Clinical Presentation, Haematological Indices and Management of
Children with Severe and Uncomplicated Malaria in Douala, Cameroon
J.B. Pankoui Mfonkeu,
H. Fotso Kuate,
P.H. Amvam Zollo
This study carried out from January to June 2007, was
undertaken to describe the clinical presentation of childhood malaria
in Douala, a meso-endemic area as far as malaria transmission is concerned.
One hundred and seventy eight children were enrolled after informed consent
of their parents. The sample characteristics were recorded and clinical
as well as preliminary laboratory investigations were performed. Thirty
eight children coming for vaccination and counselling was targeted to
serve as control. According to the results obtained, cerebral malaria
(CM) seems to be associated with young age, whilst Malaria anaemia (MA)
was predominant among older children. Hyperpyrexia and hyperparasitaemia
were high among CM patients and 11.1% of them died, however, no neurological
squeal was noticed immediately after discharge on those who survived.
Haemoglobin and glycaemia were low on MA and CM patients; these groups
had low percentage in bed nets utilization as well. These results suggest
that the clinical presentation of the disease differ with the geographic
location and malaria disease features varies according to the severity.
Such studies could contribute to the management of the disease.
to cite this article:
J.B. Pankoui Mfonkeu, I. Gouado, H. Fotso Kuate, O. Zambou, G. Grau, V. Combes and P.H. Amvam Zollo, 2008. Clinical Presentation, Haematological Indices and Management of
Children with Severe and Uncomplicated Malaria in Douala, Cameroon. Pakistan Journal of Biological Sciences, 11: 2401-2406.
Because its roots lie deep within human communities, malaria is a unique
disease. It remains a major threat to human health, despite considerable
national and international control efforts. Malaria annually causes at
least one million deaths, most of which occur in African children. Continued
progress in understanding this scourge is required (Snow et al.,
2004). Even though several studies on childhood malaria have been undertaken
in sub-Saharan Africa (Modiano et al., 1998; Biemba et al.,
2000; Idro et al., 2006; Guiyedi et al., 2007), the fact
is that its presentation varies with the setting, showing that there is
still a remarkable shortage of clinical description of the disease in
different endemic regions, particularly as far as the severity is concerned.
Severe malaria anaemia and cerebral malaria are considered among the major
clinical manifestations in severe childhood malaria. Their pathogenesis
are multi-factorial and are not fully understood; there is then the need
to address their complex aetiology (Mockenhaupt et al., 2004).
The disease pattern and the relative contribution of individual symptoms
to poor prognosis and mortality differ with endemicity, geographic location,
access to health services and age, among other factors. As severe malaria
results largely from late recognition and subsequently late intervention,
clinical research is needed on how to improve or accelerate the recognition
of severe malaria, how to accelerate referral and how to ensure that adequate
intervention is taken as early as possible (Mishra et al., 2006).
The clinical spectrum of severe malaria and it epidemiology were described
in different settings in Cameroon (Chiabi et al., 2004; Akenji
et al., 2005).
The results of a study on childhood malaria are reported in the most
populous city of Cameroon: Douala town. It was taken up in order to describe
the clinical spectrum and haematological characteristics, as well as to
understand the trend in pattern of morbidity of the disease in our setting,
particularly to look for variations in different disease severity groups:
Uncomplicated Malaria (UCM), Malaria Anaemia (MA), Cerebral Malaria (CM)
and the combine symptoms of MA and CM. We cannot assume that lessons learnt
in some observational studies in other part of Africa will automatically
apply to a different epidemiological, genetic, cultural and healthcare
MATERIALS AND METHODS
Study area: Malaria continues to be the major cause of morbidity
and mortality in Cameroon. The overall level of the disease is mesoendemic.
Douala is the most populous city, situated near the Atlantic Ocean, in
the south-western part of the country. The major epidemiological feature
of malaria in this area is it perennial transmission throughout the year.
This study took place from January to June 2007 at 4 hospital centres
scattered in Douala town: Laquintinie Hospital, Deido District Hospital,
Palmier District Hospital and Emilie Saker Paediatric centre. The study
protocol was reviewed and approved by Cameroon Bioethics Committee and
by the Provincial Delegation of Public Health covering the town of Douala.
