Association of Schistosoma haematobium infection morbidity and severity on co-infections in pre-school age children living in a rural endemic area in Zimbabwe

Human schistosomiasis is a parasitic disease caused by blood flukes called trematode worms of the genus Schistosoma. Schistosomiasis predominantly affects people in low- and middle-income countries [1], where there is poor provision of water and sanitation. The mainstay of morbidity control is currently through provision of mass drug administration (MDA) to target age groups. However, children under 5 years old are usually left out of the MDA exercise due to lack of paediatric size medicine. From the 78 countries affected by schistosomiasis about 206.4 million people required treatment [2, 3]. In sub-Saharan Africa alone, about 52 endemic countries reported moderate to high prevalence of schistosomiasis infection [4]. Individuals living in schistosomiasis-endemic areas are often at risk to several pathogens simultaneously [5]. These coinfections could occur by chance or through host exposure to other locally endemic disease agents [6]. Alternatively, schistosomiasis may increase or decrease the risk for another infection [7]. Studies on co-infection in adults have shown that schistosomiasis co-infection hinders diagnosis and treatment of other communicable diseases [8, 9]. To date, however, little focus has been given to pre-school age children (PSAC), who were hitherto regarded as a low risk group. However, recent studies suggest that they may have similar risk to adults [10]. The associations of schistosomiasis to co-infections in PSAC has not yet been fully described.

The World Health Organization (WHO) Sustainable Developmental Goal (SDG) 3 aims to reduce under-5 mortality to at least as low as 25 per 1000 live births in every country by 2030 [4]. In Zimbabwe, the top causes of morbidity and mortality in PSAC include acute respiratory tract infections (ARI), malaria, diarrhoea, fever and skin diseases [11, 12]. In this study we investigated the prevalence and extent of morbidity associated with S. haematobium coinfections in children under the age of 5 years in a Schistosoma endemic district of Zimbabwe. Furthermore we investigated the relationship between the selected condition’s severity and under-5 mortality rate.

Screening involved 465 PSAC, aged 1 to 5 years from the Shamva district, 415 met the eligibility criteria and consented to be part of the study (Fig. 2). Participants has an equal sex ration and the mean age was 3.4 years. Relative risk (RR) based on schistosomiasis and sex was 0.93 (95% CI 0.76–1.14) with p = 0.48, based on age it was also statistically insignificant. Age was shown to increase the risk of S. haematobium infection; as the children grew older (Table 1). Children suffering from malaria had P. falciparum as the parasite.

Children growing up in resource limited rural areas have high exposure to schistosomiasis infection and a high likelihood of associated coinfections with diseases prevalent in these communities. A strong positive association between schistosomiasis and URTI; dermatophytosis and FUO was observed. The trends revealed an association between schistosomiasis and under-5 mortality rate from the national data provided by the Ministry of Health in Zimbabwe. There was a negative association between schistosomiasis and malaria, though participants with the two as co-infections had a greater likelihood of presenting with complicated malaria. Similarly, participants with URTI, FOU and dermatophytosis as coinfections had a higher likelihood of having severe sequelae of the diseases.

A positive association of schistosomiasis prevalence in under-5 and child mortality rate in the district mirrored the trends in different provinces of Zimbabwe. The provinces that had a high schistosomiasis rate also had high mortality rate [11, 15]. This made us wonder if schistosomiasis co-infections was possibly worsening the disease courses as we also found that in co-infections there was a greater chance of the diseases running a severe course [15]. It is necessary to explore the effects of schistosomiasis and other diseases co-infections in all the top morbidity and mortality causes in PSAC. Early schistosomiasis treatment in PSAC has the potential to lower the under-five mortality rate, by reducing the incidence of severe sequelae of the top morbidity conditions, which are also top causes for mortality in this age group. The development of a co-infection algorithm advocating for intensified screening for co-infections should be shared with policy makers in low and middle income countries.

S.haematobium infection was shown to increase with age, this is in keeping with other studies done [42‐46]. This is probably due to the fact that the older children do more activities in contaminated water like swimming and house chores unlike the younger PSAC who are only exposed during bathing. In most cases caregivers know to boil the water before bathing the infants which decreases the chance of acquiring S. haematobium infection. Focus has to be made to decrease exposure of the older PSAC to contaminated water. This might need to include tackling schistosomiasis from the snail host stage.

