Malaria and Schistosomiasis are among the most important parasitic diseases with significant economic and public health consequences, particularly in Africa. Both parasites exert significant health, social, and financial burdens on infected individuals, households, and the health care system of the country in general (WHO, 2022; WHO, 2023). The two parasites have been associated with poverty, climate change, and several other related factors, which may result in their co-distribution and a high co-infection rate in humans (Brooker et al., 2007; Degarege et al., 2016).

Malaria causes an estimated 241 million cases and 627,000 deaths worldwide in 2020. The African region continues to carry the highest burden of malaria, accounting for about 95% of all malaria cases and 96% of all malaria deaths worldwide (WHO, 2023). In Ethiopia, malaria continues to be a major public health problem with over 68 percent which is approximately 74 million of the country’s total population living in areas at risk of malaria (Girum et al., 2019). In 2016, Ethiopia had an estimated three million new cases of malaria, resulting in 4,782 deaths and 365,900 Disability Adjusted Life Years (DALYs) in the same year (Girum et al., 2019). According to a malaria trend analysis conducted in the southern Ethiopian region’s Wolaita zone, Damot Woyide district is a high-transmission area where the prevalence of malaria is continuously rising (Legesse et al., 2015).

Schistosomiasis, on the other hand, remains a major cause of morbidity and mortality in several tropical and subtropical countries, with an estimated 240 million people infected worldwide and more than 700 million people living in endemic areas, mostly (90%) in Africa (W.H.O., 2018; WHO, 2022). In Ethiopia, intestinal schistosomiasis due to Schistosoma mansoni also remains the most widespread and predominant public health problem despite implementing several rounds of preventive chemotherapy. Every year, more than 35 million are at risk of infection, resulting in a pooled prevalence of 18% (Hussen et al., 2021; Ponpetch et al., 2021). Suitable environmental factors and human activities such as washing clothes, fetching water, swimming in rivers, bathing in open freshwater bodies, and engaging in irrigation farming are among the significant risk factors associated with schistosomiasis (Calasans et al., 2018; Bekana et al., 2021).

Several epidemiological studies show malaria and schistosomiasis co-endemic in many geographical areas. Due to this co-endemicity, multifactorial determinants like social-demographic (Abay et al., 2013; Getie et al., 2015), environmental (Booth et al., 2004; Chimbari et al., 2004), and behavioral factors (Juma et al., 2018) contribute to co-infection with schistosomiasis and malaria. Not only this, the different studies conducted in many countries reported different co-infection rates (Mazigo et al., 2010; Degarege et al., 2012; Mulu et al., 2013; Getie et al., 2015; Kinung’hi et al., 2017). Malaria and schistosomiasis co-infection, in turn, can affect parasitological (Getie et al., 2015; Dufera et al., 2016), hematological (Getie et al., 2015; Kinung’hi et al., 2017; Hailu et al., 2018; Abebe et al., 2024a), and biochemical parameters (Getie et al., 2015; Abebe et al., 2024b) among malaria patients thereby affecting the malaria clinical outcome

However, the current state of knowledge on the impact of co-infection on transmission dynamics and disease is contentious and inconclusive. Several studies found conflicting results regarding the effect of co-infection on malaria clinical outcomes. Some studies reported that co-infection increases malaria parasitemia (Degarege et al., 2012; Dufera et al., 2016).In contrast, others reported an association of co-infection with lower parasitemia (Sangweme et al., 2010; Getie et al., 2015), and still, others reported no correlation (Mazigo et al., 2010; Mulu et al., 2013). The disparity in findings was also observed concerning the hemoglobin level. Several studies have shown that co-infection reduces hemoglobin level (Degarege et al., 2012; Getie et al., 2015; Kinung’hi et al., 2017), while others found no effect of co-infection on hemoglobin level (Sangweme et al., 2010). Regarding pathological outcomes, some reported that co-infection with cerebral malaria was protective (Waknine-Grinberg et al., 2010), while others reported exacerbated hepatosplenomegaly (Wilson et al., 2011).

