A longitudinal study on anaemia in children with Plasmodium falciparuminfection in the Mount Cameroon region: prevalence, risk factors and perceptions by caregivers

With about 216 million cases of malaria and an estimated 3.3 billion people reported at risk, malaria is still a major public health challenge [1]. Greater than 80% of malaria-related morbidity and mortality occurs in sub- Saharan Africa due to infections with Plasmodium falciparum[2]. In heavily endemic malaria areas, it is almost inevitable that malarial infection will be associated with anaemia, although malaria may not be the prime cause of it [3, 4].

Anaemia an indicator of both poor nutrition and poor health is a common and sometimes serious complication of P. falciparum infection [5, 6]. Anaemia impairs normal development in children and it constitutes a major public health problem in young children in the developing world with wide social and economic implication [7].The highest prevalence of anaemia exists in the developing world where its causes are multi-factorial [8]. The complex aetiology of anaemia involves the interaction between multiple factors including nutritional deficiencies, genetic red blood cell disorders, infectious diseases particularly malaria, hookworm and human immunodeficiency virus infections [9].

Data on the prevalence of anaemia are limited in this area. Cornet et al. [7] reported that 42% of the children less than three years of age in Southern Cameroon were anaemic. Furthermore, a 2004 national survey on anaemia in preschool children (< 5 years) revealed anaemia to be a severe public health problem in Cameroon with a prevalence of 68.3% [6]. Information on anaemia prevalence must be collected in order to assess the impact of interventions, the adequacy of strategies implemented, and the progress made in the fight against anaemia. However, estimates of anaemia prevalence by themselves are only useful if they are associated with a picture of the various causal factors that contribute to the development of anaemia in a specific setting [6].

One strategy for reducing the morbidity and mortality that may be associated with anaemia is to identify the predictors that can be readily recognized to facilitate prompt therapeutic interventions especially in children residing in resource-poor settings. Family size, residence, younger age, duration of illness, a palpable spleen or liver, gender, history of fever, pale body, general body weakness, diarrhoea, soil-eating, stunting, malaria parasitaemia and recrudescent infections have been associated with mean haemoglobin levels [10‐15]. The factors which identify patients at risk of developing anaemia during malaria have been infrequently studied in this region. It is unclear whether these factors alone or in addition to others, are associated with the anaemia of uncomplicated malaria infection in Cameroonian children. We hypothesized that, factors other than falciparum malaria account for anaemia in the study area.

Anaemia is a major public health problem in Cameroon. In addition to measuring the haemoglobin concentration which is the most reliable indicator of anaemia at the population level [6], the causes of anaemia need to be identified as they may vary according to the population. The high prevalence of anaemia (80.3%) observed in the study population is comparable to the 82% obtained by Jourdan et al. [24] in children attending a clinic in Northern Cameroon and the > 70% obtained by Desai et al. [13] in pre -school children in Kenya. This is not unexpected in a semi rural community where malaria is hyperendemic [17] and majority of the household heads are farmers with no steady source of income [16]. Furthermore Mogensen et al. [22] reported 30%–90% of children to be anaemic at any time in malaria endemic areas of sub-Saharan Africa.

Following treatment more than half of the children (63/117) never achieved haematological recovery. In line with Obonyo et al. [18] haematological recovery in the children was associated with the clearance of parasitaemia. While the occurrence of clinical malaria after day 28 prevented haematological recovery in some of the children, the presence of persistent anaemia in children who were clinically and parasitologically cured suggests factors other than malaria may be involved in the pathogenesis of anaemia in the population.

While our findings showed a significant negative correlation (P < 0.01) between haemoglobin level and parasite density, others [7, 25] failed in finding such a correlation, even though they identified malaria as a risk factor for anaemia. Kahigwa et al. [26] reported P. falciparum parasitaemia to be the single most important factor associated with anaemia. Hyperparasitaemia has been considered as one of the possible manifestations of severe and complicated malaria, depending on the endemic area [27]. Anaemia in acute falciparum malaria is caused by increased destruction of both infected and non-infected erythrocytes and decreased erythropoiesis. However, we observed that even the very low density infections were associated with moderate anaemia in the children.

