Puberty and Age-intensity Profiles in Schistosome Infections: Another Hypothesis

Abstract

In an excellent focus article on puberty and age-related changes in susceptibility to schistosome infection, Fulford et al.[1xFulford, A.J.C. et al. Parasitol. Today. 1998; 14: 23–26Abstract | Full Text | Full Text PDF | PubMed | Scopus (91)See all References[1]provide a new explanation for the characteristic age-intensity profile in areas where schistosomiasis is endemic. An age-dependent host factor seems to override—at least during adolescence—the variation in intensity of infection expected both from the variability of exposure with changing age and from the dynamics of acquired immunity. Fulford and colleagues put forward the hypothesis that physiological changes in the production of sex hormones could be one explanation. The authors explore how sex hormones might exert a regulatory effect on the immune system, eventually leading to an increased resistance to infection. Other modes of action by which sex hormones, particularly in females, may influence parasites are only mentioned briefly, but not commented on.Pelvic vascularization alters when girls enter puberty, resulting in multiple anastomoses between the rectal and the vesical plexus, and between the plexus of external and internal genital organs[2xSee all References, 3xSee all References]. These adaptive changes are accentuated during pregnancy. As adult worms tend to migrate, the adaptive changes in pelvic vascularization add to the chance that parasites reach the adjacent vascular beds, thereby increasing the probability of a settlement in female genital organs. In fact, at least in Schistosoma haematobium infection, involvement of external and internal genital organs is extremely common. Of women infected with this parasite species 40–80% are considered to have manifestations in the lower reproductive tract[4xFeldmeier, H. et al. Trop. Geogr. Med. 1995; 47: 1–15See all References, 5xKjetland, E. et al. Acta Trop. 1996; 62: 239–255Crossref | PubMed | Scopus (65)See all References, 6xLeutscher, P. et al. Acta Trop. 1997; 66: 27–34Crossref | PubMed | Scopus (27)See all References]. How many women also have worms located in the internal genital organs is unknown; post-mortem studies in female schistosomiasis patients, however, show that the ovaries, the fallopian tubes and the uterus are affected in 10–80% of cases[7xEdington, G.M. et al. Trans. R. Soc. Trop. Med. Hyg. 1971; 20: 846–849See all References, 8xGelfand, M. and Ross, W. Trans. R. Soc. Trop. Med. Hyg. 1953; 47: 218–220PubMed | Scopus (17)See all References, 9xYoussef, A.F. et al. J. Obstet. Gynaecol. Br. Commonw. 1970; 77: 847–851Crossref | PubMedSee all References].A shift of adult worms to topographic sites from which eggs cannot reach the lumen of the bladder, and thus are not excreted, obviously has an important consequence on age-intensity profiles: even if reinfection rates remain unchanged, egg excretion in urine will diminish and thus create the impression that there is an age-associated decrease of intensity of infection with onset of puberty.Two lines of evidence support this assumption. First, according to the literature, female genital schistosomiasis (FGS) occurs mainly after girls have reached sexual maturity[4xFeldmeier, H. et al. Trop. Geogr. Med. 1995; 47: 1–15See all References[4], ie. at an age when intensity of infection—as measured by egg excretion—decreases. Recently, these clinical observations were supported by data from a community-based study in Tanzania; the existence of FGS as measured by the presence of eggs in cervical biopsies and the prevalence/intensity of egg excretion in urine were inversely correlated during adolescence (Poggensee et al., unpublished).Second, if with the beginning of puberty a topographic shift of adult worms, rather than a diminished worm burden, is responsible for a decrease of egg excretion in urine, then the simultaneous measurement of egg excretion and circulating antigens should provide an important clue. Agnew et al.[10xAgnew, A. et al. Am. J. Trop. Med. Hyg. 1996; 55: 338–343PubMedSee all References[10]examined S. haematobium- or S. mansoni-infected populations for egg excretion as well as circulating anodic antigen (CAA). Schistosoma haematobium egg output relative to serum CAA was significantly reduced with onset of puberty. Nothing like that was observed in patients infected with S. mansoni, a parasite less commonly affecting the genital tract[4xFeldmeier, H. et al. Trop. Geogr. Med. 1995; 47: 1–15See all References[4]. Moreover, the effect observed by Agnew et al.[10xAgnew, A. et al. Am. J. Trop. Med. Hyg. 1996; 55: 338–343PubMedSee all References[10]was highly significant in women, but not in men, whose genitals are less frequently affected by ectopic schistosomiasis.Taken together, these circumstantial facts favour the hypothesis that in S. haematobium infection in women yet another mechanism may explain the familar age-intensity profile with the typical decline of the curve after onset of puberty. Whether vascular changes induced by sex hormones during puberty and pregnancy and subsequent anatomical compartmentalization of adult worms also have a regulatory effect on protective immune mechanisms is another intriguing question. The dynamics of schistosomiasis are probably much more complex than we still know. Why should it not be different between women and men?