Prevalence and associated risk factors of asymptomatic malaria and anaemia among school-aged children in Dara Mallo and Uba Debretsehay districts: results from baseline cluster randomized trial

Malaria is an infectious disease caused by Plasmodium species of protozoan parasites. There are five known Plasmodium parasites causing malaria in humans. Plasmodium falciparum and Plasmodium vivax are the two dominant species causing malaria in Ethiopia [1, 2]. Due to intensified malaria prevention measures, malaria substantially declined between 2010 and 2015 globally, but this decline was halted between 2015 and 2017. Thus, malaria remains a public health concern and a major cause of death and disease among infectious diseases in tropical and economically deprived areas [1‐3]. According to the World Health Organization (WHO) Report 2020, there were an estimated 229 million malaria cases and 4,09,000 deaths globally in the year 2019. About 94% of those cases and more than 95% of deaths occurred in the WHO African region [4].

Nowadays, there is an age shift in the susceptibility to malaria. Malaria prevention measures targeting children under 5 years old leads to decreased exposure of them to Plasmodium species [5‐7]. Less frequent exposure of children in their early life leads to delayed development of anti-malarial immunity. A study conducted in Malawi revealed that school-aged children (SAC) were as susceptible as under-five children to Plasmodium species [8]. As compared to pregnant women, SAC were at two-fold increased risk for malaria and 1% increase in malaria among pregnant mothers was equivalent to 4% increase in malaria among SAC in sub-Saharan Africa (SSA) [9]. The other explanation for high prevalence of malaria among SAC was the duration of persistent infection. Buchwald et al. [8] noted that the duration of persistent Plasmodium infection was 38% higher in SAC than children under 5 years old.

The prevalence of malaria and its determinants varies widely in the different contexts. Up to 73.9% of SAC in SSA were infected by Plasmodium species [10]. It was 47% in Equatorial Guinea [11], 10.8% in Malawi [12], 1.7–18.4% in Tanzania [13‐15], 6.4–38.3% in Kenya [5, 16‐18], 40% in South Sudan [19], and 73.9% in Côte d’Ivoire [20]. Malaria burden in this population segment was related to access and adherence to malaria prevention interventions, place of residence and certain socio-demographic factors [11, 17, 19‐23]. Malaria was responsible for up to 50% death among SAC in SSA [10].

The other consequences of malaria are life-threatening anaemia and metabolic acidosis [10]. Anaemia is a physiologic condition in which the red blood cell mass is low to meet the physiological need (oxygen carrying capacity) of the body, or concentration of haemoglobin below the recommended threshold. The physiological need of an individual varies depending on age, gender, residence, altitude, smoking, and the different stages of pregnancy [24, 25]. Plasmodium infections cause anaemia through direct destruction of the red blood cells, clearance of infected and uninfected red blood cells by the spleen and impaired production of the red blood cells by the bone marrow [26, 27].

Anaemia was used as an important health indicator in the population. It is more common in economically deprived populations where malaria and other infectious diseases were highly prevalent. For each gross domestic product (GDP) increase in China, there was a 40% reduction in the prevalence of anaemia among SAC [28]. The major cause of anaemia in developing countries is iron deficiency. In addition, it is influenced by a child’s nutritional status, family income, gender, households owning poultry, household size, and residing in a rural area [11, 16, 17, 29‐33]. Globally, about an estimated 305 million SAC were suffering from anaemia [26]. Articles reviewed indicate that the prevalence of anaemia among SAC ranged from 10.8% in Brazil [34] to 85.2% in Equatorial Guinea [11]. The estimated prevalence of anaemia was 73.3% among SAC in Haiti [29], 33.3% in Uganda [30] and 50.8% in Kenya [31].

Despite the dramatic reduction in malaria in the last two decades, malaria remains a major public health and economic problem in Ethiopia [4]. According to the national malaria elimination strategy in Ethiopia, about 52% of the total population are at risk of malaria. Ethiopia is classified into five distinct malaria transmission strata based on the annual parasite index (API). These are high malaria endemic (API  ≥  50), moderate endemic (API  ≥  10 and   <  50), low endemic (API  >  5 and  <  10), very low endemic (API  ≤  5 and  >  0) and malaria-free areas (API  =  0) [35]. Although there is growing evidence that SAC become vulnerable and serve as the main reservoir for malaria [5, 13, 21], there is no study primarily targeting SAC to assess the prevalence and associated risk factors. A stratified analysis of a recent whole population-targeted epidemiological study [36], national malaria indicator survey [37] and facility-based surveys [19] revealed that malaria was high in this population segment. Furthermore, studies of anaemia among SAC in Ethiopia were more focused in areas near to universities or research institutions, which are easily accessible [32, 38]. Studies primarily focusing on malaria and anaemia among SAC and the corresponding associated factors are of paramount importance for integrated intervention for this population segment. Thus, this study was aimed to assess the prevalence of malaria and anaemia and corresponding associated risk factors among SAC in Dara Mallo and Uba Debretsehay districts, hard-to-reach areas, by using data collected at baseline of a cluster-randomized controlled trial in October to December 2019 to assess the effect of malaria prevention education on malaria, anaemia and cognitive development of SAC.