Children infected with S. haematobium had a 20-fold higher odds of severe dermatophytosis, after adjusting for other clinical conditions. S. haematobium infection had a 38% increased risk of getting dermatophytosis. There is no previous documentation between S. haematobium and dermatophytosis. In literature, extensive dermatophytosis was noted in a case reports involving S. mansoni [47, 48]. It is postulated that S. mansoni exacerbated dermatophytosis by lowering immunity due to the liver involvement or by suppression of the T- helper 1 system which is involved in suppressing fungal infections [49, 50]. Dermatophytosis cause great morbidity in PSAC in Zimbabwe [11]. Dermatophytosis, when severe is associated with psychological trauma via discrimination. Clinicians in schistosomiasis endemic areas need to be aware of this condition in order to decrease the morbidity associated with dermatophytosis. Further studies on schistosomiasis association with dermatophytosis and immunological profiling are recommended.

Children with schistosomiasis associated with plasmodium malaria coinfection had reduced risk. However, malaria infection has been documented to be exacerbated/ameliorated by schistosomiasis co-infection [18‐20]. The enhanced T-helper 1 cellular activity and an increase in anti-interferon-gamma cytokine production causes a protective effect against the malarial parasite [51]. Of note is that although schistosomiasis was demonstrated to have a protective effect on malaria, in the event of co-infection; malaria infection had 7-fold chance of exacerbating to complicated malaria requiring hospital admission in the PSAC. This finding makes it crucial for PSAC to be included in national schistosomiasis control programs, to reduce or eliminate morbidity and mortality in children in this age group. However, the conundrum in PSAC coinfections and schistosomiasis require urgent attention, as this is the age of growth and development during which the immune system is developing; and when childhood vaccines are delivered. Further studies are required to understand co-infection in PSAC inclusive of malaria infection outcome.

There was a 10-fold chance of finding FUO and schistosomiasis as a coinfection, children with schistosomiasis had 138% risk of FUO. The proportion of patients discharged with undiagnosed FUO remain unchanged even though there has been enormous development in medicine over time [52]. The cause of febrile illness is not identified in approximately 9–51% of patients, this is even higher in resource limited areas endemic for childhood illnesses [53]. Children who had both FOU and schistosomiasis had a 2-fold chance of having serious sequelae such as seizures. Most clinician tend to think of other conditions in contrast to neglected tropical diseases when patients present with a fever [33]. It might be necessary to make it a priority to screen for schistosomiasis when a child from an endemic area presents with a fever. However, further immunological investigations are necessary in-order to find out if the fever is due to schistosomiasis infection or exacerbation of a co-infection, during the early immunological responses to diseases manifestation.

In our study the odds of having URTI was 2% higher in schistosomiasis infected children with a 1% increased risk of S. haematobium infected children acquiring URTI. Furthermore, in the coinfected cohort odds of ending up with severe pneumonia was 7-fold compared to schistosomiasis negative population. This is a very significant finding as acute respiratory infections (ARIs) are the leading cause of morbidity and mortality in children under the age of five in Zimbabwe [11]. Thus tackling schistosomiasis crisis in this age group will have enormous contribution in reducing the childhood mortality and morbidity in schistosomiasis endemic areas.

The strength of this study revealed the major morbidity and mortality causes in PSAC from our study area which also fit into most of the low income countries were schistosomiasis is endemic. The main limitation of this study is there is a possibility that the children may have had more than two co-infections which might make our data biased, however we did thorough clinical examinations and laboratory tests in all the participants to rule this out. We also considered socioeconomic status as a confounding factor by focusing on children with a similar background and in the same villages with similar lifestyles. Given the likelihood of co-infections, children who present with schistosomiasis should be screened for other conditions.

This study revealed an association between schistosomiasis and top morbidity conditions of URTI, dermatophytosis, malaria and FUO in PSAC living in a schistosomiasis endemic area. The study also showed that there is need for an appropriate clinical diagnostic method to identify associated infectious diseases and initiate early treatment of schistosomiasis and co-infections in PSAC. Furthermore, we demonstrated that coinfection led to severe sequelae of the clinical conditions, that have a high impact on morbidity and mortality in children under the age of five. This brings out the importance of including PSAC in national schistosomiasis control programs and the development of appropriate diagnostic tools.