Manhiça Health Research Centre

facility📍 Maputo, Mozambique
2
Alpha-gal Syndrome Publications
5
Alpha-gal Syndrome Researchers

Publications

Helminth coinfections mitigate clinical, parasitological, and immune outcomes in Mozambican children with malaria.

Cuamba I, Santano R, Grau-Pujol B, Vidal M, Aguilar R, et al.
BMC medicine •

Clearance of Plasmodium falciparum infection requires a T1 immune response with production of pro-inflammatory cytokines, IgG1, and IgG3 responses. In contrast, infections with helminths are dominated by T2/T immune responses characterized by production of anti-inflammatory cytokines, IgE, and IgG4, which could potentially interfere with malaria outcomes and immune responses. We recruited 441 malaria-symptomatic children aged 2-10 years attending two hospitals in the Manhiça District (Mozambique) and assessed infection by rapid antigen diagnostic test, microscopy, and/or quantitative PCR. Using Luminex, we measured concentrations of 30 cytokines and IgA, IgM, IgE, IgG, and IgG1-4 levels against 12 P. falciparum antigens and total IgE. Among 74 children diagnosed with malaria, 22% (16) were coinfected with STH, and 78% (58) had only P. falciparum. Soil-transmitted helminths (STH) coinfection associated with lower P. falciparum density (P = 0.005) and fever (P = 0.047). Coinfected children also had lower concentrations of plasma pro-inflammatory (IL-8, TNF, IFNα, IP-10, MCP1, MIG, MIP1β, and GM-CSF) and anti-inflammatory cytokines (IL-5, IL-10) (P < 0.05). Furthermore, antibody responses to a set of P. falciparum antigens, including SSP2 (IgG1, IgG4, IgG), PTRAMP (IgG3), MSP3 (IgG), RH5 (IgG1), and α-gal (IgG1), as well as total IgE, were elevated in STH coinfected children (P < 0.05). STH infections were associated with decreased P. falciparum parasitemia, downregulation of inflammatory cytokines, and enhanced antibody responses, potentially resulting in milder malaria episodes, suggesting enhanced protective immunity.

Antibody responses to α-Gal in African children vary with age and site and are associated with malaria protection.

Aguilar R, Ubillos I, Vidal M, Balanza N, Crespo N, et al.
Scientific reports •

Naturally-acquired antibody responses to malaria parasites are not only directed to protein antigens but also to carbohydrates on the surface of Plasmodium protozoa. Immunoglobulin M responses to α-galactose (α-Gal) (Galα1-3Galβ1-4GlcNAc-R)-containing glycoconjugates have been associated with protection from P. falciparum infection and, as a result, these molecules are under consideration as vaccine targets; however there are limited field studies in endemic populations. We assessed a wide breadth of isotype and subclass antibody response to α-Gal in children from Mozambique (South East Africa) and Ghana (West Africa) by quantitative suspension array technology. We showed that anti-α-Gal IgM, IgG and IgG levels vary mainly depending on the age of the child, and also differ in magnitude in the two sites. At an individual level, the intensity of malaria exposure to P. falciparum and maternally-transferred antibodies affected the magnitude of α-Gal responses. There was evidence for a possible protective role of anti-α-Gal IgG3 and IgG4 antibodies. However, the most consistent findings were that the magnitude of IgM responses to α-Gal was associated with protection against clinical malaria over a one-year follow up period, especially in the first months of life, while IgG levels correlated with malaria risk.