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Hindawi Publishing Corporation

Malaria Research and Treatment


Volume 2016, Article ID 1240962, 7 pages
http://dx.doi.org/10.1155/2016/1240962

Research Article
Severe Malaria Associated with Plasmodium falciparum and
P. vivax among Children in Pawe Hospital, Northwest Ethiopia

Getachew Geleta and Tsige Ketema


Department of Biology, College of Natural Sciences, Jimma University, P.O. Box 378, Jimma, Ethiopia

Correspondence should be addressed to Tsige Ketema; tsigeketema@gmail.com

Received 9 November 2015; Revised 8 February 2016; Accepted 11 February 2016

Academic Editor: Ananias Escalante

Copyright © 2016 G. Geleta and T. Ketema. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.

Despite rigorous effort made to control malaria for more than a century, it is still among the main public health problems in
least developed regions of the world. Majority of deaths associated with malaria occur in sub-Sahara Africa among biologically
risked groups. Thus, this study was designed to assess the incidence of severe malaria syndromes among children in Pawe Hospital,
Northwest Ethiopia. Children seeking medication for malaria infection in Pawe Hospital during the study period were recruited.
Sociodemographic characteristics, physical, hematological, and clinical features of complicated malaria were assessed following
standard parasitological and clinical procedures. A total of 263 children were found malaria positive. Among these, 200 were
infected with Plasmodium falciparum. Most of the severe malaria symptoms were observed among children infected with P.
falciparum and P. vivax. The study showed that significant number of the children developed severe life threatening malaria
complications. This calls for prompt early diagnosis and effective treatment of patients to reduce mortality and complications
associated with malaria in the study site.

1. Introduction from Indonesia, Papua New Guinea, Latine America Guyana,


India, and Ethiopia show a strong association of this parasite
Malaria is one of the life threatening infections caused by with severe malaria symptoms [6–11].
protozoan parasite. It is still a major public health concern According to President’s Malaria Initiative [12] of
of most endemic areas of the world. Five human Plasmodium Ethiopia, malaria is ranked as the leading communicable
species (Plasmodium falciparum, P. vivax, P. ovale, P. knowlesi, disease in Ethiopia, accounting for about 30% of the overall
and P. malariae) [1] cause malaria infection. The major disability adjusted life years lost. Approximately 75% of the
complications are caused by P. falciparum and P. vivax, with country is malarious with ∼68% of the total population living
P. falciparum being the more virulent. It is indicated that in areas at risk of malaria. As reported by Ethiopia’s Federal
about 1–3 million mortalities per year, mainly in children Ministry of Health (FMOH) [13], in 2009, malaria was the
and pregnant women, are due to severe malaria caused first cause of outpatient visits, health facility admissions, and
by P. falciparum [2]. These pathologies are severe anemia, inpatient deaths, accounting for 12% of outpatient visits and
cerebral malaria, and acute respiratory distress [3]. According 9.9% of admissions. Thus, this study was designed to assess
to WHO/UNICEF report [4], of all malaria cases in the incidence of severe malaria syndromes associated with P.
world, 60% were occurring in Africa. Of the 75% of global falciparum and P. vivax among children in one of the malaria
P. falciparum malaria cases, 80% mortality is documented in endemic areas in Ethiopia.
the same region.
Although the public health importance of P. vivax is 2. Materials and Methods
overshadowed by P. falciparum, it is the most important
parasite in Asia and South America. It accounts for about 390 2.1. Study Area. A descriptive hospital based study was
million clinical cases annually [5]. Apart from these, studies conducted at Pawe district, Benishangul Gumuz Regional
2 Malaria Research and Treatment

N 2.2. Study Population and Sample Size. Malaria infected chil-


W E dren seeking medication at Pawe Hospital and fulfilling the
S
inclusion criteria were considered in the study. Accordingly,
Pawe district
children < 10 years, symptomatic, malaria positive, with no
prior medication to the current illness, willing to participate
in the study, and without chronic infections (none admitted
to ART and Tb clinics) were enrolled in the study.

