Acta Tropica 173 (2017) 1–10

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Acta Tropica
journal homepage: www.elsevier.com/locate/actatropica

Relationship between exposure to malaria and haemoglobin level of MARK

children 2–9 years old in low malaria transmission settings
⁎
Zewdie Birhanua, , Yemane Ye-ebiyo Yihdegob, Daniel Emanac, Damtew Feyissad, Silashi Kenated,
Estifanos Kebedec, Kefelegn Getahune, Delenasaw Yewhalawf
a
Department of Health Education and Behavioral Sciences, Institute of Health, Jimma University, P.O. Box 378, Ethiopia
b
Abt Associates, Africa Indoor Residual Spraying, Accra, Ghana
c
Department of Medical Laboratory Sciences and Pathology, Institute of Health, Jimma University, Ethiopia
d
Oromia Regional Health Bureau, Jimma Zone Health Department, Jimma, Ethiopia
e
College of Social Sciences and Humanities, Jimma University, Ethiopia
f
Tropical and Infectious Diseases Research Center, Jimma University, Jimma, Ethiopia

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

Keywords: In the context of reduced transmission of malaria, it is essential to examine the association between exposure to
Malaria anaemia malaria and haemoglobin level. This study measured the Haemoglobin level of children 2–9 years of age and
Haemoglobin examined its association with malariometric indices. A cross sectional study was conducted, during June 2016,
Malaria antibody on 763 children 2–9 years old, recruited from ten sites representing different malaria transmission settings in
Serology
Ethiopia. Haemoglobin concentration was determined using HemoCue analyzer. Malariometric indices
(splenomegaly rate, parasite rate and serological marker) were measured. The overall prevalence of anaemia
was 17.3% (95% CI: 14.6–19.9) in the study population. Mild, moderate and severe anaemia accounted for 7.3%,
7.2% and 2.8% respectively. Of the children with anaemia (132), only 7 (5.3%) had malaria parasitaemia. The
prevalence of malaria parasitaemia was 3.6% (2/56), 9.1% (5/55) and 0.0% (0/21) among children with mild,
moderate and severe anaemia, respectively. Malaria reactive antibody and anaemia co-occurred in 3.13% (21/
672) of the samples. Seroprevalence and parasitaemia did not have significant association with anaemia
(p > 0.05). However, splenomegaly was significantly associated with increased risk of anaemia (AOR = 14.93;
p = 0.001). Anaemia was significantly higher among children 2–4 years old (22.2%), and children living in
households without any insecticide treated bed net (34.0%). The prevalence of anaemia was lower by 55.0%
among children living in households with at least one net (AOR = 0.45, 95% CI: 0.21–0.96). Repeated exposure
to malaria infections (seropositive) and parasitaemia was less likely to contribute to development of anaemia
among children 2–9 years in this study setting. Thus, in low malaria endemic settings, anaemia prevention and
control program required to reconsider the historical evidence that suggests malaria is one of the major risk
factor for anaemia.

1. Introduction under the age of five had mild and moderate anaemia, respectively
(EHNRI, 2012). According to the Ethiopian Demographic and Health
Anaemia is a condition in which the haemoglobin concentration Survey (EDHS), about 44% of Ethiopian children were anaemic in
falls below an established cut-off value thereby consequently impairing which mild, moderate and severe anaemia accounted for 21%, 20% and
the capacity of the blood to transport oxygen around the body (World 3% respectively. According to this report, the prevalence of anaemia
Health Organization, 2014). In anaemic individuals, the number of red was higher among rural children (45%) as compared to children urban
blood cells and their oxygen carrying capacity is inadequate to meet settings (35%) (Central Statistical Agency of Ethiopia, 2011). Similar
physiologic needs, resulting in an increased morbidity (World Health community based studies also reported a magnitude of anaemia that is
Organization, 2014, 2008). In developing countries, over half of as high as 66.6% (Gutema et al., 2014; Mesfin et al., 2015; Assefa et al.,
preschool children are estimated to be anaemic (World Health 2014; Deribew et al., 2010). According to the World Health Organiza-
Organization, 2014, 2008). In Ethiopia, 43.1% and 6.9% of the children tion (WHO), anaemia is a major public health problem in Ethiopia

⁎
Corresponding author.
E-mail addresses: zbkoricha@yahoo.com (Z. Birhanu), yemaneyy@gamil.com (Y.Y.-e. Yihdego), aga.danie2009@gmail.com (D. Emana), dfjebessa@gmail.com (D. Feyissa),
siles2009@yahoo.com (S. Kenate), estifka@yahoo.com (E. Kebede), kefish2002@gmail.com (K. Getahun), delenasawye@yahoo.com (D. Yewhalaw).

http://dx.doi.org/10.1016/j.actatropica.2017.05.021
Received 25 January 2017; Received in revised form 12 May 2017; Accepted 14 May 2017
Available online 15 May 2017
0001-706X/ © 2017 Elsevier B.V. All rights reserved.
Z. Birhanu et al. Acta Tropica 173 (2017) 1–10

Fig. 1. Map of the study area.

(World Health Organization, 2008). In tropical areas, malaria control measures have significant impacts
Anaemia has numerous short and long term health impacts on on overall reduction of anaemia, and as a result, malaria control
children: It affects their cognitive and psychomotor development and program is considered to be a collateral strategy for reduction of
learning performance; impairs behavioral and physical growth with anaemia particularly among highly susceptible group (Korenromp
increased risk of morbidity and mortality (World Health Organization, et al., 2004; World Health Organization, 2015a; Brooker et al., 2007;
2014; WHO et al., 2001). Furthermore, anaemia impairs language Crawley, 2004). These days, malaria elimination program has received
coordination capacity of children and is also linked to poor intelligent utmost global and national priorities (World Health Organization,
quotient (WHO et al., 2001). Overall, anaemia remains one of the 2015b, 2016). Likewise, Ethiopia has given a considerable attention
obstacles to national development, and it is an indicator of both poor to malaria elimination program with the aim to maintain the current
nutrition and poor health status (World Health Organization, 2008). gains and accelerate the progress towards elimination targets (Ministry
Even though anaemia involves a variety of causes, the majority of of Health, 2014). Hence, malaria elimination program has great
Plasmodium infections are concomitant with some degree of anaemia advantage for anaemia prevention and control efforts suggesting the
among children especially in tropical areas where malaria is endemic need to carefully combine anaemia prevention strategies with malaria
(WHO et al., 2001; Douglas et al., 2012; Collins et al., 2003; Satpathy elimination initiatives. In malaria endemic settings and in areas with
et al., 2004). Although its severity depends on a number of factors recently reduced malaria transmission, many children with malaria
including individual and parasite-specific factors, malaria anaemia is parasitaemia are asymptomatic, thus malaria remains undiagnosed
capable of causing severe morbidity and mortality especially in (Okell et al., 2012; Okell et al., 2009; World Health Organization,
individuals infected with P. falciparum (World Health Organization, 1988). This situation could also contribute to under-diagnosis of
2008; Douglas et al., 2012; Collins et al., 2003). Essentially, severe form anaemia associated with malaria. Therefore, it is vital to measure the
of malaria contributes up to 62% of severe malaria admissions in association between exposure to malaria and anaemia, particularly in
malaria endemic settings (Satpathy et al., 2004). Thus, malaria the context of reduced transmission of malaria. Previous scientific
anaemia, particularly, severe malaria anaemia (SMA) is a complex inquiries mainly focused on classical metrics of malaria such as
disease leading to rapid haemoglobin reductions of 20–50% (Sowunmi parasitaemia and spleen size to assess the association between exposure
et al., 2011). Studies done in Ethiopia and elsewhere widely documen- to malaria and haemoglobin level and little is known about the
ted that infections with malaria parasite associated with anaemia association between cumulative exposure (i.e. presence of anti-malarial
(Gutema et al., 2014; Douglas et al., 2012; Collins et al., 2003; antibodies) to malaria and its effects on haemoglobin level among
Satpathy et al., 2004; Jamal et al., 2015; Newton et al., 1997; children in most malaria endemic settings including Ethiopia. There-
Carneiro et al., 2006; Rogerson, 2017; Sumbele et al., 2016; Deribew fore, this study aimed at examining the association between malario-
et al., 2013; Gari et al., 2017; Ketema and Bacha, 2013; Kateera et al., metirc indices (parasitaemia, spleen rate and anti-malarial antibody
2015; Alemu et al., 2012; Barreiro et al., 2017; Magalhães and levels) and haemoglobin level/anaemia among children of 2–9 years
Clements, 2011; Menendez et al., 2000; Safeukui et al., 2015; old living in different malaria transmission settings of Ethiopia.
Erhabor et al., 2014; Crawley, 2004). Moreover, systematic reviews Consequently, this study could add to a growing body of literature on
and meta-analysis also support that malaria is one of the major risk effects the relationship between malaria and anaemia in the context of
factors for anaemia (Kassebaum et al., 2014; McCuskee et al., 2014; malaria elimination targets.
Korenromp et al., 2004; World Health Organization, 2015a; Brooker
et al., 2007). In addition, some evidences implied that the amount of
2. Material and methods
anaemia in a population is a proxy for estimating the endemicity and
burden of malaria (World Health Organization, 2015a; Brooker et al.,
2.1. Study setting
2007; Korenromp et al., 2004; McCuskee et al., 2014; Senn et al., 2010;
Savage et al., 2007).
The study was conducted in June 2016 as part of a larger