In Ethiopia, a previous related study was conducted to assess the prevalence and clinical correlates of Schistosoma mansoni co-infection among malaria-infected patients in Northwest Ethiopia, but, essential liver enzymes were not investigated in this study. In addition, renal involvement was not assessed, and potential risk factors were not considered in the analysis (Getie et al., 2015). The clinical and parasitological effects of Plasmodium–Schistosoma mansoni co-infection and factors favoring co-occurrence remain poorly understood. Therefore, this study aimed to assess parasitological and clinical correlates and determinants of co-infection among malaria-infected patients.

Plasmodium–Schistosoma mansoni co-infection is a major public health concern in developing countries where their geographical distribution overlaps (Juma et al., 2018; Chimbari et al., 2004; Mazigo et al., 2010; Matangila et al., 2014; Kinung’hi et al., 2017). Previous studies conducted in Damot Woyide district, Wolaita zone, south Ethiopia regional state reported the presence of malaria and Schistosoma mansoni transmission in the district (Alemayehu and Tomass, 2015; Alemayehu et al., 2017; Tilla et al., 2019). The current study revealed that Damot Woyide district, Wolaita zone, is one of such epidemiological settings in Ethiopia where malaria and schistosomiasis transmission overlap with a co-infection rate of 18.2%.

The presence of streams(AOR = 4.1, CI: 1.65-10.15,p=0.002), small irrigation-based agricultural activities in the area (AOR = 3.24, CI: 1.69-6.18, p=0.00), as well as other social demographic characteristics such as age (AOR = 5.85, CI: 2.45-13.93, p=0.00) and sex (AOR = 3.03, CI: 1.56-5.91, p=0.001), were factors that showed significant associations with Plasmodium–Schistosoma mansoni co-infection among communities living in the study areas (Alemayehu and Tomass, 2015; Legesse et al., 2015; Alemayehu et al., 2017).In this study, living close to the water body was strongly associated with Plasmodium–Schistosoma mansoni co-infection. This is explained by a slight geographical variation in the risk of contracting schistosomiasis and malaria (Booth et al., 2004).

Moreover, the risk of co-infection was higher among individuals living around streams than in other types of water bodies. The possible explanation was that the previous study in the area identified the Bisare Stream and Adacha River as sources of Schistosoma mansoni infection (Alemayehu et al., 2017). Even though residents use both sources of water for irrigation, during a snail survey, most adult and cercaria-shedding snail intermediate hosts were identified from the stream compared to the river. Also, the physical characteristics, the slow velocity of the water body, vegetation density, and the presence of substrate like aquatic vegetation, mud, or rocks, of the stream are more conducive to Biomphalaria pfeifferi snail’s existence compared to the river, This might increase the co-infection rate (Alemayehu et al., 2017).

Another risk factor that was identified as an important determinant for Plasmodium -Schistosoma mansoni co-infection was the presence of irrigation practice. This result was in agreement with earlier studies conducted in Zimbabwe and Kenya (Juma et al., 2018; Chimbari et al., 2004). The presence of water bodies with suitable ecological conditions (Mereta et al., 2019), and irrigation practices create an ideal habitat for mosquitoes found in fields and irrigation ditches with stagnant water to lay their eggs and breed. Because more mosquitoes carrying the malaria parasite can flourish in these environments, there is an increased risk of malaria transmission. Similar to this, irrigation systems can produce stagnant or slow-moving water, which is preferred by the snails that serve as intermediate hosts for the schistosomiasis infection.

In the present study, co-infection status is strongly associated with gender. Males have been shown to have a higher co-infection rate compared to females. The observed difference between females and males can be linked with a higher frequency of contact with cercariae-contaminated water bodies by engaging in farming activities and outdoor night activities of males like irrigation, livestock care, and wild animal control that are active at night to minimize damage to their crops. This finding is supported by previous studies conducted in Ethiopia (Abay et al., 2013; Dufera et al., 2016; Kinung’hi et al., 2017). In contrast to this finding, a study from Kenya found no association between sex and co-infection; this is probably because of the few participants included in the study (Juma et al., 2018).

