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Neglected tropical diseases as a cause of chronic liver disease: the case of Schistosomiasis and Hepatitis C Co‐infections in Egypt

The year 2011 will be remembered as an important one for highlighting the global burden of diseases that result from chronic non-communicable diseases (CNCDs). Several landmark events occurred, including a highlevel United Nations General Assembly meeting in September 2011 that addressed the prevention and control of CNCDs. To date an important emphasis on CNCDs has been lifestyle changes leading to rapidly increasing rates of obesity, diabetes and heart disease in developing countries. However, we believe that neglected tropical diseases (NTDs) also represent important hidden factors underlying the emergence of CNCDs in developing countries (1). The NTDs are chronic and disabling conditions that include all of the highly prevalent helminthic and protozoan infections as well as selected bacterial, viral and fungal infections (2). Several NTDs contribute to the burden of chronic gastrointestinal and liver disease in lowand middleincome countries (LMICs), including trichuriasis now recognized as an important cause of inflammatory bowel disease, Chagas disease as a cause of megacolon and megaesophagus, amebiasis and echinococcosis as causes of liver cysts, and schistosomiasis as a leading cause of liver fibrosis (1). High rates of co-infections from two leading diseases affecting the liver have been recognized in Egypt: schistosomiasis caused by Schistosoma mansoni and hepatitis C virus (HCV) infection. We have found that these two co-infections and their synergies in promoting liver disease in Egypt represent an illustrative example of a burden of a CNCD in LMICs. Schistosomiasis has plagued Egypt and other African countries along the Nile River since antiquity (3). During the first half of the 20th century, up to 80% of the populations of impoverished Egyptian villages were infected with schistosomes, leading one writer to declare that ‘no other people on earth suffer the ravages of bilharzia to the extent of the Egyptian fellaheen (farmers)’ (3). Factors favouring schistosomiasis endemicity include improper water and sanitation facilities along with bodies of freshwater, which are often contaminated with infected snails. Chronic morbidities associated with repeated infection include impaired child growth and development, chronic inflammation of liver, anaemia and other nutritional deficiencies with some estimates of up to 56 million disabilityadjusted life years (DALYs) lost annually, a value that exceeds the estimated global burden of malaria (4). Prior to the availability of praziquantel, the primary treatment of schistosomiasis in Egypt was with parenteral administration of tartar emetic (potassium antimony tartrate) (3). Hundreds of thousands of Egyptian fellaheen received the medication following World War I, which was often effective in curing schistosomiasis although it was also highly toxic. The mechanism of action of tartar emetic is inhibition of DNA synthesis (5) with a side effect profile including nausea, vomiting, coughing, acute circulatory failure and electrocardiographic changes (6). Sadly, it was often dispensed without due attention to sterilization of needles between patients leading to an unanticipated consequence of an epidemic of HCV infections (7–13). It was unknown during this period of administration that infectious agents could be transmitted via syringes and human blood (13). As tartar emetic was administered parenterally, both HCV and hepatitis B virus (HBV) were also transmitted through this process (14). It has also been proposed that Egyptians are particularly susceptible to both schistosomiasis and HCV co-infections (15, 16). Today, the prevalence of chronic HCV infections and seropositivity in Egypt has been reported as high as one in 10 people, compared with the global rate of one in 50 people (17). In contrast, the seroprevalence of HCV and schistosomiasis in neighbouring Sudan seem to be much lower, the basis of which is still not clear (18). The epidemic of schistosome (past or present infection) and HCV infections in Egypt also revealed synergies in liver disease progression resulting from these two pathogens. Several studies have shown that patients co-infected with schistosomiasis and HCV infections suffer from an increased rate of liver fibrosis than would be present with either disease alone ultimately leading to a more advanced liver disease (19– 28); although, other studies have not illustrated a direct causal linkage between the two infections (29–31). One possible reason for the elevated fibrosis is from the shift