A total of 2167 SAC participated in the study, which gave a response rate of 94.1% (2,167/2,304). Of these, 64.0% were from Uba Debretshay district, 85.0% were from rural areas, 50.1% were boys and the mean (SD) age of children was 8.75 (1.53) years. About 39.2, 28.3 and 32.5% of children were attending grades 1, 2 and 3 education, respectively. Household residence lies at an altitude between 754 and 1988 masl with mean (SD) altitude of 1192 m (145 m) masl (Table 1).

About 1.62% (35/2,167) of SAC were RDT-positive with 95% CI of 1.15–2.27%. Of the total, 35 SAC-positive for malaria 20, 3 and 12 were due to P. falciparum, P. vivax and mixed infection with P. falciparum and P. vivax, respectively (Fig. 2). The prevalence of malaria ranges from 0.0 to 17.1% in the schools involved in the study. None of the positive children had a temperature above 37.5 °C.

There was no Plasmodium infection among SAC residing at an altitude above 1500 masl. Household ownership of bed nets was not associated with malaria in univariable analysis (COR  =  0.76; 95% CI 0.28–2.06), but none of the children who slept under bed net the night before the survey was positive for malaria. The prevalence of malaria was 1.79% in rural areas while it was 0.62% in other areas although the difference was not statistically significant (COR  =  0.38; 95% CI 0.07–2.07). The prevalence of malaria was 1.75% in boys and 1.48% in girls with no statistically significant difference (COR  =  1.22; 95% CI 0.62–2.41). Literate educational status of household head (COR  =  0.34; 95% CI 0.15–0.80), malnourished children (COR  =  3.37; 95% CI 1.49–7.63), wasted children (COR  =  0.70; 95% CI 0.50–0.98), and being resident in a household located at an altitude above 1,109.89 masl (COR  =  0.40; 95% CI 0.17–0.94) significantly influenced malaria among SAC in univariable mixed effect logistic regression. However, after fitting the multivariable mixed effect logistic regression and taking care of collinearity between malnourishment and wasted children, only literate educational status of household head (AOR  =  0.38; 95% CI 0.15–0.95) and being resident in a household at an altitude above 1109.89 masl (AOR  =  0.40; 95% CI 0.17–0.94) remained statistically significant (Table 2).

There is growing evidence that SAC become highly vulnerable to malaria and associated morbidities. They are playing a major role in the transmission dynamics of malaria. The prevalence of malaria among SAC in Dara Mallo and Uba Debretsehay districts was 1.62% and it was affected by educational status of the household head and the household location above 1,109.89 msal. Mean altitude-adjusted Hb concentration and anaemia among SAC were 12.43 g/dL and 20.0%, respectively. Anaemia was low amongst children who ate vegetables, nuts and seeds in their 24-h self-reported dietary recall.

The point prevalence of malaria in the present study area was low. Since all infections were asymptomatic, such individuals went undiagnosed but contribute the major role in the transmission dynamics of malaria. A study conducted in Malawi demonstrated that asymptomatic malaria infections persist for long periods in this population. WHO recommended identification and treatment of all infections of malaria in its Global technical strategy (GTS) for malaria, 2016–2030. There was a high heterogeneity in the burden of malaria in schools participating in the study, which calls for well-tailored malaria prevention interventions where prevalence of malaria is high. High uneven spatial distribution of malaria was also demonstrated in the previous epidemiology study in Ethiopia [36].

