A Recurring Theme: From Apes to Man

Abstract & Commentary

Synopsis: In what may be a harbinger of a changing host preference, it was found that over one-half of cases of malaria in an area of Malaysian Borneo were caused by Plasmodium knowlesi, monkey pathogen. Such cases are likely to go unrecognized because of the great difficulty in distinguishing this organism from Plasmodium malariae by microscopy.

Source: Singh B, et al. A large focus of naturally acquired Plasmodium knowlesi. Lancet. 2004;363:1017-1024

Singh and colleagues noted atypical features among the one-fifth of cases of malaria identified as apparently caused by Plasmodium malariae in the Kapit administrative division in Sarawak, Malaysian Borneo. Five isolates identified by microscopy as P. malariae were confirmed by a nested PCR assay to contain plasmodial DNA. The DNA, however, was not that of P. malarie or any of the other 3 human malaria species. Phylogenetic analysis of these and additional isolates showed that they were indistinguishable from Plasmodium knowlesi. PCR assay of the blood of 208 people with malaria found that 120 (58%) were positive for P. knowlesi, while none were positive for P. malariae. There was no evidence of clustering of cases. Examination of blood smears from these cases confirmed that P. knowlesi could be distinguished from P. malariae only with great difficulty. Patients, mostly adults, were successfully treated with chloroquine and primaquine.

Comment by Stan Deresinski, MD, FACP

P. malariae generally causes chronic asymptomatic infection with low level parasitemia. This investigation was triggered by the observation that the affected individuals were ill enough to seek medical care and had denser parasitemia than expected, with 18.5% having more than 5000 plasmodia per microliter of blood. Molecular analysis found that the isolates, previously misidentified as P. malariae, were genetically indistinguishable from P. knowlesi, a malaria parasite of macaque monkeys.

Injection with blood containing P. knowlesi was at one time used in the attempt to treat humans with neurosyphilis. Natural infection of a human has also previously been identified, with confirmation by monkey inoculation. Other than a single unconfirmed case, no other human infections with this protozoan have been identified. Experimental transmission to humans by mosquitoes has been demonstrated.

More than half the cases of malaria in the area studied were due to P. knowlesi. This raises the possibility that infection with this organism is no longer zoonotic and that humans may have now become a natural host.

Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford; Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor of Infectious Disease Alert