Asian Pacific Journal of Tropical Medicine (2013)126-130
Document heading doi:
Prevalence of parasitemia and associated immunodeficiency among
HIV-malaria co-infected adult patients with highly active antiretroviral
Caroline E. Omoti1*, Chiedozie K. Ojide2, Patrick V. Lofor2, Emeka Eze3, Joy C Eze1
1Department of Haematology and Blood Transfusion, University of Benin Teaching Hospital, Benin City, Nigeria
2Department of Medical Microbiology, University of Benin Teaching Hospital, Benin City,Nigeria
3Department of Internal Medicine, University of Benin Teaching Hospital, Benin City, Nigeria
Contents lists available at ScienceDirect
Asian Pacific Journal of Tropical Medicine
ARTICLE INFO ABSTRACT
Received 24 August 2012
Received in revised form 31 October 2012
Accepted 5 December 2012
Available online 20 February 2013
*Corresponding author: Caroline Edijana Omoti, Department of Haematology and
Blood Transfusion, University of Benin Teaching Hospital, P.M.B 1111, Benin City,
Malaria and HIV/AIDS are two disease conditions that are
of great public health concern in sub-Saharan Africa. The
dual infection of HIV and malaria fuels the spread of both
diseases in sub-Saharan Africa. Malaria is responsible for
more than 1 million deaths worldwide every year with about
90% occurring in sub-Saharan Africa[1,2]. Also an estimated
28 million individuals are currently infected with HIV in
sub-Saharan Africa with almost 3 million deaths annually.
Expectedly, the overlap in the distribution of these two
disease conditions makes co-infection and interaction
inevitable even as morbidity and mortality increases.
In East and Southern Africa where HIV prevalence is near
30%, it is estimated that by the end of 2009, an estimated
3.3 million people would be living with HIV in Nigeria.
Nigeria is considered an area of stable Plasmodium
falciparum transmission. Her adult prevalence of HIV has
dropped from 5.8% in 2001 to 4.4% in 2005 and 21%-
28% of people living with HIV/AIDS are co-infected with
Previous studies have shown evidence of detrimental
relationship between the two disease conditions especially
in areas where they are co-endemic[6-9]. On one hand,
HIV infection has been reported to roughly double the risk
of malaria parasitemia and increase the frequency and
severity of clinical malaria[8,9]. On the other hand, clinical
malaria has been reported to facilitate the HIV replication
through incitement of cytokine production and immune-
cell activation[10-12]. The increased rate of HIV replication
Objective: To investigate the malaria parasitemia, CD4+ cell counts and some haematological
indices among HIV-malaria co-infected adult patients with highly active antiretroviral therapy
(HAART). Methods: A total of 342 adult HIV positive subjects were recruited at the consultant
outpatient HIV/AIDS clinic, University of Benin Teaching Hospital, Benin City, Nigeria between
June 2011 to November 2011. Blood samples were taken for malaria parasite count, CD4+ cell
count and other haematological counts. Results: Out of the 342 adult HIV positive subjects a
total of 254 patients (74.3%) were found to have malaria parasitemia. The incidence of malaria
parasitemia increased with advancing clinical stage of HIV infection and this was statistically
significant (P=0.002). There was no statistical significance when gender was compared with the
HIV-malaria status (P >0.05). Of the 254 co-infected patients, 134 (52.8%) had high parasitemia
significant association between CD4+ cell count and having significant parasitemia (P < 0.000 1).
About half (50.8%) of co-infected patients had CD4+ cell count ≤ 200/毺L, and majority (44.9%)
of this population also had significant parasitemia. Anaemia and thrombocytopenia were not
significantly associated with HIV-malaria co-infection (P > 0.05). Conclusions: The prevalence
of parasitemia is high among the HIV/AIDS infected patients.
9/L). Sixty patients were found to be hyperparasitemic (>2.5 parasites/L). There was a
Caroline E. Omoti et al./Asian Pacific Journal of Tropical Medicine (2013)126-130
leads to a lasting elevation in viral load, which in turn
hasten immune system decline and HIV disease progression
to AIDS and death or increase the risk of its transmission[13-
The potential risks of adverse drug interactions have critical
implications for effective management of co-infection. Such
interactions may result in treatment failures, especially
with sulfa-based drugs, or toxicity. While antiretroviral
protease inhibitors have demonstrated some antimalarial
effects, co-trimoxazole prophylaxis have been reported
to prevent malaria episodes in HIV-infected patients.