Study population: All children less than 15 years old, who presented
to the participating health institution for health problem were screened
for the study. Children with diarrhoea, non malaria infections and those
with a positive HIV status were excluded. Finally, 178 eligible ones with
different disease severity were enrolled. To recruit controls, we had
2 possibilities: either to go to a primary school in order to recruit
healthy subjects (this would mean others procedures), or to do it in hospitals
where we already have permission to carried out this research. We chose
the 2nd option and 38 children coming to hospital for nutritional counselling
and for vaccination were targeted to serve as control, provided they were
malaria free after thin blood film examination and HRP2 test. After informed
consent, 3 mL of blood was collected by venipuncture from arm. Blood was
then stored in 2 kinds of sample tubes: one with 0.124 M trisodium citrate
in it (2 mL) and one EDTA tube (1 mL). Furthermore, one drop of blood
was used for malaria diagnosis. Lumbar puncture was performed in Children
with history of coma, if clinically indicated and Cerebrospinal fluid
examined in order to assess the cause, either cerebral malaria or Non
Malaria Encephalopathy (NME). Patients were assigned to the various groups
on the basis of World Health Organisation guidelines for the definition
of uncomplicated and severe malaria (Imbert, 2003). Children with a positive
HIV status were excluded from the study.
Malaria diagnosis: Blood was spotted on the slide and thick films
were prepared in duplicate. The slides were labelled, allowed to dry,
stored in a slide rack and transported to the laboratory of health and
nutrition of the University of Douala. The tick film was then stained
in 10% Giemsa solution for 20 min and then allowed to dry. The parasites
were counted with a microscope (Motic) using the thick film on the basis
of number of parasites per 200 white blood cells; this was converted to
the number of parasites per μL of blood. For control subjects, in
addition to the thick film, we carried out the more sensitive antigenic
test to detect PfHRP2 (P. falciparum specific Histidin Rich Protein
2) using ParaHit dipstick (Span Diagnostics Ltd., India).
Definition of categories: Malaria anaemia was taken to be a haemoglobin
concentration of <8.0 g dL-1 or a PCV <18. Malaria anaemia
was defined as a haemoglobin concentration of this level in a patient
who had a positive malaria smear. Cerebral malaria was diagnosed if a
patient with a positive smear for malaria presented with impaired consciousness
as measured by a Blantyre coma score of ≤2 (range: 0-5) and had a normal
cerebro-spinal fluid. The coma score was determined as described by Molyneux
et al. (1989) for all comatose patients. Children without any of
the above mentioned symptoms, but presenting with usual malaria symptoms
and a positive malaria smear were classified as UCM patients.
Clinical care of subjects
Baseline evaluation: Demographic data, information on the use of impregnated
bed net to prevent malaria (whether or not bed net was used to cover the
bed when resting or sleeping) or on recent drugs use and significant medical
history were obtained. A complete physical examination, including neurological
status according to the Blantyre coma scale (Molyneux et al., 1989)
and prostration assessment (define as inability to sit unassisted in a
child who can normally do so, or inability to drink in a child who cannot
normally sit up) were performed.
Inpatient care: Clinical monitoring of patients included measurement
of axillary`s or rectal temperature, neurological and prostration status
every 6 h. A physician evaluation was performed every 24 h or more frequently
if clinically indicated. In addition, standard nursing care was provided.
For example, paracetamol was administered for temperatures >38°C
at a dose of 10 to 17 mg kg-1 every 8 h.
Antimalarial therapy: Cameroon national treatment guidelines for
malaria management were used for treatment. Children with UCM were given
Quinine base (25 mg kg-1 24 h in 500 mL of glucose solution
5%) for 3 days and after that were discharged; Those with SMA (Haemoglobin
level <5 g dL-1) were given blood followed by Quinine base
(25 mg kg-1 24 h in 250 mL of glucose solution 5%) for 3 days
and an Iron supplementation (6 to 10 mg kg-1 24 h); They were
discharged at least 7 days after admission; CM patients were given Quinine
base (25 mg kg-1 24 h in 500 mL of glucose solution 5%) for
3 days followed by an Artemisinin combination therapy and an Iron supplementation;
They were discharged at least 7 days after admission as well. Some antibiotics
like Dexametazone or Ceftriaxone was given as clinically indicated in
order to treat non-detected infections following paediatrician`s recommendations.
Laboratory evaluation: Malaria diagnosis was performed as previously
describe. Haematological parameters (including: White and Red blood cells,
platelets counts, as well as Haemoglobin level and Hematocrit) were determined
using an automated coulter (Celly 70, France) with the blood collected
on EDTA tube. The plasma obtained after centrifugation of the blood collected
on citrated tube was used for glycaemia determination by a colorimetric
enzymatic method using Glucose oxidase and peroxidase (SGM, Italy); the
optical density was read at 510 nm using a spectrophotometer (Helios β,
Thermospectronic UVB 102615).
Quality control: As stated earlier, slides for malaria diagnosis
were prepared in duplicate. One slide was read by a hospital labs technician,
who was not involved in the research work and the other was read by one
member of our research team. The two results were confronted and a consensus
was found in term of parasitaemia. The haematological measurements were
made at Deido district hospital using the same model of machine (coulter)
and the same technique. Glycaemia for all recruitment sites was measured
using the same spectrophotometer and the same method at the laboratory
of Health and Nutrition of the University of Douala. All these measurements
were blinded, with the technician unaware of the background of the sample.