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community based cross sectional study aimed at quantifying malaria ‘2’ spleen palpable below the costal margin, but not projected beyond a
endemicity in Ethiopia. The data were collected mainly from sentinel horizontal line half way between the costal margin and the umbilicus,
sites established for malaria surveillance in Ethiopia (Fig. 1). The measured along a line dropped vertically from the left nipple; ‘3’ spleen
surveillance sites consisted of ten Primary Health Care Units (PHCUs) with lowest palpable point projected more than half way to the
covering a different eco-epidemiologic settings with low to high malaria umbilicus but not below a line drawn horizontally through it; ‘4’ spleen
transmission in Ethiopia (Yukich et al., 2014). Eight of the ten sentinel with lowest palpable point below the umbilical level but not projected
sites (i.e. Kersa, Goro, Metehara, Bulbula, Tulu Bollo, Asebot, Dhera, beyond a horizontal line situated half way between the umbilicus and
and Dembi) were included in the study and two sentinel sites were the symphysis pubis; ‘5’ spleen with lowest point palpable beyond the
replaced by similar primary health care units (i.e Goda Dhera and lower limit of class. Spleen rate was estimated as proportion of children
Shebe Sombo) due to local priorities and some problems associated with palpable spleens; individuals of with classes 1–5 of the size of
with accessing the study community (Yukich et al., 2014). palpated spleen.

2.2. Sample size and sampling techniques 2.5.2. Malaria parasitaemia

For detection of malaria parasitaemia and antibody, 3–5 ml venous
For the main study, samples were collected from children 2–9 years blood was collected into ethylenediaminetetraacetic acid (EDTA) tubes
of age as per the WHO’s recommendation for malaria endemicity study from each child who participated in the study. For children who refused
(World Health Organization, 1968). The sample size was determined to give venous blood or venous blood was insufficient, finger prick was
using single population formula, n = (z 1-α/2)2 p (1 − p)/d2, based on used to get the blood sample for Rapid Diagnostic Test (RDT), blood
the following assumptions: Prevalence of malaria (parasite rate) among film examinations and Haemoglobin determination. For RDT, CareStart
children (p = 10.5%) (Deribew et al., 2012), 2% marginal error, 95% malaria Pf/Pv (HRP2/pLDH) Ag Combo RDT was used. For microscopic
confidence interval, and 15% non-response rate. This yields a sample examination, thick and thin films were prepared and air-dried in the
size of 1038 children. field, and the thin film was fixed with methanol; both smears were
stained with 10% Giemsa stain. Each slide was read by an experienced
2.3. Sampling procedure laboratory technologist at Jimma University Specialized Hospital.
Absence of malaria parasite in 100x oil immersion objective in thick
Children were sampled from ten PHCUs (eight malaria sentinel blood film was considered as negative. A slide was considered as
sites, and two non-malaria sentinel sites) in Oromia Regional state, negative after 100 fields were examined and no parasite seen (World
Ethiopia. In brief, sampling process was implemented as follows: First, Health Organization, 2010).
the sample size (1038 children) was equally allocated to each PHCU.
Second, considering resource available for the study, two satellite 2.5.3. Enzyme immuno assay (EIA) malaria antibody detection
health posts/villages, which are parts of the PHCU were selected Malaria EIA test (BioRad) that uses four recombinant antigens in a
randomly. Equal numbers of children were considered from each of sandwich form was used to detect antibodies to malaria during all
the selected health posts. Within the selected health posts, list of stages of infections. The test detects specific antibodies (i.e. IgG, IgM
households with eligible children (age 2–9 years) was obtained from and IgA) to the four species of Plasmodium parasites; P. falciparum, P.
family register which was employed to select eligible households using vivax, P. ovale and P. malariae. Whole blood collected into EDTA was
simple random sample. Then, parents were invited to the nearest health centrifuged to get plasma for malaria antibody detection. The test was
facility through community based health workers. Up on arrival, based on the binding of specific antibodies present in the plasma to
parents were given detail information about the study purpose and antigens immobilized on a 96-well EIA plate. The assay was performed
signed written consent for children that participated in the study. as recommended by the manufacturer (Malaria EIA AbAssay and
Parents were interviewed to collect children’s demographic data, Clinical Diagnostics, 2016). The plate was read at absorbance wave-
history of malaria attack, fever, ownership, access to and use of Long- length of 450 nm using automated EIA plate reader. The cut-off value
Lasting Insecticidal Net (LLIN) (Roll Back Malaria Partnership, 2011; was calculated as the mean of the optical density (OD) of value of the
Roll Back Malaria and WHO, 2009). three negatives control plus 0.100. Samples with OD values greater
than cut-off value were considered as positive for specific antibody to
2.4. Determination of haemoglobin concentration Plasmodium species. The test does not distinguish between Plasmodium
species, nor IgG and IgM and between an acute and chronic infection.
Haemoglobin concentration was determined using HemoCue analy-
zer in the field (HemoCue Hb 301, Sweden). Anaemia was classified 2.6. Data processing and analysis
according to WHO’s guideline (INACG, 2002) using altitude and age
adjusted haemoglobin (Hb) values: non-anaemia (Hb ≥ 11.0 g/dL), The data were analyzed using stata version 12.0. In this study,
mild anaemia (10.0–10.9 g/dL), moderate (7.0–9.9 g/dL), severe anaemia status was the main outcome variable and independent
(< 7.0 g/dL) for children 2–5 years. For children 5–9 years of age variables included background characteristics (age, sex, place of
Hb ≥ 11.5 was considered as non-anaemic and mild anaemia; moder- residence, family size), LLIN indicators (ownership, previous night
ate and severe anaemia was defined as Hb 11.0–11.4 g/dL, 8.0–10.9 g/ use, and access). Ownership of LLIN was defined as the proportion of
dL, and Hb < 8.0 g/dL respectively (INACG, 2002; World Health sampled households with at least one LLIN. On the other hand, access to
Organization, 2011). LLIN was defined as 1) sufficient LLIN access-a situation in which at
least two nets were available for every two people in the household and
2.5. Malariometric indices 2) no access to LLIN means households who had some nets or no nets at
all (Roll Back Malaria Partnership, 2011; Roll Back Malaria and WHO,
2.5.1. Splenomegaly rate (SR) 2009). In addition, life time history of malaria attack, two weeks history
Spleen palpation was conducted by clinician at the ‘standing of fever, fever (axillary body temperature ≥37.5 °C), malariometric
position’ technique as suggested by WHO (World Health indices (parasitaemia, reactive antibody, and splenomegaly) was con-
Organization, 1968). For the determination of the degree of enlarged sidered as independent variables. Analyses were done segregated by
spleens, Hackett’s method of classification was used. Consequently, the study sites and with demographic factors like age and sex. One-way
size of enlarged spleen was graded as ‘0’ normal spleen (not palpable ANOVA was used to compare mean optical density by anaemia status.
even on deep inspiration); “1” spleen palpable below the costal margin; Logistic regression was used to assess association of some background

