Recent evidence recognises the silent and persistent reservoir of parasites as one of the key drivers of continued malaria transmission, which hampers elimination efforts globally. It is still somewhat unknown how the asymptomatic infection state of parasitaemia is tolerated by the human host without presenting as an illness, and therefore detected and treated.

This collaborative study between London School of Hygiene & Tropical Medicine, Imperial College London, and the West African Centre for Cell Biology of Infectious Pathogens (WACCBIP), University of Ghana, explored the possibility that the response of blood cells of children with symptomatic or asymptomatic P. falciparum infections, assessed by genes turned on and off, would reveal how the asymptomatic infection state is maintained. If specific features of the asymptomatic malaria could be detected, they could lead to strategies to identify and eliminate the transmission reservoir, and built into malaria control programming.

Surprisingly, the results revealed the opposite of what was expected. Whilst symptomatic malaria induces large-scale changes in gene being turned on or off, the analysis of asymptomatically infected individuals showed no difference from uninfected healthy control children. Within the asymptomatic infections and the uninfected children, no genes were being switched on or off by the infection - in stark contrast to hundreds of genes being turned on and off for symptomatic malaria.

The finding indicates that the parasite numbers are staying below a limit needed to switch on any sort of immune response in the blood, leading to a malaria infection effectively going “under the radar”. As a result, the human host stays healthy, does not seek treatment and the parasites can survive and be transmitted onwards.  

Lead co-author, Dr Julius Hafalla, Associate Professor of Immunology at London School of Hygiene and Tropical Medicine, explains ‘It is unlikely that we will be able to find a human biomarker that can be used as a test to detect asymptomatically infected individuals. If we want to detect them, we would need a more sensitive test for the parasites, which can detect lower levels of parasites than our conventional rapid diagnostic tests and microscopy. So, we are really talking about molecular tests like PCR. Currently these tests are not easily portable, so we would need innovation in diagnostics to make cheap and portable molecular tests for malaria parasites.”

Diana Ahu Prah, a PhD student who led the work at WACCBIP, University of Ghana, praised this important discovery as a step forward to create new diagnostics “the fact symptomatic malaria produces a strong response in the blood, as compared to asymptomatic cases, means that response could be the basis of future diagnostic tests to distinguish symptomatic malaria from other causes of fever. This would prevent the misclassification of patients who incidentally have parasites but actually have another cause of illness.”

The authors also emphasise the importance of strengthening surveillance efforts, especially in countries nearing elimination, where this recent addition to our understanding of malaria provides a tool in the arsenal to create better diagnostics, vaccines, and treatment.

Publication
Prah et al. Asymptomatic Plasmodium falciparum infection evades triggering a host transcriptomic response Journal of Infection