Plasmodium knowlesi - an emerging pathogen

Abstract

Ten years have passed since the publication of a large focus of Plasmodium knowlesi infections in the human population. The discovery was made during a molecular investigation of atypical P. malariae cases in the Kapit Health Division, Sarawak, Malaysian Borneo. Patients were more symptomatic with higher parasite counts than expected in P. malariae infections. The investigation found only P. knowlesi DNA present in patient blood samples. Morphological similarity had allowed P. knowlesi to masquerade as P. malariae during routine diagnostic microscopy for malaria. P. knowlesi, a malaria parasite of macaque monkeys, had entered the human population. The subsequent development of P. knowlesi species-specific PCR assays soon demonstrated that the entry was not confined to the Kapit Division but extended across island and mainland Southeast Asia. Relevant clinical descriptions and guidelines for the treatment and management of patents with P. knowlesi malaria were not available. Nor was it clear whether P. knowlesi had undergone a host switch event into the human population or if infections were zoonotic. The outputs of studies on P. knowlesi malaria during the past 10 years will be summarized, highlighting major findings within the context of pathophysiology, virulence, host switch events, treatment, control and importantly malaria elimination.

Keywords: Plasmodium; knowlesi; malaria; pathophysiology; virulence; zoonosis.

Fig 1

Complicated vs. uncomplicated Plasmodium knowlesi disease groups. Patients with P. knowlesi malaria grouped by uncomplicated disease [U = Green] and complicated disease [C = Red]. Plasma lactate results from a subset of patients (U = 91, C = 20, n = 111). P values were calculated using the Mann–Whitney U-test for nonparametric data and the unpaired t-test for normally distributed data (Prism 4 for Macintosh; GraphPad Software, Inc. San Diego).

Fig 2

The number of expected and observed cases of Plasmodium knowlesi malaria infected with parasites with Plasmodium knowlesi normocyte binding protein (pknbp) xa cluster 1 or cluster 2 parasites. Pknbpxa haplotypes were generated for 138 patient isolates in a subset of 147 patients. In the study, 44% of patients were infected with Pknbpxa cluster 1 type parasites and 56% with Pknbpxa cluster 2 type parasites. The patients were then grouped into uncomplicated (UC) n = 112 and complicated (C) n = 28 groups. The expected (Exp) number of patients in the UC and C groups was calculated based on the 44:56 ration of cluster 1 to cluster infections and compared to the number observed (Obs). More patients with complicated disease (C Obs) were infected with Pknbpxa cluster 2 parasites. Chi-square P = 0·048; with Yates correction P = 0·08 (http://vassarstats.net/tab2x2.html).