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factors with anaemia. In addition, the relationship between malario- 73), of the studied children had anaemia. In this community, 13.7%
metric indices and anaemia was explored using logistic regression. A (10/73) of the children had severe anaemia. A large proportion of
95% confidence interval and level of significance less than 0.05 were children in Kersa (24.2%, 12/50) and Dhera (24.0%, 23/95) also
used to declare statistically significant association. suffered from Anaemia. In contrast, the prevalence of anaemia was
very low in Shebe (5.0%, 4/80) and Metehara (6.0%, 5/84).
2.7. Ethical consideration
3.4. Demographic factors associated with anaemia
The study was reviewed and approved by Jimma University
Institutional Review Board (Ref. No. RPGC/112/2015) and the World Table 1 presents results of multivariate analyses of selected demo-
Health Organization Ethics Review Committee (Protocol ID: B40082, graphic characteristics associated with anaemia among children aged
approval date: 15/06/2015). In addition, the study was reviewed and 2–9 years old. Consequently, only age of the child and ownership of
approved by Oromia regional health bureau (Ref. No. BEFO/ LLIN significantly associated with anaemia. Anaemia was significantly
AHITQFTF050/83). Permission to undertake the study was obtained higher among children of 2–4 years (22.2%) and households without
at all levels. Parents were given detailed information about the purpose LLIN (34.0%). Accordingly, children aged 2–4 years old were 2.24
of the study, specimen collection procedures and possible risks/ times more likely to be anaemic compared to children in the age group
discomforts and benefits of participating in the study through consent of 7–9 years. Likewise, prevalence of anaemia was lower by 55.0%
process. Informed written consent was obtained from all parents/ among children living in households with at least one LLIN.
caretakers whose children participated in the study. In this case,
caretakers were mostly parents (either mother or father), and in few 3.5. Malariometric indices and anaemia
cases, sisters, brothers or other close relatives were presented as
caretakers. A child was included in the study only if the child the Table 2 presents malariometric indices by degree of anaemia.
caretakers both agreed. Despite parental consent, a child’s decision not Overall, malaria parasitaemia was found in 2.5% (19/763) of the cases
to give blood was respected. Children diagnosed with malaria para- (using RDT), and infection rate was 1.6% (12/763), and 1.2% (9/763)
sitaemia (using RDT) received anti-malarial treatment, according to the for P. falciparum and P. vivax respectively. Generally, detectable
national malaria treatment guideline. Parents’ whose children had mild parasitaemia and anaemia co-occurred in 0.9% (7/763) of the children.
and moderate anaemia were counseled on nutritional management of In other words, of the 132 children with anaemia, 5.3% (7/132) had
anaemia. Children with severe anaemia were referred directly to the detectable malaria parasitaemia. Only 3.6% (2/56) children with mild
nearest health facility for further evaluation and treatment. anaemia had detectable malaria parasitaemia. Malaria parasitaemia
was relatively prevalent among children with moderate anaemia, 9.1%
3. Results (5/55). However, none of the children with severe anaemia had
detectable malaria parasitaemia. P. falciparum more frequently co-
3.1. Demographic characteristics of the participants occurred with moderate anaemia; of the six P. falciparum infections
associated with anaemia, five were found among children with
Seven hundred sixty-three children participated in the study, moderate anaemia.
making an overall response rate of 73.1%. Haemoglobin analysis, The study also indicated that malaria reactive antibody and
spleen rate and examination of malaria parasitaemia was based on anaemia co-occurred in 3.1% (21/672) of the samples available for
763 samples. However, due to inadequate blood sample, malaria EIA EIA antibody test. The prevalence of anaemia was approximately equal
antibody test was done only for 672 samples. Males represent more among malaria EIA reactive (16.7%, 21/126) and non-reactive (88/
than half, 53.1% (405), of the participants, and the mean age was 546) children. The study found that as the severity of anaemia
5.2 ± 1.9 years. In terms of place of residence, 72.7% (555) were increased, the seropositive rate for malaria decreased. The prevalence
recruited from rural areas. of reactive malaria antibody was 20.4% (10/49), 19.0% (8/42) and
16.7% (3/18) among children with mild, moderate and severe anaemia,
3.2. Haemoglobin levels among children respectively. In terms of age, the prevalence of reactive malaria
antibody was lower among under five children (13.1%) compared to
The overall mean haemoglobin level of the children was 12.6 g/ children ≥five years old (22.1%) whereas anaemia was higher among
dL ± 1.7 (min = 3.3 g/dL, max = 16.3 g/dL). The mean haemoglobin under five children and lower among older children (data not shown).
level significantly varied by study sites (F test = 17.5, p = 0.001). With respect to relationship between splenomegaly and anaemia, of the
Fig. 2 shows the distribution of haemoglobin level by study sites. The children with enlarged spleen (n = 13), 61.5% (8/13) had anaemia.
lowest mean haemoglobin level was seen in Asebot (10.6 g/dL) which
was significantly lower compared to all other study sites (p = 0.001). 3.6. Association between malariometric indices and anaemia
On the other hand, highest mean haemoglobin level was recorded in
Tullu Bollo (13.4 g/dL) and it was significantly different as compared to Even though in multivariate analysis no significant association was
mean haemoglobin level from Asebot (p = 0.001), Kersa (p = 0.005), observed, bivariate analysis indicated that children infected with P.
Dhera (p = 0.004), and Metehara (p = 0.041). Altitude has a signifi- falciparum were 4.96 times more likely to be anaemic as compared to
cant effect on haemoglobin concentration; a unit increase in altitude (in children with no detectable falciparum (OR: 4.96, 95% CI: 1.57–15.63,
meter) was associated with 0.01 g/L increment of haemoglobin con- p = 0.006). On the contrary, of children with P. vivax infections, only 2
centrations (β = 0.01 g/L, 95% CI: 0.00–0.02, p = 0.001). were anaemic and infections with P. vivax did not show significant
association with anaemia. Moreover, no significant association was
3.3. Prevalence of anaemia among children observed between prolonged exposure to malaria (reactive immunity)
and anaemia, (p > 0.05). However, children with enlarged spleen
The overall prevalence of anaemia was 17.3% (132/763, 95% CI: were 14.93 times more likely to have anaemia as compared to children
14.6–19.9%). Mild, moderate and severe anaemia accounted for 7.3% with non-palpable spleen (AOR = 14.93, 95% CI: 3.57–62.40;
(56/763), 7.2% (55/763) and 2.8% (21/763) respectively. The pre- p = 0.001) (Table 3).
valence of anaemia was significantly different by study sites The mean haemoglobin concentration also did not vary significantly
(x2 = 107.75, p = 0.001). Fig. 3 shows the distribution of anaemia with malaria serostatus (p > 0.05). The mean haemoglobin level was
by study sites. Accordingly, in Asebot site, more than half, 56.1% (41/ 12.79 ± 1.43 g/dL and 12.62 ± 1.68 g/dL among the exposed (i.e.

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Fig. 2. Probability density function of Haemoglobin level by study sites, June 2016, Ethiopia.

reactive antibody) and the unexposed (non-reactive antibody), respec- malaria antibody test. Haemoglobin level was regressed against malaria
tively. Fig. 4 shows the distribution of haemoglobin level by reactive antibody optical density (OD) (Fig. 5) and the result indicated that the
malaria antibody. The distribution of haemoglobin level in both regression model explained none of the variability of haemoglobin level
reactive and non-reactive subjects approximately follow the same among children (R2 = 0.0%). Only few children with mild (10/56),
distribution, with slight skewed to left for subjects’ non-reactive to moderate (8/55) and severe (3/21) anaemia were found in reactive (OD

Fig. 3. Prevalence of anaemia by study sites, June 2016, Ethiopia.

