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      Atlantic Forest Malaria: A Review of More than 20 Years of Epidemiological Investigation

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          Abstract

          In the south and southeast regions of Brazil, cases of malaria occur outside the endemic Amazon region near the Atlantic Forest in some coastal states, where Plasmodium vivax is the recognized parasite. Characteristics of cases and vectors, especially Anopheles (Kerteszia) cruzii, raise the hypothesis of a zoonosis with simians as reservoirs. The present review aims to report on investigations of the disease over a 23-year period. Two main sources have provided epidemiological data: the behavior of Anopheles vectors and the genetic and immunological aspects of Plasmodium spp. obtained from humans, Alouatta simians, and Anopheles spp. mosquitoes. Anopheles (K.) cruzii is the most captured species in the forest canopy and is the recognized vector. The similarity between P. vivax and Plasmodium simium and that between Plasmodium malariae and Plasmodium brasilianum shared between simian and human hosts and the involvement of the same vector in the transmission to both hosts suggest interspecies transfer of the parasites. Finally, recent evidence points to the presence of Plasmodium falciparum in a silent cycle, detected only by molecular methods in asymptomatic individuals and An. (K.) cruzii. In the context of malaria elimination, it is paramount to assemble data about transmission in such non-endemic low-incidence areas.

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          First case of a naturally acquired human infection with Plasmodium cynomolgi

          Since 1960, a total of seven species of monkey malaria have been reported as transmissible to man by mosquito bite: Plasmodium cynomolgi, Plasmodium brasilianum, Plasmodium eylesi, Plasmodium knowlesi, Plasmodium inui, Plasmodium schwetzi and Plasmodium simium. With the exception of P. knowlesi, none of the other species has been found to infect humans in nature. In this report, it is described the first known case of a naturally acquired P. cynomolgi malaria in humans. The patient was a 39-year-old woman from a malaria-free area with no previous history of malaria or travel to endemic areas. Initially, malaria was diagnosed and identified as Plasmodium malariae/P. knowlesi by microscopy in the Terengganu State Health Department. Thick and thin blood films stained with 10% Giemsa were performed for microscopy examination. Molecular species identification was performed at the Institute for Medical Research (IMR, Malaysia) and in the Malaria & Emerging Parasitic Diseases Laboratory (MAPELAB, Spain) using different nested PCR methods. Microscopic re-examination in the IMR showed characteristics of Plasmodium vivax and was confirmed by a nested PCR assay developed by Snounou et al. Instead, a different PCR assay plus sequencing performed at the MAPELAB confirmed that the patient was infected with P. cynomolgi and not with P. vivax. This is the first report of human P. cynomolgi infection acquired in a natural way, but there might be more undiagnosed or misdiagnosed cases, since P. cynomolgi is morphologically indistinguishable from P. vivax, and one of the most used PCR methods for malaria infection detection may identify a P. cynomolgi infection as P. vivax. Simian Plasmodium species may routinely infect humans in Southeast Asia. New diagnostic methods are necessary to distinguish between the human and monkey malaria species. Further epidemiological studies, incriminating also the mosquito vector(s), must be performed to know the relevance of cynomolgi malaria and its implication on human public health and in the control of human malaria. The zoonotic malaria cannot be ignored in view of increasing interactions between man and wild animals in the process of urbanization.
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            Outbreak of human malaria caused by Plasmodium simium in the Atlantic Forest in Rio de Janeiro: a molecular epidemiological investigation

            Malaria was eliminated from southern and southeastern Brazil over 50 years ago. However, an increasing number of autochthonous episodes attributed to Plasmodium vivax have recently been reported from the Atlantic Forest region of Rio de Janeiro state. As the P vivax-like non-human primate malaria parasite species Plasmodium simium is locally enzootic, we performed a molecular epidemiological investigation to determine whether zoonotic malaria transmission is occurring.
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              African great apes are natural hosts of multiple related malaria species, including Plasmodium falciparum.

              Plasmodium reichenowi, a chimpanzee parasite, was until very recently the only known close relative of Plasmodium falciparum, the most virulent agent of human malaria. Recently, Plasmodium gaboni, another closely related chimpanzee parasite, was discovered, suggesting that the diversity of Plasmodium circulating in great apes in Africa might have been underestimated. It was also recently shown that P. reichenowi is a geographically widespread and genetically diverse chimpanzee parasite and that the world diversity of P. falciparum is fully included within the much broader genetic diversity of P. reichenowi. The evidence indicates that all extant populations of P. falciparum originated from P. reichenowi, likely by a single transfer from chimpanzees. In this work, we have studied the diversity of Plasmodium species infecting chimpanzees and gorillas in Central Africa (Cameroon and Gabon) from both wild-living and captive animals. The studies in wild apes used noninvasive sampling methods. We confirm the presence of P. reichenowi and P. gaboni in wild chimpanzees. Moreover, our results reveal the existence of an unexpected genetic diversity of Plasmodium lineages circulating in gorillas. We show that gorillas are naturally infected by two related lineages of parasites that have not been described previously, herein referred to as Plasmodium GorA and P. GorB, but also by P. falciparum, a species previously considered as strictly human specific. The continuously increasing contacts between humans and primate populations raise concerns about further reciprocal host transfers of these pathogens.
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                Author and article information

                Journal
                Microorganisms
                Microorganisms
                microorganisms
                Microorganisms
                MDPI
                2076-2607
                08 January 2021
                January 2021
                : 9
                : 1
                : 132
                Affiliations
                [1 ]Unidade de Medicina Tropical, Universidade Federal do Espírito Santo, Vitória 29047-105, Brazil; tomenaalencar@ 123456hotmail.com (F.E.C.d.A.); vicentecrachel@ 123456gmail.com (C.R.V.); lmendesf1@ 123456gmail.com (L.M.F.); blimafux@ 123456yahoo.com.br (B.F.); fil.cris@ 123456terra.com.br (C.C.J.)
                [2 ]Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade NOVA de Lisboa, 1349-008 Lisboa, Portugal; marcia.medeiros@ 123456ihmt.unl.pt (M.M.M.); PCravo@ 123456ihmt.unl.pt (P.C.); aparez@ 123456ihmt.unl.pt (A.P.A.)
                [3 ]Instituto de Medicina Tropical de São Paulo, Universidade de São Paulo, São Paulo 05403-000, Brazil; amrcd2@ 123456gmail.com
                [4 ]Superintendência de Controle de Endemias do Estado de São Paulo, São Paulo 01027-000, Brazil
                [5 ]Instituto Nacional da Mata Atlântica, Santa Teresa 29650-000, Brazil; carol.loss@ 123456gmail.com
                Author notes
                Author information
                https://orcid.org/0000-0003-0182-7969
                https://orcid.org/0000-0002-0281-2892
                https://orcid.org/0000-0002-0497-6532
                Article
                microorganisms-09-00132
                10.3390/microorganisms9010132
                7826787
                33430150
                f5857be8-623c-4a28-aaf2-6ebca8556f69
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 11 December 2020
                : 06 January 2021
                Categories
                Review

                malaria,molecular epidemiology,anopheles,plasmodium,dna, mitochondrial,sequence analysis, dna,zoonoses

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