Malaria in patients with sickle cell anaemia: burden, risk factors and outcome at the Laquintinie hospital, Cameroon

According to WHO, worldwide there was an estimated 219 million malaria cases and 435,000 deaths attributed to malaria in 2017. Approximately 41% of Cameroon population has at least 1 episode a year, with a prevalence of 29% and has an overall mortality of 30–35% [1, 2]. Despite the fact that malaria has lost its crown as the first cause of mortality in Cameroon, it is still a major cause of morbidity and mortality especially in children accounting for 67% of childhood mortality [2]. In sub-Saharan Africa, malaria claims the life of a child every twominutes [3]. It is proposed that hemoglobinopathies protect from severe life-threatening manifestation of malaria [4]. The most important of which is the mutation that causes sickle cell disease (SCD) which leads to a 90% risk reduction of severe Plasmodium falciparum malaria in sub-Saharan African children [5]. Sickle cell disease is an inherited chronic hematological disorder, where a point mutation in the β globin gene resulting in substitution of glutamic acid with valine at position 6 of the peptide [6, 7]. SCD is a serious public health concern, present mainly in tropical countries, especially sub-Saharan Africa [8, 9]. The World health organization (WHO) estimates that 300,000 children are born with SCD each year, 75% of whom are in sub-Saharan Africa [10, 11]. Cameroon has a sickle cell trait (SCT) prevalence of 18.2% (ranges from 8 to 34%) and a SCD prevalence of 2–3% [12‐14]. The gene does not protect against infection by the malaria parasite, but it prevents establishment of disease following infection [15]. As SCT offers relative protection against malaria, one might expect the protection to be at least as effective in the homozygous state (SS) [16]. However, cinical experiences have shown it to be more dangerous since malaria does not only worsen the preexisting anemia in patients with SCD, to the point of becoming life threatening but also, the abnormal splenic function in SCD patients hinders clearance of parasitized RBCs [17]. In Africa, malaria contributes substantially to the early mortality in patients with SCD [8]. Despite this, in many countries and in Cameroon in particular, national malaria control programs do not consider this populationas a population to be at high risk of severe malaria disease. Thus, they do not benefit from free malaria treatment instituted by the program for high risk and vulnerable population as a means to tackle the burden of malaria in the country. The prevalence of malaria in the population of Douala is 24% and malaria represents 9% of admissions in this hospital. Sickle cell patients constitute 6% of all admissions at Laquintinie (non-published data). The goal of the study is to identify the SCD population as a population at risk of severe disease and identify the factors associated with severe disease and clinical outcome. This might serve as preliminary data which could be used for further studies with the aim to insert this population in the malaria control program.

Children with SCD in sub Saharan Africa are presumed to be at increased risk of malaria morbidity and mortality. This study aimed at evalutating differences between hospitalised children with SCD and those without SCD using selected clinical and para-clinical factors associated with malaria through retrospective review of hospital records. In doing so it was hoped to demonstrate the increased burden children with SCD present with and therefore the need to include SCD as a criterion to benefit from free malaria treatment.

We had a total of 6563 admissions of which 1438 admissions were SCD patients. In our study the male to female ratio of SCD was 1.20. This compares to a sex ratio of 1.37 by Mbassi Awa et al. in Yaounde (Cameroon) but less than 3.2 obtained Nansseu et al., [19, 20]. Meanwhile studies by Chemegni et al. and Aninagyei et al. found ratios of 0.96 and 0.8 respectively [21, 22]. This implies males and females should benefit from prevention programmes equally.

The prevalence of SCD was 16.4%. This was considerably higher than other studies carried out by Purohit et al. (8.95%), Komba et al. (1.6%), and Ngolet et al. (10.64%) [23‐25]. The higher SCD prevalence in our study might be explained by the fact that most SCD patients living in Douala are followed in the Laquintinie hospital and thus they usually seek primary care in this health institution as compared to the non SCD population who turn to seek primary care in lower level health centers first.

Vaso-occlusive crisis was the major cause of admissions, accounting for 31.6% of all hospital admission, and malaria the second with 23.5%. This could be compared to the findings of Mbassi et al., Ngolet et al., and Aluoch et al. who had malaria prevalences of 25.5, 29.8, and 20% respectively [19, 25, 26]. This finding was lower than that found by Diop et al., Abhulimhen-Iyoha et al. who found a prevalence of 47 and 56.2% respectively [27, 28]. This might be explained by the fact that Nigeria has a very high prevalence of malaria accounting for 25% of global burden. A lower prevalence was reported by Douamba et al. (16.5%) and Aninagyei E et al. (13.4%) [22, 29]. This might be explained by the fact that only patients with parasitemia were considered to have malaria.

