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Asian Pac J Trop Dis 2016; 6(3): 199-203 199

Contents lists available at ScienceDirect

Asian Pacific Journal of Tropical Disease


journal homepage: www.elsevier.com/locate/apjtd

Parasitological research doi:10.1016/S2222-1808(15)61013-1 2016 by the Asian Pacific Journal of Tropical Disease. All rights reserved.

The correlation between platelet count and parasite density in children with malaria infection

Suryani Margono, Bidasari Lubis, Syahril Pasaribu, Hendri Wijaya, Ayodhia Pitaloka Pasaribu*
Department of Pediatrics, Medical Faculty, University of Sumatra Utara, Medan, Indonesia

A RT I C L E I N F O A B S T R AC T

Article history: Objective: To assess the correlation between platelet count and parasite density.
Received 14 Sep 2015 Methods: A cross-sectional study of febrile children was conducted in Batubara Regency,
Received in revised form 13 Jan 2016 North Sumatra, Indonesia. We used rapid diagnostic tests and blood smears to identify children
Accepted 22 Feb 2016 with malaria infection. Platelet counts and measurement of parasite density were performed
Available online 14 Mar 2016 manually using a microscope.
Results: A total of 72 children with positive malaria infection were enrolled in the study.
Sixty one children had Plasmodium vivax, two children had Plasmodium falciparum, and nine
children had mixed infection. The mean platelet count from all patients was (230940.00
Keywords: 96611.53)/L and the mean parasite density was (2254.83 1432.55)/L. There was a weak
Malaria negative correlation between the platelet count and the parasitemia count (r = 0.145). The
Children platelet count in the mixed infection group was significantly lower [(175444.44 48093.95)/
Platelet count L] than that in the vivax malaria group [(231927.87 99475.28)/L] (P = 0.024). Children
Parasitemia with splenomegaly had a significantly lower platelet count [(189655.56 80115.76)/L versus
Splenomegaly (245230.77 98380.74)/L, P = 0.04] and a higher parasite density [(3635.78 1623.70)/L
versus (1789.88 927.29)/L, P < 0.0001] than those without splenomegaly.
Conclusions: There was a weak negative correlation between the platelet count and parasite
count.

1. Introduction of malaria infection in acute febrile patients in endemic areas; in


addition, it was correlated with a higher degree of parasitemia
Malaria remains a leading cause of infection, with significant levels[6].
mortality and morbidity rates. It is estimated that approximately 250 There has been no data on platelet count and parasite density in
million malaria cases and more than 500000 deaths occur annually, children with malaria in endemic region in Indonesia. Therefore,
86% of which are children under five years of age[1]. The burden of the aims of this study were to investigate the correlation between
malaria in Southeast Asia has been under appreciated, despite recent platelet count and parasite density and to determine the effect of
evidence suggests that the continent has approximately 40% of thrombocytopenia severity on diagnosis and prognosis of malaria
malaria cases worldwide[2]. patients.
Thrombocytopenia is a common sign found in patients with
Plasmodium falciparum (P. falciparum) infection, but it has been 2. Materials and methods
recently reported in Plasmodium vivax (P. vivax) or mixed infection
cases in several endemic countries[3-5]. A systematic review study 2.1. Study design
reported that thrombocytopenia ranged from 24% to 94% in patients
with acute malaria, and that it was considered to be one marker An observational analytical cross-sectional design study was
conducted on May to June 2015 in Lima Puluh Sub-district,
*Corresponding author: Dr. Ayodhia Pitaloka Pasaribu, Department of Pediatrics,
Medical Faculty, University of Sumatra Utara , Dr. Mansyur No. 5 Street, Medan
Batubara Regency, North Sumatra Province, Indonesia.
20156, Indonesia.
Tel: +62812 602 4392
E-mail: ayodhia_pitaloka@yahoo.com 2.2. Inclusion and exclusion criteria
The study protocol was performed according to the Helsinki declaration and
approved by the Ethics Committee of the Faculty of Medicine University of Sumatra
Utara. Informed written consent was obtained from the patients guardians. The inclusion criteria were children 018 years old with fever or
The journal implements double-blind peer review practiced by specially invited
international editorial board members.
history of fever in the last 48 h and rapid diagnostic tests malaria
200 Suryani Margono et al./Asian Pac J Trop Dis 2016; 6(3): 199-203

