-- Molecular analysis of 28 human cases of malaria confirms presence of Plasmodium simium, a parasite usually only found in monkeys, and not P vivax (a human parasite) as previously diagnosed
Malaria was eliminated from southern and southeastern Brazil over 50 years ago, but a number of cases each year in areas of the Atlantic Forest prompted researchers to investigate the possibility of zoonotic transmission - where human beings become infected, via a mosquito bite, with a malaria parasite that usually infects monkeys.
Now, analysis of DNA samples has confirmed that 28 such cases of malaria were caused by zoonotic transmission of Plasmodium simium, a parasite usually only found in monkeys, and not the human parasite Plasmodium vivax, as previously thought.
The authors of the analysis say that screening of local monkeys and mosquitos will be required to evaluate the extent of the emerging zoonotic threat to public health, and to the potential of malaria elimination in Brazil. The study is published in The Lancet Global Health journal.
Once prevalent in the whole country, malaria transmission in Brazil now occurs almost entirely (over 99% of cases) in the northern Amazon region. However, between 2006 and 2014, 43 cases of malaria were reported in the Atlantic Forest area in southern Brazil, and an additional 49 occurred in 2015-16.
Samples from 33 of these cases were included in this study. DNA from 28 cases was successfully sequenced and all were confirmed to be P simium, rather than P vivax. All patients had entered the forest or visited the surrounding area. Fever was the main symptom, no patient was admitted to hospital, and all made full recoveries following treatment.
"There is no evidence that zoonotic malaria can be transmitted from human to human via mosquitoes. In addition there is no current threat to people in the city of Rio de Janeiro, or in other non-forest areas of the Rio de Janeiro state, where transmission of the disease does not exist. However, its unique mode of transmission via monkeys and the fact that it occurs in areas of high forest coverage mean that zoonotic malaria poses a unique problem for malaria control efforts and may complicate the drive towards eventual elimination of the disease. Although benign and treatable, visitors should follow measures to avoid insect bites when going into the forest", says author Dr Patrícia Brasil, Instituto Nacional de Infectologia Evandro Chagas, Rio de Janeiro, Brazil. 
Zoonotic malaria occurs when human beings become infected with a mosquito-borne malaria parasite that usually infects non-human primates only. The zoonotic parasite Plasmodium knowlesi, transmitted from the macaque monkey, is responsible for a high proportion of human malaria cases in southeast Asia. P simium is transmitted via the Anopheles mosquito and is known to infect some species of howler and capuchin monkeys in the Atlantic Forest region of south and southeastern Brazil.
"In the 1960s, there was a probable case of zoonotic malaria described in a forest guard in the Atlantic Forest of São Paulo, but until now, there has been no molecular evidence of the parasite being present in humans. This is the first demonstration of P simium naturally infecting human beings in forest locations in a region considered to have eliminated transmission of malaria at least 50 years ago", says author Dr Cláudio Tadeu Daniel-Ribeiro, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil. 
The authors note that since samples from previous years have not yet been tested, it is not possible to establish whether the parasite has only recently acquired the ability to frequently infect human beings, or if zoonotic malaria has previously infected human beings in this region, prior to the region eliminating the disease.
In a linked Comment, Matthew J Grigg, Menzies School of Health Research, Darwin, Australia and Georges Snounou, Sorbonne University, Paris, France, write: "A large focus of zoonotic P knowlesi human infections (historically misdiagnosed as Plasmodium malariae by microscopy) was reported in Malaysia in 2004, where it is now the predominant cause of malaria (...)." They note that the findings make "this part of Brazil the site of a second global focus of zoonotic malaria." They add: "This important study raises a number of remaining questions. Firstly, it becomes imperative to obtain the full genome of P simium to confirm or reject synonymy with P vivax. An anthropozoonotic P vivax reservoir in Brazilian monkeys would pose a substantial threat to malaria elimination throughout the continent and possibly beyond, including potential onwards transmission from hypnozoite relapses. One priority should be to investigate the natural history and biology of these two parasites in their non-human primate hosts. Evaluation of the geographical distribution and prevalence of P simium in both monkey hosts and mosquito vectors will also assist in accurately defining the population at risk. The clinical features and pathogenesis of P simium also remain poorly defined."
NOTES TO EDITORS
The study was funded by the Fundação Carlos Chagas Filho de Amparo a Pesquina do Estado de Rio de Janeiro, the Brazilian National Council for Scientific and Technological Development (CNPq), JSPS Grant-in-Aid for scientific research, Secretary for Health Surveillance of the Ministry of Health, Global Fund, and PRONEX Program of the CNPq.
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