A Pain

C Daneshvar

E Tjitra

J Cox-Singh

Janet Cox-Singh

Malaria Journal

English

PubMed

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Insights from monkey malaria that can change thinking about human infections

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INVITED SPEAKER PRESENTATION Open Access
Insights from monkey malaria that can change
thinking about human infections
Janet Cox-Singh
From Parasite to Prevention: Advances in the understanding of malaria
Edinburgh, UK. 20-22 October 2010
Despite prolonged and intense effort to understand and
control the health impact of malaria morbidity and mor-
tality, malaria remains third in the global ranking for
severe and fatal infections. P. falciparum is responsible
for most malaria morbidity and mortality [1]. The more
widespread Plasmodium vivax is considered less patho-
genic but now appears to cause severe acute disease
with some fatal cases [2]. Nevertheless among the
human malarias virulent acute P. falciparum malaria
attracts most research attention.
Falciparum malaria has several characteristics not-
found in P. vivax or the other two human adapted spe-
cies, Plasmodium ovale and Plasmodium malariae.
Differences include parasitemias >100 000/uL and the
ability to sequester from the peripheral blood in deep
post-capillary venules. Both are strong contenders for
increased pathophysiology in this species. Unfortunately
because of few similarities between the four human-host
malarias it is difficult distinguish virulence factors from
interspecies differentiation.
The monkey malaria, Plasmodium knowlesi may
change this and our views on malaria pathophysiology.
The discovery of severe and fatal cases of knowlesi
malaria in the human population was unexpected and
for the first time offers a comparator disease for falci-
parum malaria. In Sarawak, Malaysian Borneo 10% of P.
knowlesi cases are complicated, with at least 1% of all
human cases becoming fatal [3]. Complicated knowlesi
malaria presents as organ dysfunction, acute and delayed
acute respiratory distress syndrome, but not coma or
severe malarial anaemia that are often associated with
falciparum malaria. Preliminary studies show a direct
correlation between P. knowlesi parasitemia and compli-
cations, parasitemias >100 000/uL are common. Blood
vessels in the brain from a fatal knowlesi case were
congested with sequestered heavily pigmented mature
stage parasites [4]. The patient did not present with cer-
ebral malaria, a complication often associated with P.
falciparum sequestration in post capillaries of the brain.
Descriptions of naturally acquired P. knowlesi malaria
in humans are enhanced by the wealth of baseline mole-
cular information available for P. knowlesi gathered
from experimental primate infections and the knowlesi
genome project [5]. P. knowlesi is permissive in various
primates and some infections are representative of
human knowlesi malaria. Pathophysiology of naturally
acquired P. knowlesi malaria in humans and P. falci-
parum compare well and there are important differ-
ences. Comparisons will lead to the identification of
testable candidate virulence factors. The ability to speci-
fically test virulence in representative primate models
may well offer much needed means to understand
malaria pathophysiology and to help distinguish P. falci-
parum virulence from inconsequential species-specific
characteristics.
Published: 20 October 2010
References
1. WHO: MalaFact Sheet No. 94. World Health Organization , January 2009
2009.
2. Tjitra E, Anstey NM, Sugiarto P, Warikar N, Kenangalem E, Karyana M,
Lampah DA, Price RN: Multidrug-resistant Plasmodium vivax associated
with severe and fatal malaria: a prospective study in Papua, Indonesia.
PLoS Med 2008, 5:e128.
3. Daneshvar C, Davis TM, Cox-Singh J, Rafa’ee MZ, Zakaria SK, Divis PC,
Singh B: Clinical and laboratory features of human Plasmodium knowlesi
infection. Clin Infect Dis 2009, 49:852-60.
4. Cox-Singh J, Hiu J, Lucas SB, Divis PC, Zulkarnaen M, Chandran P, Wong KT,
Adem P, Zaki SR, Singh B, Krishna S: Severe malaria-a case of fatal
Plasmodium knowlesi infection with post-mortem findings: a case
report. Malar J 2010, 9:10.
Centre for Infection, St George’s University of London, London, UK
Cox-Singh Malaria Journal 2010, 9(Suppl 2):I2
http://www.malariajournal.com/content/9/S2/I2
© 2010 Cox-Singh; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
5. Pain A, Böhme U, Berry AE, Mungall K, Finn RD, Jackson AP, Mourier T,
Mistry J, Pasini EM, Aslett MA, Balasubrammaniam S, Borgwardt K, Brooks K,
Carret C, Carver TJ, Cherevach I, Chillingworth T, Clark TG, Galinski MR,
Hall N, Harper D, Harris D, Hauser H, Ivens A, Janssen CS, Keane T, Larke N,
Lapp S, Marti M, Moule S, Meyer IM, Ormond D, Peters N, Sanders M,
Sanders S, Sargeant TJ, Simmonds M, Smith F, Squares R, Thurston S,
Tivey AR, Walker D, White B, Zuiderwijk E, Churcher C, Quail MA,
Cowman AF, Turner CM, Rajandream MA, Kocken CH, Thomas AW,
Newbold CI, Barrell BG, Berriman M: The genome of the simian and
human malaria parasite Plasmodium knowlesi. Nature 2008, 455:799-803.
doi:10.1186/1475-2875-9-S2-I2
Cite this article as: Cox-Singh: Insights from monkey malaria that can
change thinking about human infections. Malaria Journal 2010
9(Suppl 2):I2.
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Page 2 of 2


Clinical and laboratory features of human Plasmodium knowlesi infection. Clin Infect Dis

Severe malaria-a case of fatal Plasmodium knowlesi infection with post-mortem findings: a case report.

Submit your next manuscript to BioMed Central and take full advantage of: • Convenient online submission • Thorough peer review • No space constraints or color ﬁgure charges • Immediate publication on acceptance

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Insights from monkey malaria that can change thinking about human infections

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