Plasmodium knowlesi Malaria in Humans and Macaques, Thailand

Somchai Jongwutiwes , Pattakorn Buppan, Rattiporn Kosuvin, Sunee Seethamchai, Urassaya Pattanawong, Jeeraphat Sirichaisinthop, and Chaturong Putaporntip

Author affiliations: Chulalongkorn University, Bangkok, Thailand (S. Jongwutiwes, P. Buppan, R. Kosuvin, U. Pattanawong, C. Putaporntip); Naresuan University, Phitsanulok, Thailand (S. Seethamchai); Vector Borne Disease Training Center, Saraburi, Thailand (J. Sirichaisinthop)

Abstract

Naturally acquired human infections with Plasmodium knowlesi are endemic to Southeast Asia. To determine the prevalence of P. knowlesi malaria in malaria-endemic areas of Thailand, we analyzed genetic characteristics of P. knowlesi circulating among naturally infected macaques and humans. This study in 2008–2009 and retrospective analysis of malaria species in human blood samples obtained in 1996 from 1 of these areas showed that P. knowlesi accounted for 0.67% and 0.48% of human malaria cases, respectively, indicating that this simian parasite is not a newly emergent human pathogen in Thailand. Sequence analysis of the complete merozoite surface protein 1 gene of P. knowlesi from 10 human and 5 macaque blood samples showed considerable genetic diversity among isolates. The sequence from 1 patient was identical with that from a pig-tailed macaque living in the same locality, suggesting cross-transmission of P. knowlesi from naturally infected macaques to humans.

Plasmodium knowlesi circulates mainly among long-tailed macaques (Macaca fascicularis) and pig-tailed macaques (M. nemestrina) that inhabit a wide area of Southeast Asia (1). Microscopy-based detection of P. knowlesi has failed because morphologic features of young trophozoites of P. knowlesi resemble those of P. falciparum and characteristic band-shaped growing trophozoites resemble those of P. malariae (2–4). To date, the effective tool for diagnosing P. knowlesi infection is PCR specific for multicopy genes, such as small subunit rRNA and mitochondrial cytochrome b (3–5).

Human infections with P. knowlesi vary by geographic location (highest prevalence in Malaysian Borneo), but individual cases have been increasingly identified in countries in Southeast Asia (6). Our large-scale molecular-based survey of malaria in Thailand during 2006–2007 showed that P. knowlesi was widely distributed at a low prevalence (in 0.57% of all malaria cases identified) in several malaria-endemic areas bordering Myanmar, Cambodia, and Malaysia (7). Correct diagnosis of malaria has a major effect on malaria control in terms of treatment outcomes, disease transmission, and interpretation of efficiency of a given control measure.

Although malaria caused by P. knowlesi is generally benign and responsive to chloroquine treatment, severe and fatal cases similar to complicated P. falciparum malaria cases have been documented (6,8). To date, it has been unknown whether human infections with P. knowlesi in Thailand were caused by a new emergence of this parasite species or whether the parasite had been circulating cryptically with other human malaria parasites. Furthermore, it would be useful to explore spatiotemporal distribution of malaria species in humans and analyze genetic characteristics of P. knowlesi circulating among naturally infected macaques and humans. These data could lead to a better understanding of malaria transmission and provide information for a more effective malaria control policy at a nationwide level. Therefore, we sought to determine the prevalence of this simian malaria in malaria-endemic regions of Thailand.

Materials and Methods

Prospective Study and Sample Collection

Figure 1

Thumbnail of Provinces of Thailand where blood samples were obtained and tested for malaria, 1996–2009. Tak: blue, n = 210 in 1996, n = 681 in 2006–2007, and n = 1,216 in 2008–2009; Prachuab Khirikhan: orange, n = 215 in 2006–2007; Yala: purple, n = 286 in 2006–2007 and n = 1,408 in 2008–2009; Narathiwat: yellow, n = 370 in 2006–2007 and n = 421 in 2008–2009; and Chantaburi: red, n = 261 in 2006–2007 and n = 401 in 2008–2009.

Figure 1. Provinces of Thailand where blood samples were obtained and tested for malaria, 1996–2009. Tak: blue, n = 210 in 1996, n = 681 in 2006–2007, and n = 1,216 in 2008–2009;...

Most malaria infections in Thailand occur in forests or forest fringes along its borders with other countries, and malaria transmission exhibits a bimodal pattern that peaks in May–July and October–November (9,10). During October 2008–September 2009, venous or finger prick blood samples were obtained from 3,770 febrile persons (2,577 male and 1,193 female; mean age 27.4 years, range 1–87 years) who came to malaria clinics in northwestern (Tak Province, n = 1,354), eastern (Chantaburi Province, n = 401), and southern (Yala Province, n = 1,552, and Narathiwat Province, n = 463) Thailand (Figure 1). These 3,770 persons represented 12.4% of the 30,425 malaria cases in these areas during the study period (10). A total of 470 blood samples from these persons were negative for malaria parasites by microscopy (153 in Tak, 179 in Yala, and 138 in Narathiwat). The study was reviewed and approved by the Institutional Review Board of Faculty of Medicine, Chulalongkorn University.

full-text:
Plasmodium knowlesi Malaria in Humans and Macaques, Thailand - Vol. 17 No. 10 - October 2011 - Emerging Infectious Disease journal - CDC

Suggested citation for this article: Jongwutiwes S, Buppan P, Kosuvin R, Seethamchai S, Pattanawong U, Sirichaisinthop J, et al. Plasmodium knowlesi malaria in humans and macaques, Thailand. Emerg Infect Dis [serial on the Internet]. 2011 Oct [date cited]. http://dx.doi.org/10.3201/eid1710.110349