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Table 1 Table 3
Selected background factors associated with anaemia, Ethiopia, June 2016. Association of malaria indices with anaemia among children 2–9 years old, Ethiopia.

Variables Anaemia AOR(95%CI) Malaria indices and related variables p-value AOR (95%IC)

No Yes Two weeks history of fever (Yes, Noa) 0.375 0.75 (0.39–1.42)
Fever (Yes, Noa) 0.087 0.13 (0.01–1.35)
Sex Male 338 (83.5) 67 (16.5) 0.92 (0.62–1.37) History of malaria (reported) (Yes, Noa) 0.309 0.77 (0.46–1.28)
Female 293 (81.8) 65 (18.2) 1 Splenomegaly (Yes, Noa) 0.001 14.93 (3.57–62.40)
Malaria parasitaemia (RDT) (Yes, No*) 0.462 5.22 (0.06–426.79)
Place of residence Rural 440 (79.3) 115 (20.7) 1.67 (0.79–3.52)
P. falciparum (Yes, Noa) 0.784 1.79 (0.03–115.12)
Urban 102 (93.6) 7 (6.4) 0.44 (0.14–1.36)
P. vivax (Yes, Noa) 0.539 0.31 (0.01–13.20)
semi-urban 89 (89.9) 10 (10.1) 1
Reactive malaria antibody (Yes, Noa) 0.252 0.68 (0.35–1.32)
Age of child 2–4 242 (77.8) 69 (22.2) 2.24
(1.33–3.77)* a
Reference category.
5–6 186 (83.4) 37 (16.6) 1.48 (0.84–2.63)
7–9 203 (88.6) 26 (11.4)
(mean OD = 0.414).
Family size 1–4 228 (86.0) 37 (14.0) 0.67 (0.40–1.09)
≥5 340 (79.1) 90 (20.9) 1

Ownership of LLIN Yes 535 (82.9) 110 (17.1) 0.45

3.8. Levels of anaemia and seropositive rate by study sites
(0.21–0.96)**
No 33 (66.0) 17 (34.0) 1 The pattern of anaemia and reactive malaria antibody was irregular.
Previous night Yes 401 (83.7) 78 (16.3) 0.88 (0.55–1.42) In Asebot and Kersa where overall anaemia was very high, reactive
LLIN use No 167 (77.3) 49 (22.7) 1 malaria antibody was extremely low. Conversely, in areas with high
Access to LLIN No 319 (79.6) 82 (20.4) 0.89 (0.55–1.46) reactive malaria antibody such as Goro and Goda Dhera, overall
Yes 249 (84.7) 45 (15.3) 1 anaemia was relatively low (Fig. 6).
Altitude above seas < 1500m 263 (84.0) 50 (16.0) 2.22 (0.89–5.52)
level 1500–2000 m 302 (79.9) 76 (20.1) 2.20 (0.88–5.46)
4. Discussion
> 2000 m 66 (91.7) 6 (8.3) 1

* Significant at 0.01. This study measured haemoglobin level and magnitude of anaemia
** Significant at 0.05. among children aged 2 − 9 years old in malaria endemic settings of
Ethiopia and explored its relationship with malariometric indices and
cut-off value > 0.149) region of malaria antibody. selected demographic factors. Haemoglobin concentration is the most
reliable indicator of anaemia at the population level (World Health
3.7. Intensity of malaria antibody and anaemia Organization, 2008). The mean haemoglobin level (12.6 g/dL ± 1.7)
obtained in the present study was somewhat higher as compared to
Strength of malaria antibody (i.e. as measured mean optical density) earlier finding in Ethiopia (Assefa et al., 2014). Of course, there was
did not significantly vary with degree of anaemia (P > 0.05). also a study that reported a similar level of haemoglobin concentration
Nevertheless, highest mean OD value was recorded among children from Ethiopia (Mesfin et al., 2015). Moreover, magnitude of anaemia
with mild anaemia (mean OD = 0.561) followed by moderate anaemia was low as compared to many earlier studies (Assefa et al., 2014;
(mean OD = 0.430), but it decreased as severity of anaemia increased. Ketema and Bacha, 2013; World Health Organization, 2011; Mesfin
Lowest mean OD value was noted for children with severe anaemia et al., 2015; Choge et al., 2014; Noland et al., 2014). Correspondingly,
(mean OD = 0.327), even compared to children without anaemia the prevalence of mild, moderate and severe anaemia was also low

Table 2
Malariometric indices and anaemia among children 2–9 years old, Ethiopia.

Malariometric indices and related variables Category Anaemia status Degree of anaemia

Non-anaemia Anaemia Mild anaemia Moderate anaemia Severe anaemia

Malaria Parasitaemia (RDT) Negative 619 (98.1) 125 (94.7) 54 (96.4) 50 (90.9) 21 (100)
Positive 12 (1.9) 7 (5.3) 2 (3.6) 5 (9.1) 0 (0)

Malaria Parasitaemia (Microscopy) Negative 620 (98.3) 125 (94.7) 54 (96.4) 50 (90.1) 21 (100.0)
Positive 11 (1.7) 7 (5.3) 2 (3.6) 5 (9.9) 0 (0.0)

P. falciparum Negative 625 (99.0) 126 (95.5) 55 (98.2) 50 (90.9) 21 (100)

Positive 6 (1.0) 6 (4.5) 1 (1.8) 5 (1.9) 0 (0)

P. vivax Negative 624 (98.9) 130 (98.5) 55 (98.2) 54 (98.2) 21 (100)

Positive 7 (1.1) 2 (1.5) 1 (1.8) 1 (1.8) 0 (0)

Spleen size Normal 626 (99.2) 124 (93.9) 52 (92.9) 53 (96.4) 19 (90.5)
Enlarged 5 (0.8) 8 (6.1) 4 (7.1) 2 (3.6) 2 (9.5)

Malaria antibody Negative 458 (81.3) 88 (80.7) 39 (79.6) 34 (81.0) 15 (83.3)

Positive 105 (18.7) 21 (19.3) 10 (20.4) 8 (19.0) 3 (16.7)

Reported history of malaria No 466 (82.0) 102 (18.0) 37 (68.5) 38 (73.1) 17 (81.0)
Yes 109 (85.8) 18 (14.2) 17 (31.5) 14 (26.9) 4 (19.0)

Fever No 373 (65.7) 195 34.3) 55 (98.2) 54 (98.2) 21 (100)

Yes 92 (72.4) 35 (27.6) 1 (1.8) 1 (1.8) 0 (0)

Two weeks history of fever No 466 (82.0) 102 (18.0) 44 (81.5) 45 (86.5 20 (95.2)
Yes 109 (85.8) 18 (14.2) 10 (18.5) 7 (13.5) 1 (4.8)

6
Z. Birhanu et al. Acta Tropica 173 (2017) 1–10

Fig. 4. Distribution of haemoglobin level among children 2–9 years old, by reactive malaria antibody status, Ethiopia (June 2016).

compared to the findings of previous studies (Central Statistical Agency

of Ethiopia, 2011; Assefa et al., 2014; Ketema and Bacha, 2013; Choge
et al., 2014; Noland et al., 2014; EHNRI, 2012). One recent study in
Ethiopia reported zero prevalence of severe anaemia among children
(Assefa et al., 2014). There was also a study that documented
comparable results on prevalence of severe anaemia (Deribew et al.,
2010). In contrast with previous studies which cited anaemia as a
severe public health problem in Ethiopia (Ethiopian Health and
Nutrition Research Institute, 2011; Central Statistical Agency of
Ethiopia, 2011), the present study found that a ‘mild’ public health
problem in the study community (World Health Organization, 2008).
This may indicate that the burden of childhood anaemia was declining
in Ethiopia. In fact, it is somewhat difficult to compare the results of
this study with the findings of many previous studies since there were
some methodological and measurement variations. Most studies on
anaemia among children were focusing on either pre-school or school
age children (WHO et al., 2001) which is somewhat different from the
Fig. 5. Regression of haemoglobin levels (g/dL) against malaria antibody optical density specific study population addressed in the present study (i.e. children
(OD) among children aged 2–9 years, in the study area.
2–9 years of old). Thus, these variations could account for the observed

Fig. 6. sualization of degree of anaemia and reactive malaria antibody by study sites, June 2016.

