Journal des maladies infectieuses et de la médecine

Falciparum malaria is a major cause of morbidity and mortality worldwide. Plasmodium infected patients carry a wide range of parasitic loads and exhibit asymptomatic, mild or severe malaria. Among host intrinsic factors which likely influence development of malaria type, controversies remain on the relationship between malaria infection and ABO blood groups types. This cross-sectional study was designed to investigate any relationship between ABO blood types, Plasmodium loads and clinical type of malaria among outpatients received in Bonassama hospital. Each outpatient who volunteered for the study was examined, tested for ABO blood types and malaria parasites carriage. Data were statistically analyzed for any association. Of 375 Plasmodium falciparum infected patients included, ABO blood group frequency was 45.3% (O), 25.3% (A), 21.6% (B), 7.8% (AB). All ABO blood groups harboured predominantly light intensities of falciparum infections; however high intensities of infections were significantly frequent in blood group A. Gender did not significantly influence P. falciparum infection prevalence. Infection prevalence was significantly high in less than 15 years blood group A patients. P. falciparum infection prevalence was not significantly different among blood group patients (p>0.05). Although all ABO blood group patients exhibit different clinical malaria types, severe-like malaria symptoms were exhibited more frequently among blood group A and group B patients. Blood group O patients exhibited predominantly asymptomatic and uncomplicated malaria. No significant association was found between Plasmodium loads, gender and age groups. Under five year blood groups A and B patients were likely more affected by severe malaria whereas blood group O patients suffered predominantly from mild and symptomless malaria. Findings from this study demonstrated that in Douala, young blood group A and B patients were more predisposed to high intensities of P. falciparum infections and severe malaria whereas blood group O exhibited mostly light infections associated to mild and asymptomatic malaria.

The so-called ARMD (‘accelerated resistance to multidrug’) phenotype of the human malaria parasite Plasmodium falciparum that is prevalent in South East Asia is believed to confer a special hypermutator characteristic upon parasite strains in which it is expressed. Examination of the ARMD phenotype suggests that alternative mechanisms may be responsible for this ability that is unique among strains of P. falciparum parasite worldwide, but over which there is concern that further dissemination may lead to widespread loss of sensitivity to current chemotherapeutic regimens. Therefore, other recently discovered mechanisms that demonstrate potential in contributing to this noted drug resistance phenomenon merit further investigation. One important example, the cell-to-cell communication pathway in P. falciparum-infected erythrocytes, is being examined as a potential target for intervention and forms the subject of this article.

Glyco-engineered recombinant antibodies are currently being developed as the next generation therapeutics to treat human diseases, including cancer, autoimmunity and infection. Antibodies lacking core fucosylation show great increase in affinity for FcγRIIIA, leading to an improved receptor-mediated effector function. While afucosyl human IgG1 exhibits 50-100-fold increase in antibody-mediated cellular cytotoxicity (ADCC), a key immune effector mechanism underlying the anti-cancer effect of some approved therapeutic antibodies, it is not clear whether such glyco-engineered antibodies would find similar use for infectious disease. Due to the species difference, human antibodies may have different binding properties towards corresponding IgG receptors from animals used for modeling infection and intoxication. During the course of studying a recombinant human IgG1 in neutralizing diphtheria toxin (DT) in Guinea pigs (Cavia porcellus), we identified a previously uncharacterized Guinea pig protein H0VDZ8 from UNIPROT database that shows high sequence homologies to human FcγRIIIA and mouse FcγRIV. This Fcγ receptor, which we named as gpFcγRIV, also demonstrates functional similarity although not to the same extent as the human and mouse counterparts, in that it binds to afucosyl human and mouse IgG much stronger than to the wild type antibodies. Thus, Guinea pigs can be used to compare the efficacies of wild type vs. afucosyl anti-DT human IgG1 in toxin removal and animal protection. Molecular and functional characterization of human FcγRIIIA and mouse FcγRIV equivalents in other species could expand the list of preclinical animal models for testing afucosyl human antibodies in treating various human diseases.