Therefore identification of the best methods for reducing the
incidence of malaria in adults with HIV infection and better
understanding of the relationship between HIV disease and
malaria could improve clinical and public health strategies.
The aim of this paper is to study the prevalence of malaria
parasitemia, CD4+ cell count and some haematological
indices among co-infected HIV/malaria individual on highly
active antiretroviral therapy (HAART) in an endemic region
for both disease.
2. Materials and methods
2.1. Participants and study design
The study group comprised 342 adult HIV subjects with
HAART attending the consultant outpatient HIV/AIDS clinic
in the University of Benin Teaching Hospital, Benin City,
Nigeria between June to November 2011. The hospital has
a 700 bed capacity and is a major referral and treatment
centre for the South-South geopolitical zone of Nigeria
where two major HIV/AIDS treatment units exist: the Federal
Government Sponsored Project and President Emergency
Plan for AIDS Relief, USA.
After informed consent was obtained, individuals attending
the clinic had detailed clinical history and examination,
and biodata documented. Each patient was assigned an
HIV stage according to the proposed WHO hierarchical
staging classification based on clinical and performance
criteria. For the purpose of this study they were grouped into
asymptomatic (stage 1 and 2) and symptomatic (stage 3 and
4) staging system of HIV/AIDS for Africa.
2.2. Laboratory methods
All participants had regular CD4+ cell count and complete
blood count measurements as part of routine workup to
assess the disease severity. The haematological counts
were determined by automation and CD4+ cell counts
were counted by flow cytometry. The HIV status of each
participant was already determined by screening their
plasma samples with two parallel rapid tests for detecting
HIV 栺 and 栻 antibodies (Abbott determine 1 & 2 and
Capillus HIV-1/HIV-2) following the manufacturers’
instructions. Samples concordantly positive or negative on
both assays were not tested further.
Thick and thin peripheral blood smears for malaria
parasites were prepared from capillary blood harvested
through finger prick on each subject, stained with 3%
Giemsa stain at pH 7.2 for 30 minutes and was examined
under 伊100 oil-immersion fields. Initially, the thin blood
film was screened by observation of 100 fields, each
representing about 200 erythrocytes, and the result was
then adjusted to 5 million erythrocytes per one microliter to
obtain the parasite count. In case of negative thin film, the
parasite: leukocyte ratio was measured on the observation of
1 000 leukocytes in the thick blood film, and the total white
blood cell count of each participant was used in calculating
the parasite count. Non-falciparum plasmodium species
were excluded. A slide was positive for malaria with any
level of parasitemia and significant parasite count at cut-off
and thrombocytopenia as platelet count less than 150伊10
L. All the participants investigated were already on HAART
therapy and appropriate antimalaria drug regimen was given
when diagnosis of malaria parasitemia was made. None of
the patient was on antimalaria prophylaxis.
The study was given ethical approval by the hospital. The
first-line ART treatment regimen consisted of stavudine,
lamivudine and either nevirapine or efavirenz. For
participants who later developed clinical or laboratory
evidence of ART treatment-failure or toxic effects, available
second-line agents were didanosine, zidovudine, tenofovir
9 parasites/L. Anemia was defined as Hb<10 g/dL
A total of 342 adult HIV infected patients were recruited
during the study period. This comprised of 90 males (26.3%)
and 252 females (73.7%) with a male-to-female ratio of
1:2.8. The overall mean age of the patients was (40依10)
years with a median of 39 years. The baseline demographic
characteristics of the subjects are captured in Table 1.