7
Z. Birhanu et al. Acta Tropica 173 (2017) 1–10

differences in the magnitude of anaemia. Perkins et al., 2011; Castro-Gomes et al., 2014; Imam, 2009). Some
Consistent with existing evidences, this study indicated that young- studies (Fendel et al., 2010; Gosling and Hsiang, 2013; Perkins et al.,
er children (pre-school children) were at increased risk of developing 2011; Castro-Gomes et al., 2014; Imam, 2009) documented that severe
anaemia (Mesfin et al., 2015; Noland et al., 2014; Menon and Yoon, malaria anaemia is common in settings with high malaria transmission.
2015). Global data have also shown that the risk and burden of anaemia However, the context of this study was characterized by reduced or low
is highest among pre-school children (American society of hematology, malaria transmission in which the impact of malaria would be insig-
2016) suggesting that anaemia prevention and control efforts need to nificant (Schellenberg et al., 2003; Menendez et al., 2000). Certainly, in
preferentially address most vulnerable age groups of children, espe- the context of reduced transmission of malaria, it is appropriate to
cially children under the age of five. Unlike in some earlier studies conduct further study on etiology of anaemia to generate better
(Central Statistical Agency of Ethiopia, 2011; Ketema and Bacha, 2013; evidence on the relative contributions of malaria to the overall burden
Menon and Yoon, 2015), demographic factors such as sex, place of of anaemia using sufficient sample sizes of malaria cases. Interestingly,
residence and family size did not show significant association with despite lack of association between anaemia and malaria, the overall
anaemia. Nevertheless, the magnitude and severity of anaemia vary prevalence of both indices is nearly the same (18.7% reactive antibody,
considerably by localities and altitude calling for designing and vs 17.3% anaemia). This conveys important messages to malaria and
implementing tailored and location specific interventions strategies anaemia prevention program. Some evidence suggests that iron supple-
that fit into the local burden of anaemia. mentation in malaria endemic regions may increase risk of severe
In malaria endemic settings, the prevalence of anaemia decreases malaria (Sazawal et al., 2006; Goheen et al., 2016; Consultation WHOS,
with age since children gradually build up their acquired immunity 2007), and efforts to integrate iron supplementation with malaria
against malaria and its outcome, anaemia (Centers for Disease Control control programs should be made with caution.
and Prevention, 2010). In line with this assumption, the present finding In this study, splenomegaly was the only malariometric indice that
has shown that younger children (2–4 years old) were more likely to be significantly associated with increased risk of anaemia. Some evidence
affected by anaemia. Since degree of cumulative exposure to malaria suggest that enlarged spleen may also filter normal red blood cells as
increased with age (i.e. as measured through reactive malaria anti- well as abnormal ones, which actually increases risk of anaemia
body), this repeated exposure might have helped older children to (Safeukui et al., 2015; Price et al., 2001; Del Portillo et al., 2012;
develop protective immunity against malaria and its consequence such Chen et al., 2016). Nevertheless, since the proportions of children with
as anaemia. In fact, this is not a plausible argument since a large enlarged spleen were so few in the study, the association of splenome-
proportion (80.7%) of children with anaemia was non-reactive to galy with anaemia maybe accepted as plausible or reasonable. Yet, this
malaria antibody test. This finding is in contrast with historical evidence could be useful as it suggests the need to carefully screen
evidence which widely cited that repeated exposure to malaria is one anaemia among children with enlarged spleen during routine child care
of the major risk factor for anaemia, especially in malaria endemic service provisions. Some earlier studies attempted to predict malaria
areas (Sowunmi et al., 2011; Ketema and Bacha, 2013; Safeukui et al., transmission levels and burden from haemoglobin level of the popula-
2015; Crawley, 2004; Kassebaum et al., 2014; McCuskee et al., 2014; tion and results were mixed (Korenromp et al., 2004; McCuskee et al.,
Selvam and Baskaran, 1996; Price et al., 2001; Miller et al., 2002; 2014; Savage et al., 2007; Senn et al., 2010; Muwonge et al., 2013;
Koukounari et al., 2008; Taylor et al., 2012). Probably, other causes of Philipose and Umashankar, 2016; World Health Organization, 2017). In
anaemia such as nutritional deficiencies, infections with intestinal the present study, even though spleen rate was strongly correlated with
parasites, feeding habits and availability of food might be largely anaemia, other indices of malaria, namely parasite rate and serostatus
contributed to anaemia in this setting. were not associated with anaemia. Thus, in the present settings,
In this study, P. vivax (detectable parasitaemia) infection was less haemoglobin levels are not useful marker for estimating malaria
likely to be associated with anaemia which is less congruent with transmission.
existing evidences (Douglas et al., 2012; Ketema and Bacha, 2013). In this study, ownership of LLIN had a significant positive effect on
Evidence has shown that repeated exposure to the same strain of P. children’s haemoglobin level: owning at least one LLIN significantly
vivax causes little hematological disturbances (Boyd and Kitchen, 1936) reduced anaemia among children. Earlier evidences also documented
whereas repeated exposure to different strains of P. vivax usually causes that ownership and use of LLIN improved anaemia-related outcomes in
more prominent hematological effects that lead to anaemia (Collins young children (McCuskee et al., 2014; Menon and Yoon, 2015;
et al., 2003). Specially, if individuals are repeatedly exposed to Carneiro et al., 2006; Casals-Pascual et al., 2006; Kuile et al., 2003;
different and/or homologous strains of P. vivax before haemoglobin Deribew et al., 2012; Smithson et al., 2015). However, in this study,
concentration has returned to normal state, even with the infection LLIN use did not have association with anaemia. In fact, there was a
could have significant hematologic effect (Douglas et al., 2012; Selvam study which reported similar findings (WHO, 2016). It is important to
and Baskaran, 1996). Possibly, the lack of association between infec- explore in depth how the presence of LLIN in the household contributes
tions with P. vivax and anaemia, in the present study suggests children to reduction of anaemia since utilization did not have impact on
might have been infected with the same strain of P. vivax with adequate anaemia. Yet, malaria prevention programs are beneficial to anaemia
recovery time for haemoglobin level. On the other hand, it may also prevention among children.
show that the P. vivax strain being circulating in the study community is
less virulent to cause significant hematologic insult that led to anaemia. 5. Strength and limitations of the study
Further studies are required to better understand the hematologic
impacts of infections with homologous and heterologous strains of P. This study assessed the association between exposure to malaria and
vivax, particularly in areas with reduced transmissions of malaria. Even haemoglobin level of children, using combination of classical and
though the association was insignificant, this demonstrated that immunological technique through community based approach invol-
children were more likely to develop moderate anaemia during ving multiple sites with diverse eco-epidemiologic areas in Ethiopia.
infections with P. falciparum which is supported by previous studies Thus, we anticipate that the findings of the study are generalized to
(Price et al., 2001; Miller et al., 2002). settings with different malaria transmission spectra in Ethiopia and
In this study, neither P. vivax nor P. falciparum was associated with other similar malaria endemic settings in tropical areas. Furthermore,
severe anaemia. None of the children with severe anaemia had the study is the first of its kind in Ethiopia in assessing the association
detectable malaria parasitaemia, which is against existing evidences between exposures to malaria (as measured using serological marker)
(Ketema and Bacha, 2013; Kassebaum et al., 2014; McCuskee et al., and anaemia. Thus, it can serve as first-hand information on the
2014; Taylor et al., 2012; Fendel et al., 2010; Gosling and Hsiang, 2013; relationship between exposure to malaria and anaemia on among