2.3. Data Collection. All guardians of children were pro-


vided with informed consent, and the sociodemographic
and clinical data (age, weight, height, bed net utilization,
fever, headache, presence of vomiting and diarrhea, prior
medication, and body temperature) and any history of
0 240 480 720 fever of the children were collected using predesigned data
(km) record form by health professionals working in the hospi-
tal. Also, signs of complicated malaria symptoms such as
Figure 1: Map of the study site. prostration, jaundice, impaired consciousness, hyperpyrexia,
hyperparasitemia, persistent vomiting, respiratory distress,
and hemoglobinuria were further assessed for all participants
State, Northwest Ethiopia (Figure 1). The study site is geo- by trained physician and other health professionals at the hos-
graphically located at 11.009󸀠 N latitude, 36.003󸀠 E longitude, pital in accordance with WHO guidelines for the treatment of
and an altitude of 1050 meters above sea level (masl). In malaria [16].
this district, the major and minor malaria transmission peak
seasons are from September to December and from April
to May, respectively, coinciding with the major harvesting 2.4. Parasitological and Hematological Tests. About 2 mL
and planting seasons. The peak rainfall occurs from July to of blood samples from each participant was collected in
August. The mean annual rain fall and maximum tempera- EDTA precoated tubes. Few drops were used for parasite
ture of the area are 1555.1 mm and 32∘ C (with mean monthly identification and count. The remaining blood sample was
values ranging in 27–37∘ C), respectively. Pawe district has a used for further analysis. Briefly, two drops of the blood
total population of 45,552, of whom 23,265 were men and sample was collected on clean glass slide for preparation
22,287 were women. About 10,068 (22.1%) of population were of thin and thick blood smears in duplicate. Thick and
urban inhabitants [14]. In the hospital, patients due to P. thin blood smears were stained with 10% Giemsa (pH =
falciparum and P. vivax malaria are treated with Coartem 7.2, for 10 min), while thin smears were fixed in methanol
(artemether-lumefantrine, 20 mg base/kg) and chloroquine prior to Giemsa staining. Malaria parasites were identified
(25 mg base/kg), respectively, following National Diagnosis under a microscope (100x oil immersion field) and parasite
and Treatment Guideline [15]. Moreover, as the hospital has load was calculated after counting asexual parasites per
all facilities for malaria diagnosis standard microscopic inves- 200 white blood cells (WBC) using the following formula
tigation was carried out for all patients following standard [16], assuming that the mean WBC count of human is
procedure recommended by WHO [16]. 8,000/𝜇L:

Number of observed asexual parasites × 8000 WBC count/𝜇L


Parasite count/𝜇L = . (1)
200 WBCs

The remaining blood sample was used for measurement and drink in infants], and hyperpyrexia (body temperature >
of hematological parameters such as hemoglobin (Hb), 40∘ C) [17–19].
hematocrit (HCT), neutrophils, eosinophils, monocytes, and
lymphocytes using autosampler CBC machine (Automated
CBC Analyzer: Sysmex KX-21). 2.5. Data Analysis. Data were analyzed using SPSS software
Severe malaria symptoms were classified following WHO (version 20.0, Armonk, NY: IBM Corp). Descriptive statis-
guideline for the management of severe malaria as severe tical tests were used for analysis of clinical, demographic,
anemia (Hb < 5 g/dL or hematocrit level < 15%), hyperpar- and parasitological data. Association between variables was
asitemia (parasite load > 100,000 parasites/𝜇L), persistent evaluated using Pearson correlation test. Median (range)
vomiting, respiratory distress, convulsion (more than two in was considered over mean (SD) for nonnormally distributed
24 hours), comma, hemoglobinuria (discoloration of urine), variables. Multiple logistic-regression model was used to
prostration [unable to walk, sit, and stand or unable to feed assess predictive variables of severe malaria complications.
Malaria Research and Treatment 3

Table 1: Sociodemographic and clinical manifestation of uncom-


5000.00
plicated malaria infected children in Pawe Hospital, Northwest
Ethiopia.