positive for malaria falciparum and or Pan (other malaria species Table 1
such as P. vivax, Plasmodium ovale, or Plasmodium malariae). Characteristics of the subjects. n (%).
Characteristics Subjects No. (n = 72)
Rapid diagnostic tests were examined using Parascreen devices
Sex Male 38 (52.8)
produced by Zephyr Biomedicals, India. We excluded children with Female 34 (47.2)
a history of bleeding disorders, severe illnesses (e.g., chronic liver Age (year) 11.10 4.80
disease, malignancies, and heart disease) and a history of drugs uses Weight (kg) 31.01 15.42
Height (cm) 131.74 21.68
(e.g., aspirin, chloramphenicol and chemotherapy drugs) for the
Nutritional status Mild malnutrition 14 (19.4)
previous 2 weeks prior to the data collection. Patients who fulfilled Moderate malnutrition 5 (7.0)
the inclusion criteria were enrolled in this study. Normal 47 (65.3)
Overweight 6 (8.3)
Fever Yes 0 (0)
2.3. Data collection No 72 (100.0)
Anemic Yes 59 (81.9)
Interviews were performed and questionnaires were completed No 11 (15.3)
Splenomegaly Yes 19 (26.4)
by the patients guardians; physical examinations including weight
No 53 (73.6)
and height measurement, and spleen palpation using the Hackett
methods were performed. Thick and thin peripheral blood films were Using Spearmans correlation analysis, the results showed that
obtained, stained with Giemsa and examined microscopically under there is a weak negative correlation between the platelet count
oil immersion. Parasite species and parasite density were confirmed and parasite density among all study subjects (r = 0.145) and in
and counted by a parasitologist. Platelet counts were performed the group of patients with malaria vivax infection (r = 0.225).
by a hematology analyst. Antimalarial therapy was administered However, in the group of patients with mixed infection, we found a
to positive malaria patients, including dihydroartemisinin 24 mg/ strong positive correlation (r = 0.844) between the platelet count and
kg body weight and piperaquine 1632 mg/kg body weight, each parasite density (P = 0.004, Table 2, Figures 13).
administered once daily for 3 days. 10000

2.4. Ethics 8000


Parasite density/mcL

The study protocol was performed according to the Helsinki


6000
declaration and approved by the Ethics Committee of the Faculty
of Medicine University of Sumatra Utara. Informed written consent
4000
was obtained from the patients guardians.

2.5. Statistical analysis 2000

The data were presented as the means, percentages and standard 0


deviations. Spearman correlation analysis was used to determine 0 100000 200000 300000 400000 500000 600000
correlations between the platelet count and parasite density. The Platelet count/mcL
Figure 1. Correlation between platelet count and parasite density in all subject.
Mann-Whitney U-test was performed to assess the presence of
splenomegaly and its association with both platelet count and 10000
parasite density. This study used a 95% confidence interval (CI), and
a P value < 0.05 to denote significance. All analyses were conducted 8000
with SPSS software (version 17.0).
Parasite density/mcL

6000
3. Results

4000
A total of 320 children were screened and 72 children with
positive malaria infection and who fulfilled the inclusion criteria
2000
were enrolled. Sixty-one children had vivax (85%), two children
had falciparum (3%), and nine children had mixed infection (12%).
The characteristics of the subjects are shown in Table 1. In a study 0

of 72 patients were positive for malaria infection, nine (12.5%) 0 100000 200000 300000 400000 500000 600000
Platelet count/mcL
had thrombocytopenia, five (55.56%) had vivax malaria, and four Figure 2. Correlation between platelet count and parasite density in
(44.44%) had mixed malaria cases. malaria vivax infection group.
Suryani Margono et al./Asian Pac J Trop Dis 2016; 6(3): 199-203
201
Table 2
Correlation between platelet count and parasite density.
Patients No. Platelet count/L Parasite density/L P r (correlation)
All subject 72 230940.00 96611.53 2254.83 1432.55 0.230a 0.145
P. vivax infection 61 231927.87 99475.28 2151.11 1323.36 0.081a 0.225
Mixed infection 9 175444.44 48093.95 2957.78 1981.83 0.004b 0.844
a
: Spearman; b: Pearson.