Majority of the patients (39.2%) were in the age bracket 31-
40 years with a female preponderance. A total of 214 (62.6%)
participants were asymptomatic, presenting in stage 1 and
2, while 128 (37.4%) symptomatic patients presented in
advanced stage disease (3 and 4). Of the 342 participants,
134 (39.2%) had a CD4+ cell count less than 200 cells/毺L,
42 (12.3%) were in 201-350 cells/毺L, 54 (15.8%) in 351-500
Caroline E. Omoti et al./Asian Pacific Journal of Tropical Medicine (2013)126-130
cells/毺L, and 112 (32.7%) were >500 cells/毺L.
Baseline information on study population.
Table 2 revealed that 254 subjects (74.3%) were found to
have malaria parasitemia. This gives a negative smear for
Plasmodium falciparum in 25.7% of the study patients. A
total of 214 (62.6) with HIV progression were symptomatic
(stage 3-4), out of which 147 (43.0%) had parasitemia. The
odds of having malaria parasitemia increased with advancing
clinical stage of HIV infection and this was statistically
significant (P=0.002, OR=2.32). The 254 co-infected HIV and
malaria infections had a mean age of 39.8依9.7. There was no
statistical significance when gender was compared with the
malaria status (P >0.05).
There was a significant association between CD4+ cell
count ≤200 cells/毺L and having significant parasitemia
(P < 0.0001) as shown in Table 3. About half (50.8%) of
co-infected patients had CD4+ cell count ≤200 cells/毺L
with majority (44.9%) of this population having significant
parasitemia. The odds of significant parasitemia increased
with falling CD4+ cell count. Individuals with CD4+ cell
count≤200 cells/毺L had higher risk of malaria parasitemia
compared to those with CD4+ cell count >200 cells/毺L.
The selected blood findings obtained from the co-
Clinical stage and gender prevalence of Plasmodium malaria infection in study population.
Relationship between CD4 cell count and significant parasitemia among co-infected patients (n = 254).
CD4+ cell count(/毺L)
Selected laboratory data of co-infected malaria and HIV patients during the study period (n =254).
Parasite density (伊109/L)
High (> 1.25)
infected patients are shown in table 4. The overall mean
parasite count was (2.37依0.20)伊10
had high parasitemia (>1.25伊10
count of (3.78依0.37)伊10
(Hb≤10g/dL) in HIV and malaria co-infected patients was
33.1% with a mean value of (9.15依0.11) g/dL while 21.7%
were thrombocytopenic (≤150伊10
9/L with a median of
9/L) with a mean parasite
9/L). The prevalence of anaemia
9/L. Of the 254 co-infected patients, 134 (52.8%)
9/L. Sixty patients were found to be
9/L) with a mean of (107.5依
9/L and a range of (33-150)伊10
Mounting evidence has revealed pathological interactions
between HIV and malaria in dually infected patients, but
the implications of the interplay have remained unclear.
Given the extensive overlap in the geographic distribution
of malaria and HIV infections, even modest interactions
between them would have enormous public health
importance. Recent evidence clearly supports presence
of the significant impact of each infection on the other
and by extension on the individuals[18,19]. Majority of the
HIV subjects were within the age bracket 31-40 years,
representing the economic age bracket and this has serious
socio-economic impact on the nation.
The CD4+ T cells are crucial in immune responses against
HIV virus and malaria parasite infection. Plasmodium
falciparum has been shown to stimulate HIV replication
through the production of cytokines (inteleukin 6 and tumor
necrosis factor alpha) by activated lymphocytes[11,12]. Our
study revealed that 39.2% of the subjects had low CD4 cell
Malaria infected (%)
Malaria uninfected (%)
Significant parasitemia (≥1.25伊109/L)
Non significant parasitemia (<1.25伊109/L)
Low (0.1-0.6) 0.37依0.03
Caroline E. Omoti et al./Asian Pacific Journal of Tropical Medicine (2013)126-130
count of 200 cells/毺L and below. This is not surprising as
the CD4+ T cells are targeted for destruction by HIV virus
in addition to the malaria parasite. Former reports mention
that HIV-1 patients with a CD4 count 200 cells/毺L have a
higher risk of parasitemia or clinical malaria compared to
those with a higher CD4 count[8,20]. Cellular mechanisms,
including CD4+ cells, responsible for protection against
malaria, built up over a period of time as a result of repeated
malaria attacks are destroyed in HIV infected individuals,
thus leading to increased parasitemia and clinical malaria.
