Depleted circulatory complement-lysis inhibitor (CLI) in childhood cerebral malaria returns to normal with convalescence.

BACKGROUND: Cerebral malaria (CM), is a life-threatening childhood malaria syndrome with high mortality. CM is associated with impaired consciousness and neurological damage. It is not fully understood, as yet, why some children develop CM. Presented here is an observation from longitudinal studies on CM in a paediatric cohort of children from a large, densely-populated and malaria holoendemic, sub-Saharan, West African metropolis. METHODS: Plasma samples were collected from a cohort of children with CM, severe malarial anaemia (SMA), uncomplicated malaria (UM), non-malaria positive healthy community controls (CC), and coma and anemic patients without malaria, as disease controls (DC). Proteomic two-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry were used in a discovery cohort to identify plasma proteins that might be discriminatory among these clinical groups. The circulatory levels of identified proteins of interest were quantified by ELISA in a prospective validation cohort. RESULTS: The proteome analysis revealed differential abundance of circulatory complement-lysis inhibitor (CLI), also known as Clusterin (CLU). CLI circulatory level was low at hospital admission in all children presenting with CM and recovered to normal level during convalescence (p < 0.0001). At acute onset, circulatory level of CLI in the CM group significantly discriminates CM from the UM, SMA, DC and CC groups. CONCLUSIONS: The CLI circulatory level is low in all patients in the CM group at admission, but recovers through convalescence. The level of CLI at acute onset may be a specific discriminatory marker of CM. This work suggests that CLI may play a role in the pathophysiology of CM and may be useful in the diagnosis and follow-up of children presenting with CM.

Abundance, Distribution, and Diversity of Freshwater Snail and Prevalences of Their Infection by Cercaria of Fasciola gigantica and Schistosoma spp at Mayo-Vreck River, Far North Region of Cameroon.

Malacological and parasitological studies were conducted from April 2020 to March 2021 to determine the abundance and distribution of molluscs and cercariae of Schistosoma spp and Fasciola gigantica. Collected molluscs are exposed to strong light to induce cercarial release. Mollusc densities were higher at station 1 (Gamak) than in station 8 (Patakai), with Bellamya unicolor and Biomphalaria pfeifferi more abundant and Bulinus truncatus, B. tropicus, and B. globosus less abundant. The overall prevalence of cercariae (19.87%) is higher in station 3 (Yaye orchard), station 9 (Gougni), station 4 (Madiogo), station 5 (Madiogo pasture), and station 6 (Ziam 3). It varies significantly between 15.76% in station 8 and 25.77% in station 3, between 8.48% in B. truncatus and 25.53% in B. globosus, and between 19.27% for cercariae of Schistosoma spp and 21.60% for those of F. gigantica. Cercarial emissions in L. natalensis and B. pfeifferi were higher in hot and cold dry seasons; on the other hand, cercarial emissions in B. globosus were higher in hot dry seasons (31.48%) and rainy seasons (23.38%). Emissions of cercariae from S. haematobium are related to areas of human activity and defecation, while those of F. gigantica in L. natalensis, Schistosoma haematobium in B. tropicus, and S. mansoni in B. pfeifferi are related to grazing areas. Mayo-Vreck is a site that favors the endemicity of fascioliasis and human schistosomiasis.

Tabanid-transmitted animal trypanosomiasis in Cameroon: Evidence from a study in the tsetse free pastoral zone of Galim.

