Epidemiological and clinical profile of paediatric malaria: a cross sectional study performed on febrile children in five epidemiological strata of malaria in Cameroon

Malaria is a disease associated with great morbidity and mortality especially in children in sub-Saharan Africa (SSA). According to the WHO, there were 214 million cases and 438,000 deaths attributed to malaria in 2015 [1]. A vast majority of cases and deaths occurred in children in SSA [1]. A declining trend has been observed in the global incidence of malaria in recent years; compared to the year 2000 (where global incidence stood at 262 million cases and 839,000 deaths), the incidence and number of deaths due to malaria have decreased by 18% and 48% respectively [1]. A similar trend has been observed in paediatric malaria where the incidence decreased from 33% in 2000 to 16% in 2015 [1]. Most of the reduction in malaria incidence and deaths was in Africa chiefly in Central Africa [2]. Although malaria incidence is decreasing, there has hardly been a reduction in the role of malaria as a major cause of death in children particularly in SSA, claiming the life of a child every 2 min [1].

In malaria endemic areas, the rate of severe malaria attack varies considerably from as low as 6.4% to as high as 74.7% [3‐11]. In children, the clinical spectrum of malaria usually ranges from asymptomatic carriage of malaria parasites to a febrile disease that may evolve into a severe, life-threatening illness [12]. The mortality resulting from malaria is largely associated with the parasite’s ability to induce complications presenting as cerebral malaria, severe anaemia, and respiratory distress (also known as acidotic breathing). In addition other severe malaria manifestations commonly observed at enrollment include: hyperlactataemia, multiple or prolonged convulsions, hyperparasitaemia, circulatory collapse, hypoglycaemia, prostration, jaundice, persistent vomiting and intravascular haemolysis [5, 13, 14].

Cameroon, a malaria endemic country in Central Africa has witnessed a decline in the incidence of malaria, largely attributed to the relentless effort by Cameroon’s government to ensure that every household in the nation is entitled to insecticide treated bed nets (ITNs) [15, 16]. Although malaria has lost its crown as the number one cause of mortality in Cameroon [17], it is still a major cause of morbidity and mortality especially in children. In Cameroon, malaria accounts for 48% of all hospital admissions, 30% of morbidity and 67% of childhood mortality per year [18, 19]. Records show that the entire Cameroon’s population of over 22 million is at risk of malaria infection [17]. Moreover, severe malaria cases (including cerebral and severe anaemia, which are known to be the two major contributors to overall malaria mortality, are frequent in Cameroon [20‐23].

The epidemiology of malaria in Cameroon has been described as unique, having all the different epidemiological strata present in all of Africa [24, 25]. Six epidemiological strata have been identified and mapped in Cameroon namely: the Sudano-sahelian strata, High inland plateau strata, Savannah-forest transmission strata, South Cameroon Equatorial forest strata, High western plateau altitude strata, and the Coastal strata [25]. These epidemiologic strata differ in terms of their geographical and ecological characteristics, transmission pattern and endemicity level, and in terms of the main vectors transmitting malaria parasites [25]. Due to these differences, it is likely that exposure and the risk of development of severe malaria among children (who present the most vulnerable group) will vary considerably across the different epidemiologic strata of malaria, which may have particular implications in the control of malaria in the country.

As Cameroon pursues its ambitious goal to reduce malaria-associated morbidity and mortality and eventually eliminate malaria from the country, there is an urgent need of empirical studies to establish an evidence-based distribution of malaria and its clinical features in the population living in the different epidemiological strata that supposedly characterize malaria transmission pattern in the country. Although a few studies aimed at describing the clinical and epidemiological profile of paediatric malaria have been performed in Cameroon, none of these studies has actually taken into consideration populations living in the different epidemiological strata. In view of this, we carried out this survey to describe the epidemiology of malaria and its clinical features in children residing in five epidemiological strata, so as to inform control policies in the country.

