Carlos Penha-Gonçalves and his team, at the Disease Genetics Laboratory, have developed an authentic mouse model of severe malaria in pregnant women. In a separate study, the group identified a genetic region which makes mice less vulnerable to infection of the liver by malaria parasites.
It is estimated that over 50 million pregnancies occur each year in malaria endemic areas. Indeed, pregnancy-associated malaria is one of the major public health burdens in Africa, leading to 100,000 infant deaths annually. Pregnant women who are infected with the Plasmodium parasite show more critical symptoms of malaria, their pregnancies rarely go to term, the growth of the fetus is delayed, babies have low birth weight and often die during infancy.
Carlos and his team have now developed a mouse model of pregnancy-induced malaria which reliably recapitulates the symptoms of the disease, both in the mother and in the fetus. Using this mouse model, the researchers have already begun to unpick some of the events which may underlie the severity of malaria infection during pregnancy.
Says Carlos, ‘What we have achieved would have been impossible to do in humans, and we hope that our model will now provide clues of key molecules and cells that could be targets for treatment’.
Malaria symptoms occur when the parasite reaches the blood stream. However, before moving to the blood stream, the malaria parasite infects liver cells, where it multiplies manifold. In another key study, Carlos and his team have identified a genetic region on chromosome 17 of mice which appears to make it more difficult for the parasite to expand in the liver cells.
The team noticed that a certain breed of mice that they work with showed poorer expansion of the parasite Plasmodium berghei in the liver, and, subsequently, lower numbers in the blood stream. They used genetic mapping techniques to identify the gene or genes responsible for this effect. They called this region berl1, for berghei liver resistance 1.
Says Lígia Gonçalves, first author of this study, ‘We narrowed it down to a region which contains over 300 genes, and we are now trying to restrict it even further, to test individual candidate genes’.
According to Carlos, the next step will be to look at the human equivalent of the berl1 region in humans, and investigate whether it too is able to convey resistance to liver infection. The researchers will study patients who show asymptomatic liver infections.
This research was supported by the Fundação para a Ciência e a Tecnologia, in Portugal.
Ana Godinho | alfa
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