Plasmodium Knowlesi Infection - A New Threat

7/30/2019 Plasmodium Knowlesi Infection - A New Threat

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THE 5TH MALARIA INFECTION: A

NEW THREAT?


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Introduction

Malaria is caused by infection of red blood cellswith protozoan parasites of the genus Plasmodium

The parasites are inoculated into the human host bya feeding female anopheline mosquito (A. donaldi,A. balabcensis, A. maculatus)

The four Plasmodium species that infect humans areP. falciparum, P. vivax, P. ovale and P. malariae


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Shrinking the malaria map

Feachem et al. Lancet 2010

40% of world population (3.3 billion people) at risk

More than 650,000 deaths every year


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Eliminating Malaria

Malaysiaunstable malaria transmission

Minimal acquisition of immunity

Results in people of all ages suffering acute clinical

malaria

High risk of progression to severe malaria if

untreated

Pre-elimination phase.


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MALARIA CASES REPORTED IN MALAYSIA 1961-2012

243,870

181

,495

151,822

87,432

44,2

26

49,

526

48,007

41,70

8

55

,068

69,127

54

,831

43,545

36,853

39,89

0

5

8,958

5

9,208

51,921

26,649

13,491

11,106

12,705

12,780

11,019

6,338

6,154

5,569

5,294

5,456

7,390

7,010

6,650

5,306

4,725

0

50,000

100,000

150,000

200,000

250,000

300,000


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Emergence of a new Plasmodium

species - Plasmodium knowlesi

Series of severePlasmodium malariae infection in

2004 in Sarawak

---- including 4 fatal cases

PCR-confirmed asPlasmodium knowlesi

Minimal knowledge about the virulence orpathogenicity in human (know-less)

Reported by a group from UNIMASSingh et al. A large focus of naturally acquired Plasmodium knowlesi infections in human beings. Lancet

2004; 363:101724.


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P. knowlesi in human is not NEW

The first case was reported in 1968 by Fong et al.A presumptive case of naturally occurring Plasmodium knowlesi malaria in man in Malaysia.

Trans R Soc Trop Med Hyg 1968; 65:83940

Back to the picture 36 years later.


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Tracking back the history

Archival review- Plasmodium knowlesi DNA was

detected in 35 (97.2%) of 36 blood films taken in

1996 (Malaysian Borneo) that were positive for

Plasmodium malariae(Lee K-S et al. Int J Parasitol. 2009 ; 39: 11251128.)

2000-2006: 266 (Sabah, Sarawak and Pahang)were diagnosed as P. knowlesi and only four were P.

malariae cases, although 312 had been diagnosed

as P. malariae by microscopy

(Cox-Singh et al., 2008)


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From simian to human malaria

A malaria parasite of

Old World monkeys

Commonly found in

long-tailed (Macacafascicularis) and pig-

tailed macaques

(Macaca nemestrina)

Macaca nemistrina

Macaca fasicularis


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Transmission

It is transmitted mainly in forests and along forest

fringes.

Anophleles latens has been incriminated as the

vector of P. knowlesi.

--- equally attracted to monkeys and humans.

Local residents and travellers to or from this region

are at risk for infection.


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Transmission

More cases - have no contact with monkeys or travel

into the jungle.

Transmission ecology is changing.


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Changing Epidemiology

De-forestation and

urbanisation

Population migration

Changes in agriculturalpractices


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MALARIA CASES ACCORDING TO TYPE OF SPECIES

2007-2010

25%

57%

7% 8%

3%

0%

10%

20%

30%

40%

50%

60%

70%

P. Falciparum P. vivax P. malariae P. knowlesi Mixed

2006 2007 2008 2009 2010


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MALARIA CASES ACCORDING TO TYPE OF SPECIES

2007-2010

25%

57%

7% 8%

3%

0%

10%

20%

30%

40%

50%

60%

70%

P. Falciparum P. vivax P. malariae P. knowlesi Mixed

2006 2007 2008 2009 2010


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MALARIA CASES ACCORDING TO TYPE OF

SPECIES 2011

JHR KDH KTN MLK NS PHG PRK PRL PP SGOR TGU WPKL

Pv 64 22 80 11 149 180 82 1 29 183 7 29

Mixed 6 2 1 1 3 2 7 0 2 5 3 4

Pm 0 1 3 0 2 44 17 0 1 19 4 2

Pk 7 1 108 0 3 45 45 0 4 29 20 1

Pf 14 34 48 3 12 21 13 0 50 45 16 18

0

50

100

150

200

250

300

350

Bilkes

SABAH SARAWAK

Pv 634 943

Mixed 102 5

Pm 605 307

Pk 71 399

Pf 591 95

0

500

1000

1500

2000

2500

Bilkes


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MALARIA CASES ACCORDING TO TYPE OF