4000.00 Characteristics Proportion


Age: median (range) 4.1 (1 month–10 years)
Sex:
Number of children

3000.00 Male 139 (52.8%)


Female 124 (47.14%)
Mean body temperature (∘ C) 38.14 ± 0.21
2000.00 Bed net utilization 76 (28.89%)
BMI (Body Mass Index) (kg/m2 ) 19.15 ± 0.58
Vomiting 162 (61.59%)
1000.00 Diarrhea 94 (35.74%)
Mean Hb level (g/dL) 7.78 ± 2.4
Mean hematocrit level (HCT) (%) 27.52 ± 4.91
0.00 Geometric mean parasite (parasite/𝜇L) 9898 ± 5138.2
2009 2010 2011 2012 2013 Headache 141 (53.6%)
Year
Premedication 92 (34.98%)
Suspected Anemia (mild) 194 (73.76%)
Confirmed

Figure 2: Five-year malaria prevalence report among children in


Pawe Hospital, Northwest Ethiopia (Source: Annual reports of Pawe
Hospital, unpublished data). The median age of children enrolled in this study was
4.1 years (one month–10 years). Mean auxiliary body tem-
perature of the children was 38.14∘ C. Proportion of children
with vomiting and diarrhea symptoms was 162 (61.59%) and
94 (35.74%), respectively. Bed net coverage was very limited,
One-way ANOVA (analysis of variance) was employed to with only 76 (28.89%) of the study participants using bed
compare WBC indices. In all analysis, significance level was net. Mean hemoglobin and HCT level were 7.78 g/dL and
considered at 95% confidence interval (𝑃 < 0.05). 27.52%, respectively. Geometric mean parasite count was
9898 parasites/𝜇L (Table 1). The number of anemic children
(Hb level < 11 g/dL) encountered was 194 (73.76%).
2.6. Ethical Consideration. The study was ethically approved
by Research and Ethical Review Committee of College of
Natural Sciences, Jimma University, Ethiopia. From all study 3.3. Clinical Characteristics of Children Infected with Different
participants, oral and written assent were obtained prior to Plasmodium spp. Geometric mean parasite count (asexual
data collection. Malaria positive cases were treated according stage) and mean body temperature for P. falciparum and P.
to national malaria diagnosis and treatment guidelines [15]. vivax infected children were 10963 and 3902 parasites/𝜇L
and 38.63 and 38.62∘ C, respectively. Some participants had
3. Results symptom of splenomegaly due to P. falciparum (𝑛 = 6,
60%) and P. vivax (𝑛 = 2, 20%). About 15 (12.4%) of
3.1. Prevalence of Malaria in the Study Area. Malaria was the study participants were self-reported for self-medication
still among the top health concerns in the study area. prior to coming to the health facility. The BMI of the study
Although the trend of malaria positive cases is showing an participants were 18.44, 19.15, and 19.30 for mixed, mono-P.
overall declining pattern, the five-year malaria prevalence falciparum, and P. vivax infection, respectively (Table 2).
data from the hospital (2009–2013) revealed that the numbers Although there was no significant association (𝑟 = 0.038,
of infected children ≤ 10 years are still higher (Figure 2). 𝑃 = 0.54) between age and Hb level, as age of children
The prevalence of malaria among children over the five-year increased Hb level also showed an increment. Most of the
period in the hospital was reduced from 41.45% (2009) to children with hemoglobin level <5 g/dL (an indicator of
25.7% (2013). severe anemia) were found in age group <1 year.
There were no significant differences (𝑃 > 0.05) in
3.2. Sociodemographic and Clinical Characteristics of the Study level of WBC indices among children infected with different
Participants. During the study period, a total of 1523 blood Plasmodium species. In P. falciparum and mixed infected
samples were collected from presumptive malaria patients children, counts of neutrophils, eosinophil, and monocytes
(Figure 3). Among these, 263 (17.27%) were children, of had similar pattern, except for lymphocyte whose level rose
which 139 (52.85%) and 124 (47.14%) were males and females, in P. falciparum infection. However, in P. vivax infected
respectively. children eosinophils and lymphocytes were lower, but other
4 Malaria Research and Treatment