The prevalence of malaria in the present study area was in agreement with the last national malaria indicator survey of Ethiopia, the recently stratified estimate made in Arba Minch Zuria district [36] and one similar study undertaken in Tanzania [15]. In contrast, the prevalence of malaria in the present study area was lower than findings in Tanzania [13, 14], Kenya [5, 16‐18], South Sudan [48], Côte d’Ivoire [20], demonstrated in stratified data analysis in some studies [19, 37]. The low prevalence of malaria might be attributable to the difference in level of malaria endemicity or different interventions undertaken prior to the data collection period. There was high malaria transmission in the study area before the data collection period. In response to this, different levels of health systems in the country were involved to overcome the transmission of malaria in the area. In addition to regular malaria prevention interventions in Ethiopia, screening and treatment at community level was done to halt the high transmission of malaria. One of the consequences of malaria is anaemia since the parasites destroy red blood cells after completing the developmental life cycle [47].

Unlike the previous hypothesis that malaria was significantly associated with anaemia, this was not demonstrated in the present study. Failure to demonstrate significant association between malaria and anaemia in this study might be due to the low number of Plasmodium-infected children and subsequent loss of power to detect the difference of anaemia among Plasmodium-infected and uninfected children. The prevalence of anaemia was moderate among SAC in Dara mallo and Uba Debretsehay districts. It was lower than prevalence of anaemia in similar population groups in Jima town [49], Arba Minch Zuria district [50] and the national pooled estimate in Ethiopia [38], while it was higher than the estimate made in Durbete town [32]. This finding was higher than the estimate made in Brazil [34] while it was lower than the prevalence of anaemia among SAC in Haiti [29], Uganda [30] and Kenya [31]. The differences in the estimated prevalence of anaemia compared to estimates made in Ethiopia and other developing countries might be related to variation in level of socio-economic development [28], and low prevalence of malaria and lower intensity of parasitic infections such as STH and intestinal schistosomiasis which did not significantly affected anaemia in the current study. Unlike this study, parasitic infections among SAC was one of the predictors of anaemia in Arba Minch Zuria district [50] and northern Ethiopia [51]. This difference might be related to difference in the type of parasitic infections involved in the diagnosis.

Apart from parasitic infections [49, 52, 53], anaemia is influenced by nutritional status [47] of children, which was not revealed after taking care of potential confounders in the present study. It was similar to the study conducted in Arba Minch Zuria district as stunting was not associated with altitude-adjusted anaemia [50], but in contrast, a community-based survey conducted in Gonder town [53] and the systematic review and meta-analysis of articles originated from Ethiopia [38]. The insignificant association between nutritional status and anaemia might be due to high prevalence of non-nutritional anaemia. Among the dietary diversity that significantly reduced anaemia in SAC was the category of vegetables, nuts and seeds. The significant effect of this dietary category on anaemia may be related to high iron and other micronutrient content, important for growth and maturation of normal red blood cells. The significant influence of eating legumes was also demonstrated by a study conducted in eastern Ethiopia [54]. Unlike a study conducted in South Africa [55], the insignificant association of food groups obtained from animals sources could be related to such foods being taken very rarely or inadequately in quantity, mainly in rural parts of the study area. The significant association between legumes, nuts and seeds in this study was corroborated by a cluster-randomized trial, where taking bio-fortified or not-fortified beans improved the Hb concentration among SAC in both the control and intervention arms [56]. The beans grown in rural parts were considered “meat of the poor” [57], to satisfy the nutritional demand of people who were at high risk of anaemia.

There were certain limitations associated with this study. The first was due to the design in which both outcome and predictor variables were assessed at the same time. Such studies were not strong in generating causal evidence. Secondly, the low power of the study to detect significant difference of malaria in its predictor variables and malaria as predictor for anaemia. The third limitation was related to the biomass of malaria-positive individuals. The number of Plasmodium parasites per μl of blood or the percentage of Plasmodium-infected red blood cells was not calculated. The fourth limitation is due to recruiting only school-enrolled children into the study as the situation may be different for children not enrolled to a school. The strength of this study is the area of the study being conducted in hard-to-reach areas, not previously explored.

The overall prevalence of malaria among SAC in Dara Mallo and Uba Debretsehay districts was low, but there was uneven distribution of malaria in the schools. Malaria was more common among children from household heads who were illiterate and where the residence was located at an altitude range below 1100 masl. This calls for targeted intervention in schools where the prevalence of malaria is high with due emphasis given to schools at an altitude below 1100 masl and households with illiterate household heads. Anaemia was moderate in the area, being eligible for interventions to improve the haemoglobin concentration of SAC. Anaemia was negatively affected by 24-h dietary recall of eating legumes, nuts and seeds. Studies evaluating the micronutrient content of these foods and their daily intake for nutritional adequacy shall be studied.