally low, limiting in vitro studies.

A major forthcoming sanitary issue concerns the apparition and spreading of drug-resistant microorganisms, potentially threatening millions of humans. In low-income countries, polluted urban runoff and open sewage channels are major sources of microbes. These microbes join natural microbial communities in aquatic ecosystems already impacted by various chemicals, including antibiotics. These composite microbial communities must adapt to survive in such hostile conditions, sometimes promoting the selection of antibiotic-resistant microbial strains by gene transfer. The low probability of exchanges between planktonic microorganisms within the water column may be significantly improved if their contact was facilitated by particular meeting places. This could be specifically the case within biofilms that develop on the surface of the myriads of floating macroplastics increasingly polluting urban tropical surface waters. Moreover, as uncultivable bacterial strains could be involved, analyses of the microbial communities in their whole have to be performed. This means that new-omic technologies must be routinely implemented in low- and middle-income countries to detect the appearance of resistance genes in microbial ecosystems, especially when considering the new ‘plastic context.’ We summarize the related current knowledge in this short review paper to anticipate new strategies for monitoring and surveying microbial communities.

Recent studies suggest shared pathogenic pathways during malaria and allergy. Indeed, IgE, histamine, and the parasite-derived Plasmodium falciparum histamine-releasing factor translationally controlled tumor protein (PfTCTP) can be found at high levels in serum from patients experiencing malaria, but their relationship with basophil activation remains unknown. We recruited P. falciparum -infected patients in Senegal with mild malaria (MM; n = 19) or severe malaria (SM; n = 9) symptoms and healthy controls (HC; n = 38). Levels of serum IgE, PfTCTP, and IgG antibodies against PfTCTP were determined by enzyme-linked immunosorbent assays (ELISA). Basophil reactivities to IgE-dependent and -independent stimulations were measured ex vivo using fresh blood by looking at the expression level of the basophil activation marker CD203c with flow cytometry. Unstimulated basophils from MM had significantly lower levels of CD203c expression compared to those from HC and SM. After normalization on this baseline level, basophils from SM showed an enhanced reactivity to calcimycin (A23187) and hemozoin. Although SM reached higher median levels of activation after anti-IgE stimulation, great interindividual differences did not allow the results to reach statistical significance. When primed with recombinant TCTP before anti-IgE, qualitative differences in terms of a better ability to control excessive activation could be described for SM. IgE levels were very high in malaria patients, but concentrations in MM and SM were similar and were not associated with basophil responses, which demonstrates that the presence of IgE alone cannot explain the various basophil reactivities. Indeed, PfTCTP could be detected in 32% of patients, with higher concentrations for SM. These PfTCTP-positive patients displayed significantly higher basophil reactivities to any stimulus. Moreover, the absence of anti-PfTCTP IgG was associated with higher responses in SM but not MM. Our results show an association between basophil reactivity and malaria severity and suggest a pathogenic role for plasmodial PfTCTP in the induction of this allergy-like mechanism.