Susceptibility of Human Plasmodium knowlesi to Anti-malarials
Susceptibility of Human Plasmodium knowlesi to Anti-malarials
From its natural simian hosts in Southeast Asia, Plasmodium knowlesi has emerged as a significant human pathogen, particularly in Malaysian Borneo. Human P. knowlesi infections cause febrile illnesses that can rapidly progress to severe and sometimes fatal outcomes. Ominously, the incidence of P. knowlesi malaria is increasing in geographic areas where Plasmodium falciparum and Plasmodium vivax are coming under control, thereby threatening the aim of eliminating malaria. Determining the efficacy of conventional anti-malarials against P. knowlesi is a priority, particularly as there are no reports of anti-malarials assessed against human isolates of P. knowlesi ex vivo.
Here, the drug sensitivity profiles of P. knowlesi isolates obtained from patients being recruited into a study of the pathophysiology of knowlesi malaria in an endemic area of Sarawak, Malaysian Borneo were investigated. Currently, the WHO recommends artemisinin-based combination therapy (ACT) as first-line treatment for malaria in most endemic areas, so artemisinin and its clinically useful derivatives artesunate, dihydroartemisinin (DHA) and artemether were tested. Mefloquine, used as a partner drug in certain artemisinin-based combinations and in prophylaxis against malaria, and chloroquine that is recommended for treatment of Plasmodium malariae (the species which P. knowlesi is often confused with when diagnosed by microscopy) were also included. In addition, results from P. falciparum and P. vivax studied contemporaneously are presented, together with those obtained with the H strain laboratory isolate of P. knowlesi (cultured in vitro in rhesus erythrocytes) to confirm the methodologies used. Insights into the drug susceptibility patterns of this important emerging parasite, may prove useful in guiding the best choice of anti-malarial treatment regimens for P. knowlesi infection.
Background
From its natural simian hosts in Southeast Asia, Plasmodium knowlesi has emerged as a significant human pathogen, particularly in Malaysian Borneo. Human P. knowlesi infections cause febrile illnesses that can rapidly progress to severe and sometimes fatal outcomes. Ominously, the incidence of P. knowlesi malaria is increasing in geographic areas where Plasmodium falciparum and Plasmodium vivax are coming under control, thereby threatening the aim of eliminating malaria. Determining the efficacy of conventional anti-malarials against P. knowlesi is a priority, particularly as there are no reports of anti-malarials assessed against human isolates of P. knowlesi ex vivo.
Here, the drug sensitivity profiles of P. knowlesi isolates obtained from patients being recruited into a study of the pathophysiology of knowlesi malaria in an endemic area of Sarawak, Malaysian Borneo were investigated. Currently, the WHO recommends artemisinin-based combination therapy (ACT) as first-line treatment for malaria in most endemic areas, so artemisinin and its clinically useful derivatives artesunate, dihydroartemisinin (DHA) and artemether were tested. Mefloquine, used as a partner drug in certain artemisinin-based combinations and in prophylaxis against malaria, and chloroquine that is recommended for treatment of Plasmodium malariae (the species which P. knowlesi is often confused with when diagnosed by microscopy) were also included. In addition, results from P. falciparum and P. vivax studied contemporaneously are presented, together with those obtained with the H strain laboratory isolate of P. knowlesi (cultured in vitro in rhesus erythrocytes) to confirm the methodologies used. Insights into the drug susceptibility patterns of this important emerging parasite, may prove useful in guiding the best choice of anti-malarial treatment regimens for P. knowlesi infection.
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