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Plasmodium knowlesi - an emerging pathogen.

Ahmed MA, Cox-Singh J - ISBT Sci Ser (2015)

Bottom Line: The investigation found only P. knowlesi DNA present in patient blood samples.Relevant clinical descriptions and guidelines for the treatment and management of patents with P. knowlesi malaria were not available.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.

View Article: PubMed Central - PubMed

Affiliation: School of Medicine, University of St Andrews St Andrews, UK.

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.

No MeSH data available.


Related in: MedlinePlus

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).
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fig02: 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).

Mentions: Plasmodium knowlesi isolates collected from human infections are genetically diverse [7,9]. Parasitaemia is associated with disease severity and we asked the question are some P. knowlesi variants more virulent than others? We sequenced two P. knowlesi genes responsible for parasite invasion of erythrocytes and found two genetically distinct clusters of one of the P. knowlesi genes encoding erythrocyte invasion proteins, P. knowlesi normocyte binding protein xa (Pknbpxa) [19, 21]. We found that 44% and 56% of patients were infected with Pknbpxa cluster 1 and Pknbpxa cluster 2, respectively. The clusters contained single nucleotide polymorphisms that allowed for differentiation of haplotype groups with 2 or three alleles among the P. knowlesi isolates. Analysis of the alleles with the clinical and laboratory variables in the patient cohort found that patients infected with particular allelic forms of cluster 2 had increased markers of disease severity including parasitaemia [19]. Not all patients with complications were infected with cluster 2 parasites but there were more patients than expected with complications in this cluster (Fig.2). This suggests that, in nature, some P. knowlesi variants may be more virulent in the human-host population than others. This study was conducted in Sarawak, Malaysian Borneo, and may explain some of the apparent differential susceptibility of humans to P. knowlesi infection in Malaysia and other areas within the region. More work is required to determine genetic diversity of P. knowlesi across the Southeast Asian region and associated parasite virulence.


Plasmodium knowlesi - an emerging pathogen.

Ahmed MA, Cox-Singh J - ISBT Sci Ser (2015)

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).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4440384&req=5

fig02: 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).
Mentions: Plasmodium knowlesi isolates collected from human infections are genetically diverse [7,9]. Parasitaemia is associated with disease severity and we asked the question are some P. knowlesi variants more virulent than others? We sequenced two P. knowlesi genes responsible for parasite invasion of erythrocytes and found two genetically distinct clusters of one of the P. knowlesi genes encoding erythrocyte invasion proteins, P. knowlesi normocyte binding protein xa (Pknbpxa) [19, 21]. We found that 44% and 56% of patients were infected with Pknbpxa cluster 1 and Pknbpxa cluster 2, respectively. The clusters contained single nucleotide polymorphisms that allowed for differentiation of haplotype groups with 2 or three alleles among the P. knowlesi isolates. Analysis of the alleles with the clinical and laboratory variables in the patient cohort found that patients infected with particular allelic forms of cluster 2 had increased markers of disease severity including parasitaemia [19]. Not all patients with complications were infected with cluster 2 parasites but there were more patients than expected with complications in this cluster (Fig.2). This suggests that, in nature, some P. knowlesi variants may be more virulent in the human-host population than others. This study was conducted in Sarawak, Malaysian Borneo, and may explain some of the apparent differential susceptibility of humans to P. knowlesi infection in Malaysia and other areas within the region. More work is required to determine genetic diversity of P. knowlesi across the Southeast Asian region and associated parasite virulence.

Bottom Line: The investigation found only P. knowlesi DNA present in patient blood samples.Relevant clinical descriptions and guidelines for the treatment and management of patents with P. knowlesi malaria were not available.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.

View Article: PubMed Central - PubMed

Affiliation: School of Medicine, University of St Andrews St Andrews, UK.

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.

No MeSH data available.


Related in: MedlinePlus