Knowlesi malaria: Human risk factors, clinical spectrum, and pathophysiology

Anstey, Nicholas M.; Grigg, Matthew J.; Rajahram, Giri Shan; Cooper, Daniel J.; William, Timothy; Kho, Steven; Barber, Bridget E.

doi:10.1016/bs.apar.2021.08.001

Cited by 25 publications

(14 citation statements)

References 135 publications

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“…Malaria has a variety of clinical symptoms, and the development of these clinical manifestations is in uenced by host, parasite, and social and geographic variables. Asymptomatic infections, acute febrile illnesses, severe malaria, and fatal cases are all on the clinical spectrum [10]. The patient in this study had a wide range of malarial signs and symptoms, such as joint pain, nausea, vomiting ingested material, chills, ank pain, fever, tiredness, and nausea.…”

Section: Discussionmentioning

confidence: 84%

A Case Report of Severe Malaria Associated Acute Renal Failure in an Adult

Bereda¹

2022

Preprint

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Malaria continues to be a significant global public health problem, particularly in endemic nations. A 28-year-old male was brought into the emergency room with significant complaints of fatigue, chills, fever, and lack of appetite. The patient had no prior history of malaria. He was not given any anti-malarial medication as prophylaxis while traveling to his workplace. As a result of laboratory investigations to identify malarial parasites in peripheral blood using thin and thick smears, malaria parasites were found in the patient. Cardiovascular testing confirmed that S1 and S2 were audible. At the border of the colitis, the liver was palpable. Both the chest X-ray and abdominal ultrasonography were clear. His level of consciousness assessment indicated a Glasgow coma scale reading of 10 out of 15. As part of her supportive care, he received 1000 mL of normal saline solution with 40% glucose solution. He received intravenous artesunate 60 mg (2.4 mg/kg) when he was admitted to the intensive care unit, and then every twelve and twenty-four hours for the following three days (a total of three doses, 540 mg).

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Section: Discussionmentioning

confidence: 84%

A Case Report of Severe Malaria Associated Acute Renal Failure in an Adult

Bereda¹

2022

Preprint

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“…Lower median parasite counts for symptomatic P. knowlesi infections compared to P. falciparum and P. vivax are well-established, indicating a lower fever threshold ( Grigg et al., 2018a ). Submicroscopic P. knowlesi infections have been widely reported across Southeast Asia ( Anstey et al., 2021 ), including in Malaysia ( Fornace et al., 2016 ; Siner et al., 2017 ; Grignard et al., 2019 ; Noordin et al., 2020 ), however the majority of these were asymptomatic. Further study is required to understand the role of submicroscopic and asymptomatic infections in P. knowlesi transmission, including what proportion resolve spontaneously and whether they may facilitate onwards transmission to human or macaque hosts.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic accuracy and limit of detection of ten malaria parasite lactate dehydrogenase-based rapid tests for Plasmodium knowlesi and P. falciparum

Tan¹,

Sakam²,

Rajahram³

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundPlasmodium knowlesi causes zoonotic malaria across Southeast Asia. First-line diagnostic microscopy cannot reliably differentiate P. knowlesi from other human malaria species. Rapid diagnostic tests (RDTs) designed for P. falciparum and P. vivax are used routinely in P. knowlesi co-endemic areas despite potential cross-reactivity for species-specific antibody targets.MethodsTen RDTs were evaluated: nine to detect clinical P. knowlesi infections from Malaysia, and nine assessing limit of detection (LoD) for P. knowlesi (PkA1-H.1) and P. falciparum (Pf3D7) cultures. Targets included Plasmodium-genus parasite lactate dehydrogenase (pan-pLDH) and P. vivax (Pv)-pLDH.ResultsSamples were collected prior to antimalarial treatment from 127 patients with microscopy-positive PCR-confirmed P. knowlesi mono-infections. Median parasitaemia was 788/µL (IQR 247-5,565/µL). Pan-pLDH sensitivities ranged from 50.6% (95% CI 39.6–61.5) (SD BIOLINE) to 87.0% (95% CI 75.1–94.6) (First Response® and CareStart™ PAN) compared to reference PCR. Pv-pLDH RDTs detected P. knowlesi with up to 92.0% (95% CI 84.3-96.7%) sensitivity (Biocredit™). For parasite counts ≥200/µL, pan-pLDH (Standard Q) and Pv-pLDH RDTs exceeded 95% sensitivity. Specificity of RDTs against 26 PCR-confirmed negative controls was 100%. Sensitivity of six highest performing RDTs were not significantly different when comparing samples taken before and after (median 3 hours) antimalarial treatment. Parasite ring stages were present in 30% of pre-treatment samples, with ring stage proportions (mean 1.9%) demonstrating inverse correlation with test positivity of Biocredit™ and two CareStart™ RDTs.For cultured P. knowlesi, CareStart™ PAN demonstrated the lowest LoD at 25 parasites/µL; LoDs of other pan-pLDH ranged from 98 to >2000 parasites/µL. Pv-pLDH LoD for P. knowlesi was 49 parasites/µL. No false-positive results were observed in either P. falciparum-pLDH or histidine-rich-protein-2 channels.ConclusionSelected RDTs demonstrate sufficient performance for detection of major human malaria species including P. knowlesi in co-endemic areas where microscopy is not available, particularly for higher parasite counts, although cannot reliably differentiate among non-falciparum malaria.

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“…Cytoadherent parasitised erythrocytes are not the only contributors to disease severity. Very high parasitaemias caused by non-sequestering malaria parasites cause severe malaria across the animal kingdom, and the simian parasite P. knowlesi is potentially lethal in humans – but these parasites do not cause cerebral malaria [ 2 , 84 ]. At very high parasite densities, erythrocyte dysfunction contributes to aggregation and impaired microcirculatory flow and oxygen delivery without cytoadherence.…”

Section: Pathophysiology Of Severe Falciparum Malariamentioning

confidence: 99%

“…Plasmodium knowlesi, with its quotidian cycle, can sometimes cause fulminant infections in humans [ 84 , 128 , 129 ]. It does not sequester markedly so the parasite count is a good guide to biomass.…”

Section: Severe Malaria Caused By Other Malaria Speciesmentioning

confidence: 99%

Severe malaria

White

2022

Malar J

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Severe malaria is a medical emergency. It is a major cause of preventable childhood death in tropical countries. Severe malaria justifies considerable global investment in malaria control and elimination yet, increasingly, international agencies, funders and policy makers are unfamiliar with it, and so it is overlooked. In sub-Saharan Africa, severe malaria is overdiagnosed in clinical practice. Approximately one third of children diagnosed with severe malaria have another condition, usually sepsis, as the cause of their severe illness. But these children have a high mortality, contributing substantially to the number of deaths attributed to ‘severe malaria’. Simple well-established tests, such as examination of the thin blood smear and the full blood count, improve the specificity of diagnosis and provide prognostic information in severe malaria. They should be performed more widely. Early administration of artesunate and broad-spectrum antibiotics to all children with suspected severe malaria would reduce global malaria mortality.

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Knowlesi malaria: Human risk factors, clinical spectrum, and pathophysiology

Cited by 25 publications

References 135 publications

A Case Report of Severe Malaria Associated Acute Renal Failure in an Adult

A Case Report of Severe Malaria Associated Acute Renal Failure in an Adult

Diagnostic accuracy and limit of detection of ten malaria parasite lactate dehydrogenase-based rapid tests for Plasmodium knowlesi and P. falciparum

Severe malaria

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