The overall mortality in the sickle cell population was 3.4% and of the patients who died, the highest number of deaths occurred in the 1-5 yr age group. Malaria accounted for 20.4% of these deaths, this finding is similar to the 19.6% deaths from malaria found by Purohit et al. and 16.0% found by Komba et al. [23, 24]. Two out of every 10 sickle cell patient who died had malaria. This is an important indicator that malaria affects many SCD patients and should be targeted accordingly.

We found that impaired consciousness and convulsions were lower among the SCD population as compared to the non SCD population. This was similar to findings obtained of Komba et al. and Makani [18, 24]. This can be explained by the fact that individuals with sickle cell mutation have lower adhesive properties therefore are less susceptible to damages which occur on the vascular endothelium in the pathogenesis of cerebral malaria. The lack of convulsions in this population therefore doesn’t necessarily imply less severe disease.

Splenomegaly, hepatomegaly and icteric sclerae were all higher among the SCD population as compared to those without sickle cell. Studies of Komba et al. and Makani report similar findings [18, 24]. This is thought to be due to the chronic hemolysis which characterises this condition. This argument was supported by the finding of Makani [18] who found no statistically significant difference between hepatomegaly, splenomegaly and icterus between SCD patients admitted with and without malaria. Of these, our study found only splenomegaly to be significantly associated with malaria in SCD population. This can be explained by the increased splenic clearance of parasitised RBCs. Generally, autosplenectomy occurs before the age of 5 due to chronic microvascular arteriolar occlusions in the spleen. As such the finding of splenomegaly in a SCD patient should generate a high index of suspicion for malaria.

We found a lower parasite density among SCD patients compared to non SCD population as similarily reported by Makani et al., Aninagyei et al., and Komba et al. [18, 22, 25]. This can be explained by the protective effect of the sickle mutation which causes increased clearance of parasite and the hypoxia in the RBCs which constitute an inhospitable environment for the growth of the parasite. Therefore, criteria like hyperparasitemia may not be sufficient in this population to categorize severity of disease.

Severe malaria anaemia was higher among patients with SCD as equally demonstrated by Komba et al., Makani et al. and Aninayei et al. (as shown by either a low mean hemoglobin or hemoglobin < 5 g/dl) [18, 22, 25]. As all infections in the sickle cell population, malaria worsens the preexisting anemia. Malaria was found to be the cause of most severe anaemia in hospitalized patients as demonstrated by Sumbele et al. [30]. In our study, SCD patients with malaria had a lower mean hemoglobin level than in SCD patients without malaria similar to findings by McAuley et al. [31]. Though some authors disagree with these findings [32], most agree that prevention of malaria may be useful in reducing the deleterious effect of malaria on haemoglobin and therefore reducing need for transfusions and its associated risks, and also reducing death from severe anemia in SCD patients.

In our study, we found no clinical nor laboratory characteristics associated with death in SCD population with malaria when compared to non SCD patients. Komba et al. [24] found no association between malaria parasitemia and death in SCD population as compared to the non SCD population. Makani et al. [18] had similar findings for the two sub populations (SCD and non SCD), but within the SCD population there was an increased risk of death in relation to malaria parasitemia (9.5% vs 2.2%, OR:4.9, CI;1.04–23.20), p-value 0.04). A high risk of death in SCD patients with malaria as compared to SCD admitted for other pathologies was observed in our study and was equally statistically significant (3% vs 1%, OR:2.2, CI:1–5, p-value: 0.05).

SCD patients in endemic regions are recommended by WHO to receive antimalarial prophylaxis [33, 34]. Malaria is the second cause of admission in the SCD population. Though this study could not conclude that malaria was associated with higher mortality in hospitalized SCD patients compared to hospitalized non-SCD patients like in other studies [18, 35], it however demonstrated that within the SCD population, those admitted for malaria were twice at risk of death. Though no specific risk factor for death was identified, it is widely known that malaria worsens anemia and hemolysis in this population [36], and as such predisposes to more adverse outcomes.

Based on the afore mentioned findings we recommend to maintain a high index of suspicion of malaria in patients with sickle cell anaemia and be prompt to care. Strategies to reduce incidence of and mortality from malaria in this sub population (risk group) should be implemented.