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Parasitology International xxx (2008) xxx-xxx
Parasitology International
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / p a r i n t
Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
The Bangkok School of Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
d
Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
e
Department of Appropriate Technology Development and Transfer, Research Institute, International Medical Center of Japan, Ministry of Health, Labour and Welfare of Japan, Tokyo, Japan
b
c
A R T I C L E
I N F O
Article history:
Received 15 January 2008
Received in revised form 18 June 2008
Accepted 21 June 2008
Available online xxxx
Keywords:
White blood cell counts
Uncomplicated malaria
Plasmodium falciparum
Plasmodium vivax
A B S T R A C T
Total and differential white blood cell (WBC) counts are basic and essential indicators in any type of illness
resulting from infection. In malaria, WBC counts are generally characterized as low to normal during
treatment. WBC-counts data, before and during treatment with artemisinin derivatives, was gathered for
patients with either Plasmodium falciparum or Plasmodium vivax infection (at 28-day follow-up), to
investigate dynamic changes in WBC count. We analyzed and compared the WBC counts of 1310 inpatients
presenting with uncomplicated P. falciparum and P. vivax malaria at the Hospital for Tropical Diseases, in
Bangkok, Thailand. Before-treatment, a statistically signicant negative correlation was found between initial
WBC count and highest temperature on admission. Before and during treatment, WBC counts were
signicantly lower in P. falciparum than P. vivax infection on days 0 and 7, but the numerical difference was
small. We also found clinically signicantly low WBC counts during the acute stages of both types of malaria,
which subsequently normalized by day 28 follow-up. This nding has important clinical implications for the
conventional method of estimating parasitemia using an assumed WBC count of 8000 cells/L. The most
signicant nding in our analysis is that WBC counts in acute P. falciparum and P. vivax malaria are
signicantly lower than previously assumed for estimating malaria-parasite density. However, these
abnormalities returned to normal within several weeks after artemisinin-derivative-based treatment.
2008 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
Total and differential white blood cell (WBC) counts are basic and
essential indicators in any type of illness resulting from infection. They
can help to differentiate between different types of infections and
serve as a tool in monitoring the patient's progress during illness.
Malaria infections can produce low, normal, or high WBC counts.
Plasmodium falciparum (P. falciparum) and Plasmodium vivax (P.
vivax) are the two predominant malaria species causing human
disease in Thailand and Southeast Asia, and many other parts of the
world. P. falciparum malaria is generally regarded as the more severe
of the two infections. It differs from P. vivax malaria in many respects,
including its pathophysiology, laboratory data, clinical manifestations,
treatments, and outcomes.
Corresponding author. Department of Clinical Tropical Medicine, Faculty of Tropical
Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok, 10400
Thailand. Tel.: +66 2354 9159; fax: +66 2354 9158.
E-mail address: tmntp@mahidol.ac.th (N. Tangpukdee).
1
Deceased.
1383-5769/$ see front matter 2008 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.parint.2008.06.005
Please cite this article as: Tangpukdee N, et al, Dynamic changes in white blood cell counts in uncomplicated Plasmodium falciparum and P.
vivax malaria, Parasitol Int (2008), doi:10.1016/j.parint.2008.06.005
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2
Table 1
Baseline patient characteristics
Characteristic
P. falciparum
(N = 718)
P. vivax
(N = 592)
p-values
544(76%)/
174(24%)
24 (1565)
11,840
(130179,040)
4 (17)
381(64%)/
211(36%)
22 (1561)
9970
(12288,480)
4 (15)
b 0.001
38.3
(37.941.2)
37.9
(37.642.3)
b 0.001
Fig. 1. Percentage of patients whose data were still available at each scheduled follow-up.
0.017
b 0.001
0.858
Fig. 2. Median for white blood cell (WBC) counts in patients infected with P. falciparum
and P. vivax malaria. : p-values b 0.001. : Mean of WBC count in healthy Thai volunteer is 7.5 1.7 (103/L) [21].
Please cite this article as: Tangpukdee N, et al, Dynamic changes in white blood cell counts in uncomplicated Plasmodium falciparum and P.
vivax malaria, Parasitol Int (2008), doi:10.1016/j.parint.2008.06.005
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N. Tangpukdee et al. / Parasitology International xxx (2008) xxx-xxx
Table 2
Relationships between white blood cell counts on day 0 (WBC0), age (age), malarial
parasite densities on admission (parasite density), highest temperature on admission
(highest temp) and days of fever preceding admission (days of fever) in patients
infected with P. falciparum
Spearman's correlation coefcient ()
Parasite density
WBC0
Age
Highest temp
a
b
c
WBC0
Age
Highest temp
Days of fever
0.03
1.00
(0.08)
(0.11)b
0.08
(0.08)
1.00
0.10
0.16a
(0.11)b
0.10
1.00
(0.14)c
(0.04)
0.03
(0.01)
p-value b 0.001.
p-value = 0.032.
p-value = 0.014.
Fig. 3. Differential WBC counts on days 0, 7, 14, 21, and 28 for patients infected with P.
falciparum and P. vivax (MOD: Median of differential).
to test for normality, but the data distributions generally did not
exhibit normality. Therefore, the data were expressed as median
(MinMax) and number of observations, with percentage (%). Three
statistical tests were performed: the Chi-square test was used to test
for any association between qualitative variables; the Mann-Whitney
U test was used to test for differences between quantitative variables;
and the Spearman's rank correlation coefcient was used to analyze
the relationships between initial WBC counts, initial parasite
densities, age, highest temperature on admission, and reported days
of fever before admission.
