Kemri scientists shed light on how malaria parasite adapts to host environment
What you need to know:
- The researchers analysed data from 828 children in Kilifi with severe, mild and asymptomatic malaria between 1994 and 2014.
- Across this cohort, they examined markers of host immune responses and metabolism and compared markers of parasite growth and transmission investment.
Researchers at the Kenya Medical Research Institute have figured out how the malaria-transmitting mosquito rapidly responds to changes in its host environment.
The scientists carried out a study which characterised the factors that cause the malaria parasite, Plasmodium falciparum, to invest resources into reproduction – to maximise transmission to other hosts – or replication – to ensure survival within its current human host.
The findings show that the inflammatory responses to malaria infection in the human body during low transmission are associated with reduced levels of a chemical called lysophospatidylcholine (LPC) in the blood plasma. These low levels of LPC are associated with increased parasite investment into transmission to another host, by increasing sexual reproduction and decreasing asexual replication.
“The results shed further light on how malaria parasites adapt to changing within-human environments as a result of changing transmission intensity – a measure of the level of transmission of the malaria parasite in a particular area,” the researchers told Healthy Nation.
According to lead author Abdirahman Abdi, a senior research scientist at the KEMRI Wellcome Trust Research Programme, in order to transmit from one human host to another, the parasite must first transfer to a mosquito. This requires the parasite to differentiate into specialised cells called gametocytes – cells which eventually become gametes that are necessary for sexual reproduction.
“Plasmodium falciparum has a complex life cycle involving asexual replication in human blood and differentiation into gametocytes required for transmission to mosquitoes.”
Differentiation in gametocytes is known to be marked by the activation of a gene called ap2-g in the parasite. However, the factors that lead to activation of this gene have not previously been well characterised.”
This is why Abdi and his colleagues analysed data from 828 children in Kilifi with severe, mild and asymptomatic malaria between 1994 and 2014. Across this cohort, they examined markers of host immune responses and metabolism and compared markers of parasite growth and transmission investment. In particular, they examined two parasite genes: ap2-g (a transcription factor required for gametocyte activation) and PfSir2a (an environmental sensor linked to regulation of antigenic variation and replication), and a marker for parasite biomass. Investigating these parameters together allowed the team to determine parasite investment in the context of changing transmission intensity and host immunity.
“We propose a model where falling host immunity and declining transmission intensity modifies the host environment for the parasite, resulting in increased parasite investment in transmission and a limiting of replication,” says senior author Matthias Marti, a Professor at the Wellcome Center for Integrative Parasitology.
“Our findings provide critical information to accurately model parasite dynamics, particularly at low transmission intensity. This could inform timelines for successful elimination of malaria parasites. They also provide a strong argument for the potential use of gametocytocidal drugs once transmission has successfully been reduced,” notes the author.
Malaria is one of the world’s biggest public health concerns. In 2021, an estimated 619,000 deaths and 247 million cases were reported worldwide. Around 70 per cent of malaria deaths occur in children under the age of five in Africa and are caused by Plasmodium falciparum.
According to the US President’s Malaria Initiative, approximately 70 per cent of Kenya’s population is at risk for malaria, with 14 million people in endemic areas and another 17 million in areas of epidemic and seasonal malaria.
Additionally, there are an estimated 3.5 million new clinical cases and 10,700 deaths each year; with those living in western Kenya being at a high risk of the disease according to the Centers for Disease Control and Prevention.