Human infections and detection of Plasmodium knowlesi

Abstract

Plasmodium knowlesi is a malaria parasite that is found in nature in long-tailed and pig-tailed macaques. Naturally acquired human infections were thought to be extremely rare until a large focus of human infections was reported in 2004 in Sarawak, Malaysian Borneo. Human infections have since been described throughout Southeast Asia, and P. knowlesi is now recognized as the fifth species of Plasmodium causing malaria in humans. The molecular, entomological, and epidemiological data indicate that human infections with P. knowlesi are not newly emergent and that knowlesi malaria is primarily a zoonosis. Human infections were undiagnosed until molecular detection methods that could distinguish P. knowlesi from the morphologically similar human malaria parasite P. malariae became available. P. knowlesi infections cause a spectrum of disease and are potentially fatal, but if detected early enough, infections in humans are readily treatable. In this review on knowlesi malaria, we describe the early studies on P. knowlesi and focus on the epidemiology, diagnosis, clinical aspects, and treatment of knowlesi malaria. We also discuss the gaps in our knowledge and the challenges that lie ahead in studying the epidemiology and pathogenesis of knowlesi malaria and in the prevention and control of this zoonotic infection.

Fig 1

Plasmodium knowlesi infections reported in humans and macaques and limits of natural distribution of mosquito vectors and of macaques. The numbers in parentheses represent numbers of P. knowlesi cases reported for each Southeast Asian country or region in Malaysia. (Adapted from reference with permission from Elsevier.)

Fig 2

Erythrocytic stages of P. knowlesi, P. malariae, and P. falciparum observed in Giemsa-stained peripheral blood films. (A to C) Thin blood films with early trophozoites of P. knowlesi (Aa to e), P. falciparum (Ba to f), and P. malariae (Ca); late trophozoites, including band forms, of P. knowlesi (Af to l) and P. malariae (Cb to i); schizonts of P. knowlesi (Am to o) and P. malariae (Cj); and gametocytes of P. knowlesi (Ap to r), P. falciparum (Bg and h), and P. malariae (Ck and l). (D and E) Thick blood films showing early trophozoites of P. knowlesi resembling those of P. falciparum (D) and heavy parasitemia from a fatal P. knowlesi infection (E). (Photographs in panels Aa to e, m, and o and Cc, j, and l have been reproduced from reference with permission from Elsevier, and photographs in panels A and C have been reproduced from reference .)

Fig 3

Complications and outcomes (A) and the number of complications and outcomes (B) for 86 cases of severe knowlesi malaria. ARDS, hypoxia with a respiratory rate of >30, presence of pulmonary infiltrates, or requiring ventilation; acute kidney injury, creatinine levels of >265 μmol/liter (3 mg/dl) or requiring dialysis; hypotension, systolic blood pressure of <80 mm Hg or started on ionotropes; jaundice, total bilirubin level of ≥43 μmol/liter (3 mg/dl); acidosis, lactate level of >6 mmol/liter; hypoglycemia, glucose level of <2.2 mmol/liter (40 mg/dl). (Data obtained from references , –, , , and .)