This paper records an attempt to assess the prophylactic value of immune gammaglobulin, prepared from the serum of recently vaccinated adults, in the protection of close contacts of smallpox in Madras. The results serve to confirm findings of a previous study made in Madras in 1953, and show that the incidence of smallpox in close contacts given immune gamma-globulin prophylactically was about a quarter of that in the control contacts who received no such passive immunization-a statistically significant difference. Because of the limited supply of immune gamma-globulin, it is likely that its prophylactic use will be restricted to those especially at risk, for example, close unvaccinated family contacts, newborn infants and pregnant women.In a previous field trial of hyperimmune gammaglobulin for the prevention of smallpox'1 the number of cases involved was insufficient to give conclusive evidence of prophylactic value, although the results were highly suggestive. For this reason, the experiment was repeated in a co-operative venture involving the

SUMMARYIn practically all acute fulminating smallpox infections—haemorrhagic type I cases—there is severe viraemia with 104 or more infective particles of virus per ml. of blood. In most of these patients soluble antigen can be demonstrated in serum by precipitation in agar gel tests, or by the complement-fixation technique. In late haemorrhagic cases (type II) the degree of viraemia is less and soluble antigen is less often demonstrated in the blood. Five of forty type II patients recovered. The majority of the 77 patients studied were adults and bore scars of previous vaccination. Thirteen were pregnant women and 10 of these suffered from type I infections.The antibody response in patients who survived 6 days or longer as determined by the estimation of precipitins, CF antibodies and neutralizing antibodies in serum, was considerably less than that seen in non-haemorrhagic smallpox patients.In acute fulminating smallpox infections, the finding of virus or soluble antigen in the blood is of value in establishing the diagnosis. Soluble antigen is usually found in the blood of patients suffering from severe viraemia and with the methods used has been demonstrated only in patients who are to die of their disease. Haemorrhagic smallpox represents a generalized virus infection of unusual severity in patients who show little resistance to their infection. The cause of this unusual susceptibility is unknown but there is little evidence that specific allergy to the virus is a feature of this form of the disease.This investigation was supported in part by Public Health Service Grant AI–1632–16 VR from the National Institute of Allergy and Infectious Diseases, by the World Health Organization and by the Marcus T. Reynolds III Fund.

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