3. Results
3.1. Patient characteristics
The sample consisted of a total of 1 310 inpatients, 718 of whom
were infected with P. falciparum and 592 with P. vivax. Around 5%
were lost to follow-up due to social reasons unrelated to adverse
effects (Fig. 1). The data obtained for such patients, before loss to
follow-up, were included in the analysis.
The patients' characteristics are shown in Table 1. There was a
statistically signicant difference (p-value = 0.017) between the age
distributions of the two groups. Nevertheless, the median age for the
P. falciparum group was only 2 years older than the P. vivax group; the
oldest patient in the P. falciparum group was 65 years, and in the P.
vivax group 61. Clinically or biologically, these differences were
unlikely to be signicant. There were statistically signicant differences (p-value b 0.001) between the two patient groups for gender,
malaria-parasite density, and highest temperature on admission.
3.2. WBC counts
The median WBC counts (MinMax) for the two patient groups
are shown in Fig. 2. The median WBC counts for P. falciparum patients
were lower than for P. vivax patients on days 0, 7, 14, and 28. The
differences were only statistically signicant for days 0 and 7 (pvalue b 0.001). In contrast, the median WBC counts for P. falciparum
patients were statistically signicantly higher on day 21 (pvalue b 0.001). The WBC counts in each patient group on different
days were also compared. Fig. 2 shows relatively low WBC on day 0
for both patient groups (P. falciparum group median WBC count =
5.10 103 cells/L; P. vivax group = 5.70 103 cells/L). This is statistically signicantly different from other days (all p-valuesb 0.001), which
had median WBC counts of 7.50 103 cells/L to 8.00 103 cells/L, which
were closer to the assumed WBC count of 8.00 103 cells/L used in
conventional parasite-density estimation methods. To investigate
leukocyte changes during malaria infection, weekly differential WBC
counts during 28 days' follow-up are shown in both percentages and
absolute numbers (Figs. 3 and 4). The results showed that lymphopenia
(dened as absolute lymphocyte counts 1500 cells/L) was common in
acute-stage malaria infection. We also found that patients with acute
falciparum and vivax infection had low eosinophil levels. Eosinophil
levels (normal values 350 cells/L) were low in the early stage, and then
increased over the following few weeks.
3.3. Correlational relationships between WBC counts and other variables
Values for Spearman's correlation coefcient () and p-values are
shown in Table 2 (P. falciparum group) and Table 3 (P. vivax group).
Different variables were analyzed for possible correlational
relationships.
For both groups, we found statistically signicant, but weak,
negative correlations between WBC count on day 0 and highest
temperature on admission ( = (0.11), p-value = 0.03 for P. falciparum
group; = (0.16), p-value b 0.001 for P. vivax group). There were also
weak negative correlations between malarial parasite densities and
reported days of fever pre-admission ( = (0.14), p-value = 0.01 for P.
falciparum group; = (0.15), p-value b 0.001 for P. vivax group). In the
Table 3
Relationships between white blood cell counts on day 0 (WBC0), age (age), malarial
parasite densities on admission (parasite density), highest temperature on admission
(highest temp) and days of fever preceding admission (days of fever) in patients
infected with P. vivax
Spearman's correlation coefcient ()
Parasite density
WBC0
Age
Highest temp
a
b
Fig. 4. Differential (absolute number) for WBC counts on days 0, 7, 14, 21, and 28 of
patients infected with P. falciparum and P. vivax (AMD: Absolute median of differential).
c
d
WBC0
Age
Highest temp
Days of fever
0.08
1.00
(0.11)a
(0.16)c
( 0.04)
( 0.11)a
1.00
0.01
0.16b
(0.16)c
0.01
1.00
(0.15)d
(0.02)
(0.06)
(0.02)
p-value = 0.023.
p-value b 0.001.
p-value b 0.001.
p-value b 0.001.
Please cite this article as: Tangpukdee N, et al, Dynamic changes in white blood cell counts in uncomplicated Plasmodium falciparum and P.
vivax malaria, Parasitol Int (2008), doi:10.1016/j.parint.2008.06.005
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Table 4
Comparison of parasite density using actual WBC count and assumed WBC count
(8000 cells/L)
Malaria
infection
P-values
P. falciparum,
n = 358
P. vivax,
n = 266
All cases,
n = 624
640 (3017920)
b 0.001
812 (3228623)
1 040 (4403480)
b 0.001
719 (3018623)
920 (4403680)
b 0.001
Please cite this article as: Tangpukdee N, et al, Dynamic changes in white blood cell counts in uncomplicated Plasmodium falciparum and P.
vivax malaria, Parasitol Int (2008), doi:10.1016/j.parint.2008.06.005
ARTICLE IN PRESS
N. Tangpukdee et al. / Parasitology International xxx (2008) xxx-xxx
Please cite this article as: Tangpukdee N, et al, Dynamic changes in white blood cell counts in uncomplicated Plasmodium falciparum and P.
vivax malaria, Parasitol Int (2008), doi:10.1016/j.parint.2008.06.005