A. W. Downie

The use of vaccinia hyperimmune gamma-globulin in the prophylaxis of smallpox.

This paper records an attempt to assess the prophylactic value of immune gamma-globulin, 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.

Antibody response in non-haemorrhagic smallpox patients.

Various studies have been made on the antibody response in smallpox. In some of these haemagglutinin inhibition tests (HI) have been used for measurement of antibody (Collier & Schonfeld, 1950) in others, complement-fixation tests (CFT), precipitation tests (pt.) and HI tests (Herrlich, Mayr & Mahnel, 1959) or CF, HI and neutralization tests (Downie & McCarthy, 1958). In the present study, all four tests were used and the findings have been used for a comparative study of cases of haemorrhagic smallpox and for assessment of possible subclinical infection in contacts of smallpox patients and the antibody response in minimal infections.

Antibody response following smallpox vaccination and revaccination

Three groups of post-vaccination sera were studied for vaccinial antibody by precipitation, haemagglutinin-inhibition, complement-fixation and neutralization tests. All sera were negative by precipitation and many by haemagglutinin-inhibition and complement-fixation tests, but most showed neutralizing activity at serum dilutions of 1/10 or higher. The differences in antibody titres between the three groups of sera were most probably related to the past history of revaccination. 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.

Conjunctivitis and subclinical infection in smallpox.

Attempts were made to demonstrate variola virus in the conjunctival exudate of 84 smallpox patients who developed conjunctivitis in the acute stage of the illness or during convalescence. Variola virus was isolated from 60 but not from the remaining 24. Of the 64 from whom virus was isolated the conjunctivitis developed from the onset up to the 15th day of illness. From conjunctivitis developing later virus was not recovered. In some patients who developed conjunctivitis early in the disease we failed to recover virus from the conjunctival exudate. Of 55 close family contacts who stayed in hospital with smallpox patients four developed smallpox. In 21, conjunctivitis but no other illness developed. From 12 of these, variola virus was recovered from the conjunctival exudate and four of these 12, who were further investigated, showed after the appearance of conjunctivitis antibody titres similar to those seen in typical smallpox cases. From nine of the contacts who developed conjunctivitis virus was not recovered. One of these had antibody titres in serum collected before the onset of conjunctivitis which indicated recent smallpox infection. In another there was a marked antibody rise during her hospital stay although examination of conjunctival exudate on three separate occasions failed to yield variola virus. Twenty-six family contacts who developed no illness in hospital had antibody determinations made on sera collected soon after admission to hospital. In eight of these antibody titres were such as to indicate recent smallpox infection although there were no signs, in the form of scarring, or history of recent smallpox infection. These findings have been discussed in relation to the occurrence of minimal and subclinical infection in close family contacts of smallpox patients. 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.

Comparison of dried vaccine with fresh Indian buffalo-calf lymph in revaccination against smallpox

It was known that the liquid glycerinated buffalo-calf lymph issued for routine use in smallpox vaccination in Madras gave a high take rate in primary vaccination but that successful takes on revaccination amounted to less than 10%. In the course of studies on smallpox carried out in Madras, it was therefore decided to compare a potent freeze-dried English vaccine with the current Madras lymph by revaccinations carried out on persons admitted to the Madras Infectious Diseases Hospital for ailments other than smallpox. The take rate of the freeze-dried preparation in these tests was 63% as against 27% for the liquid preparation. It would seem that, in the conditions prevailing in Madras at the time of the tests, the local lymph is not sufficiently potent for successful revaccination or for maintaining the immunity of the population at a satisfactory level. The authors suggest that freeze-dried vaccine produced in embryonated eggs might be more effective and economical.