In addition to the density of parasitaemia, hypersplenism is also thought to contribute to the early anaemia of acute malaria through sequestering red blood cells in the spleen [28]. Our studies confirm this finding since a significant difference in the prevalence of anaemia was observed in children with enlarged spleens (92.0%) when compared with those having normal spleen sizes (76.4%). Children with a palpable spleen were 4.04 (95% CI: 1.79 – 9.08) times at risk of presenting with anaemia than those with normal spleens. The spleen is a key site for removal of parasitized red blood cells, generation of immunity and production of new red blood cells during malaria [29].

Protracted infections with malaria parasite are associated with clinically significant RBC destruction [12]. Children with length of fever ≥ 3 days were significantly at risk of developing anaemia. Contrary to Ong’echa et al. [30] and Grenfell et al. [31] who reported fever not to be associated with haemoglobin concentration, our findings revealed a significant negative correlation (r = − 0.18, P < 0.01) between haemoglobin concentration and temperature and a direct relationship between temperature and parasitaemia with the fever rate decreasing with increased age. The observed negative association between temperature and haemoglobin may be due to certain immunologic responses such as the secretion of high levels of tumour necrosis factor-α (TNF-α), a potent pyrogen. Chronic low grade production of TNF- α, in response to P. falciparum parasitaemia may induce dyserythropoiesis thus contributing to the pathogenesis of malarial anaemia [32]. However, a timely evaluation of all febrile illness, case-recognition and use of appropriate antimalarial therapy are indispensable to malaria and anaemia control in order to optimize clinical outcomes [17].

We found a significant inverse association between WBC count and haemoglobin concentration. Studies by Ladhani et al. [33] associated a high WBC count with severe anaemia. While normal total WBC count has been associated with malaria infection [34], leucopoenia appears to be a common finding in both non-immune patients with falciparum malaria and semi-immune children living in malaria-endemic regions, where WBC may be as low as 1-2×10⁹/L [3]. In view of the fact that our study included children with different degrees of malaria with a WBC count ranging from 2.2 – 33.5 ×10⁹/L, it may be possible that some of these children had concurrent bacterial infections which were not clinically apparent and were beyond the scope of this study. Nonetheless bacteraemia most commonly due to nontyphoid salmonella, has been strongly associated with severe anaemia [35, 36].

Although no significant difference was observed in the prevalence of anaemia between the different sexes, anaemia was higher in males than in females. Males were 0.84 (95% CI: 0.59 – 1.20) times more likely to be anaemic than females. Similar observations were made in Kenya [30, 37], Tanzania [38] and Ghana [39]. This may be attributed to the fact that males were significantly more malnourished than females. Also male children were 1.4 times (95% CI: 0.85 -2.1) at risk of carrying gametocytes than their female counterpart. The higher gametocyte carriage observed in males (32.8%) when compared with females (26.5%) may have exacerbated a decrease in the haemoglobin concentration. Even though the MLR model did not significantly identify gametocyte carriage as a risk factor of anaemia, the prevalence of anaemia was higher in children who were gametocyte positive than those negative.

Ferritin and transferrin were significantly associated with haemoglobin concentration in the IVM model. Further observations highlighted a significant difference in the prevalence of anaemia between children with abnormal (96.6%; 92.5%) and normal (59.8%; 70.3%) ferritin and transferrin values respectively. Stoltzfus et al. [38] reported the strongest relationship of serum ferritin and haemoglobin to occur in children who were malaria free and < 30 months of age. The usefulness of transferrin in monitoring infections has been controversial and the behaviour of ferritin as an acute phase reactant may obscure the relationship of haemoglobin to iron stores. However, a large proportion of anaemia in this population could not be explained by iron deficiency.

