A Protective Inter-Organ Communication Response Against Life-Threatening Malarial Anemia

Anemia is a clinical hallmark and independent risk factor of malaria caused by Plasmodium spp. infection. While it is known that anemia arises from parasite-induced hemolysis, whether and how host metabolic adaptation to malaria regulate anemia severity is less understood. Here we demonstrate that reprogramming of renal iron (Fe) metabolism is a central component of the host metabolic response regulating the pathogenesis of life-threatening malarial anemia. Renal proximal tubule epithelial cells (RPTEC) are the main cell compartment responsible for Fe storage and recycling during Plasmodium infection in mice. Transcriptional reprogramming of RPTEC couples immune resistance to Plasmodium infection to renal Fe export via the induction of the cellular Fe exporter SLC40A1/ferroportin 1. This integrated defense strategy is essential to deliver Fe to erythroblasts and support compensatory erythropoiesis to prevent the development of life-threatening anemia. Failure to mobilize Fe from RPTEC causes AKI and is associated with life-threatening anemia in P. falciparum-infected individuals. These findings reveal an unexpected role of the kidneys in the control of organismal Fe metabolism during malaria.

ETUDE DE LA NUISANCE DES MOUSTIQUES EN MILIEU UNIVERSITAIRE DE LA FACULTE DES SCIENCES ET TECHNIQUES, BAMAKO, MALI

Mosquitoes are potentially harmful and vectors of pathogens. They compromise the rest and well-being of humans and animals. The main goal of this study is to determine the composition of mosquitoes responsible of human biting at the Faculty of Sciences and Technics of Bamako-Mali. Longitudinal monitoring with monthly cross-sectional visit was carried out from September to December 2019, in order to collect the endophilic and endophagic mosquitoes. The spray-catch was used as a collection methodin 21 rooms selected randomly at the FST. Mosquitoes were identified morphologically andthen by PCR. ELISA-CSP test was used for Plasmodium infection index and the ELISA blood-meal test was to determine mosquitoes blood origin. In total, 802 mosquitoes were collected: 794Culex and 8Anopheles. There were 200 males and 602 females. Female mosquitoes were separated by gonotrophic stages: 231 unfed, 223 fed, 80 semi-gravid and 68 gravid. Up to 34% of Culex and 67% of Anopheles had a preference for human blood, but no female tested positive for Plasmodium infection. This result would be due to the small number of Anopheles captured. An. coluzzii is the only Anopheles species collected.This study shows that mosquitoes are linked to serious problems of nuisance and risk of pathogens transmission in the university. They highly prefer to feed on human host.

Toll signaling enhances mosquito antiplasmodial immunity by promoting differentiation of hemocytes to the Megacyte lineage

Activation of Toll signaling in Anopheles gambiae, by silencing Cactus, eliminates Plasmodium ookinetes by enhancing local release of hemocytes-derived microvesicles that promote activation of the mosquito complement-like system. A new effector hemocyte subpopulation of large granulocytes, the megacytes, was recently identified. We report that Cactus silencing dramatically increases the proportion of megacytes, from 5 to 79% of circulating granulocytes. Transcriptomic and morphological analysis, as well as in situ hybridization and expression of cell-specific markers, indicate that Cactus silencing triggers granulocyte differentiation into megacytes. Megacytes are very plastic cells that can extend long filopodia and tend to form clusters in vivo. Moreover, megacytes are massively recruited to the basal midgut surface in response to bacterial feeding and Plasmodium infection. We propose that Toll signaling promotes differentiation of granulocytes to the megacyte lineage, a major cellular effector of antibacterial and antiplasmodial immunity.

Mapping of Malaria Receptivity Areas in Buton Regency, Southeast Sulawesi Province

Malaria is an acute and chronic infectious disease caused by Plasmodium infection that attacks erythrocytes and is characterized by the discovery of asexual forms in the blood with symptoms of fever, chills, anemia and enlarged spleen. Buton Regency is a district with an Annual Parasite Incidence (API) that is less than 1 per 1000 population for 4 consecutive years and is a low endemic area. This study aims to determine the level of receptivity of malaria transmission areas in Buton Regency, Southeast Sulawesi Province. This type of research is descriptive observational with a cross sectional study approach. The results showed that there were 3 species of Anopheles identified in adult mosquitoes, namely An.Minimus, An.Indifinitus and An.Kochi. Habitat Index (HI) of Anopheles vector, sp > 1, breeding places for Anopheles vector wallows, rivers, ditches, ponds, rivers, swamps and rice fields with the characteristics of the presence of temporary and clear water, moss and mud, with a pH of 6 on a scale 6-6.5 and zero salinity. Vector confirmation by PCR is negative for all species. It was concluded that the level of malaria receptivity in Buton Regency, especially in the Village of Face Jaya, was at a moderate receptivity level.

