The author describes a number of important studies carried out at the U.S.A. Dengue Research Unit established by the Army Department in 1944 at Cincinnati to investigate the possibility of improving methods of prevention and diagnosis of dengue.

Several papers dealing with various aspects of the dengue problem have already been published by the author and his colleagues; abstracts of most of these will be found in this Bulletin in the years 1945, 1947, 1948 and 1949. In the present paper many of the remaining gaps in knowledge of the virus of dengue have been filled by the author and his team of experts who enjoyed the great advantages of having at their disposal exceptional laboratory facilities, a large and constant supply of human volunteers and numerous samples of sera from dengue patients. Infected serum, even after prolonged storage in dry ice, was found to contain up to a million human infective doses per ml. The size of the virus particles was found to be 12-25 millimicrons (mu) and by electron microscopic examination dumbell-shaped bodies were found in highly infective human serum.

Numerous attempts at direct cultivation of the virus in yolk sacs completely failed but after adaptation by passage through mice successful passages were made. The disease was caused in volunteers by instilling large doses of the virus into the nose or conjunctiva; smaller doses-up to 10, 000 minimum infecting doses-gave negative results. Infective serum in the frozen state remained active for long periods, up to 5 years in one case. The virus was inactivated by 0.05 per cent. formalin.

Volunteers remained immune after an attack, up to at least 18 months against challenge inoculation with the same strain, but against a heterologous strain the immunity was partial and lasted only about 2 or 3 months.

Two distinct immunological types of virus were found; one included a strain from Hawaii, two strains from Calcutta and one from New Guinea.

Three other strains from New Guinea belonged to the other types. The 4 strains from New Guinea were isolated from patients who had no rash, and two of them were from patients whose febrile attacks lasted only about two days, yet the inoculated volunteers developed typical dengue with a rash.

The authors suggest that atypical cases of dengue may be due to reinfection with heterologous strains; they refer to the frequent finding that cases which medical men refused to diagnose as dengue were proved by human inoculation and by immunological tests to be caused by the virus of dengue.

The simultaneous inoculation of volunteers with yellow-fever vaccine and dengue virus, the latter in amounts ranging from 10 to 1, 000, 000 minimum infecting doses, was followed by short mild attacks of dengue with a prolonged incubation period. The same result followed when the dengue virus was injected 7 days after the yellow fever vaccine, but when the interval between the injections was 5 weeks a typical attack of dengue occurred. Six out of 7 rhesus monkeys survived inoculation with lethal doses of yellow fever virus when these were given 2-3 days after the animals had been inoculated with dengue virus. When the interval between the two injections was one month 6 of the 8 experimental monkeys died. Aëdes mosquitoes infected with dengue were found incapable of transmitting yellow fever to monkeys in conditions in which normal mosquitoes readily transmitted the infection; this finding suggests to the author that yellow fever infection introduced to an area in whioh dengue is endemic may fail to establish itself among the local mosquitoes.

By repeated intracerebral passage through very young mice the virus …