Asymptomatic malaria and febrile infection: what is the difference?

Barcelona Institute for Global Health (ISGlobal)
  • Both symptomatic and asymptomatic malaria is transmissible, which presents a problem for disease containment and control
  • Parasites causing asymptomatic and febrile malaria differ in the expression of certain genes: var group B, var group C and DC8
  • The study provides useful information to understand better the situation leading to “hidden reservoir” malaria patients


Malaria and its impact

Malaria is a disease that can affect humans, but also birds, bats, lizards and antelopes. Symptoms include fever, tiredness, vomiting, and headaches, with severe cases being cause for epilepsy (in cerebral malaria), coma or even death.

The disease is widespread in tropical and subtropical regions. It has a large economic impact as a result of increased healthcare costs, decreased work productivity and a negative impact on tourism. According to the World health organisation, in 2018, there were 228 million cases of malaria worldwide resulting in an estimated 405,000 deaths.

Anopheles punctipenis mosquito, vector of Plasmodium vivax, one of the five species of Plasmodium causing malaria in humans.

The disease is spread via the bite of an infected female Anopheles mosquito. The contact with the infected mosquito saliva introduces malaria Plasmodium parasites into the blood flow. Then, the parasites travel to the liver where they eventually mature and reproduce.

The risk of contracting and spreading of the disease in endemic areas can be reduced by preventing mosquito bites through the use of mosquito nets and insect repellents, or with mosquito control measures such as spraying insecticides and draining standing water.

Alas, an existing problem for the eradication of malaria is the existence of patients whose infected status is not evident. This poses a challenge connected to the potential for disease transmission going on unchecked.


Comparing Plasmodium in asymptomatic and febrile patients

Researchers of IS Global have looked into the differences between afebrile and febrile infections, focusing on the malaria parasite itself in those conditions. The findings suggest that the parasites are equally transmissible in both situations. It appears that parasites in one and other situation differentially express genes related to cell adhesion and immune evasion.

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

Plasmodium falciparum is cause of close to 50 % of malaria cases in humans. In the picture, two P. falciparum gametophytes.

Researcher Alfredo Mayor of IS Global and his colleagues performed a case-control study, collecting blood samples from 61 infected individuals without fever at the time of recruitment. These individuals were paired with 61 other infected individuals with fever, of the same age, gender and with the same parasite density in blood.

The expression level of different parasite genes involved in pathogenicity was studied, such as those related to cell adhesion and immune evasion. The results show that parasites causing febrile infections expressed higher levels of certain genes genes called var group B and DC8 that are linked to cell adhesion. The finding of these increased gene expression levels “suggests a higher pathogenic potential that could lead to clinical manifestations,” explains Himanshu Gupta, first author of the study.

Parasites from afebrile infections, on their hand, 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.

Life cycle of the malaria parasite. The gametocyte is the stage transmitted by the Anopheles mosquito.

Of the various stages of the parasite life cycle, the transmissible form is one particular stage called: the gametocyte. In the research by Mayor and colleagues, both febrile and afebrile infections expressed similar levels of the genes that gametocytes express. As in both situations the expression of gametocyte genes is equivalent, this suggests 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. The study, led by ISGlobal, an institution supported by “la Caixa”, was undertaken in collaboration with the Manhiça Health Research Centre (CISM) in Mozambique. 


Image credits:

Anopheles punctipenis mosquito picture was downloaded from Flickr and licensed via an Attribution 2.0 Generic (CC BY 2.0) license.

Plasmodium falciparum gametocytes picture was downloaded from Flickr and licensed via an Attribution-ShareAlike 2.0 Generic (CC BY-SA 2.0).

Malaria parasite life cycle diagram was adapted from original .svg file at Wikipedia, and licensed via an Attribution-ShareAlike 4.0 International (CC BY-SA 4.0) license.