Disease burden from P. vivax and P. knowlesi malaria in
children in Sabah, Malaysia
Grigg MJ1, William T1,2,3, Menon J2, Barber BE1, Wilkes CS1, Price RN1, Yeo TW1, Anstey NM1
1. Infectious Disease Society Sabah, Malaysia - Menzies School of Health Research, Australia
3. Jesselton Medical Centre, Kota Kinabalu, Sabah, Malaysia
2. CRC & Ministry of Health, Sabah, Malaysia
Background
P. vivax malaria in Malaysia
Results
• Significant reductions in Plasmodium vivax
malaria cases have occurred in Malaysia due
to effective ongoing national malaria
eradication efforts
• In other areas the prevalence of P. vivax has
risen as P. falciparum decreases, while
contrastingly in Eastern Malaysia, zoonotic
P. knowlesi malaria has instead increased
• In Eastern Malaysia, P. vivax, unlike P.
knowlesi, continues to predominantly infect
children
• Rates of P. vivax recurrence or relapse and
associated morbidity remain poorly defined
in Malaysia, particularly given increasing
resistance to chloroquine currently used as
the first line blood stage treatment
• No previous prospective studies of P.
knowlesi in children have been reported
Fig. 2: Baseline symptoms
Fig. 1: Enrolment flowchart of PCR
confirmed malaria cases
Malaria admissions
602
Children
(age<12)
107
P. vivax
65
P. knowlesi
25
P. vivax
(n=65)
Study sites
P. knowlesi
(n=25)
P. falciparum
(n=12)
P-value
Age
8
8
9
median (IQR)[range]
(5-10)[0.7-12]
(5-10)[0.1-12]
(7.5-10.5)[3-12]
Gender
54
64
50
0.514
Weight
21
23
21
median kg (IQR)
(15-25)[9-52]
(17-29)[3-37]
(19-29)[10-56]
0.294
Parasite count/μL
4739
1034
9596
geometric mean (CI95)
(3290-6828)
(504-2120)
(2706-34028)
<0.001 (vs. Pk)
0.322 (vs. Pf)
16 (25)
1 (4)
1 (8)
0.015
10.1
10.3
10.9
(9.4-11.3)
[5.8-13.1]
(9.4-11.1)
[7.1-12.6]
(8.8-11.6)
[6.8-13.9]
12 (19)
24 (50)
3 (13)
12 (57)
3 (30)
3 (43)
0.816
0.764
46 (72)
4 (6)
17 (71)
0
6 (50)
1 (8)
0.859
0.587
% male
Gametocytaemia
positive at baseline n (%)
Anaemia (WHO criteria)
Baseline n (%)
Day 28 post treatment
Thrombocytopenia n (%)
• Patients 12 years or younger with confirmed
malaria were enrolled as part of prospective
malaria studies over a 2-year period from
October 2013 to March 2015.
P. falciparum/
P. vivax
1
Fig. 3: Clinical and laboratory features
g/dL
Baseline median (IQR)[range]
Study participants
P. malariae
4
P. falciparum
12
Haemoglobin
Methods
Adults
495
Platelets <150x103/uL
Platelets <50x103/uL
Acute kidney injury n (%)
0.451
0.649 (vs. Pk)
0.762 (vs. Pf)
8 (13)
1 (4)
1 (8)
0.277 (vs. Pk)
0.558 (vs. Pf)
G6PD deficiency n (%)
3 (5)
1 (4)
1 (8)
0.951
Severe malaria
0
0
0
(AKIN criteria or creat>132/ul)
n (%)
• Patients admitted to hospital were enrolled
at 3 district hospital sites in Sabah, Malaysia
Chloroquine Artesunatemefloquine
P. vivax recurrence
19 (51)
0
P. vivax relapse
0
0
Target dose (mg/kg)
25
12 / 25
Actual dose (mg/kg)
22
9 / 23
median (IQR)
(20-26)
(8-12) / (20-28)
Before day 28
Fig. 4: Survival curve CQ vs. ACT
Fig. 5: Haematological recovery
Acknowledgements
• Kudat, Kota Marudu, Pitas and QEH clinical and
laboratory research staff
• Sabah Department of Health & Ministry of Health,
Malaysia
• MSHR research staff and NHMRC, Australia
• Asia-Pacific Malaria Elimination Network (APMEN):
project number 108-07
• Monkeybar ESEI (UK) MRC project
Study procedures
• Demographic, clinical and epidemiological
data were obtained after informed consent
• Clinical, parasitological and biochemical
features in children were compared at
baseline and during 28 day follow-up where
possible
• Therapeutic efficacy of chloroquine (CQ)
versus artemesinin-combination therapy
(ACT) was assessed as part of a larger RCT
• Ethics approval was given by the Malaysian
Medical Research Ethics Committee (MREC)
and Menzies School of Health Research,
Australia (HREC)
Conclusions
• Anaemia is common in malaria due to each
species, particularly post treatment
• No P. vivax relapses were documented in passive
follow up within the 2 year study period
• Unlike in adults, thromboctyopenia was not
present in all children with P. knowlesi malaria
• No severe malaria was noted in children with any
Plasmodium species (in contrast to that
documented in adults)
• There was no difference in the prevalence of
anaemia, thrombocytopenia or acute kidney
injury between malaria species
• Parasite counts were higher in children with
P. vivax compared to P. knowlesi malaria
• 19/37 (51%) of children with P. vivax malaria
treated with chloroquine had recurrent
parasitaemia within 28 days
• Those with recurrent P. vivax parasitaemia had a
higher prevalence of anaemia at day 28