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Editorial: Circulating antibodies and antigens in schistosomiasis.

Most of the major endemic infectious diseases in tropical countries have shown a proportional decrease in prevalence with the increase in their economic growth. Schistosomiasis is an exception: in many areas economic development consequent on the provision of water resources either for irrigation or for hydroelectricity has caused an increase in the numbers of water snails, the intermediate hosts of the parasites. The result has been that the disease has not only become more prevalent in much of the tropical world but its severity (which is related to the parasite densities in the individual) has also increased, owing to more intense transmission. Many of the more severe complications of schistosomiasis are due to fibrosis, such as the clay-pipe-stem fibrosis of the liver first described by St. Clair Symmers and the fibrosis of the urinary system which leads to the contracted bladder and hydronephrosis. These complications are the end result of a granulomatous reaction around the eggs in the tissues, and it has been shown that this is mainly due to a cell-mediated immunological response.' Damage to the kidneys may also occur as a result of immunological reactions, with the deposit ofimmune complexes in the glomeruli.2 3 The amount of infection in the individual and in the community may be determined by detecting eggs in the urine of patients with Schistosoma haematobium and in the faeces of patients with S.mansoni and S.japonicum, but there are difficulties in collecting specimens in field surveys, and especially repeated specimens, for the evaluation of control measures. Many attempts have been made to develop alternative immunodiagnostic methods; methods now in use include skin tests, complement fixation, haemagglutination, fluorescent antibody, or a variety of gel diffusion tests all dependent on the demonstration of antibodies. But they all suffer from the same defects, in that they often produce non-specific cross reactions with other helminths and especially with other species of schistosomes from birds and animals -for example, the schistosomes of birds which produce swimmer's itch. This common dermatological condition occurs in most parts of the world: it affected competitors in a water skiing competition at Rickmansworth in Britain in 1970 and several of the patients produced positive serological reactions for schistosomiasis.4 A similar situation with false positive fluorescent antibody reactions has been reported from Sardinia, where there is no human schistosomiasis, but where S.bovis is common in cattle.5 Though these cross reactions cause considerable confusion in diagnosis they may be to some extent protective-the phenomenon of zooprophylaxis, defined6 as "the prevention or amelioration of disease in man as a result of previous exposure to heterologous infection of animal origin" and first exploited by Jenner in the use of cowpox to protect against smallpox. Attempts to measure antibodies in the sera of patients suspected of being infected with schistosomiasis are not only plagued by these non-specific reactions; they are also confused by the fact that antibody titres are not indicative of active infection, nor is there any correlation between antibody levels and parasite densities or with the degree of resistance to reinfection, and false negative reactions may occur in people who are passing eggs.7 Measurement of antigens secreted in the urine might be thought likely to be more informative, but experimental studies have shown that they can be detected only in massively infected animals with parasite densities far in excess of anything recorded in man.8-10 More recent observations by Madwar and Voller" and Phillips and Draper12 from the London School of Hygiene and Tropical Medicine and by Mary Smith and her colleagues from the nephrology unit in the Claude Bernard Hospital in Paris have suggested that either free antigen or antigen-antibody complexes may be detected in a considerable proportion of patients with schistosomiasis. The circulating antigen was detected by a gel diffusion method and complexes unmasked either by splitting with citric acid and detecting both antibody and antigen by counter-current immunoeletrophoresis or by showing inhibition of complement-dependent rosette formation. These observations are of immediate relevancefor the diagnosis and understanding of some of the pathological features of schistosomiasis. The methods used may have a wider application in other parasitic infections and in other diseases where circulating immune complexes are ofimportance.