Statistical analysis: Data was analysed using GraphPad Prism version
4.00 for Windows, GraphPad Software, San Diego California USA, www.graphpad.com.
Categorical variables were compared using Fisher`s exact test and continuous
variables with Student`s t-test. p-values were used as measure of significance,
a p<0.05 was considered significant.
Figure 1 is an overview of patient`s recruitments profile.
Table 1 shows that the medium age of CM patients was
significantly lower than the one of MA patients (27.48±25.59 and
47.84±39.33 months respectively, p = 0.0107) and Table
3 confirm that bed nets uses decrease with disease severity, being
lower in CM patients than in MA patients.
Clinical data on admission: On admission, temperature was significantly
higher in CM patients than MA and UCM patients (39.64±0.98°C,
38.99±0.85°C and 38.58±0.94°C, respectively; p<0.0001).
However when we observed our population, hyperpyrexia (T°≥40°C)
was more prevalent in children with CM and MA than in children with CM
alone (54.54 and 36%, respectively). All children with CM, CM and MA were
prostrated on admission, while we had only 74.51 and 45.88%, respectively
with MA and UCM patients. It is noteworthy that 49.02 and 16.47% of children
who were finally classified, respectively as MA and UCM patients had Blantyre
Coma Score (BCS) between 2 and 4, signalling an impaired consciousness.
Clinical outcome: Four children (3 males and 1 female) in the
CM group died. These were the only fatal cases reported (median age: 17.75±5.74
months). Two of them were coming from small private health centres and
had severe parasitaemia (≥250000 parasites μL-1), whilst
the 2 other had high parasitaemia (between 50000 and 250000 parasites
μL-1). However no neurological sequelae were observed
immediately after discharge among those who survived. According to Table
2, fever resolution time (FRT) seems to last longer in children with
CM and MA than CM alone (81.6±30.36, 66±37.44, 45.14±28.46,
33.9±22.88 h in children with CM and MA, CM alone, MA, UCM, respectively;
p<0.0001). Coma Resolution Time (CRT) seems to be almost the same in
CM and MA and CM alone (16.2±8.02 and 16.3±10.04 h in children
with CM and MA and MA alone, respectively; p = 0.9716). Prostration resolution
time (PRT) increased with disease severity (28.70±19.19, 45.45±23.91,
56.25±26.55, 59.4±36.93 h in children with UCM, MA, CM alone
and CM and MA respectively; p = 0.0002).
Laboratory data: Parasitaemia increase from UCM to CM, as the
log transformed Parasitaemia shows (3.65±0.73, 4.36±0.74,
4.72±0.79, 5.04±0.43 for UCM, MA, CM only and CM and MA,
respectively; p<0.0001), however hyperparasitaemia seems to be more
prevalent among CM patients than children with SMA (32 and 5.88%, respectively).
White blood cell (WBC) counts and hyperleucocytosis (WBC≥10000 μL-1)
have the same trend than parasitaemia and hyperparasitaemia in our population
(80.95 and 53.49% for hyperleucocytosis in children with CM alone and
SMA, respectively). As expected, haemoglobin (Hgb) level is very low in
children with malaria anaemia, this is irrespective of whether this MA
is combine with CM or not (5.72±1.35 and 6.15±1.27 g dL-1
in children with MA and CM and MA respectively, p = 0.3379); Obviously
Haematocrit follows this same trend. Complicated malaria (namely MA and
CM) is associated with low glycaemia (0.67±0.21 and 0.64±0.14
g L-1, respectively).
|| Study profile of patient
||Baseline characteristics of malarial patients (according
to disease severity) and controls
|a: Means±SD, NR: Not relevant, MA: Malaria anaemia,
UCM: Uncomplicated malaria, CM: Cerebral Malaria, WBC: White Blood
Cells, RBC: Red Blood Cells, Hb: Haemoglobin, Hct: Haematocrit
||Clinical outcome of malarial patients according to disease
|A: Means±SD, NR: Not relevant, MA: Malaria anaemia,
UCM: Uncomplicated malaria, CM: Cerebral Malaria
|| Use of bed net and prevalence of some abnormalities
|MA: Malaria anaemia, UCM: Uncomplicated malaria, CM:
SMA compared to CM: Of the 62 children with MA, 51 had this anaemia
without cerebral complications (28.7% of subjects recruitments), while
11 patients suffered combined severe anaemia and cerebral malaria (6.2%
of recruitments). An additional 25 children had strictly defined CM alone
(14% of recruitments). Compared to children with MA, children with CM
were younger (27.48±25.59 months and 47.84±39.33 months,
respectively, p = 0.0107) and consequently weighed less (11.66±4.52
and 15.02±7.95 kg respectively). They also had higher admission
temperatures and longer hospital stays. The case fatality rate was 11.1%
in children with CM, but no death has been reported in MA patients.