Blood sample examined


(n = 1523)

623 were malaria positive

Mixed P. vivax
P. falciparum (n = 140, 22.47%) (n = 63, 10.1%)
(n = 420, 67.4%)

Adult Children Pregnant


Adult Children Pregnant (n = 29, women (n = 22,
(n = 200, women (n = 129, (n = 12,
(n = 91, 19.04%) 46.03%) 34.9%)
21.67%) 47.62%) 30.7%)

Children
Adult (n = 61, (n = 34, Pregnant women
43.57%) 24.28%) (n = 45, 32.1%)

Uncomplicated Complicated Uncomplicated Complicated


(n = 154, 77%) (n = 46, 23%) (n = 20, 68.9%) (n = 9, 31.03%)

Uncomplicated Complicated
(n = 24, 70.59%) (n = 10, 29.41%)

Figure 3: Flow chart of the study.

Table 2: Clinical features of malaria infected children with respect Table 3: Levels of WBC indices among children infected with
to different spp. of Plasmodium infections in Pawe Hospital, North- different Plasmodium species at Pawe Hospital, Northwest Ethiopia.
west Ethiopia.
Mean ± SD
WBC indices 𝑃 value
Characteristics P. f (𝑛 = 200) Mix (𝑛 = 34) P. v (𝑛 = 29) P. f (𝑛 = 200) P. v (𝑛 = 29) Mix (𝑛 = 34)
Temperature 38.63 ± 0.25 38.62 ± 0.73 38.62 ± 0.14 Neutrophil 46.4 ± 15.1 47.82 ± 13.06 46.7 ± 23.13 0.816
(∘ C) Lymphocyte 29.03 ± 10.9 27 ± 12.63 28.2 ± 20.55 0.701
Bed net 42 (55.26) 23 (30.26) 11 (14.47) Eosinophil 14.9 ± 9.76 13.3 ± 11.99 14.7 ± 11.68 0.769
Hb (g/dL) 7.87 ± 1.03 8 ± 3.6 8 ± 2.69 Monocyte 9.12 ± 8.56 11.4 ± 10.36 8.85 ± 13.02 0.252
HCT P. f = P. falciparum, P. v = P. vivax, Mix = mixed infection.
(hematocrit) 27.52 ± 2.4 28.14 ± 1.98 26.17 ± 3.11
(%)
Mean parasite 10963 ± 3692 7923 ± 2756 3902 ± 1569
(parasite/𝜇L) 16 (8%), respiratory distress, 10 (5%), hemoglobinuria, 14
BMI (kg/m2 ) 19.15 ± 1.28 18.44 ± 0.99 19.2 ± 1.1 (7%), persistent vomiting, 16 (8%), and hyperparasitemia,
Vomiting 119 (73.45) 27 (16.67) 16 (9.87) 33 (16.5%), but none had pathology of hepatomegaly and
comma. These symptoms of severe malaria complications
Diarrhea 68 (72.34) 18 (19.15) 8 (8.5)
among the children were significantly higher (𝑃 < 0.05)
Hepatomegaly 0 (0) 0 (0) 0 (0) than other Plasmodium infections except symptoms such
Splenomegaly 6 (60) 2 (20) 2 (20) as confusion and splenomegaly (Table 4). Likewise, a total
P. f = P. falciparum, P. v = P. vivax, Mix = mixed infection; numbers within of 29 of children enrolled in the study were infected with
bracket are %. P. vivax malaria. Among these cases, those that showed
symptoms of severe malaria complications and the respec-
tive symptoms were 4 (13.8%), severe anemia, 9 (31.03%),
WBC indices such as monocytes and neutrophils were higher prostration, 7 (24.13%), hyperpyrexia, 3 (10.3%), respiratory
(Table 3). distress, 2 (6.89%), hemoglobinuria, 1 (3.4%), confusion, and
1 (3.4%), persistent vomiting, but none had symptoms such
3.3.1. Incidence of Severe Malaria Symptoms among Children as hyperparasitemia, hepatomegaly, and comma (Table 4).
Infected with Different Plasmodium spp. Among the 263 Logistic-regression analysis identified that there were
study participants enrolled in the study, a total of 46 P. three key predictive indicators of severe malaria: respiratory
falciparum positive children showed at least one of the distress, hyperpyrexia, and severe anemia [odd ratio (OR)
WHO recommended criteria of severe malaria. These were = 1.26, 95% CI = 1.115–2.59, OR = 1.033, 95% CI = 1.04–
severe anemia, 36 (18%), prostration, 41 (24%), hyperpyrexia, 2.01, and OR = 1.325, 95% CI = 1.56–3.14, resp.]. These severe
Malaria Research and Treatment 5