The overall prevalence of malaria in the current study was 15.0%. This decreased steadily from the South towards the North of the country, being highest in Limbe (C strata) and lowest in Maroua (SS strata). The association between prevalence of malaria and study site was significant (p < 0.001). The variation in the prevalence of malaria between the study sites could be attributed to the different levels of transmission; malaria could be described as hyperendemic in Limbe [22], holoendemic in Yaounde [16, 33, 34], mesoendemic in Bamenda and Ngaoundere and hypoendemic in Maroua. Transmission of malaria in an area is known to be influenced by environmental variables including temperature, rainfall and humidity. Optimal temperature is needed for the development of the juvenile [35, 36], and adult stages of the mosquito vector [37], and optimal rainfall is equally needed for the creation of breeding sites. All the study sites surveyed offered favourable conditions for malaria transmission with the exception of Maroua which could be considered as arid with very little vegetation, low rainfall and very high temperatures in some months of the year. Thus, this may account for the low prevalence of malaria in the area. An entomological survey performed in Maroua also confirmed the low transmission of malaria in the area [38]. Site-specific analysis revealed a general decline in the prevalence of malaria in three of the study sites compared to earlier studies: the prevalence in Bamenda was lower compared to the 53.21% reported in 2006 [39], the prevalence in Yaounde was lower compared to the 34% reported in 2003 [40], and also lower in Ngaoundere compared to the 35% reported in 2006 [41]. The decrease in the prevalence of malaria in the current study could be accounted for by the increase in vector control chiefly by increased usage of ITNs which has been made available to almost every household in the country by the government [15, 16].

Malaria prevalence was higher in children between 60 and 119 months of age (p < 0.001), and this is consistent with studies performed elsewhere [42‐44]; but contradicts the findings of other studies [45‐47], in which no significant association was observed between prevalence of malaria and age. This trend was observed in all the sites except for Maroua, where the prevalence was highest in children aged 120 months and above. This could be attributed to the differences in the level of endemicity of malaria. In Maroua, malaria is hypoendemic and in hypoendemic areas, malaria is reported to be more common in older children compared to younger ones [48].

No significant association was observed between prevalence of malaria and gender in the current study (p = 0.459), which is consistent with studies performed elsewhere [27, 39, 42, 45‐47]. Site-specific analysis also did not revealed any significant difference in the prevalence of malaria between males and females.

In the current study, Plasmodium falciparum was the only species identified as the cause of malaria. Molecular analysis further confirmed this [49]. The finding of P. falciparum as the sole cause of malaria in the target population is contrary to studies that have reported other Plasmodium species causing malaria including P. vivax [24, 50]. These discrepancies could be attributed to differences in the study designs; our study targeted febrile children presenting to hospitals in the different study sites meanwhile theirs targeted asymptomatic adults and children.

We found an overall geometric mean parasite density (GMPD) of 22,576.9 parasites/μl. This varied considerably across the different study sites, being highest in Yaounde and lowest in Maroua (p = 0.004). The observation of higher GMPD in Yaounde had previously been reported by Achidi et al. [22]. The precise reason for the underlying variation in malaria parasite density in different populations is not imminent. Some studies have shown that the parasite density is influenced by the time of specimen collection [51, 52], as well as uncontrolled environmental factors [53]. The GMPD was significantly higher in children with severe malaria (SM) compared to those with uncomplicated malaria (UM) (p < 0.001). High parasite density (hyperparasitaemia) is a known risk factor for severe malaria and this may explain the higher parasite density in severe malaria cases.

The rate of severe malaria (SM) attack in the current study was 29.3%. This rate is similar to that reported in a similar study [54], but differ considerable with those reported in other studies: the rate of SM attack was higher compared to the 12% reported in Sudan [4] and 19.4% reported in Nigeria [55]. The differences in the rate of SM in these studies and ours may be due to different levels of malaria endemicity in the study sites. The rate of SM attack in the current study was lower compared to the 61.8% reported in a study performed in Ghana [5]. This disparity could be attributed to the differences in the study design; our study targeted children of 15 years and below meanwhile the Ghanaian study targeted children of 59 months and below, a group that is most vulnerable to severe malaria attack [30]. The rate of SM attack was highest in children below 60 months in this study, which is in conformity with other studies [22, 23]. The high rate of severe malaria attack observed in children below 5 years of age is attributable to their low immunity, which has been observed to increase with age [41]. There was no significant association between rate of SM attack and gender, which is in conformity with studies performed elsewhere [23, 55]. The rate of SM although not significant, was observed to increase steadily from the South to the North of the country i.e. from Limbe in the Coastal strata (22.1%) to Maroua in the Sudano-sahelian strata (42.1%). It is important to note that this trend is in the opposite direction to that observed with the distribution of malaria. The increasing trend of SM attack towards the northern regions could be attributed to the differences in the exposure of the population residing in the different epidemiological strata, and this is related to their immunity against malaria parasites. The population in the C strata, where transmission is highest, are more exposed hence will tend to be more immune compared to the population in the other epidemiological strata. Studies designed to evaluate the immunologic responses to malaria parasites in the different epidemiological strata will therefore be required to confirm this hypothesis.