This study set out to describe the clinical spectrum and haematological
characteristics, as well as to understand the trend in pattern of morbidity
of the disease in our setting, particularly to look for variation in different
disease severity groups. We found that there seems to be a strong link
between bed net usage and the reduction of the disease severity (60.53,
52.94, 41.18 and 28% prevalence of bed net utilization in Control, UCM,
MA and CM, respectively). This prove that impregnated mosquitoes bed net
to prevent malaria transmission is still working and remain a very interesting
tool to implement in order to prevent severity when its occur (Noor et
CM seems to be predominant in younger children and MA in older children.
A different trend was noticed in others studies in Burkina-Faso, Ghana
and Zambia as well as in some part of Uganda (Modiano et al., 1998;
Biemba et al., 2000; Idro et al., 2006). This difference
is essentially due to transmission intensity that differs with the settings.
In these others African settings, the fact that severe malaria tends to
affect children of relatively older ages could be related to slower acquisition
of clinical immunity in the urban environment as a consequence of lower
levels of exposure to infected mosquitoes (Imbert et al., 1997).
However, since we are under high transmission, it is likely that CM (who
seems to be more associated with poor prognosis) will affect much younger
children (Snow et al., 1999; Gupta et al., 1999). In present
setting, due to the high transmission intensity, children get continuous
exposure to infection and quickly develop protective immunity against
the deadly CM, so that during subsequent episodes, they suffer less severe
forms or uncomplicated malaria (Barragan et al., 1998; Rogier et
al., 1999). However, MA is generally more prevalent than CM in our
setting; a similar trend has been observed in Zambia (Biemba et al.,
2000). Any way, CM seems to be more associated with poor prognosis than
SMA; this is particularly noteworthy from present study, as far as the
clinical outcome is concerned. As stated earlier, fatal cases have been
reported in the CM group, whilst none has been reported in the SMA group;
Biemba et al. (2000), in a study performed in Zambia, reported
a case fatality rate of 18.9% in all CM cases, but only a case fatality
rate of 7.3% in children with SMA.
In this study, anaemia occurred more frequently at low parasite densities
than CM. This is consistent with findings from Ghana where more than 80%
of severely anaemic children exhibited no parasiteamia but presented with
detectable plasma levels of soluble malaria antigens (Mockenhaupt et
al., 2004). This result may reflect chronic and/or repeated infections
that eventually lead to gradual decrease in Hgb concentrations. Moreover,
the low prevalence of hyperpyrexia in our patients with severe anaemia
provides evidence for a chronic course of the disease. This corresponds
to findings in a study of Tanzanian children with severe anaemia who were
frequently asymptomatic or showed non-specific symptoms (Schellenberg
et al., 2003).
A non to be neglected prevalence of prostration and impaired consciousness
were observed in children who were finally classify as UCM patients; Although
prostration has been described in similar frequencies in other areas of
Africa with high or low transmission, most large studies of severe malaria
have not included assessment of the frequency of prostration, a defining
criterion in the WHO, 2000 definition of severe malaria (Imbert, 2003).
Prostration appears to have a lower case fatality rate than some other
manifestations of severe malaria; however, because it is the main reason
for hospital admission for patients with malaria, it will be important
to educate health care workers about the characteristics and frequency
of this presentation of severe malaria (Idro et al., 2005).
CM and MA both seem to be strongly associated with hypoglycaemia (28
and 37%, respectively). This confirms the WHO 2000 definition of severe
malaria where glycaemia is among the main criteria.
This study highlights differences in clinical presentation and outcome
as well as in some laboratory parameters according to disease severity.
Such study would also contribute to the management of the disease. The
pattern in clinical presentation varies in different geographic location
and in years and seasons, due to transmission intensity and climate changes.
Therefore, it is necessary to monitor it time to time, taking into account
some parameters which have been undermined up to now, like prostration,
impaired consciousness and hypoglycemia. Future studies will focus on
investigating and identifying parameters associated with disease severity,
so as to be able to understand pathways leading to severe malaria.
This study was supported by the EC under the FP6 framework programme,
Call number 3; Project No. LSHP-CT-2006-037749. We are indebted to the
medical, nursing and laboratory staff of hospitals where we carried this
study for their service in patients` recruitments and management; the
study participants and their parents/guardians; Serge Tiyong, Gaelle Ngassa
and Adelaïde Demasse for their help in recruiting patient.
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