A comparison of the clinical, laboratory and epidemiological features of two divergent subpopulations of Plasmodium knowlesi

Ting Huey Hu ,Adeline A Dihom,Nawal Rosli,Paul Cliff Simon Divis ,Cyrus Daneshvar,Dayang Shuaisah Awang Mohamad ,Sing Ling Kong ,Irene P F Chai,Khamisah Abdul Kadir ,Zhen Hao Ching,Edmund K Y Wong ,Timothy Davis ,Yaw Hung Chai ,Linda S C Ting,Tiana Ti,Nur Naqibah Ideris ,King Ching Hii ,Jenny E H Sia,Wei Tang ,Balbir Singh

doi:10.1038/s41598-021-99644-8

Abstract

Plasmodium knowlesi, a simian malaria parasite responsible for all recent indigenous cases of malaria in Malaysia, infects humans throughout Southeast Asia. There are two genetically distinct subpopulations of Plasmodium knowlesi in Malaysian Borneo, one associated with long-tailed macaques (termed cluster 1) and the other with pig-tailed macaques (cluster 2). A prospective study was conducted to determine whether there were any between-subpopulation differences in clinical and laboratory features, as well as in epidemiological characteristics. Over 2 years, 420 adults admitted to Kapit Hospital, Malaysian Borneo with knowlesi malaria were studied. Infections with each subpopulation resulted in mostly uncomplicated malaria. Severe disease was observed in 35/298 (11.7%) of single cluster 1 and 8/115 (7.0%) of single cluster 2 infections (p = 0.208). There was no clinically significant difference in outcome between the two subpopulations. Cluster 1 infections were more likely to be associated with peri-domestic activities while cluster 2 were associated with interior forest activities consistent with the preferred habitats of the respective macaque hosts. Infections with both P. knowlesi subpopulations cause a wide spectrum of disease including potentially life-threatening complications, with no implications for differential patient management.

Highlights

Plasmodium knowlesi, a simian malaria parasite responsible for all recent indigenous cases of malaria in Malaysia, infects humans throughout Southeast Asia
The simian malaria parasite, Plasmodium knowlesi was found to be the commonest cause of human malaria infections in the Kapit Division of Sarawak, Malaysian Borneo in 20041
In our first prospective clinical study of 107 cases of knowlesi malaria presenting to Kapit Hospital from 2006 to 2008, we found that P. knowlesi infections covered a wide spectrum of disease

Summary

Introduction

Plasmodium knowlesi, a simian malaria parasite responsible for all recent indigenous cases of malaria in Malaysia, infects humans throughout Southeast Asia. The simian malaria parasite, Plasmodium knowlesi was found to be the commonest cause of human malaria infections in the Kapit Division of Sarawak, Malaysian Borneo in 20041. A recent study, using allele-specific PCR to define further the molecular epidemiology of subpopulations, identified cluster 1 infections to be the commonest in all locations across Malaysian Borneo13 It showed that, amongst 1204 knowlesi malaria patients admitted to Kapit Hospital between 2000 and 2018, cluster 1 accounted for two-thirds of cases with no evidence of seasonal or temporal influence on this proportion. The higher proportion of patients seen at Kapit Hospital with cluster 1 P. knowlesi infections may be due to differences in abundance of the reservoir macaque hosts or to rural communities predominantly conducting activities such as subsistence farming and fishing in close proximity to their longhouses, and overlapping with the preferred habitats of long-tailed macaques. P. knowlesi parasites appear in the blood between 7 and 9 days after a person has been bitten by an infected mosquito, so a history of travel within 14 days of hospital admission would indicate the most likely place a patient acquired the infection

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Conclusion