Prevalence of Malaria and Associated Factors among Delivering Mothers in Northwest Ethiopia

Background. Malaria is one of the leading causes of morbidity and mortality especially in pregnant women and under-five-year-old children. However, data on the prevalence among delivering mothers, potential fetal transmission, and associated birth outcomes is lacking in Ethiopia. Objective. To assess the prevalence of Plasmodium infection from peripheral, placental, and cord blood samples among delivering mothers in Kuch health center, Northwest Ethiopia. Methods. An institution-based cross-sectional study was conducted among 218 delivering mothers from February to May 2021 in Kuch health center. Data on sociodemographic characteristics and clinical and obstetric history of mothers were collected using a structured questionnaire. Giemsa stained blood films from maternal capillary and placental and umbilical cord blood were examined for plasmodium infection. Data were analyzed using Statistical Package for the Social Sciences version 23 software package. Results. The prevalence of maternal, placental, and umbilical cord malaria was 6.4% (14/218), 2.3% (5/218), and 0.5% (1/218), respectively. Plasmodium falciparum and Plasmodium vivax accounted 3.7% (8/218) and 2.8% (6/218), respectively, in maternal peripheral blood but only Plasmodium falciparum was detected in placental and umbilical cord blood samples. Maternal malaria had significant association with primigravida ( χ 2 = 12.611 , p = 0.002 ) and low birth weight ( χ 2 = 8.381 , p = 0.004 ). Placental malaria was also significantly associated with low birth weight ( χ 2 = 32.255 , p ≤ 0.001 ). Conclusion. The prevalence of malaria among delivering mothers was considerable. Maternal peripheral malaria had a significant association with gravidity and birth weight. Placental and umbilical cord malaria also had a significant association with birth weight. Pregnant mothers should be examined for malaria and receive appropriate treatment to prevent adverse birth outcomes.

Detection of IgG Antibodies to Glycosylphosphatidylinositol (GPI) as a Biomarker of Immune Status to Plasmodium species

Finding new ways to eliminate malaria is critical and this would greatly be influenced by developing indicators of exposure as well as distribution of effective vaccines against Plasmodium. This study was aimed at detecting Immunoglobulin G(IgG) antibodies, to glycosylphosphatidylinositol (GPI) as a biomarker of immune status to Plasmodium species. In this study, blood samples were gotten from apparently healthy individuals and patients having symptoms of malaria attending Ahmadu Bello University Teaching Hospital, Zaria. Thick and thin blood smears were prepared and stained with Giemsa stain. The smears were observed microscopically. Parasite densities were estimated on positive slides. Samples positive and some negative for Plasmodium were further tested to detect IgG antibodies to GPI among both the Asymptomatic and Symptomatic participants using ELISA. The prevalence of Plasmodium infection among both asymptomatic and symptomatic participants in this study was 18.9% and the prevalence of asymptomatic malaria was 15.6%. There was a significant association between the level of parasitemia and concentration of IgG antibodies to GPI among the asymptomatic participants and a no significant association among symptomatic participants. Type of housing amongst other risk factors was the only factor significantly associated with malaria in this study. This study suggests PGPI as a biomarker of immunity to Plasmodium and may be a vaccine candidate for programs of malaria control.

Antiplasmodial Activities of Some Locally Prepared Herbs Against Plasmodium falciparum Obtained from Asymptomatic School Children in Zaria, Kaduna State, Nigeria

The efficacy of current or any intended antimalarial can only be resolute by cultivation and susceptibility studies. The aim of this research was to cultivate Plasmodium falciparum in vitro and comparing the antiplasmodial effects of standard antimalarial medications including herbaceous preparation. Asymptomatic pupils attending some schools in Zaria, Kaduna state, Nigeria were recruited into this research and blood samples were collected from them. Microscopy was done after thin and thick blood films were prepared and stained. The antiplasmodial activities of antimalarial drugs as well as herbal preparation were determined after the successful culturing of red blood cells in the Jatropha curcas medium.The phytochemical constituents of the herbs that made up the concoction were determined. The incidence of asymptomatic Plasmodium infection amongst school kids was 17.5%. There was no statistical association of location, gender and age with the obtained prevalence. Presence of alkaloids was observed in every plant screened while the same was also observed for tannins except in Enantia chloranta.Steroids and phlobatanins were observed in Citrus aurantifolia while there was presence of saponins in all the plant extracts except Cymbopogbon citratus. All the plants except Enantia chloranta contained flavonoids. There was presence of terpenoids in all screened plants except Azadirachta indica and Cymbopogbon citratus while cardiac glycosides were found in every plant except Magnifera indica and Enantia chloranta. Results obtained from the in vitro cultivation of the Plasmodium falciparum with Athemether/lumefanthrine, amodiaquine and herbal concoction showed average percentage parasite inhibition of 80%, 37.8% and 38.6% respectively. This implies that Arthemether/lumefanthrine was capable of inhibiting the growth of the parasite best. The herbal concoction also inhibited growth (38.6% inhibition). There is need for additional investigation on a wider variety of plants to explore their antiplasmodial activities since there is evidence that it works, and it is quite available and affordable.

