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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

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).
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fig01: 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).

Mentions: Serial blood passage of a limited number of experimental lines of P. knowlesi in neurosyphilis patients, pre-antibiotic pyretic treatment in the 1950s, was associated with increased parasite virulence [6]. The next account of P. knowlesi pathophysiology came with the first documented case of naturally acquired P. knowlesi published in 1965 [14]. The case was diagnosed retrospectively and, while the patient was symptomatic, he recovered fully following treatment and no other cases were confirmed. In fact, when we published the large focus of P. knowlesi in patients with single-species P. knowlesi infections in Kapit, Sarawak, we stated that P. knowlesi caused the usual symptoms of malaria; all patients responded to treatment and no deaths were reported [7]. This changed during a subsequent study when four P. knowlesi deaths were confirmed retrospectively. Only one of these was reported as a malaria death, P. falciparum, the others were attributed to other causes [11]. There was no information on severe knowlesi malaria in the literature or medical texts to guide healthcare professionals towards correct diagnosis and treatment of these patients. P. knowlesi malaria was new to the medical field, clinicians and other healthcare professionals were unaware that they were dealing with a newly described virulent form of malaria that, in practice, was most often misdiagnosed as the more benign P. malariae. A prospective clinical study on PCR-confirmed single-species P. knowlesi infected patients confirmed the need for knowlesi-specific treatment and management guidelines [12]. In that study 107 patients had P. knowlesi malaria, ten had complications and two died [12]. Complications included >100 000 parasites/μl blood, acute renal impairment, jaundice, hypotension, lactate acidosis, acute and late onset respiratory distress syndrome. All of these complications are included in the WHO guidelines for severe falciparum malaria in the non-immune [15]. Notably in this and subsequent studies, severe malaria with coma was not described in severe P. knowlesi infections [11,12,16,17]. Severe malarial anaemia was reported in children but not adults and was not as severe as in the P. falciparum comparator group [18]. In a recent study, 232 adult patients with PCR-confirmed single-species P. knowlesi infections were recruited in Sarawak Malaysian Borneo [19]. Twenty-eight (12%) of these had complications and four (1·7%) patients died, Table 1. Parasitaemia, total bilirubin, serum creatinine and plasma lactate were significantly higher in the complicated group, Fig.1. Parasitaemia was not used as a criterion to score severe disease. The study of P. knowlesi malaria is relatively new, and markers of severe disease are preliminary but suggest that patients with parasitaemia >35 000 parasites/μl, bilirubin > 43 μmol/l, serum creatinine >256 μmol/l or platelets <45 000/μl are at risk [12,19]. P. knowlesi is unusual among the parasites that infect human and non-human primates because the asexual part of the life cycle, the erythrocytic cycle associated with clinical signs and symptoms, takes 24 h to complete rather than 48 and 72 h in other types of malaria. Therefore, parasitaemia increases daily in P. knowlesi infections, increased parasitaemia is associated with disease severity, and while multiplication rates are probably variant specific and the number of merozoites produced will need to be factored in, patients with suspected P. knowlesi infection require urgent diagnosis and rapid access to optimal treatment.


Plasmodium knowlesi - an emerging pathogen.

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

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

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

fig01: 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).
Mentions: Serial blood passage of a limited number of experimental lines of P. knowlesi in neurosyphilis patients, pre-antibiotic pyretic treatment in the 1950s, was associated with increased parasite virulence [6]. The next account of P. knowlesi pathophysiology came with the first documented case of naturally acquired P. knowlesi published in 1965 [14]. The case was diagnosed retrospectively and, while the patient was symptomatic, he recovered fully following treatment and no other cases were confirmed. In fact, when we published the large focus of P. knowlesi in patients with single-species P. knowlesi infections in Kapit, Sarawak, we stated that P. knowlesi caused the usual symptoms of malaria; all patients responded to treatment and no deaths were reported [7]. This changed during a subsequent study when four P. knowlesi deaths were confirmed retrospectively. Only one of these was reported as a malaria death, P. falciparum, the others were attributed to other causes [11]. There was no information on severe knowlesi malaria in the literature or medical texts to guide healthcare professionals towards correct diagnosis and treatment of these patients. P. knowlesi malaria was new to the medical field, clinicians and other healthcare professionals were unaware that they were dealing with a newly described virulent form of malaria that, in practice, was most often misdiagnosed as the more benign P. malariae. A prospective clinical study on PCR-confirmed single-species P. knowlesi infected patients confirmed the need for knowlesi-specific treatment and management guidelines [12]. In that study 107 patients had P. knowlesi malaria, ten had complications and two died [12]. Complications included >100 000 parasites/μl blood, acute renal impairment, jaundice, hypotension, lactate acidosis, acute and late onset respiratory distress syndrome. All of these complications are included in the WHO guidelines for severe falciparum malaria in the non-immune [15]. Notably in this and subsequent studies, severe malaria with coma was not described in severe P. knowlesi infections [11,12,16,17]. Severe malarial anaemia was reported in children but not adults and was not as severe as in the P. falciparum comparator group [18]. In a recent study, 232 adult patients with PCR-confirmed single-species P. knowlesi infections were recruited in Sarawak Malaysian Borneo [19]. Twenty-eight (12%) of these had complications and four (1·7%) patients died, Table 1. Parasitaemia, total bilirubin, serum creatinine and plasma lactate were significantly higher in the complicated group, Fig.1. Parasitaemia was not used as a criterion to score severe disease. The study of P. knowlesi malaria is relatively new, and markers of severe disease are preliminary but suggest that patients with parasitaemia >35 000 parasites/μl, bilirubin > 43 μmol/l, serum creatinine >256 μmol/l or platelets <45 000/μl are at risk [12,19]. P. knowlesi is unusual among the parasites that infect human and non-human primates because the asexual part of the life cycle, the erythrocytic cycle associated with clinical signs and symptoms, takes 24 h to complete rather than 48 and 72 h in other types of malaria. Therefore, parasitaemia increases daily in P. knowlesi infections, increased parasitaemia is associated with disease severity, and while multiplication rates are probably variant specific and the number of merozoites produced will need to be factored in, patients with suspected P. knowlesi infection require urgent diagnosis and rapid access to optimal treatment.

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