8
Z. Birhanu et al. Acta Tropica 173 (2017) 1–10

children in Ethiopia. However, our study has some limitations. We did American society of hematology, 2016. New Report Illustrates Persistent Global Burden of
Anemia Among High-Risk Populations Including Young Children and Women
not collect data on nutritional status and other potential risk factors for [Internet]. [cited 2016 Aug 11]. Available from: http://www.hematology.org/
anaemia. Moreover, EIA test was not done for some children due to Newsroom/Press-Releases/2013/1326.aspx.
inadequate blood sample. This might have affected the estimates. In Assefa, S., Mossie, A., Hamza, L., 2014. Prevalence and severity of anemia among school
children in Jimma Town, Southwest Ethiopia. BMC Hematol. 14, 3.
addition, we relied on existing lists for selection of children which Barreiro, P., Tiziano, G., Fano, H., Yohannes, T., Gosa, A., Reyes, F., et al., 2017. Malaria
might be introduced selection bias. and severe anemia over eight years at Gambo Rural Hospital, Southern Ethiopia.
Pathog. Glob. Health 1–18 (ja).
Boyd, M.F., Kitchen, S.F., 1936. On the efficiency of the homologous properties of
6. Conclusions acquired immunity to plasmodium vivax1. Am. J. Trop. Med. Hyg. s1–16 (July (4)),
447–457.
Despite these limitations, the following conclusions can be made Brooker, S., Akhwale, W., Pullan, R., Estambale, B., Clarke, S.E., Snow, R.W., et al., 2007.
Epidemiology of plasmodium-helminth co-infection in africa: populations at risk,
from the findings of this study. Compared to the findings of previous
potential impact on anemia, and prospects for combining control. Am. J. Trop. Med.
studies, the magnitude and degree of anaemia was somewhat low, Hyg. 77 (December (6_Suppl.)), 88–98.
making anaemia a mild public health in the study community. This Carneiro, I.A., Smith, T., Lusingu, J.P.A., Malima, R., Utzinger, J., Drakeley, C.J., 2006.
study revealed that infection with detectable parasitaemia and malaria Modeling the relationship between the population prevalence of Plasmodium
falciparum malaria and anemia. Am. J. Trop. Med. Hyg. 75 (August (2 Suppl.)),
serostatus did not have significant effect on haemoglobin levels of 82–89.
children. Thus, malaria attributable anaemia was less likely in present Casals-Pascual, C., Kai, O., Cheung, J.O.P., Williams, S., Lowe, B., Nyanoti, M., et al.,
context; instead other risk factors for anaemia might have played more 2006. Suppression of erythropoiesis in malarial anemia is associated with hemozoin
in vitro and in vivo. Blood 108 (October (8)), 2569–2577.
prominent roles. This suggests that the use of haemoglobin concentra- Castro-Gomes, T., Mourão, L.C., Melo, G.C., Monteiro, W.M., Lacerda, M.V.G., Braga,
tion as a useful metric of malaria burden and transmission is not É.M., 2014. Potential immune mechanisms associated with anemia in Plasmodium
worthwhile in low transmission settings. Thus, malaria prevention vivax malaria: a puzzling question. Infect. Immun. 82 (October (10)), 3990–4000.
Centers for Disease Control and Prevention, 2010. Human Factors and Malaria [Internet].
program has little benefit to anaemia prevention efforts among children [cited 2017 Mar 9]. Available from: https://www.cdc.gov/malaria/about/biology/
aged 2–9 years even though focusing on P. falciparum might help to human_factors.html.
reduce moderate anaemia. In fact, ownership of LLINs plays some Central Statistical Agency of Ethiopia, 2011. Ethiopian Demographic and Health Survey
[Internet]. Central Statistical Agency of Ethiopia, Addis Ababa [cited 2016 Dec 8].
positive roles in the prevention of anaemia among children and could
Available from: https://www.unicef.org/ethiopia/ET_2011_EDHS.pdf.
be emphasized in malaria prevention program Given that anaemia due Chen, I., Gosling, R., Clarke, S.E., Hamainza, B., Killeen, G., Magill, A., et al., 2016.
to malaria was very minimal in this study, interventions aimed at Asymptomatic Malaria: a chronic and debilitating infection that should be treated.
PLoS Med. 13 (1), e1001942. http://dx.doi.org/10.1371/journal.pmed.1001942.
anaemia prevention and management must be carefully designed
Choge, J.K., Magak, N.G., Akhwale, W., Koech, J., Ngeiywa, M.M., Oyoo-Okoth, E., et al.,
considering ground level risk factors and the etiology of anaemia. 2014. Symptomatic malaria diagnosis overestimate malaria prevalence, but
Therefore, in settings with low malaria transmission, it is imperative to underestimate anaemia burdens in children: results of a follow up study in Kenya.
review the historical evidence and quantify the relative contribution of BMC Public Health 14, 332.
Collins, W.E., Jeffery, G.M., Roberts, J.M., 2003. A retrospective examination of anemia
malaria to anaemia for development of effective and evidence based during infection of humans with Plasmodium vivax. Am. J. Trop. Med. Hyg. 68 (April
anaemia prevention and control strategies. (4)), 410–412.
Consultation WHOS on behalf of the participants to the, 2007. Conclusions and
recommendations of the WHO consultation on prevention and control of iron
Authors’ contributions deficiency in infants and young children in malaria-endemic areas. Food Nutr. Bull.
28 (December (4 suppl4)), S621–S627.
ZB and DY conceived the study and were involved in the design and Crawley, J., 2004. Reducing the burden of anemia in infants and young children in
malaria-endemic countries of Africa: from evidence to action. Am. J. Trop. Med. Hyg.
conduct of the study. DY and YY were involved in the design and 71 (August (2 Suppl)), 25–34.
conduct of the study. DE, DF, EK, SK and KG involved in the design, Del Portillo, H.A., Ferrer, M., Brugat, T., Martin-Jaular, L., Langhorne, J., Lacerda,
conduct of the study and sample analysis. ZB drafted the manuscript M.V.G., 2012. The role of the spleen in malaria. Cell. Microbiol. 14 (March (3)),
343–355.
while DY, YY, DE, DF, EK, SK and KG critically reviewed it for Deribew, A., Alemseged, F., Birhanu, Z., Sena, L., Tegegn, A., Zeynudin, A., et al., 2010.
intellectual content. All authors read and approved the final version Effect of training on the use of long-lasting insecticide-treated bed nets on the burden
of the manuscript. of malaria among vulnerable groups, south-west Ethiopia: baseline results of a cluster
randomized trial. Malar. J. 9, 121.
Deribew, A., Birhanu, Z., Sena, L., Dejene, T., Reda, A.A., Sudhakar, M., et al., 2012. The
Acknowledgements effect of household heads training on long-lasting insecticide-treated bed nets
utilization: a cluster randomized controlled trial in Ethiopia. Malar. J. 11, 99.
This study was supported by the World Health Organization Special Deribew, K., Tekeste, Z., Petros, B., 2013. Urinary schistosomiasis and malaria associated
anemia in Ethiopia. Asian Pac. J. Trop. Biomed. 3 (April (4)), 307–310.
Programme for Research and Training in Tropical Diseases (TDR) Douglas, N.M., Anstey, N.M., Buffet, P.A., Poespoprodjo, J.R., Yeo, T.W., White, N.J.,
(Grant Numbers: B40082). We express our heartfelt thanks to WHO/ et al., 2012. The anaemia of Plasmodium vivax malaria. Malar. J. 27 (April (11)),
TDR for the financial assistance to carry out this study. WHO/TDR 135.
Ethiopian Health and Nutrition Research Institute (EHNRI), 2012. Manual for the
reviewed the study protocol and gave ethical clearance for the study but Laboratory Diagnosis of Malaria [Internet]. Ministry of Health, Addis Ababa [cited
did not have a role in the design, sample collection, analysis, report 2017 Jan 15]. Available from: https://www.scribd.com/document/240276896/
writing and decision on manuscript submission. The authors also Manual-for-the-Laboratory-Diagnosis-of-Malaria#.
Erhabor, O., Mohammad, H.J., Onuigue, F.U., Abdulrahaman, Y., Ezimah, A.C., 2014.
acknowledge Oromia Regional Health Bureau, zonal and district level Anaemia and Thrombocytopenia among Malaria Parasitized Children in Sokoto,
health managers, health centers and health post staffs for their North Western Nigeria. Nigeria J. Hematol. Transfus. 2 (2).
cooperation and support during the field work. Enzyme immunoassay Ethiopian Health and Nutrition Research Institute, 2011. Ethiopia National Malaria
Indicator Survey [Internet]. Ethiopian Health and Nutrition Research Institute, Addis
was performed at Tropical and Infectious Disease Research Center Ababa [cited 2016 Dec 8]. Available from: https://www.unicef.org/ethiopia/ET_MIS_
(TIDRC), Jimma University and the authors extend their appreciation to 2011_Report.pdf.
the center and its staffs. The authors also express sincere acknowl- Fendel, R., Brandts, C., Rudat, A., Kreidenweiss, A., Steur, C., Appelmann, I., et al., 2010.
Hemolysis is associated with low reticulocyte production index and predicts blood
edgement to the study participants.
transfusion in severe malarial anemia. PLoS One 5 (April (4)), e10038.
Gari, T., Loha, E., Deressa, W., Solomon, T., Atsbeha, H., Assegid, M., et al., 2017.
References Anaemia among children in a drought affected community in south-central Ethiopia.
PLoS One 12 (March (3)), e0170898.
Goheen, M.M., Wegmüller, R., Bah, A., Darboe, B., Danso, E., Affara, M., et al., 2016.
Alemu, A., Shiferaw, Y., Ambachew, A., Hamid, H., 2012. Malaria helminth co-infections Anemia offers stronger protection than sickle cell trait against the erythrocytic stage
and their contribution for aneamia in febrile patients attending Azzezo health center, of falciparum malaria and this protection is reversed by iron supplementation.
Gondar, Northwest Ethiopia: a cross sectional study. Asian Pac. J. Trop. Med. 5 EBioMedicine 1 (December (14)), 123–130.
(October (10)), 803–809. Gosling, R.D., Hsiang, M.S., 2013. Malaria and severe anemia: thinking beyond