A mosquito AgTRIO monoclonal antibody reduces early Plasmodium infection of mice

Malaria begins when an infected mosquito injects saliva containing Plasmodium sporozoites into the skin of a vertebrate host. Passive immunization of mice with mosquito AgTRIO antisera offers significant protection against Plasmodium infection of mice. Furthermore, passive transfer of both AgTRIO antisera and an anti-circumsporozoite protein monoclonal antibody provides synergistic protection. In this study, we generated monoclonal antibodies against AgTRIO to delineate the regions of AgTRIO associated with protective immunity. Monoclonal antibody 13F-1 markedly reduced Plasmodium infection in mice and recognized a region, VDDLMAKFN, in the carboxyl terminus of AgTRIO. 13F-1 is an IgG2a isotype monoclonal antibody and the Fc region is required for protection. These data will aid in the generation of future malaria vaccines that may include both pathogen and vector antigens.

Susceptibility of Field-Collected Nyssorhynchus darlingi to Plasmodium spp. in Western Amazonian Brazil

Mosquito susceptibility to Plasmodium spp. infection is of paramount importance for malaria occurrence and sustainable transmission. Therefore, understanding the genetic features underlying the mechanisms of susceptibility traits is pivotal to assessing malaria transmission dynamics in endemic areas. The aim of this study was to investigate the susceptibility of Nyssorhynchus darlingi—the dominant malaria vector in Brazil—to Plasmodium spp. using a reduced representation genome-sequencing protocol. The investigation was performed using a genome-wide association study (GWAS) to identify mosquito genes that are predicted to modulate the susceptibility of natural populations of the mosquito to Plasmodium infection. After applying the sequence alignment protocol, we generated the variant panel and filtered variants; leading to the detection of 202,837 SNPs in all specimens analyzed. The resulting panel was used to perform GWAS by comparing the pool of SNP variants present in Ny. darlingi infected with Plasmodium spp. with the pool obtained in field-collected mosquitoes with no evidence of infection by the parasite (all mosquitoes were tested separately using RT-PCR). The GWAS results for infection status showed two statistically significant variants adjacent to important genes that can be associated with susceptibility to Plasmodium infection: Cytochrome P450 (cyp450) and chitinase. This study provides relevant knowledge on malaria transmission dynamics by using a genomic approach to identify mosquito genes associated with susceptibility to Plasmodium infection in Ny. darlingi in western Amazonian Brazil.

Transcriptome Profiles of Anopheles Gambiae Harboring Natural Low-Level Plasmodium Infection Reveal Adaptive Advantages For The Mosquito

Anopheline mosquitoes are the sole vectors for the Plasmodium pathogens responsible for malaria, which is among the oldest and most devastating of human diseases. The continuing global impact of malaria reflects the evolutionary success of a complex vector-pathogen relationship that accordingly has been the long-term focus of both debate and study. An open question in the biology of malaria transmission is the impact of naturally occurring low-level Plasmodium infections of the vector on the mosquito’s health and longevity as well as critical behaviors such as host-preference/seeking. To begin to answer this, we have completed a comparative RNAseq-based transcriptome profile study examining the effect of biologically salient, salivary gland transmission-stage Plasmodium infection on the molecular physiology of Anopheles gambiae s.s. head, sensory appendage, and salivary glands. When compared with their uninfected counterparts, Plasmodium infected mosquitoes exhibit increased transcript abundance of genes associated with olfactory acuity as well as a range of synergistic processes that align with increased fitness based on both anti-aging and reproductive advantages. Taken together, these data argue against the long-held paradigm that malaria infection is pathogenic for anophelines and, instead, suggests there are biological and evolutionary advantages for the mosquito that drive the preservation of its high vectorial capacity.