Data on incidence of cervical cancer by histologic subtype and mortality for the Canadian provinces of Ontario, Saskatchewan, and British Columbia were used to examine time trends by age, calender period, and birth cohort. Age-adjusted incidence rate of squamous cell carcinoma of the cervix decreased from 11.1 per 100,000 women in 1970-72 to 5.3 in 1994-96, while the rate for cervical adenocarcinoma increased from 1.1 per 100,000 women to 1.5 over the same period. Age-adjusted mortality rate declined from 7.9 per 100,000 women in 1953-55 to 1.9 in 1995-97. The patterns in age-specific mortality rates in 1953-72 were different from those in 1973-97; younger women experienced larger reductions in mortality during the earlier period while older women benefited to a greater extent during the latter period. Age-period-cohort modeling showed that cohort effects were responsible for the decreasing trends in incidence of squamous cell carcinoma of the cervix and increasing trends in adenocarcinoma, and both period and cohort effects account for the observed trends in mortality. The results suggest that Pap smear screening has played a significant role in the reduction in squamous cell cervical carcinoma. The causes for the increase in cervical adenocarcinoma are unclear.
Host immune responses have been shown to enhance the efficacy of several schistosomicidal drugs. The evidence derives mainly from experiments on Schistosoma mansoni infections in the mouse with their immune status variously modulated; this review emphasises praziquantel (PZQ), which is now the main drug used for treatment of human schistosomiasis. Electron microscopy and indirect immunofluorescence indicate that PZQ disrupts the integrity of the surface membranes of S. mansoni, particularly those covering the dorsal tubercles of adult male worms, and this causes antigens which are the targets of antibody attack to be revealed. We review the evidence that two S. mansoni antigens in particular are implicated in the immune-dependent action of PZQ: a 200 kDa glycoprotein and a 27 kDa antigen with non-specific esterase activity. Consistent with the involvement of the latter antigen, increased non-specific esterase activity was demonstrated histochemically on the surface of intact PZQ-treated male worms, and we describe a chromogenic substrate assay for quantifying the amount of esterase activity that is exposed after drug treatment. The potential relevance of these observations for enhancing the efficacy of drugs currently used to treat human schistosomiasis, and for devising novel therapeutic strategies, is discussed.
Male and female BK-TO mice were infected with different numbers of Schistosoma mansoni cercariae under standard environmental conditions. Promutagenic methylation damage (O6-methyldeoxyguanosine; O6-MedG) was detected in liver DNA, but not in kidney, spleen or bladder DNA of infected animals. It was shown that levels of hepatic O6-MedG increased with increasing intensities of schistosomal infection. Possible mechanisms of action are discussed. These include the activating effects of schistosomes and their products on murine macrophages and subsequent endogenous formation of N-nitroso compounds by the activated macrophages.
Three species of bulinid snails were monitored to determine the effect of infection with 2 sympatric strains of Schistosoma haematobium on longevity, growth, and reproductive output, from the onset of cercarial production until death. Bulinus senegalensis was least affected by infection, with total fecundity reduced by less than 34%. Infected Bulinus truncatus showed an acceleration in growth accompanied by a 63% reduction in fecundity, although the majority of snails continued to oviposit at a low level. The longest-lived snails in this study, Bulinus globosus, showed decreased growth and survival when infected. In addition a significant proportion of infected individuals of this species failed to oviposit, and those that retained some reproductive capacity produced fewer embryos than controls. Total fecundity of B. globosus was reduced almost 90% by infection with S. haematobium, yet long-term monitoring of individuals showed that reproductive activity recovered when parasite productivity was low. Results from this and similar studies indicate that the time of infection by a trematode in relation to reproductive maturity of the molluscan host is important in determining the subsequent effects on host growth and fecundity.
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