Parasites that Cause Asymptomatic Malaria Differ in Gene Expression as Compared to Febrile Infections, but Seem to Be Equally Transmissible

The comparison of malaria parasites causing afebrile or febrile infections suggests that they are equally transmissible but may differentially express genes related to cell adhesion and immune evasion. These are the main conclusions of a study led by ISGlobal, an institution supported by “la Caixa”, in collaboration with the Manhiça Health Research Centre (CISM) in Mozambique. 

Asymptomatic infections with Plasmodium falciparum represent a hidden source of malaria transmission that can hinder elimination efforts. However, little is known on the dynamics, transmissibility and biology of parasites that cause afebrile infections.

To this end, ISGlobal researcher Alfredo Mayor and his colleagues performed a case-control study, where they collected blood samples from 61 infected individuals without fever at the time of recruitment, and paired them with 61 other individuals with fever, of the same age, gender and parasite density in blood. They compared the expression level of different parasite genes involved in pathogenicity, including those involved in cell adhesion and immune evasion.

The results show that parasites causing febrile infections expressed higher levels of genes (called var group B and DC8) linked to cell adhesion as compared to those causing afebrile infections. “This suggests a higher pathogenic potential that could lead to clinical manifestations,” explains Himanshu Gupta, first author of the study. Inversely, parasites from afebrile infections expressed higher levels of a gene variant (var group C) that has been associated with immune evasion and whose expression is epigenetically controlled by another gene (PfSir2a) that was also increased.  However, both febrile and afebrile infections expressed similar levels of genes specifically expressed by gametocytes, the transmissible form of the parasite, suggesting that both types of infection can be transmitted with the same efficiency.

“This study provides valuable information that may help guide evidence-based approaches to deal with asymptomatic malaria, a major obstacle to malaria elimination,” concludes Mayor.

Reference

Gupta H, Galatas B, Matambisso G, et al. Differential expression of var subgroups and PfSir2a genes in afebrile Plasmodium falciparum malaria: a matched case-control study. Malar J. 2019 Sep 23;18(1):326. doi: 10.1186/s12936-019-2963-z.