Epidemiology and geographical distribution

More than 80% of human opisthorchiasis cases in Russia belong to West Siberia. The highest prevalence and intensity of O. felineus infection in man are in the middle and middle-lower reaches of the Ob-Irtish river basin with its peak in Hanti-Manssi Autonomous District (HMAD) (Zavoikin 1990). The prevalence of O. felineus infection in the aboriginals (Hanti, Manssi, Komi-zirjane) of HMAD, appeared to be 100% in 10-year-olds. In spite of 15-20 years (1965-1980) of mass chloxyl (hexachlorparaxylol)

treatment, the prevalence remains at this level until the end of a life. However, egg output, which was 21924 ± 8502 per gram in untreated groups, became two-fold lower. The percentage of patients with clinical manifestations of the infection among the treated and untreated individuals was the same: 34.3 and 34.9, respectively (Bronstein 1986a). Prevalence of the infection after mass treatment in HMAD settlers (mostly Russians living there for generations), was 91.7% in

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15-19-year-olds. This went up to 100% in the 20-39-year-olds, with an egg output of 8292 per gram, decreasing to 70% in older age groups. No correlation between the intensity of infection and the rate of morbidity have been found in either group (Bronstein and Ozeretskovskaya 1985). In Jamalo-Nenezki Autonomous District (JNAD) (the western riverside of the Ob river's lower reaches) the prevalence of the disease after chloxyl mass treatment remained up to 63.6-70.6% with a low egg output (22-277 per gram). The mean prevalence of O. felineus infection in Komi-Permyatsky Autonomous District (KPAD) (the main hyperendemic foci in riverside parts of Kama basin) was up to 46%, with egg output of 392 ± 91 per gram. In the aboriginal of KPAD, the prevalence reached 73.9% by the age of 30-39 years, with a three-fold decrease at 60 years of age. In spite of a much lower intensity of infection, the percent of clinically manifesting cases of gastrocholepaty in KPAD population was two-fold higher than in HMAD (53.8 and 27.7%, respectively). The intensity of infection in the latter was almost 20-fold higher (Bronstein and Ozeretskovskaya 1985). The prevalence of infection in the upper-middle reaches of the Ob and the Irtish rivers is up to 40-60%. Opisthorchiasis is hypoendemic with 1-10% prevalence in the western riverside regions of the Enisei river and in some settlements of the Don and the Pripjat rivers basins. The incidence of human opisthorchiasis in the European part of the Russian North (Leningrad, Arkhangelsk regions) is low or sporadic (Zavoikin 1990).

Opisthorchiasis became an especially acute social and economic problem from the early 1960s with the boom of gas and oil resource exploration in West Siberia and a mass migration there of non-immune population. After having been known as a primarily chronic infection for 70 years (see above), the disease appeared as an acute and severe one with allergic manifestations in 14.5-26% of infected newcomers (Pavlov 1990). From 20 to 30% of these became infected in the first 2 years after arrival, about half got the infection in the next 5-10 years. Symptoms of gastrocholepathy in infected newcomers registered 5 years after arrival were three-fold more frequent than in non-infected ones: 48.4 and 18.6%, respectively (Ozeretskovskaya 1979, 1982). The special surveys conducted in HMAD and in JNAD in the late 1980s and the early 1990s revealed the absence of clinical signs of the acute phase of the disease in the aboriginal in the past (Ozeretskovskaya et al. 2001). However, 45% of settlers' group and 14.5% of newcomers (migrants) suffered from an acute phase. Sub-clinical course of the disease has been found in 85.1, 50.0, and 30.5% of the same groups, respectively. Trans-placental transmission of O. felineus antigens has been revealed in aboriginals and in some settlers, but not in newcomers. Minimal in vitro lymphocyte transformation responses to parasite antigen but normal responses to the mitogen PHA were found in aboriginals (Parfenov et al. 1989). Therefore, the long-term clinical and field study of O. felineus infection revealed principal differences in the pattern of the disease in the foci with the different endemicity and in different population groups. The earlier in life infection had been acquired and the heavier the infection (re-infection) was, appeared to associate with the less severe clinical manifestations. One presumes that the indigenous population may have developed some form of unresponsiveness to parasite antigens or capability to mount the effective level of immune responses that minimize parasite's development and damage (Ozeretskovskaya 1975, 1982; Ozeretskovskaya and Sergiev 1993). The appearance of genetic heterogeneity in response to infection [genetic adjustment (Capron 1995)] leads to optimal fitness of host-parasite relationships (Wakelin 1994) can probably play a role too.

The attempt to control opisthorchiasis by mass chloxyl treatment was a failure determined by the moderate activity of the drug itself and the high rate of re-infection due to the

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persistence of the habit of a raw fish consuming in the population (Bronstein et al. 1987; Sergiev 1989). The programme of 'Supressive-radical (or selective-radical) therapy of O. felineus infection in endemic foci' was proposed in the end of the 1980s (Sergiev 1989). That was based upon the principles of WHO programme of schistomiasis control and the programme of opisthorchiasis control in Thailand. According to these, azynox (praziquantel) treatment (40mg per kg of body weight, if necessary repeated 6-12 months later) should be used in all clinically manifesting and/or intensively infected cases in foci with an endemicity of more than 40%. The idea was to diminish the unfavourable pressure of the high rate of infection in individuals rather than to eliminate infection in endemic foci.

Selective-radical biltricide (Bayer-Merck) therapy was used in KPAD, in an aboriginal settlement with a prevalence of the infection of 84.4% and a mean egg output of 1588 per gram. The results showed an efficacy of 85.9% (cured or with a considerably diminished egg output) at six months and 81.5%, 12 months later. Side effects were registered in 89.7% of cases. Clinical efficacy of the treatment was 25.8% only (Bronstein et al. 1989). Praziquantel (India) therapy with the dose of 25-50mg was applied in two settlements in INAD with a mixed population (aboriginals, settlers, migrants). The prevalence of O. felineus infection there was 40.5 and 45.7% and the mean egg output about 200 per gram. Mean curerate 6 and 12 months later was 92.5 and 90%, respectively. Side-effects of a pharmacological nature were registered in 45.3% of patients. Allergic symptoms appeared in 10% of settlers and in 30% of newcomers. In total 18% cases of side effects were revealed in aboriginal and 60% ones in settlers and migrants. Clinical efficacy of the treatment was revealed in 58.6% of patients, or two-fold higher than in KPAD (Bronstein et al. 1991). The difference of efficacy was connected possibly with a higher (average) doses of the drug, a lower intensity of infection in the patients of JNAD and/or with a higher potential to cure short-term opisthorchiasis. The lower percent of side-effects in aboriginal patients seems to be an additional marker of their tolerance to the effects of O. felineus antigens (Ozeretskovskaya and Sergiev 1994).

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