Our study revealed that majority (74.3%) of HIV subjects
had malaria infection as opposed to only 25.7% who had no
malaria infection and this was statistically significant. Being
in a stable transmission area, the HIV positive individuals
are more likely to be exposed to malaria hence, the increase
prevalence of parasitemia cases seen in the study regardless
of whether symptoms were present or not. This collaborates
with other studies where there was an increase incidence,
prevalence and severity of malaria in HIV infected
individuals[18,21,22]. This is because HIV infection is known
to lead to a progressive cellular immunosuppression with a
resultant impairment in immune response to malaria.
Recent investigations suggest that HIV positive individuals
with reduced CD4 cell count may be more likely at risk to
present with malarial parasitemia. In our study, majority
of the subjects with low CD4+ cell count of 200 cells/毺L was
significantly associated with high parasitemia. A similar
study showed that individuals with CD4+cell counts less
than 200 cells/毺L had six times the odds of having malaria
compared with those with CD4+ cell counts of at least 500
cells/毺L. The odds of having clinical malaria at a routine
visit were reported to increase with advancing clinical stage
of HIV-1 infection. This increase was most evident for visits
of individuals in WHO stage 4, at which the odds were nine
times those in stage 1.
Based on WHO clinical stages, there were an increasing
number of patients with malaria infection with advancing
HIV disease, although the setback here was the difficulty
in separating stages 1 and 2. Majority of the co-infected
patients (50.8%) had significant high parasitemia with
60 patients having hyperparasitemic counts (>2.5伊10
parasite count); though we did not record any form of death
during the study period. This may be because those with a
high degree of acquired immunity may be able to sustain
sufficient antitoxic immunity to avoid severe disease despite
HIV-associated immunosuppression. Hospital-based
studies in Zambia and Burundi found increased malaria
case fatality ratios in patients with HIV compared with
HIV-seronegative individuals, but the small sample sizes
did not allow firm conclusions to be drawn[25,26]. A study in
rural Kwazulu-Natal, an area of unstable malaria reported
that HIV-infected children were more likely to experience
severe disease, coma and death. However, the high
parasite densities found in our study is in contrast to the low
parasite densities reported in an urban cohort population in
Uganda. Investigators have speculated that because HIV
infection increases parasitaemia and reduces the response
to therapy, it will increase the reservoir of infection in the
human population and hence increase transmission[21,29].
In all, they did not take into account the wide variation
in immunosuppression found at different stages of HIV-1
Haematological abnormalities are considered a hallmark of
malaria and reported to be most pronounced in plasmodium
falciparum infection. Anaemia is said to be a common
feature of malaria and HIV independently. This study
however, could not establish this assertion as majority
(66.9%) of the coinfected patients had haemoglobin level
> 10 g/dL as against 52.8% reported among HIV-positive
population and characteristics of anaemia of chronic disease
in a Nigerian study[31,32]. The mean value of (9.15依0.11) g/
dL recorded in our study is similar to 9.17依1.67 recorded for
parasitized HIV infected in another part of the country.
The pathogenesis of anaemia in plasmodial parasitized
patients is complex and multifactorial. They are thought to
result from haemolysis of parasitized red cells, exacerbated
removal of parasitized red cells, depressed and ineffective
erythropoiesis. Similarly, thrombocytopenia has been
reported as a classical feature of malaria and low platelet
count is usually seen in 72% of patients with uncomplicated
malaria. The platelet count of most individuals in this
study was within normal range. Again, this could be because
all the co infected individuals were already on the HAART
therapy. In-vitro studies have shown that some components
of the human immune response to Plasmodium falciparum
are modified by HIV-1 but that others are unaffected[10,36].
In conclusion, our findings indicate that there is an
increased prevalence of malaria parasitemia among HIV
infected individuals in an endemic region. With the
HAART therapy already instituted in Nigeria, the next step
presumably is effective prevention and interventions in form
of regular malaria prophylaxis as this is known to reduce
the risk of malaria in HIV infected patients especially in sub
Saharan areas where coinfection is common.
Conflict of interest statement
We declare that we have no conflict of interest.
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