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Fulltext First case of a naturally acquired human infection with Plasmodium cynomolgi

Ta TH, Hisam S, Lanza M, Jiram AI, Ismail N, Rubio JM

Malar J, 2014;13:68.
PMID: 24564912 DOI: 10.1186/1475-2875-13-68

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.
Entomologic investigation of Plasmodium knowlesi vectors in Kuala Lipis, Pahang, Malaysia

Jiram AI, Vythilingam I, NoorAzian YM, Yusof YM, Azahari AH, Fong MY

Malar J, 2012;11:213.
PMID: 22727041

The first natural infection of Plasmodium knowlesi in humans was recorded in 1965 in peninsular Malaysia. Extensive research was then conducted and it was postulated that it was a rare incident and that simian malaria will not be easily transmitted to humans. However, at the turn of the 21st century, knowlesi malaria was prevalent throughout Southeast Asia and is life threatening. Thus, a longitudinal study was initiated to determine the vectors, their seasonal variation and preference to humans and macaques.
Fulltext Nested multiplex PCR for identification and detection of human Plasmodium species including Plasmodium knowlesi

Miguel-Oteo M, Jiram AI, Ta-Tang TH, Lanza M, Hisam S, Rubio JM

Asian Pac J Trop Med, 2017 Mar;10(3):299-304.
PMID: 28442114 DOI: 10.1016/j.apjtm.2017.03.014

OBJECTIVE: To develop a new technique for diagnosis of Plasmodium knowlesi and at the same time to be able to discriminate among the diverse species of Plasmodium causing human malaria.
METHODS: In this study the nested multiplex malaria PCR was redesigned, targeting the 18S rRNA gene, to identify the fifth human Plasmodium species, Plasmodium knowlesi, together with the other human Plasmodium (Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariae) by amplified fragment size using only two amplification processes and including an internal reaction control to avoid false negatives.
RESULTS: The technique was validated with 91 clinical samples obtained from patients with malaria compatible symptoms. The technique showed high sensitivity (100%) and specificity (96%) when it was compared to the reference method employed for malaria diagnosis in the Instituto de Salud Carlos Ⅲ and a published real-time PCR malaria assay.
CONCLUSIONS: The technique designed is an economical, sensitive and specific alternative to current diagnosis methods. Furthermore, the method might be tested in knowlesi-malaria endemic areas with a higher number of samples to confirm the quality of the method.
Fulltext Plasmodium knowlesi in humans, macaques and mosquitoes in peninsular Malaysia

Vythilingam I, Noorazian YM, Huat TC, Jiram AI, Yusri YM, Azahari AH, et al.

Parasit Vectors, 2008;1(1):26.
PMID: 18710577 DOI: 10.1186/1756-3305-1-26
Fulltext Correction to: Evidence of asymptomatic submicroscopic malaria in low transmission areas in Belaga district, Kapit division, Sarawak, Malaysia

Jiram AI, Ooi CH, Rubio JM, Hisam S, Karnan G, Sukor NM, et al.

Malar J, 2019 Nov 21;18(1):369.
PMID: 31752865 DOI: 10.1186/s12936-019-3005-6

Please note that an author has been erroneously omitted from the author list of the published article [1].
Fulltext Evidence of asymptomatic submicroscopic malaria in low transmission areas in Belaga district, Kapit division, Sarawak, Malaysia

Jiram AI, Ooi CH, Rubio JM, Hisam S, Karnan G, Sukor NM, et al.

Malar J, 2019 May 02;18(1):156.
PMID: 31046769 DOI: 10.1186/s12936-019-2786-y

BACKGROUND: Malaysia has declared its aim to eliminate malaria with a goal of achieving zero local transmission by the year 2020. However, targeting the human reservoir of infection, including those with asymptomatic infection is required to achieve malaria elimination. Diagnosing asymptomatic malaria is not as straightforward due to the obvious lack of clinical manifestations and often subpatent level of parasites. Accurate diagnosis of malaria is important for providing realistic estimates of malaria burden and preventing misinformed interventions. Low levels of parasitaemia acts as silent reservoir of transmission thus remains infectious to susceptible mosquito vectors. Hence, the aim of this study is to investigate the prevalence of asymptomatic submicroscopic malaria (SMM) in the District of Belaga, Sarawak.
METHODS: In 2013, a total of 1744 dried blood spots (DBS) were obtained from residents of 8 longhouses who appeared healthy. Subsequently, 251 venous blood samples were collected from residents of 2 localities in 2014 based on the highest number of submicroscopic cases from prior findings. Thin and thick blood films were prepared from blood obtained from all participants in this study. Microscopic examination were carried out on all samples and a nested and nested multiplex PCR were performed on samples collected in 2013 and 2014 respectively.
RESULTS: No malaria parasites were detected in all the Giemsa-stained blood films. However, of the 1744 samples, 29 (1.7%) were positive for Plasmodium vivax by PCR. Additionally, of the 251 samples, the most prevalent mono-infection detected by PCR was Plasmodium falciparum 50 (20%), followed by P. vivax 39 (16%), P. knowlesi 9 (4%), and mixed infections 20 (8%).
CONCLUSIONS: This research findings conclude evidence of Plasmodium by PCR, among samples previously undetectable by routine blood film microscopic examination, in local ethnic minority who are clinically healthy. SMM in Belaga district is attributed not only to P. vivax, but also to P. falciparum and P. knowlesi. In complementing efforts of programme managers, there is a need to increase surveillance for SMM nationwide to estimate the degree of SMM that warrant measures to block new transmission of malaria.