9
Z. Birhanu et al. Acta Tropica 173 (2017) 1–10

plasmodium falciparum. PLoS Med. 10 (December (12)), e1001576. Rogerson, S., 2017. What is the relationship between haptoglobin, malaria, and anaemia?
Gutema, B., Adissu, W., Asress, Y., Gedefaw, L., 2014. Anemia and associated factors PLoS Med. [Internet] 3 (5) [cited 2017 May 3] Available from: http://www.ncbi.nlm.
among school-age children in Filtu Town, Somali region, Southeast Ethiopia. BMC nih.gov/pmc/articles/PMC1450019/.
Hematol. 14, 13. Roll Back Malaria Partnership, 2011. In: Changes to Guidance for Vector Control
INACG, 2002. The International Nutritional Anaemia Consultative Group (INACG); Indicators: Meeting Report of the 17th MERG Meeting, 15–17.6 [Internet]. New York,
INACG Steering Committee [Internet]. [cited 2016 Oct 23]. Available from: http:// USA. [cited 2015 Mar 21]. Available from: http://www.rollbackmalaria.org/
pdf.usaid.gov/pdf_docs/Pnacq927.pdf. partnership/wg/wg_monitoring/docs/17merg_meeting_report.pdf.
Imam, T.S., 2009. Anaemia and malaria in children attending two sellected paediatric Roll Back Malaria, WHO, 2009. Guidelines for Core Population-based Indicators: RBM
clinics in Kano Metropolis, Northern Nigeria. Int. J. Biomed. Healthcare Sci. Technical Working Paper [Internet]. Roll Back Malaria. [cited 2015 Oct 3]. Available
[Internet] 5 (3) [cited 2017 Mar 9] Available from: https://www.researchgate.net/ from: http://www.rollbackmalaria.org/partnership/wg/wg_monitoring/docs/
publication/280719432_Anaemia_and_Malaria_in_Children_attending_two_Sellected_ GuidelinesForCorePopulationFINAL9-20_Malaria.pdf.
Paediatric_Clinics_in_Kano_Metropolis_Northern_Nigeria. Safeukui, I., Gomez, N.D., Adelani, A.A., Burte, F., Afolabi, N.K., Akondy, R., et al., 2015.
Jamal, M., Hameed, A., Imtiaz, F., 2017. Burden of anemia in malarial parasite infection. Malaria induces anemia through CD8+ T cell-dependent parasite clearance and
J. Infect. Dis. Ther. [Internet] [cited 2017 May 3]; Available from: https://www. erythrocyte removal in the spleen. mBio 6 (January (1)).
esciencecentral.org/journals/burden-of-anemia-in-malarial-parasite-infection-2332- Satpathy, S.K., Mohanty, N., Nanda, P., Samal, G., 2004. Severe falciparum malaria.
0877-1000228. php?aid=59224. Indian J. Pediatr. 71 (February (2)), 133–135.
Kassebaum, N.J., Jasrasaria, R., Naghavi, M., Wulf, S.K., Johns, N., Lozano, R., et al., Savage, E., Msyamboza, K., Gies, S., D’Alessandro, U., Brabin, B., 2007. Maternal anaemia
2014. A systematic analysis of global anemia burden from 1990 to 2010. Blood 123 as an indicator for monitoring malaria control in pregnancy in sub-Saharan Africa.
(January (5)), 615–624. BJOG Int. J. Obstet. Gynaecol. 114 (October (10)), 1222–1231.
Kateera, F., Ingabire, C.M., Hakizimana, E., Kalinda, P., Mens, P.F., Grobusch, M.P., et al., Sazawal, S., Black, R.E., Ramsan, M., Chwaya, H.M., Stoltzfus, R.J., Dutta, A., et al., 2006.
2015. Malaria, anaemia and under-nutrition: three frequently co-existing conditions Effects of routine prophylactic supplementation with iron and folic acid on admission
among preschool children in rural Rwanda. Malar. J. 14, 440. to hospital and mortality in preschool children in a high malaria transmission setting:
Ketema, T., Bacha, K., 2013. Plasmodium vivax associated severe malaria complications community-based, randomised, placebo-controlled trial. Lancet Lond. Engl. 367
among children in some malaria endemic areas of Ethiopia. BMC Public Health 13, (January (9505)), 133–143.
637. Schellenberg, D., Schellenberg, J.R.M.A., Mushi, A., de Savigny, D., Mgalula, L., Mbuya,
Korenromp, E.L., Armstrong-Schellenberg, J.R.M., Williams, B.G., Nahlen, B.L., Snow, C., et al., 2003. The silent burden of anaemia in Tanzanian children: a community-
R.W., 2004. Impact of malaria control on childhood anaemia in Africa – a based study. Bull. World Health Organ. 81 (8), 581–590.
quantitative review. Trop. Med. Int. Health: TM IH 9 (October (10)), 1050–1065. Selvam, R., Baskaran, G., 1996. Hematological impairments in recurrent plasmodium
Koukounari, A., Estambale, B.B.A., Kiambo Njagi, J., Cundill, B., Ajanga, A., Crudder, C., vivax infected patients. Jpn. J. Med. Sci. Biol. 49 (4), 151–165.
et al., 2008. Relationships between anaemia and parasitic infections in Kenyan Senn, N., Maraga, S., Sie, A., Rogerson, S.J., Reeder, J.C., Siba, P., et al., 2010. Population
schoolchildren: a Bayesian hierarchical modelling approach. Int. J. Parasitol. 38 hemoglobin mean and anemia prevalence in Papua New Guinea: new metrics for
(December (14–4)), 1663–1671. defining malaria endemicity? PLoS One 5 (February (2)), e9375.
Kuile, F.O.T., Terlouw, D.J., Phillips-Howard, P.A., Hawley, W.A., Friedman, J.F., Smithson, P., Florey, L., Salgado, S.R., Hershey, C.L., Masanja, H., Bhattarai, A., et al.,
Kolczak, M.S., et al., 2003. Impact of permethrin-treated bed nets on malaria and all- 2015. Impact of malaria control on mortality and anemia among tanzanian children
cause morbidity in young children in an area of intense perennial malaria less than five years of age, 1999–2010. PLoS One 10 (November (11)), e0141112.
transmission in western Kenya: cross-sectional survey. Am. J. Trop. Med. Hyg. 68 Sowunmi, A., Okuboyejo, T.M., Gbotosho, G.O., Happi, C.T., 2011. Risk factors for
(April (4 suppl.)), 100–107. Plasmodium falciparum hyperparasitaemia in malarious children. BMC Infect. Dis.
Magalhães, R.J.S., Clements, A.C.A., 2011. Mapping the risk of anaemia in preschool-age 11, 268.
children: the contribution of malnutrition, malaria, and helminth infections in West Sumbele, I.U.N., Sama, S.O., Kimbi, H.K., Taiwe, GS.Malaria, 2016. Moderate to severe
Africa. PLoS Med. 8 (June (6)), e1000438. anaemia, and malarial anaemia in children at presentation to hospital in the mount
Malaria EIA Ab Assay, Clinical Diagnostics, Bio-Rad [Internet]. [cited 2016 Nov 8]. Cameroon area: a cross-sectional study. Anemia 2016 (November), e5725634.
