Epidemiological and clinical correlates of malaria-helminth co-infections in southern Ethiopia

Half the world’s population live in malaria-endemic areas, with an estimated 500 million clinical cases and over one million deaths annually [1]. Similarly, malaria is ranked as the leading communicable disease in Ethiopia, accounting for about 30% of the overall disability adjusted life years lost. Approximately 68% of the total population lives in areas at risk of malaria [2]. In Ethiopia, Plasmodium falciparum and Plasmodium vivax are the major parasites accounting for about 70% and 30% of infections, respectively, during peak transmission periods [3, 4].

Soil-transmitted helminths (STH), on the other hand, are a group of common parasites that infect more than a billion people worldwide [5]. In Ethiopia, like other developing countries, infections with the major STH, including Ascaris lumbricoides, Trichuris trichiura, hookworm and Schistosoma mansoni are widely spread with variable prevalences [6‐12]. In many areas of the world, malaria and STH are co-endemic, therefore co-infections are common, particularly in Africa [13, 14]. The rate of malaria and STH co-infection in Ethiopia as reported in one study was 9.6%, 6.3% and 2.1% with hookworms, A. lumbricoides and T. trichiura, respectively [15]. In another study a 2.8% prevalence of urinary schistosomiasis and P. falciparum malaria was reported [16].

However, how concurrent infections affect the epidemiology and/or the pathogenesis of each other remains controversial [17‐19] raging from increased severity of malaria to reduced severity and incidence of malaria during helminths co-infection [20‐33]. The underlying reason for such different outcomes might be due to numerous factors, including differences in study design and case definition, data analysis and interpretation, the demonstration of antigen cross-reactivity between co-infecting organisms and host factors [20]. Studies on the impact of helminths on incidence, prevalence and severity of malaria in Ethiopia where both infections are hyperendemic is lacking. Therefore, this study was conducted to assess the effects of STH on the epidemiological and clinical patterns of malaria in a hyper-endemic area for both malaria and helminths infections.

Approximately 68% of the total population of Ethiopia lives in areas at risk of malaria [2]. According to the World Malaria Report in 2011, Ethiopia was categorized among the four countries with a 25 to 50% reduction in new malaria cases [4]. However, despite the continuous efforts made to control malaria during the past decade, infections with malaria remained high in many parts of the country [36]. The current study in Wendo Genet reflected the same notion, with a very high prevalence rate of malaria. Most of the malaria infections were caused by P. falciparum (58.3%) while P. vivax and mixed infections accounted for 35.2% and 6.5% of the infections, respectively. The persistently high prevalence of malaria urges a need for evaluation of the malaria control programme in the study area. In Ethiopia, A. lumbricoides, T. trichiura, hookworm, and S. mansoni infections are widespread with variable prevalence that may reach up to 90% in some places among the general population [6‐12]. Likewise, the most predominant intestinal helminths diagnosed were T. trichiura, A. lumbricoides, S. mansoni and hookworm, with a prevalence of 64.5%, 57.7%, 28.4% and 12.2%, respectively. The high prevalence of helminthiasis in general and the predominance of specific parasites in the area were in agreement with previous reports in the region [8, 37].

In many tropical areas of the world, malaria and STH co-exist with significant co-infection rates [13, 14]. This was reflected by the high co-infection rates observed in the current study (67%) which is consistent with studies from other tropical countries from Africa and Asia [29, 31]. Higher rate of severe malaria attack among individuals co-infected with helminths as compared with those free from helminths was the reported from Thailand [31]. However, African study from Uganda failed to show such association even in heavily infected individuals [29]. In this study, trichuriasis that was found to be significantly associated with increased malaria infection. Schistosoma mansoni was not associated with increased malaria infection in the current study. This, however, contradicts the report from Senegal where the incidence rate of malaria attacks was significantly higher among S. mansoni-infected individuals [17]. On the other hand, a study in Nigeria reported that periodic deworming of children with A. lumbricoides has protective effect from malaria infection [38]. This implies prior infection with A. lumbricoides is a risk factor for malaria infection. In line with this, although it did not reach to a statistical significance level, there was a high A. lumbricoides- malaria co-infection rate in the current study. However, it is difficult to strongly conclude the epidemiological interaction of helminths and malaria infection with such cross-sectional study. Hence, it would be useful to check the incidence of malaria in a longitudinal study among cohorts of people having/not having different helminthiasis with and without treatment. Conducting further studies on the co-epidemiology of malaria and helminths in Ethiopia could be of paramount importance to a potential public health value of synergistic opportunities for control.

The current study however, tried to determine the effect of helminths co-infection on the clinical manifestation of the malaria cases with only three cases presenting with sign and symptoms of severe malaria. The absence of severe malaria cases in highly ‘wormy’ malaria patients in the current study was, however, consistent with a study conducted by Nacher et al. [31] where helminths infection was associated with protection from cerebral malaria. However, a strong association between worm burden as expressed by egg intensity and malaria parasite density was observed which suggest that with the time course of the infection, such patients with high density of both helminths and malaria will tend to develop severe form of clinical malaria by influencing the immune response during co-infection [27, 39]. Studies have reported a positive correlation between egg load of helminth infection and Plasmodium density [13, 18]. In line with this, the current study found that individuals with light T. trichiura and A. lumbricoides infections had lower Plasmodium densities than those with moderate or heavy infection. Contrary to this, heavy S. mansoni infection was associated with lower Plasmodium densities [17]. However, the effect of specific helminths on the severity of malaria and the mechanisms leading to this needs to be determined in longitudinal studies in a larger pool of clinical cases of malaria.

The majority of malaria patients in the current study were found to be multi-parasitized with up to four helminths. A strong association between worm burden as expressed by helminths egg intensity and malaria parasite density was observed which could be a dose-dependent risk factor for severe malaria attack with the course of the infection. Mass deworming may be simple practical approaches in endemic areas in reducing the risk of severe malarial attack particularly for those at high risk of both infections.