PT - JOURNAL ARTICLE AU - Patrícia Brasil AU - Mariano Gustavo Zalis AU - Anielle de Pina-Costa AU - Andre Machado Siqueira AU - Cesare Bianco Júnior AU - Sidnei Silva AU - André Luiz Lisboa Areas AU - Marcelo Pelajo-Machado AU - Denise Anete Madureira de Alvarenga AU - Ana Carolina Faria da Silva Santelli AU - Hermano Gomes Albuquerque AU - Pedro Cravo AU - Filipe Vieira Santos de Abreu AU - Cassio Leonel Peterka AU - Graziela Maria Zanini AU - Martha Cecilia Suárez Mutis AU - Alcides Pissinatti AU - Ricardo Lourenço-de-Oliveira AU - Cristiana Ferreira Alves de Brito AU - Maria de Fátima Ferreira-da-Cruz AU - Richard Culleton AU - Cláudio Tadeu Daniel-Ribeiro TI - <em>Plasmodium simium</em> causing human malaria: a zoonosis with outbreak potential in the Rio de Janeiro Brazilian Atlantic forest AID - 10.1101/122127 DP - 2017 Jan 01 TA - bioRxiv PG - 122127 4099 - http://biorxiv.org/content/early/2017/03/29/122127.short 4100 - http://biorxiv.org/content/early/2017/03/29/122127.full AB - Background Malaria was eliminated from Southern and Southeastern Brazil over 50 years ago. However, an increasing number of autochthonous episodes attributed to Plasmodium vivax have been recently reported in the Atlantic forest region of Rio de Janeiro State. As P. vivax-like non-human primate malaria parasite species Plasmodium simium is locally enzootic, we performed a molecular epidemiological investigation in order to determine whether zoonotic malaria transmission is occurring.Methods Blood samples of humans presenting signs and/or symptoms suggestive of malaria as well as from local howler-monkeys were examined by microscopy and PCR. Additionally, a molecular assay based on sequencing of the parasite mitochondrial genome was developed to distinguish between P. vivax and P. simium, and applied to 33 cases from outbreaks occurred in 2015 and 2016.Results Of 28 samples for which the assay was successfully performed, all were shown to be P. simium, indicating the zoonotic transmission of this species to humans in this region. Sequencing of the whole mitochondrial genome of three of these cases showed that P. simium is most closely related to P. vivax parasites from South American.Findings The explored malaria outbreaks were caused by P. simium, previously considered a monkey-specific malaria parasite, related to but distinct from P. vivax, and which has never conclusively been shown to infect humans before.Interpretation This unequivocal demonstration of zoonotic transmission, 50 years after the only previous report of P. simium in man, leads to the possibility that this parasite has always infected humans in this region, but that it has been consistently misdiagnosed as P. vivax due to a lack of molecular typing techniques. Thorough screening of the local non-human primate and anophelines is required to evaluate the extent of this newly recognized zoonotic threat to public health and malaria eradication in Brazil.Funding Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado de Rio de Janeiro (Faperj), The Brazilian National Council for Scientific and Technological Development (CNPq), JSPS Grant-in-Aid for scientific research, Secretary for Health Surveillance (SVS) of the Ministry of Health, Global Fund, and PRONEX Program of the CNPq.