Additionally, in the present study, the risk of co-infection is higher among school-age children compared to adults this can be linked to the behavior and lifestyle of school-age children like bathing, swimming, rare cattle along water bodies, and lower-aged males also share tasks with their father by engaging outdoor night activities. Since mosquitoes are most active at dusk and dawn, malaria is frequently transmitted at these times. Participating in nighttime outdoor activities raises the possibility of coming into contact with mosquitoes that transmit malaria, particularly in regions where the disease is prevalent. Previous studies conducted in Western Ethiopia in 2020 (Dufera et al., 2016), Northwestern Ethiopia in 2015 (Getie et al., 2015), and Northeastern Ethiopia (Abay et al., 2013)also reported the association of age with co-infection.

Even though the current study could not identify gender and age relationships with Schistosoma mansoni infection, there is a difference in mean infection intensity between gender and age groups. Higher mean Schistosoma mansoni infection intensity was observed in the lower age group than in the older age group. It is expected that school-age children are the most affected due to high levels of unsafe water contact behavior such as swimming, bathing, and rare cattle near the grassy area along with water bodies. This finding is supported by other studies (Alemayehu and Tomass, 2015; Dufera et al., 2016; Alemayehu et al., 2017). Considering gender, female participants had slightly higher mean Schistosoma mansoni infection intensity than males, which is in contrast to previous studies (Alemayehu and Tomass, 2015; Alemayehu et al., 2017), but in agreement with the other study conducted in western Ethiopia (Abay et al., 2013). The observed gender variation could be attributed to the difference in the nature of the study participants, socioeconomic status, and immune status of the patients.

The co-infection rate of 18.2% reported in the current study is comparable to the rate reported in the study conducted in Kemise town, northeast Ethiopia (18.4%) (Abay et al., 2013), but lower than a study conducted at Dore Bafeno Health Center, southern Ethiopia (38.5%) (Degarege et al., 2012), and Northwest Ethiopia (19.5%) (Getie et al., 2015), the shores of Lake Victoria, northwestern Tanzania (22.6%) (Mazigo et al., 2010), southern Ethiopia (22.6%) (Mulu et al., 2013), and the Mara region, Northwestern Tanzania(81.9%) (Kinung’hi et al., 2017). However, it was higher than the finding of another study conducted in Zambia’s Zambezi District (2.7%) (Rutagwera and Tylleskär, 2012). The differences in the prevalence of co-infections among these studies could be attributed to the environmental and micro-climatic conditions that influence the two parasites. Some of these factors include types of water bodies, water contact practices, poverty, other socioeconomic factors, lack of effective preventative measures, limited access to health care, study design, and time of survey (Booth et al., 2004; Brooker et al., 2007; Ojo et al., 2019).

In the present study, the prevalence of anemia [(Hemoglobin levels ≤ 12 mg/dl)] (41.9%) among malaria patients was comparable with an earlier study done in Northwest Ethiopia (41.4%) (Hailu et al., 2018), and Congo (41.6%) (Matangila et al., 2014), but higher than a study done in Kenya (23.3%) (Valice et al., 2018). This finding was also lower than reports from studies conducted in Ethiopia (Getie et al., 2015; Tuasha et al., 2019). The observed variation in the prevalence of anemia could be explained by changing patterns of parasitic infection, nutritional status, the density of parasites, and differences in age distribution. Similar to the result of the current study, previous studies from Congo and Northwest Ethiopia reported a higher prevalence of anemia among co-infected[66% (68/103)] compared to Plasmodium–only ( Matangila et al., 2014; Getie et al., 2015). In agreement with an earlier study (Kinung’hi et al., 2017), the current study did not find a significant statistical difference in the prevalence of anemia between sexes or age groups.

In this study, the rate of malaria attack [7.7%(19/246)] was significantly higher in patients heavily co-infected compared to those who were free from Schistosoma mansoni infection. This finding corroborates those of other studies that found that the heavy egg burden of Schistosoma mansoni increases the risk of developing severe malaria (Sokhna et al., 2004; Mulu et al., 2013; Getie et al., 2015). An increased risk of severe malaria in co-infected patients may result from the heavy egg burden of Schistosoma mansoni, which can affect liver function, exacerbate anemia, induce immunosuppression, alter cytokine profiles, and regulate the immunological response.

