ArticlesThe role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt
Introduction
Egypt has a very high prevalence of antibody against hepatitis C virus (HCV)1, 2, 3 resulting in a high morbidity and mortality from chronic liver disease, cirrhosis, and hepatocellular carcinoma. Around 20% of blood donors are seropositive by ELISA for antibodies to HCV.1 Children have lower rates of disease, but prevalence rises steeply with age.4, 5 Desert areas of Egypt have the lowest rates of infection and cities have lower rates than rural areas. Rates in the Nile Delta (Lower Egypt) are higher than in the Nile Valley (Middle Egypt and Upper Egypt).1, 3, 6, 7 Egypt has a much higher prevalence of antibodies to HCV than other countries in the region and elsewhere with comparable socioeconomic conditions and hygiene for invasive medical, dental, or paramedical procedures. The strong homogeneity of HCV isolate subtypes in Egypt (90%)8, 9, 10, 11 suggests an epidemic spread of HCV throughout the population.10
A very potent mode of transmission for blood-borne pathogens, that sets Egypt apart from other countries, is the extensive use of parenteral antischistosomal therapy (PAT) in a mass-treatment setting. A history of this type of therapy, discontinued only in the 1980s, has been previously implicated as a risk factor for HCV2, 3, 12, 13, 14, 15 and hepatitis B virus (HBV)16, 17 antibody positivity.
Schistosomiasis in Egypt dates back to dynastic times.18 Treatment of schistosomiasis became possible in Egypt in 1918 when J B Christopherson in the Sudan discovered that a series of injections with the antimony salt “tartar emetic” (potassium antimony tartrate) could kill the blood flukes and cure the patient. In Egypt, the country with the world's greatest schistosomiasis problem, PAT has been extensively practised since the 1920s. Rural health centres and travelling clinics dispensed PAT in the form of mass treatment.
Among the antimony-based PAT drugs, a few could be administered intramuscularly such as stibophen and stibocaptate, however, tartar emetic was the most widely used in Egypt. The recommended treatment regimen was 12–16 intravenous injections.19 Although these doses were originally administered over 2–3 weeks, after 1960 spacing was changed to one injection per week to lessen patients discomfort.20 Where sterilisation procedures were carried out, the observed period of boiling for the reusable injection equipment was often less than 2 min. However, it is likely that sterilisation between patients was commonly omitted because of equipment and time constraints. Patients in all stages of treatment and of all age-groups, except for children less than 6 years of age, were treated in a mixed setting.20 Egyptians in rural occupations often received multiple courses of tartar emetic in their lifetime.
Problems associated with PAT included variable cure rates, high rates of re-infection, and dangerous adverse effects.21 Most seriously, mass PAT campaigns to control schistosomiasis had great potential to transmit blood-borne pathogens, specifically HCV, because tartar emetic was given in multiple doses by intravenous injection and with insufficiently sterilised injection equipment to people of all age-groups and treatment stages in a mass setting. This would confer a higher risk of transmission among patients than in vaccination campaigns, where injection equipment was mostly reused among children who would have a low background prevalence of HCV infection. The long duration of the full course of tartar emetic and typical onset of hepatitis C viraemia within 2–4 weeks, would have allowed for those infected with HCV early on in treatment to develop infectious viraemia while still receiving injections. Thus, effective cycles of infection within the treatment units could have been established and sustained. These outbreaks would probably have gone unnoticed because of the absence of acute clinical symptoms in about 80% of recent infections with HCV, the masking side-effects of PAT, and the patients' underlying schistosomiasis. More noticeable outbreaks of hepatitis caused by HBV were probably commonplace and commonly considered to be reactions to the tartar emetic. Moreover, immunological effects of chronic schistosomiasis might make individuals less likely to clear HCV after infection.13, 22
The first effective oral medications against Schistosoma haematobium—metrifonate and niridazole—became available in the 1970s. Praziquantel, which also has a high cure rate for S mansoni, became available in Egypt in 1982 and has been the treatment of choice there since the late 1980s.23
We investigated the relative importance of PAT in the spread of HCV throughout Egypt, by comparing cumulative lifetime exposure to PAT with current cohort-specific prevalence of antibodies to HCV. We hypothesise that widespread PAT with inadequate sterilisation procedures, particularly during large schistosomiasis control programmes, was a major factor in the spread of HCV throughout Egypt.
Section snippets
Participants
The HCV transmission potential associated with PAT was assessed from contemporary sources, mainly documents from WHO archives in Geneva and other reports.20
Data on annual PAT use by governorate (administrative level comparable to a state) were provided by the Egyptian Ministry of Health and Population. The data represent all PAT done in endemic disease units and widespread rural referral centres for endemic disease treatment between 1961 and 1986, after which use of PAT stopped. To our
Results
Figure 2 describes the use of PAT in community health centres between 1961 and 1986. The data show the dominance of PAT with tartar emetic in Egypt while intramuscular antimony-based drugs, like stibophen and stibocaptate, had little effect on the overall treatment effort. Between 1964 and 1982 more than 2 million PAT injections per year were given to an average of 250 000 patients. Between 1966 and 1969 more than 3 million injection doses were annually administered, over 96% were tartar emetic
Discussion
The rate and geographical pattern of prevalence of antibodies to HCV in Egypt confirm the high prevalence and its distribution reported in previous studies.1, 3, 6 This pattern corresponds to the distribution of schistosomiasis in this century.25 Whereas Lower Egypt has always had high rates of schistosomal infection, prevalence in Middle and Upper Egypt increased only as a result of conversion from basin to perennial irrigation. City dwellers have always had lower rates of schistosomiasis.
The
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