Notes: Summary Inoculation of influenza virus into the upper respiratory tract of monkeys may result in the development of necrosis and desquamation of the epithelium, peribronchiolar and interalveolar oedema, and limited foci of pneumonitis. Staphylococcus aureus, when inoculated by the same route, may produce a slight bronchiolitis, without epithelial necrosis, and limited foci of bronchopneumonia, the cellular infiltration being leucocytic in character. Simultaneous inoculation of both influenza virus and staphylococci produces bronchiolitis with epithelial necrosis, and bronchopneumonia. Necrosis of epithelium, which is the main lesion produced by the influenza virus, may occur either through the entire respiratory tract, or may be limited to the bronchioles. As a matter of fact, epithelial lesions in the entire respiratory tract were common in monkeys inoculated with both virus and staphylococci, whereas they were mostly limited to the bronchioles in monkeys inoculated with influenza virus only. This might suggest, that the staphylococcal infection has some unfavourable influence on the resistance of the epithelium to infection with influenza virus. On the other hand, the penetration of staphylococci is apparently facilitated by the epithelial lesions and the pulmonary oedema produced by the influenza virus.

Notes: Summary Demyelinating encephalitis, very closely resembling postvaccinal encephalitis in man, has been produced in one cynomolgus monkey following vaccination against smallpox and simultaneous inoculation of a virus of the Columbia SK group, which had been isolated from stools and throat of a child suffering from postvaccinal encephalitis. Since this result was not reproducible in two subsequent experiments, it is emphasized, that a most reserved attitude has to be adopted as to the aetiological significance of the combined activity of neurotropic virus and vaccinia virus for postvaccinal encephalitis.

Notes: Summary and conclusions In cynomolgus monkeys fed the Mahoney strain of type 1 poliomyelitis virus, and bled to death after varying intervals following administration of the virus, several tissues were examined for the presence of virus by the tissue culture method using HeLa cells. The tonsils were found to be the primary sites of multiplication of the virus, from which viraemia regularly developed and was demonstrable from the 5th to the 8th day after feeding. The virus was demonstrated in several organs, i. e. spleen, liver, muscle tissue, lymph nodes, gastro-intestinal wall, nerve plexus and peripheral ganglia during the period of viraemia. The wall of the colon, however, contained already virus before viraemia was demonstrable. The presence of virus in the wall of the gastro-intestinal tract, and faecal excretion were only transitory, so that the intestinal phase does not seem to be very important in the cynomolgus monkey. Since the virus could be demonstrated in the central nervous system as late as 3 days after the last day of viraemia, it is suggested, that the CNS might not be invaded by direct haematogenous spread, but by secondary neural spread from the haematogenously invaded peripheral nerves and ganglia. In cynomolgus monkeys fed the Saukett strain of type 3 poliomyelitis virus immediately before and after tonsillectomy, the virus was shown to be present in the glossopharyngeal nerve before the period of viraemia. This suggests that bulbar forms after tonsillectomy may be a result of primary neural spread. In monkeys, which had received one intramuscular injection of aluminium phosphate-precipitated diphtheria toxoid in the right thigh, virus was demonstrated in the corresponding sciatic nerve from the third day of viraemia. This suggests a secondary neural spread of the virus from the haematogenously invaded muscle, which shows a local damage produced by the intramuscular inoculation.

Notes: Summary The monkey neurovirulence of 5 strains of type 1 and 5 strains of type 3 poliovirus isolated from stool specimens of healthy children in day nurseries, and from water samples taken from several sewage purification plants during a five-year period (1964–1968) has been examined. The neurovirulence was shown to vary between that of highly neurovirulent prototype strains (Mahoney of type 1 and Saukett of type 3) and that of oral vaccine strains. The majority of the strains examined appeared to possess an “intermediate” neurovirulence. They are considered as naturally occurring “wild” polioviruses.

Notes: Summary Fifty-four harvests of 7 different strains of vaccinia virus present in calf lymph used as smallpox vaccine have been examined for virulence, antigenicity, and resistance to neutralizing antibody, and the results were compared with those of a similar examination of smallpox vaccines that had initiated postvaccinal encephalitis. In 3 of 6 cases of post vaccinal encephalitis, the antibody level was poor, and did not agree with the high antigenicity of the virus. In one case, a child that had been vaccinated with a vaccine of low antigenicity, vaccinia virus was recovered from the blood on the 15th day following vaccination. It is suggested, that individual factors may inhibit the production of neutralizing antibody, and in animal experiments, guanidin appeared to exert such an inhibitory effect, although slight and transient. A considerably higher antibody level was obtained when rabbits and children were revaccinated on the 7th day following primary vaccination, but then the virus could be recovered from the blood from the second to the eighth day following revaccination, which proves, that the virus is not rapidly inactived in spite of the high antibody level. Immunization experiments with heat-inactivated neurovaccinia, even when incorporated in vaseline and lanoline, were unsuccessfull, since the resistance to challenge with living neurovaccinia, particularly of the central nervous system, proved unsatisfactory, although antibodies had developed. Softened foci of the brain and encephalitis could be produced by intracerebral inoculation of rabbits with mixtures of neurovaccinia, vaccinia immune serum and brain tissue, but no demyelination was observed. Bovine protein, vaccinia virus grown on the chorioallantoic membrane of the chick-embryo, and bacteriologically sterile calf lymph failed to produce demyelination after repeated injection into rabbits. Only in one rabbit, that had been injected intracerebrally with calf lymph, and that received two subsequent intramuscular injections with the same material, developed a demyelinating encephalopathy, which, however, was not identical with the demyelinating lesions in human beings suffering from postvaccinal encephalitis. It is suggested, that the vaccinia virus may produce the inflammatory lesion in the wall of the blood vessels, but that the virus particle itself has no direct action on the myelin sheaths.

Notes: Summary The A. K. strain of poliomyelitis virus, and the F strain of the Columbia SK group of viruses were adsorbed on aluminium hydroxide or on alu-Archiv f. Virusforschung, Bd. V, H. 1. minium phosphate, and subsequently partly or completely inactivated by ultraviolet irradiation. The adsorbates were inoculated intracerebrally or intramuscularly into rhesus and cynomolgus monkeys. The rate of adsorption on aluminium phosphate was higher (practically 100 percent) than on the hydroxide, and the attachment to the former was extremely fast, so that it did not produce paralysis following intracerebral inoculation. Fifty per cent of the monkeys that received two or three intramuscular injections with 1 ml of the inactivated adsorbate vaccine proved resistant to 100 PD50 of intracerebrally inoculated homologous virus. When vaccinating with attenuated adsorbed virus, 55 to 100 percent of the animals proved resistant to the challenge dose. In vaccinated mice neutralizing antibodies developed. The suitability of similarly prepared vaccines in human beings is discussed.