The current study demonstrated a significant mean difference in Plasmodium parasite density, hemoglobin, hematocrit, SGPT, SGOT, ALP, BIL-D, and TP among Plasmodium -only and Plasmodium–Schistosoma mansoni co-infected. In contrast, a previous study only reported a significant mean difference in the mean hemoglobin level; the difference between other biochemical parameters was not statistically significant (Getie et al., 2015). This difference in findings can be attributed to the laboratory method employed, unproportional study participants allocated among strata, study design, sample size, and study setting in the previous study (Getie et al., 2015). Similar to earlier reports on the association of co-infection with lower hemoglobin levels (Getie et al., 2015; Kinung’hi et al., 2017), the present study showed that co-infection significantly lowers hemoglobin levels. The observed significantly higher mean in biochemical parameters among the co-infected group can be explained by the synergistic effect on liver pathology, leading to increased inflammation, impaired liver function, fibrosis, and raising the likelihood of serious liver consequences in co-infected people (Dufera et al., 2017).

In this study, a higher prevalence of severe parasitemia (>10,000/μL) was observed among P. falciparum-infected patients. This can be explained by the fact that P. falciparum infects both young and old red blood cells, and rapid replication increases the level of parasitemia during P. falciparum malaria infection. In contrast to an earlier study (Getie et al., 2015), a higher frequency of fever was observed among Plasmodium-only than in the co-infected counterpart. This may be due to anti-inflammatory markers being unregulated due to the dominance of heavy Schistosoma mansoni infection among Plasmodium–Schistosoma mansoni co-infected individuals. In Plasmodium-only infected Th1 pro-inflammatory mediators such as Tumor Necrosis Factor- (TNF-), which is pyrogenic, resulting in an aggravated fever presentation (Karunaweera et al., 1992).

In the current study, a higher mean malaria parasitemia was observed among Plasmodium–Schistosoma mansoni co-infected participants than Plasmodium-only infected participants. This finding concurs with results from western Ethiopia and southern Ethiopia, where co-infected malaria patients were more likely to have high parasitemia than Plasmodium-only infected patients (Degarege et al., 2012; Dufera et al., 2016). However, this contradicts a result from Zimbabwe and northwest Ethiopia, where a higher mean malaria parasite density was observed among Plasmodium-only infected individuals (Sangweme et al., 2010; Getie et al., 2015). This difference can be due to variation in Schistosoma mansoni infection intensity, which would affect Plasmodium density.

In this study, higher mean malaria parasitemia was observed among heavy Schistosoma mansoni co-infected patients than light-intense co-infected ones. In concordance with this finding, a study in northwest Ethiopia shows that co-infected patients with a moderate-heavy intensity of Schistosoma mansoni had significantly higher mean malaria parasitemia than co-infected patients with light-intense Schistosoma mansoni infection (Getie et al., 2015). Similarly, a study from western Ethiopia indicates that co-infection due to Plasmodium–Schistosoma mansoni reciprocally leads to an increase in parasite density (Dufera et al., 2016). Therefore, Schistosoma mansoni co-infection could affect malaria parasite density, depending on the intensity of Schistosoma mansoni infection.

In this study, the nutritional assessment and immunological profile of study participants were not done to see the effect of nutritional status and host immune response. These considerations may have contributed to strengthening the outcome of the present study.

Our findings suggest that co-infection is associated with altered Plasmodium parasite density, hematological, and biochemical parameters in malaria patients. A strong association between the intensity of the concomitant Schistosoma mansoni infection and Plasmodium parasite density was observed, which might be a load-related factor for the development of severe malaria with the course of infection. Moreover, malaria attacks were associated with the intensity of concurrent Schistosoma mansoni infections. Being male, being in the age group of 6–15, the presence of a stream, a water body distance within 1000m, and the presence of irrigation practice are risk factors of co-infection. The severity of Schistosoma mansoni infection is affected by age.