The platelet count in subjects with mixed infection malaria with and without splenomegaly (P = 0.04, Figure 5). However,
was lower [(175444.44 48093.95)/L] compared to the we did not find any difference in the platelet count using
patients with vivax infection [(231927.87 99475.28)/L]. Hackett I and II [(190215.38 73773.10)/L versus 199500.00
The results of the Mann-Whitney U-test showed that there was 97592.520/L, P = 0.629].
a significant difference in the mean platelet count based on type With the Hackett method, there was a significant difference
of malaria infection (Figure 4). in parasite density based on the presence of splenomegaly.
Using the Hackett examination method, the mean platelet The mean parasite density was higher in the group of
count in the group of subjects with splenomegaly was malaria patients with splenomegaly [(3635.78 1623.70)/
(189655.56 80115.76)/L, which was lower than in the group L] compared with those without splenomegaly [(1789.88
of subjects without splenomegaly [(245230.77 98380.74)/ 927.29)/L], using the Mann-Whitney U-test (P < 0.0001,
L]. The Mann-Whitney U-test results showed that there was a Figure 6).
significant difference in the platelet count between the patients There were differences in parasite density using the Hackett

6000 60000
35
42
5000 50000 18

4000 40000
Parasite density/mcL
Parasite density/mcL

3000 30000

2000 20000

1000 10000

0 0

100000 150000 200000 250000 300000 (-) (+)


Platelet count/mcL Spleen size
Figure 3. Correlation between platelet count and parasite density in the Figure 5. Difference in platelet count based on splenomegaly with the
mixed infection group. Hackett method.

10000
60000
37
44
50000 18 8000
Parasite Density, /mcL

40000 6000
Parasite density/mcL

30000
4000

20000
2000
10000

0
0
(-) (+)
Malaria vivax Mixed infection Spleen size
Figure 4. Difference in platelet count based on the type of malaria Figure 6. Difference in parasite density based on the presence of
infection. splenomegaly using Hackett method.
202 Suryani Margono et al./Asian Pac J Trop Dis 2016; 6(3): 199-203

method. The mean parasite density was higher in the group of study was only approximately 0.2%. Because of the relatively
patients with more severe splenomegaly [Hackett I (3089.50 low parasite density in this study, the platelet count did not fall
1097.24)/L versus Hackett II (4920 1970/L, P = 0.029]. below 150000/L.
A weak positive correlation was observed between the platelet A study in Kenya found a strong negative correlation between
count and the patients age using Spearmans correlation platelet count and parasite density in patients with malaria
analysis (r = 0.125, P = 0.304, Figure 7). falciparum infection [11]. In contrast to that finding, a study in
Brazil found that patients with malaria vivax infection had a
20
weak negative correlation [12] . Similar to that study, we also
found a weak negative correlation between platelet count and

15 parasite density. We estimate that this result was because most


of the samples were malaria vivax. Previous research in Papua,
Indonesia, has also found a weak negative correlation in the
Age (year)