Table 4: Incidence of severe malaria symptoms among P. falciparum documented among children in the current study evidence
and P. vivax monoinfected children, Pawe Hospital, Northwest the higher risk of these groups to malaria associated mor-
Ethiopia. bidity. Furthermore, incidence of severe malaria associated
with P. vivax strengthens the fact that this parasite is no more
Proportion (%)
Characteristics mild; rather it could be responsible for some life threatening
P. falciparum (𝑛 = 200) P. vivax (𝑛 = 29) complications among children in malaria endemic regions
Severe anemia (Hb < 36 (18) 4 (13.8) [6, 9, 24–26].
5 g/dL or HCT < 15%)
The observed severe malaria complications were much
Hyperparasitemia lower than the earlier reports made from Papua New
(>100,000 33 (16.5) 0 (0)
Guinean, Ghana, and Yemen [27–29]. This variation of
parasite/𝜇L)
manifestation of severe malaria in these regions could be due
Prostration 41 (24) 9 (31.03)
to differences in intensity of malaria transmission. In areas
Hyperpyrexia 40 (20) 7 (24.13) where there is low or moderate transmission, the incidence
(≥40∘ C) of severe malaria appears the highest [30].
Confusion 3 (1.5) 1 (3.4)
Most of the children enrolled in this study were found
Splenomegaly 6 (3) 2 (6.89) in age group ≤5 years. In this age category higher load
Respiratory distress 10 (5) 3 (10.3) of parasitemia, respiratory distress, and incidence of severe
Hemoglobinuria 14 (7) 2 (6.89) anemia were observed. This might be due to the development
Persistent vomiting 16 (8) 1 (3.4) of poor immunity against the disease [31] although they could
0 (0) 0 (0)
gradually develop protective immunity to malaria as they get
Comma
older and repeatedly exposed to the disease [32]. This could
be supported by the observed reduction of anemic condition
with age possibly due to elimination of the parasite by the
immunity and reducing the hemolysis of RBCs.
malaria symptoms were highly prevalent among children less Usually anemia is a hallmark of P. falciparum infection
than five years. But other severe malaria symptoms were not due to intense hemolysis (destruction) of infected RBCs
significantly different between children of age groups < 5 and due to higher parasitemia caused by the parasite. Unlike
> 5 years infected with P. falciparum. other Plasmodium species, P. falciparum infect all types
of RBCs found at different stages of development (from
immature young to old RBCs). With additional hemolysis of
4. Discussion noninfected RBCs by host immunity, the likely occurrence
of severe anemia in P. falciparum infected children is high.
Although the prevalence of malaria has been showing declin-
However, due to selective preference to only young RBCs
ing pattern in some parts of Ethiopia [20], in the current study
by P. vivax, it appears that the number of haemolysed RBCs
area it is still the top health concern. The number of infected
during P. vivax infection is minimal. Thus, the incidence of
children aged ≤ 10 years was still higher. According to the
severe anemia associated with P. vivax might occur as a result
five-year prevalence report of the hospital, trend of malaria
of rigor inflammatory reactions due to proinflammatory
positive cases showed reduction. This overall decreasing pat-
response and cytokines activation [33] and less deformability
tern was similar to earlier report made on time series analysis
of trends in malaria cases from Ethiopia [20]. The decline of RBCs during P. vivax infection [34, 35]. On the other hand,
pattern was accounted for intensive malaria intervention the rate of noninfected RBCs hemolysis for every infected
strategies that involved vector control and symptomatic cases RBC destroyed could contribute to the incidence of anemia
treatment as a result of which the morbidity and mortality as number of nonparasitized RBCs removed from circulation
associated with malaria decreased [20, 21]. According to during P. vivax is much higher (∼32) than P. falciparum (∼8)
Aregawi et al. [20], the status of inpatients and malaria related [36]. Furthermore, lack of significant difference in levels of
death was reduced to 55% and 85%, respectively, during 2001– Hb and HCT between P. falciparum and P. vivax positive
2011 in the same hospital. children strengthens the fact that P. vivax was one of the risk
Although the two Plasmodium species, P. falciparum and factors associated with incidence of severe anemia among
P. vivax, are important parasites in malaria related problems children.
in Ethiopia, P. falciparum was the most predominant species Although bed net is unquestionable tool for prevention
accounting for about 76% of all malaria infections among of malaria vector and widely used in most malaria endemic
children assessed in this study. areas of the country, in the current study its distribution and
Malaria is a deadly disease to all humanity. But the most utilization among the biologically risked groups, supposed to
vulnerable (biologically at the highest risk) are infants and get priority in the family, were very limited and only few were
young children (due to their underdeveloped immunity) and sleeping under bed net. This situation might be among the
pregnant women (as their immunity reduces during malaria most important factors aggravating the highest prevalence of
infection). In pregnant women it causes increased risk of malaria in the study area, when the current trend of malaria
abortion, stillbirth, premature delivery, and low-birth weight infection dramatically dropped in most malaria endemic
infants besides mortality [22, 23]. Thus, severe malaria cases areas of the country.
6 Malaria Research and Treatment