SPECIES 2012


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MALARIA CASES ACCORDING TO

TYPE OF SPECIES 2012

P.Knowlesi : 1813 kes (38%)

P.Vivax : 1,461 kes (31%)

P.Falciparum : 894 (19%)

P.Malariae : 485 kes (10%)

P.Ovale : 8 kes (0.2%)

Mixed : 64 kes (1.4%)


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Life cycle

The 24-h asexual life cycle - the shortest of all the

known malaria (human and non-human)

Daily schizont rupture leading to daily appearance

of fever spikes --- loss of typical tertian orquartidian pattern.

---- also leading to rapid increase of parasite load.


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Species identification

Mature parasites are indistinguishable from those of P.

malariae andare commonly diagnosed as such.

mature schizont of P. malariae mature schizont of P. knowlesi


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Ring stages resemble those of P. falciparum.

Ring stage of P. falciparum Ring stage of P. knowlesi


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Clinical features

No presenting symptoms or signs that distinguished

knowlesi malaria from either falciparum or vivax

malariasevere or uncomplicated.

Atypical presentationsvomiting, abdominal pain.


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Thrombocytopenia is almost universal

Daneshvar et al. Clin Infect Dis 2009;49:852-860


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Severe infection

Ranges from 6.5% to 36%

Most patients developed ARDS at presentation

and/or during hospitalisation

Other manifestation (according to WHO criteria)are:

i. Hyperparasitemia

ii. Jaundiceiii. Acute renal failure

No cases of cerebral malaria has been reported.


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Cox-Singh J et al. Clin Infect Dis 2008; 46:16571


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Severe knowlesi malaria at QEH, Sabah

Retrospective study from Dec 07 - Nov 09

56 patients with knowlesi malaria

22 (36%) had severe malaria, 6 (10.7%) deaths

Complications included respiratory distress (59%), acute

renal failure (55%), shock (55%)

Risk factors for severe disease:

Older age

William et al, Emerg Inf Dis 2011


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Treatment of P knowlesi infection

A high parasite density (> 0.5% parasitaemia) with

P. malariae-like parasites should be treated for P.

knowlesi infection.

A definitive diagnosis is made by polymerase chainreaction

Severe Diseaseas for treatment ofP. falciparum

Intravenous artesunate 2.4mg/kg Hr 0, 12, 24 Thereafter - 2.4mg/kg daily


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Treatment of uncomplicated P. knowlesi

All patients should be given combination therapy

More effective

Prevents development of resistance

Recommended treatment for uncomplicated P.falciparum infection.

Artemisinin Combination Therapy Riamet (artemether/lumefantrine)

Artequine (artesunate/mefloquine)


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Artemether-lumefantrine

This is currently available in Malaysia as co-

formulated tablets containing 20 mg of artemether

and 120 mg of lumefantrine.

The total recommended treatment is a 6-doseregimen of artemether-lumefantrine twice a day for

3 days.


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Knowlesi malaria: points to remember

Nearly all reports of P. malariae are actually P. knowlesi

P. knowlesi can be severe and potentially life-threatening

Can present very similar to dengue

May not appear severe on first presentation

Older age group at risk of severe disease

Thrombocytopenia is universal, and can be severe

Resp complication is common in severe disease Treatment is the same as for P. falciparum


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Knowlesi malaria - an emerging

disease in South East Asia

P. knowlesi infectionshave also been reported frommany areas in Southeast Asia:

Thailand - 2004

Myanmar - 2006

The Philippines - 2008

Singapore - 2008

Sabah - 2008Peninsular Malaysia - 2008

The increase in tourism in Southeast Asia may mean

that more cases are detected in the future, including

in Western countries


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Summary

Plasmodium knowlesi infection has emerged as the

main type of malaria in some states in this country.

Successful control of malaria is hampered by the

changing trend of its epidemiology. Artemisinin combination therapy is the agent of first

choice for all type of malaria including knowlesi

malaria. Primary care physicians should be aware of the

possibility of malaria despite of lack of significant

travel history.

Plasmodium Knowlesi Infection - A New Threat

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