Our study revealed the level of education of the caregiver to be a significant determinant of haemoglobin concentration in children with falciparum malaria in this semi rural setting of the mount Cameroon region. Furthermore a negative trend (r = − 0.16) in the relationship between haemoglobin concentration and education level was observed. Children whose caregivers were illiterate showed a high prevalence of anaemia (90%), when compared with those whose caregivers had basic education (77.8%). Correlation between education level and anaemia has also been reported by Kahigwa et al. [26] in Tanzania, Ong’echa et al. [30] in Western Kenya and Al-Mekhlafi et al. [40] in Malaysia. This may be linked to their having knowledge about anaemia and iron containing foods as our findings showed a significant difference in the knowledge of anaemia between those with basic education (> 76.5%) and those illiterate (20.0%).

The significant association of the caretaker management ability of malaria and haemoglobin concentration may be linked to the effect of protracted febrile infection with the malaria parasite on the red blood cells. Pre-hospital antimalarial treatment of febrile children by caregivers/parents with mostly traditional herbs or drugs of questionable quality remains a significant common practice among individuals in the population as revealed by the questionnaire survey. Lack of proper education and poverty may be contributing factors to these attitudes and practices. In a previous related study [17], early treatment with effective antimalarial was demonstrated to decrease the morbidity and mortality due to malaria.

Wasting a manifestation of acute malnutrition [41] was significantly associated with the haemoglobin concentration as indicated by the IVM model. Although the prevalence of wasting (2.6%) in the children with falciparum malaria was low, 8 out of the 9 children (88.9%) were anaemic. Correlation between haemoglobin and nutritional status has also been reported by Nabakwe & Ngare [42]. Ehrhardt et al. [43] reported malnutrition to be a fundamental factor contributing to malaria-associated morbidity and anaemia, even if the latter exhibits multifactorial patterns. The high prevalence of anaemia coupled with the presence of malnutrition may have contributed to impaired growth in the children as weight significantly positively correlated with haemoglobin levels (r = 0.11, P = 0.03). Nutritional inadequacies causing stunting and underweight may also impair host immunity, further exacerbating the effects of malaria [41, 44]. However, improving the nutritional status of the children may lessen the morbidity due to falciparum malaria.

Even though the majority of caregivers were aware of pallor as a symptom of anaemia, none could detect whether the child was anaemic before assessment of haemoglobin concentration. The efficiency and applicability of pallor examination in the detection of anaemia is important in clinical circumstances [22]. Signs of pallor may be used as a tool to detect moderate (or severe) anaemia with sensitivities and specificities around 60%–86% [45]. The inability of caregivers to diagnose the paleness of the conjunctiva and palms which were apparent in those with severe anaemia (12.1%), confirms earlier findings [22] that assessment of pallor depends on training.

In addition to malaria, enlarged spleen, duration of fever > 2 days, high white blood cell count, sex, iron status indicators (ferritin and transferrin), level of education of the caregiver, management of onset of malaria by caregiver and wasting are important contributors to the pathogenesis of anaemia in the Mount Cameroon region. Improving the case management of malaria is likely to reduce the burden of anaemia hence useful health benefits. Control efforts should therefore be directed towards proper health education emphasizing on proper health seeking behaviour and attitudes of the population. In addition to malaria which is commonly considered to be a principal cause of anaemia additional diagnoses including malnutrition and helminths should be considered.

^aSignificant at P < 0.05 level, ^bSignificant at P < 0.01 level, ^csignificant at P < 0.001 level.

IUNS: PhD and Lecturer of Parasitology, Department of Zoology and Animal Physiology.

MS: MSc and Assistant lecturer of Biochemistry, Department of Medicine.

TNA: PhD and Professor of Medical Parasitology, Department of Microbiology and Parasitology, Dean Faculty of Science.