The role of tabanids as potential transmitters of animal trypanosomiasis (AAT) has not yet been established in Cameroon. The objectives of this study were: (i) to trap and determine the species richness and abundance of tabanids, (ii) to identify circulating trypansomes in cattle and tabanids in a tsetse free area. A three year (2015 to 2017) tabanid survey in six regions of Cameroon was conducted. In Galim village, which is in a tsetse free area, both tabanids and cattle blood samples were screened by PCR for the presence of trypanosome DNA. Tabanids were diverse in Littoral (13 species) and in Adamawa (13 species), but were abundant in the Far North region (36.37 to 145.58 tabanids per trap per day (t/t/d)). In Galim, the tabanid trypanosomal DNA presence was 24.4% (95% CI: 11.25-37.53), while the bovine trypanosomal DNA presence was 4.8% (95% CI: 1.68-11.20). In this village, the Trypanosoma spp. identified in tabanids were T. theileri, T. vivax and T. evansi, while those in cattle were T. theileri and T. vivax. The control of tabanids is required to stop the mechanical spread of AAT in tsetse free areas.

The COMBAT project: controlling and progressively minimizing the burden of vector-borne animal trypanosomosis in Africa.

Vector-borne diseases affecting livestock have serious impacts in Africa. Trypanosomosis is caused by parasites transmitted by tsetse flies and other blood-sucking Diptera. The animal form of the disease is a scourge for African livestock keepers, is already present in Latin America and Asia, and has the potential to spread further. A human form of the disease also exists, known as human African trypanosomosis or sleeping sickness. Controlling and progressively minimizing the burden of animal trypanosomosis (COMBAT) is a four-year research and innovation project funded by the European Commission, whose ultimate goal is to reduce the burden of animal trypanosomosis (AT) in Africa. The project builds on the progressive control pathway (PCP), a risk-based, step-wise approach to disease reduction or elimination. COMBAT will strengthen AT control and prevention by improving basic knowledge of AT, developing innovative control tools, reinforcing surveillance, rationalizing control strategies, building capacity, and raising awareness. Knowledge gaps on disease epidemiology, vector ecology and competence, and biological aspects of trypanotolerant livestock will be addressed. Environmentally friendly vector control technologies and more effective and adapted diagnostic tools will be developed. Surveillance will be enhanced by developing information systems, strengthening reporting, and mapping and modelling disease risk in Africa and beyond. The socio-economic burden of AT will be assessed at a range of geographical scales. Guidelines for the PCP and harmonized national control strategies and roadmaps will be developed. Gender equality and ethics will be pivotal in all project activities. The COMBAT project benefits from the expertise of African and European research institutions, national veterinary authorities, and international organizations. The project consortium comprises 21 participants, including a geographically balanced representation from 13 African countries, and it will engage a larger number of AT-affected countries through regional initiatives.

Low plasma haptoglobin is a risk factor for life-threatening childhood severe malarial anemia and not an exclusive consequence of hemolysis.

Severe Malarial Anemia (SMA), a life-threatening childhood Plasmodium falciparum malaria syndrome requiring urgent blood transfusion, exhibits inflammatory and hemolytic pathology. Differentiating between hypo-haptoglobinemia due to hemolysis or that of genetic origin is key to understand SMA pathogenesis. We hypothesized that while malaria-induced hypo-haptoglobinemia should reverse at recovery, that of genetic etiology should not. We carried-out a case-control study of children living under hyper-endemic holoendemic malaria burden in the sub-Saharan metropolis of Ibadan, Nigeria. We show that hypo-haptoglobinemia is a risk factor for childhood SMA and not solely due to intravascular hemolysis from underlying schizogony. In children presenting with SMA, hypo-haptoglobinemia remains through convalescence to recovery suggesting a genetic cause. We identified a haptoglobin gene variant, rs12162087 (g.-1203G > A, frequency = 0.67), to be associated with plasma haptoglobin levels (p = 8.5 × 10-6). The Homo-Var:(AA) is associated with high plasma haptoglobin while the reference Homo-Ref:(GG) is associated with hypo-haptoglobinemia (p = 2.3 × 10-6). The variant is associated with SMA, with the most support for a risk effect for Homo-Ref genotype. Our insights on regulatory haptoglobin genotypes and hypo-haptoglobinemia suggest that haptoglobin screening could be part of risk-assessment algorithms to prevent rapid disease progression towards SMA in regions with no-access to urgent blood transfusion where SMA accounts for high childhood mortality rates.