10 malaria vivax group[10]. Consistent with a study in Kenya[11],


the Taylor et al. also found a strong negative correlation
between platelet count and parasite density in the malaria
5
falciparum group[10].
Interestingly, we observed a different finding in the mixed
0 infection group, that is, the platelet count and parasite density
0
100000 200000 300000 400000 500000 600000 showed a strong positive correlation. This finding could be due
Platelet count/mcL to the relatively small sample size, therefore the result might
Figure 7. Correlation between platelet count and patients age.
not be representative. Another reason is likely because some
patients may have consumed antimalarial drugs, which might
4. Discussion have changed the platelet count and parasite density in the
blood.
Malaria infection remains a major public health problem in In this study, the platelet count in the mixed infection group
tropical countries worldwide[1], including the Batubara District, was significantly lower than that in monoinfection group.
Indonesia. P. falciparum, P. vivax, and mixed infection of both This result aligned with the theory that P. falciparum attack
types of malaria infection are found in Batubara District. In erythrocyte of all ages, while P. vivax usually only attack
our study, prevalence of P. vivax was 85%, followed by mixed young erythrocytes [13] . This finding may explain why the
infection at 12% and P. falciparum 3%. In this study, males mixed malaria infection had a higher parasite density, thereby
numbered 52.8%, and females were 47.2%. The prevalence resulting in more frequent and lower thrombocytopenia [14] .
of male might have been because of their nocturnal outdoor In accordance with this theory, a study in India has revealed
activities[7]. that severe thrombocytopenia is more common in malaria
Thrombocytopenia is a common sign in malaria infection, falciparum than in vivax [15] . Our study cannot compare the
which occurs in 24%94% of malaria cases[6]. The pathogenesis severity of thrombocytopenia between the malaria falciparum
of malaria thrombocytopenia is complex and it may be related to and vivax group because of the small sample size of the
coagulation disturbances, splenomegaly and platelet destruction falciparum group.
by macrophages, bone marrow alterations, antibody-mediated Hematopoiesis is one function of the spleen. The changes
platelet destruction, oxidative stress and platelet aggregation[6]. in the structure of the spleen during malaria infection can
Although thrombocytopenia is common, hemorrhagic events are disrupted hematopoiesis, which will decrease the platelet count
rare and are usually associated with severe thrombocytopenia or in the blood due to decreased production [16] . In this study,
disseminated intravascular coagulation[8,9]. malaria patients with splenomegaly had a significantly lower
A study conducted in Papua, Indonesia, revealed that more platelet count. This finding is consistent with a Pakistan study
than 50% of patients with high parasite density of more than of adult patients with malaria vivax infection[17].
10% had platelet count below 50000/L[10]. In this study, we The spleen captures erythrocytes that have been damaged
found only nine patients (12.5%) with thrombocytopenia (from or infected from circulation. Infected erythrocytes will be
total 72 patients), which is lower than previous studies[10]. This broken down and undergo spleen phagocytic clearance, causing
finding might be caused by a relatively low parasite density in edema in pulp and spleen lymphoma [18] , due to the spleens
the blood. The overall parasite density of the subjects in our function in controlling malaria infection [16] . Consequently,
Suryani Margono et al./Asian Pac J Trop Dis 2016; 6(3): 199-203
203
spleen enlargement will worsen with higher parasitemia. To thrombocytopenia in Iran. Iran J Parasitol 2010; 5: 69-70.
confirm this theory, we found an association between parasite [6] L a c e r d a M V, M a u r o M P, C o e l h o H C , S a n t o s J B .
density and splenomegaly in this study. Our subjects with Thrombocytopenia in malaria: who cares? Mem Inst Oswaldo
higher parasite density had more severe splenomegaly. A study Cruz 2011; 106(Suppl 1): 52-63.
in Mandailing Natal, North Sumatra, Indonesia, also found a [7] M ugwagwa N, Mberikunashe J, Gombe NT, Tshimanga M,
significant positive correlation between the parasite density Bangure D, Mungati M. Factors associated with malaria infection
and the degree of splenomegaly (using the Hackett method) in in Honde Valley, Mutasa District, Zimbabwe, 2014: a case control
malaria falciparum patients[19]. study. BMC Res Notes 2015; 8(1): 829.
This study has several limitations. First, the malaria [8] Chaudary SC, Sonkar SK, Kumar V, Gupta A. Falciparum malaria
falciparum group had a small sample size; therefore, the results presenting as subdural hematoma. J Assoc Physicians India 2011;
could not be analysed. Second, we examined the platelet 59: 325-6.
counts manually, which could cause inaccurate calculations. [9] S a i l o L , P r a d h a n D , N o n g t h o m b a m R , B h a t t a c h a r y y a P.
A prospective cohort study design with a larger sample size Disseminated intravascular coagulation in malaria: a case report.
is required to find the correlation between platelet count and Niger Med J 2014; 55(2): 171-2.
parasite density, based on the species of malaria, and to observe [10] Taylor WRJ, Widjaya H, Basri H, Ohrt C, Taufik T, Tjitra E, et
the fluctuations in platelet counts after antimalarial treatment. al. Changes in the total leukocyte and platelet counts in Papuan
There was a weak negative correlation between platelet count and non Papuan adults from Northeast Papua infected with acute
and parasite count. Plasmodium vivax or uncomplicated falciparum malaria. Malar J
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Conflict of interest statement [11] Maina RN, Walsh D, Gaddy C, Hongo C, Waitumbi J, Otiento L, et
al. Impact of Plasmodium falciparum infection on haematological
We declare that we have no conflict of interest. parameters in children living in Western Kenya. Malar J 2010;
9(Suppl 3): S4.

Acknowledgments [12] Leal-Santos FA, Silva SBR, Crepaldi NP, Nery AF, Martin TOG,
Alves-Junior ER, et al. Altered platelet indices as potential
The authors are grateful to the midwifes of Lima Puluh markers of severe and complicated malaria caused by Plasmodium
District for their enthusiastic participation in this study. The vivax: a cross-sectional descriptive study. Malar J 2013; 12: 462.
support provided by the principals and parents of these children [13] K imbi HK, Sumbele IU, Nweboh M, Anchang-Kimbi JK, Lum
was also invaluable. E, Nana Y, et al. Malaria and haematologic parameters of pupils
at different altitudes along the slope of Mount Cameroon: a cross

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