The main clinical phenotypes of SM in this study were hyperpyrexia, severe malaria anaemia, and impaired consciousness, which is in line with similar studies performed in other areas of Cameroon [22, 23, 56], and elsewhere [55]. Among the major clinical phenotypes, severe malaria anaemia (SMA) and respiratory distress (RD) were significantly higher in children below 60 months. The association between SMA and age in the current study is in conformity with studies by Achidi et al. [22]. The GMPD was also observed to be significantly higher in SMA cases suggesting that heavy parasitaemia may be important in the development of severe anaemia. On the other hand, cerebral malaria (CM) was significantly associated with the study site, with the prevalence being highest in Maroua (SS strata). The finding of a significant association between CM and study site is also in conformity with the study by Achidi et al. [22]. Contrary to the study by Achidi et al. [22], there was no association between SMA and gender or study site, and between RD and study site. The low number of severe malaria cases in our study may have accounted for these differences. In the current study, the majority of the SM cases were found in group 1 of the WHO classification of SM which corroborates the work of Kwenti et al. [23]. The distribution of SM in the different WHO categories was not associated with age, gender or the study site.

The overall case fatality rate was 5.8%, which is comparable to the rate reported by Achidi et al. [22]. The case fatality rate was however lower compared to the rate of 8.5% reported in Nigeria [55] and 14% reported in Uganda [54]. The case fatality rate reported in the current study may have been underestimated as some of the children might have died at home in the course of the study. The case fatality rate was not associated with gender nor age but did for the study sites (p = 0.034), increasing from Limbe (1.2%) northwards, where it peaked in Ngaoundere (13.8%). As mentioned above, this observation may be due to the variation in the immune responses which in turn is related to the differences in their exposure to the malaria parasites. Furthermore, univariate analysis revealed that coma, hyperparasitaemia, hypoglycaemia, circulatory collapse, cerebral malaria and severe malaria anaemia were all independent predictor of death.

This study which is one of the first of its kind, provides an interesting insight into the epidemiology of paediatric malaria in Cameroon, taking into consideration the variations across the different epidemiological strata of malaria. These findings may contribute significantly to programmes aimed at controlling malaria in the country. However, the seasonal variation of malaria and its clinical phenotypes were not investigated as the study was performed only during the rainy season during which malaria transmission is highest. These findings may not be generalizable to reflect the overall prevalence of malaria in the target population. Furthermore, study participants were recruited using health facilities in urban centers, these findings may not necessarily reflect the situation in rural areas. Larger studies involving rural areas will therefore be needed to shed more light.

The overall malaria prevalence in this study was 15.0%. Malaria prevalence was significantly higher in Limbe in the Coastal strata and in children between 60 and 119 months. Malaria prevalence was observed to decrease steadily from the Coastal strata in the South to the Sudano-sahelian strata in the North, meanwhile the mortality rate associated with malaria increased in this direction. The rate of severe malaria attack was similar across the different study sites. Children below 60 months were most at risk of severe malaria attack. Hyperpyrexia, severe malaria anaemia and impaired consciousness were observed to be the main clinical presentation of severe malaria. The clinical phenotypes of severe malaria varied considerably across age groups and epidemiological strata; severe malaria anaemia and respiratory distress were more common in children below 60 months meanwhile cerebral malaria was significantly associated with the study site. Coma, hyperparasitaemia, hypoglycaemia, circulatory collapse, cerebral malaria and severe malaria anaemia were the independent predictor of mortality associated with malaria in the current study. Larger studies will therefore be required to shed more light on the seasonal variation of malaria and its clinical phenotypes in children in the different epidemiological strata.