Monkey Malaria Infects a Large Cluster of Humans in Borneo

Abstract & Commentary

Synopsis: This is a fascinating report of a cluster of human Plasmodium knowlesi cases misdiagnosed as Plasmodium malariae in a rural rainforest area of Sarawak.

Sources: Singh B, et al. A large focus of naturally acquired Plasmodium knowlesi infections in human beings. Lancet.2004;363:1017-1024; White N. Sharing malarias. Lancet.2004; 363:1006

Between 1998 and 2002, the yearly incidence of malaria in Sarawak, Malaysian Borneo was between 2496 and 3155 cases. Plasmodium vivax represented 69.1% of all cases followed by Plasmodium falciparum (19.7%) with Plasmodium malaria accounting for 9.4%. Singh and colleagues noted that P malariae cases were mainly reported in the central divisions of Kapit and Miri; indeed, one-fifth of all malaria cases in Kapit were identified as P malariae. However, these clinical cases were noted to be atypical for P malariae infection, and nested PCR assay failed to identify P malariae DNA. Singh et al studied and sequenced the small subunit ribosomal RNA and circumsporozoite gene and characterized Plasmodium knowlesi in 58% (120/208) of cases initially identified by smear as P malariae. P knowlesi infection has a natural host in the Kapit area—long-tailed and pig-tailed macaque monkeys, which live in close proximity to humans.

Clinical cases were reviewed in 94 patients who sought care. Almost all (91%) of these patients had fever and rigors. Other major symptoms were headache, cough, and vomiting. One-third had parasitemia of over 5000 parasites per µL. All stages of the erythrocytic cycle were identified by Giemsa-stained thick and thin blood smears. Early trophozoites appeared as ring forms indistinguishable from those of P falciparum. Occasionally, more than 1 ring form was noted in each erythrocyte, and double chromatin dots were also seen. Late trophozoite band forms that are typical of P malariae were observed, but without the characteristic stippling of the erythrocytes as sometimes associated with P malariae infections. Patients responded to chloroquine and primaquine. Ten patients were given single-dose Fansidar® and 2 patients were given quinine. There was no evidence of early treatment failure as microscopy showed parasites cleared rapidly from peripheral blood after treatment.

Comment by Michele Barry, MD, FACP

Patients belonged to the Iban ethnic group and lived in river-side housing while working in the logging industry within the surrounding jungle. There was no clustering of cases within 1 housing community, and only 12.5% of diagnosed cases were in children, indicating working in the jungle was a risk factor for the mostly adult men diagnosed with this infection.

P knowlesi has an interesting history for humans, as it was used prior to the penicillin era as pyretic treatment for neurosyphilis. It was first identified in 1931 in a long-tailed macaque, and although there have been isolated single reports of natural human infection, this is the first large focus of natural infection astutely noted by the epidemiologic observation of an unusual clustering of P malariae. The course of infection with P knowlesi, the only primate infection with a 24-hr asexual blood-stage cycle, is dependent on the host. In its natural host, the macaque monkey, low-level parasitemia is observed, while in rhesus monkeys, parasitemia evolves rapidly and is lethal. In humans, when it was used as a pyretic agent, symptoms ranged from mild infection that resolved spontaneously to those that required antimalarial intervention. In this study of patients ill enough to seek clinic treatment, all responded to chloroquine and other conventional antimalarials, and no deaths were reported. Whether the parasite has switched hosts and transmission is between humans, or whether all infections were zoonotic remains to be established. Thus, a general rule for travel physicians is that malaria must be excluded in any patient with fever traveling to a tropical area—even if that travel took place in an uninhabited forest.

Michele Barry, MD, FACP, Professor of Medicine, Co-Director, Tropical Medicine and International Travelers' Clinic, Yale University School of Medicine, is Assistant Editor for Travel Medicine Advisor.