Available from: http://www.bio-rad.com/en-et/category/malaria. Taylor, S.M., Parobek, C.M., Fairhurst, R.M., 2012. Haemoglobinopathies and the clinical
McCuskee, S., Brickley, E.B., Wood, A., Mossialos, E., 2014. Malaria and macronutrient epidemiology of malaria: a systematic review and meta-analysis. Lancet Infect. Dis.
deficiency as correlates of anemia in young children: a systematic review of 12 (June (6)), 457–468.
observational studies. Ann. Glob. Health 80 (November (6)), 458–465. WHO, UNICEF, UNU, 2001. Iron Deficiency Anaemia: Assessment, Prevention, and
Menendez, C., Fleming, A.F., Alonso, P.L., 2000. Malaria-related anaemia. Parasitol. Control. A Guide for Programme Managers [Internet]. World Health Organization
Today Pers. Ed. 16 (November (11)), 469–476. [cited 2016 Oct 22]. Available from: http://www.who.int/nutrition/publications/
Menon, M.P., Yoon, S.S., 2015. Prevalence and factors associated with anemia among en/ida_assessment_prevention_control.pdf?ua=1.
children under 5 years of Age—Uganda, 2009. Am. J. Trop. Med. Hyg. 93 (September World Health Organization, 1968. Manual of Epidemiology and Epidemiological Services
(3)), 521–526. in Malaria Programmes [Internet]. World Health Organization [cited 2016 Dec 12].
Mesfin, F., Berhane, Y., Worku, A., 2015. Anemia among primary school children in Available from: http://apps.who.int/iris/bitstream/10665/40401/1/924154015X.
eastern Ethiopia. PLoS ONE [Internet] 10 (April (4)) [cited 2016 Nov 2]. Available pdf.
from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4406736/. World Health Organization, 1988. Malaria diagnosis: memorandum from a WHO
Miller, L.H., Baruch, D.I., Marsh, K., Doumbo, O.K., 2002. The pathogenic basis of meeting. Bull. World Health Organ. 66 (5), 575–594.
malaria. Nature 415 (February (6872)), 673–679. World Health Organization, 2008. Global Data Base on Anaemia [Internet]. World Health
Ministry of Health [Ethiopia], 2014. National Malaria Strategic Plan 2014–2020. Ministry Organization [cited 2016 Oct 22]. Available from: http://apps.who.int/iris/
of Health. bitstream/10665/43894/1/9789241596657_eng.pdf.
Muwonge, H., Kikomeko, S., Sembajjwe, L.F., Seguya, A., Namugwanya, C., 2013. How World Health Organization, 2010. Basic Malaria Microscopy: Part I Learners Guide
reliable are hematological parameters in predicting uncomplicated plasmodium [Internet], 2nd ed. World Health Organization, Geneva, Switzerland [cited 2016 Dec
falciparum malaria in an endemic region? Int. Sch. Res. Not. 2013 (June), e673798. 2]. Available from: http://apps.who.int/iris/bitstream/10665/44208/1/
Newton, C.R.J.C., Warn, P.A., Winstanley, P.A., Peshu, N., Snow, R.W., Pasvol, G., et al., 9789241547826_eng.pdf.
1997. Severe anaemia in children living in a malaria endemic area of Kenya. Trop. World Health Organization, 2011. Haemoglobin Concentrations for the Diagnosis of
Med. Int. Health 2 (February (2)), 165–178. Anaemia and Assessment of Severity [Internet]. [cited 2016 Oct 23]. Available from:
Noland, G.S., Graves, P.M., Sallau, A., Eigege, A., Emukah, E., Patterson, A.E., et al., 2014. http://www.who.int/vmnis/indicators/haemoglobin/en/.
Malaria prevalence, anemia and baseline intervention coverage prior to mass net World Health Organization, 2014. Global Nutrition Targets 2025: Anaemia Policy Brief
distributions in Abia and Plateau States, Nigeria. BMC Infect Dis. 26 (March (14)), [Internet]. World Health Organization [cited 2016 Aug 22]. Available from: http://
168. www.who.int/nutrition/topics/globaltargets_anaemia_policybrief.pdf.
Okell, L.C., Ghani, A.C., Lyons, E., Drakeley, C.J., 2009. Submicroscopic infection in World Health Organization, 2015a. The Global Prevalence of Anaemia in 2011 [Internet].
Plasmodium falciparum-endemic populations: a systematic review and meta-analysis. [cited 2017 May 4]. Available from: http://www.who.int/nutrition/publications/
J. Infect. Dis. 200 (November (10)), 1509–1517. micronutrients/global_prevalence_anaemia_2011/en/.
Okell, L.C., Bousema, T., Griffin, J.T., Ouédraogo, A.L., Ghani, A.C., Drakeley, C.J., 2012. World Health Organization, 2015b. Global Malaria Technical Strategy for Malaria
Factors determining the occurrence of submicroscopic malaria infections and their 2016–2030 [Internet]. [cited 2016 Aug 22]. Available from: http://apps.who.int/
relevance for control. Nat. Commun. 3, 1237. iris/bitstream/10665/148556/1/WHO_NMH_NHD_14.4_eng.pdf?ua=1.
Perkins, D.J., Were, T., Davenport, G.C., Kempaiah, P., Hittner, J.B., Ong’echa, J.M., World Health Organization, 2016. World Malaria Report [Internet]. Word Health
2011. Severe malarial anemia: innate immunity and pathogenesis. Int. J. Biol. Sci. 7 Organization, Geneva, Switzerland [cited 2016 Dec]. Available from: http://apps.
(November (9)), 1427–1442. who.int/iris/bitstream/10665/252038/1/9789241511711-eng.pdf?ua=1.
Philipose, C.S., Umashankar, T., 2016. The role of haematological parameters in World Health Organization, 2017. Anaemia Prevention and Control [Internet]. Anaemia
predicting malaria with special emphasis on neutrophil lymphocyte count ratio and Prevention and Control. [cited 2017 May 11]. Available from: http://www.who.int/
monocyte lymphocyte ratio: a single Institutional experience. Trop Parasitol. 6 (July medical_devices/initiatives/anaemia_control/en/.
(2)), 147. Yukich, J.O., Butts, J., Miles, M., Berhane, Y., Nahusenay, H., Malone, J.L., et al., 2014. A
Price, R.N., Simpson, J.A., Nosten, F., Luxemburger, C., Hkirjaroen, L., Kuile, F.T., et al., description of malaria sentinel surveillance: a case study in Oromia Regional State,
2001. Factors contributing to anemia after uncomplicated falciparum malaria. Am. J. Ethiopia. Malar. J. 13 (1), 1–13.
Trop. Med. Hyg. 65 (November (5)), 614–622.

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