First case of detection of Plasmodium knowlesi in Spain by Real Time PCR in a traveller from Southeast Asia

Abstract

Previously, Plasmodium knowlesi was not considered as a species of Plasmodium that could cause malaria in human beings, as it is parasite of long-tailed (Macaca fascicularis) and pig-tailed (Macaca nemestrina) macaques found in Southeast Asia. A case of infection by P. knowlesi is described in a Spanish traveller, who came back to Spain with daily fever after his last overseas travel, which was a six-month holiday in forested areas of Southeast Asia between 2008 and 2009. His P. knowlesi infection was detected by multiplex Real time quantitative PCR and confirmed by sequencing the amplified fragment. Using nested multiplex malaria PCR (reference method in Spain) and a rapid diagnostic test, the P. knowlesi infection was negative. This patient was discharged and asymptomatic when the positive result to P. knowlesi was reported. Prior to this case, there have been two more reports of European travellers with malaria caused by P. knowlesi, a Finnish man who travelled to Peninsular Malaysia during four weeks in March 2007, and a Swedish man who did a short visit to Malaysian Borneo in October 2006. Taken together with this report of P. knowlesi infection in a Spanish traveller returning from Southeast Asia, this is the third case of P. knowlesi infection in Europe, indicating that this simian parasite can infect visitors to endemic areas in Southeast Asia. This last European case is quite surprising, given that it is an untreated-symptomatic P. knowlesi in human, in contrast to what is currently known about P. knowlesi infection. Most previous reports of human P. knowlesi malaria infections were in adults, often with symptoms and relatively high parasite densities, up to the recent report in Ninh Thuan province, located in the southern part of central Vietnam, inhabited mainly by the Ra-glai ethnic minority, in which all P. knowlesi infections were asymptomatic, co-infected with P. malariae, with low parasite densities and two of the three identified cases were very young children under five years old.

Human Infections and Detection of Plasmodium knowlesi

“…Four different RDTs have been used on travelers with knowlesi malaria, and one has been used on macaques experimentally infected with P. knowlesi, producing mixed results (Table 2) (31,39,42,52,53,64,115). For the BinaxNOW RDT, with the exception of one report where there was a positive P. falciparum and panmalaria result, all other reports indicated a positive pan-malaria result and a negative P. falciparum result.…”

“…This is likely to reflect generally low transmission rates combined with environmental interactions that predispose adults to come into contact with infected vectors. Similarly, males are more represented in the literature, especially in case reports (31,36,39,47,52,53), case series (35), and two recent prospective studies in Sarawak and Sabah (35,118), while studies in the Kapit region of Sarawak have found a more equal distribution (3,33). Reports from selected areas of Sabah indicated that 10% of patients were under 15 years of age, and males accounted for 74% of cases (41).…”

“…In some hospitals in Malaysian Borneo, knowlesi malaria accounts for the majority of malaria cases admitted to hospitals (29,38,43). Human cases are not restricted to Malaysia, with reports of infections acquired in Thailand (48)(49)(50)(51)(52)(53), the Philippines (54-56), Myanmar (57,58), Singapore (59-61), Vietnam (62,63), Indonesia (64,65), Brunei (66), and Cambodia (67) (Fig. 1).…”

Centenary celebrations article

“…There was also a report from the Netherlands in a Malaysian immigrant (van Hellemond et al 2009). Recently a case of P. knowlesi has been identified in Spain in a traveler who spent time in three South-Asian countries, Indonesia, Vietnam and Thailand (Tang et al 2010), and in Australia in a patient who acquired the infection in Indonesian Borneo (Figtree et al 2010). All these reports suggest that P. knowlesi infections in humans are wide spread in South-east Asia.…”

Natural Plasmodium knowlesi malaria infections in humans

“…El primer caso reconocido de infección natural por P. knowlesi en humanos se reportó en 1965 (4) y luego se informó un presunto caso en 1971 (5), pero sólo desde el 2004 (2) se ha venido informando sistemáticamente la presencia de infecciones naturales en humanos en diferentes países del sureste de Asia, como en Tailandia (2004) (6), China (2006) (7), Singapur (2008) (8), Filipinas (2008) (9,10), Vietnam (2009) (11) y Malasia (12,13).…”