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of artemether-lumefantrine for Plasmodium vivax infections in
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The authors declare that there is no conflict of interests. severe malaria complications among children in some malaria
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Authors’ Contribution 637, 2013.
[12] President’s Malaria Initiative (PMI): Malaria Operational Plan
Getachew Geleta was fully involved in all phases of the (MOP), FY, 2011, http://www.pmi.gov/docs/default-source/
study including designing of the study, field and laboratory default-document-library/malaria-operational-plans/fy11/ethi-
data collection, data analysis, and writing. Tsige Ketema was opia mop-fy11.pdf?sfvrsn=6.
involved in supervision of the study, designing, data analysis [13] Federal Ministry of Health (FMOH), National Strategic Plan
and interpretation, and writing and revision of the paper. for Malaria Prevention, Control and Elimination in Ethiopia,
FMOH, Addis Ababa, Ethiopia, 2009.
[14] CSA: central statistical agency of Ethiopia, 2007.
Acknowledgments [15] FMOH (Federal Ministry of Health of Ethiopia), National
Malaria Guidelines, Federal Ministry of Health of Ethiopia,
The authors would like to thank officials, laboratory tech-
Addis Ababa, Ethiopia, 3rd edition, 2012.
nicians, and physicians of Pawe Hospital for their kind
[16] World Health Organization, Basic Malaria Microscopy. Part 1.
cooperation and support during data collection. They are
Learner’s Guide, WHO, Geneva, Switzerland, 2nd edition, 2010.
also grateful to the study participants for their willingness to
[17] M. Cheesbrough, District Laboratory Practice in Tropical Coun-
participate in the study and genuine response. The work was
tries, Cambridge University Press, Cambridge, UK, 2nd edition,
financially supported by Jimma University. 2005.
[18] WHO, Guideline for Treatment of Malaria, WHO, Geneva,
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