More research on malaria caused by Plasmodium vivax is needed
March 27, 2013
By Elton Alisson, in Tokyo
Agência FAPESP – As a result of large investments made by international philanthropic institutions in vaccine research and development, much has been learned in recent years about Plasmodium falciparum– one of the principal causative agents of malaria.
Studies of the species Plasmodium vivax – responsible for 85% of the malaria cases reported in Brazil and 50% of those reported in Asia – have been neglected however. Unlike Plasmodium falciparum, P. Vivax does not result in morbidity, is not believed to be drug resistant and cannot be cultivated in the laboratory, all of which hampers the study of its biology.
Over the last 10 years, however, cases have begun to appear all over the world – Brazil included – where patients diagnosed with malaria caused by P. vivax have begun to experience health complications and, in some instances, have died.
In order to better understand the parasite – up to now considered benign –, research teams in Australia, the United States, Singapore and Brazil have embarked on its study. Malariologists warn, however, that research efforts are falling short of what is necessary.
“There needs to be more investment in research on Plasmodium vivax because so little is known about it, partly because of the technical difficulties involved in studying it, like the fact that it cannot be cultivated,” Fábio Trindade Maranhão Costa, professor at the Institute of Biology at the State University of Campinas (Unicamp), tells Agência FAPESP. “The parasite has become increasingly lethal and there have even been reports that it has become chemoresistant [drug resistant].”
Costa gave a lecture on the pathogenesis and development of vaccines to fight Plasmodium vivax at the Japan-Brazil Symposium on Research Collaboration. Jointly organized by the São Paulo Research Foundation (FAPESP) and the Japan Society for the Promotion of Science (JSPS), the event was held March 15-16 at Rikkyo University, with support from the Embassy of Brazil in Tokyo.
According to Costa, the first cases of a worsening clinical picture of patients with malaria caused by Plasmodium vivax in Brazil were reported by researchers from the Tropical Medicine Foundation of Amazonas, in Manaus (state of Amazonas) – a city that, together with Porto Velho (state of Rondônia) and Cruzeiro do Sul (state of Acre), is responsible for 20% of all malaria cases in Brazil.
In order to obtain samples of the parasite from patients and run tests within 48 hours – which is the life cycle of the pathogen outside the host – the researcher began collaborating with the team from Manaus four years ago.
One of the team’s discoveries, within the scope of the research project supported by FAPESP, was that although the Plasmodium vivax is genetically and morphologically quite different from thePlasmodium falciparum, they share similar pathogenic characteristics.
In an article published in the Journal of Infectious Diseases in 2010, Brazilian researchers showed that the parasite also has the capacity to adhere to the pulmonary and cerebral endothelia as well as to the placenta.
“This discovery was very important because up to that point, we believed that only Plasmodium falciparum had this adhesive capacity because only it was thought to be lethal,” Costa stated.
“We also realized that, despite the fact that the health complications they cause at any given time are similar, in general, the factors that cause these complications are not the same,” he claimed.
According to Costa, one of the differences between the two parasites is that when a patient with malaria caused Plasmodium falciparum is treated quickly, indirect control of disease transmission is possible. That is not the case with malaria caused by Plasmodium vivax.
Therefore, there can be a significant reduction in the number of cases of malaria caused by Plasmodium falciparum. Control of cases where the disease is caused by Plasmodium vivaxis not possible in the same proportion, even with good medical care.
“That is why in Brazil, where there is relatively good medical treatment, most cases of malaria are caused by Plasmodium vivax,” Costa explained.
The researcher goes on to say that in Asia, Plasmodium vivax is responsible for nearly half of all malaria cases in the region. The trend is for it to exceed the number of cases of the disease caused by Plasmodium falciparum.
“Malaria caused by Plasmodium vivax, for example, can be found on the border between North Korea and South Korea, near Japan,” Costa said. The parasite also survives at milder temperatures, in addition to presenting dormant forms in the liver.
It is common, for example, to have cases where patients have been infected in the summer and the pathogen lies dormant in the liver over the winter before it reappears the following summer. “It can be transmitted again,” Costa said.
The Brazilian research team is currently studying other pathogenic characteristics of Plasmodium vivax and the relation of some aspects to the biology of the parasite. Some of the questions they are seeking answers to through a research project, conducted with FAPESP support, concerns whether the parasite has to adhere to the pulmonary and cerebral endothelia and the placenta in order to maintain its biology.
“Plasmodium falciparum, for example, can infect any blood cell. Plasmodium vivax, however, only infects the erythrocytes that we call reticulocytes,” Costa said.
Recently, in collaboration with colleagues from Singapore, the researchers were able to develop a methodology in which, when the parasite bursts a reticulocyte, it also infects other erythrocytes. The results of the study were published in the journal Blood, and may help in the development of a vaccine to treat malaria caused by Plasmodium vivax.
“Some of the questions we have studied are whether a vaccine would be able to inibit the reticulocyte penetration by Plasmodium vivax, and which molecules are involved in this process,” Costa said.
In places where cases of malaria are caused by Plasmodium vivax, the disease is treated with several medicines. In Brazil, chloroquine is the recommended treatment. However, the drug is no longer used to treat malaria caused by Plasmodium falciparum because the pathogen has become chemoresistant.
“Chloroquine is a well-known, well-studied, inexpensive drug that is also used to fight viral infections [diseases that affect the immune system],” Costa said. “Since it was widely used during the post-war period in a rather uncontrolled manner, however, Plasmodium falciparum is now chemoresistant,” explained Costa.
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