When Fred Soper became the Rockefeller Foundation's regional representative in late 1927, Brazil's Federal Yellow Fever Service (established ca. 1917) had yellow fever under control in most areas, and had been working with the Rockefeller Foundation's Yellow Fever Commission to eliminate what was thought to be the last vestiges of the disease. Prevailing theories of yellow fever epidemiology held that the disease spread from "key centers" in urban areas, that the Aedes aegypti mosquito was the sole vector and that humans were the sole hosts. Transmission was thought to depend on an unbroken chain of non-immune individuals, and so could not continue in smaller population centers once mosquitoes were controlled in larger ones.
Although this model had worked well to control yellow fever in larger towns and cities, assessing the general extent of yellow fever could be quite difficult. The yellow fever virus was not correctly identified until 1927, and reliable laboratory tests to detect it took several more years to develop. Sub-acute cases of the disease could be mistaken for other tropical fevers, and Rockefeller Foundation investigators had at times rejected Brazilian physicians' diagnoses of yellow fever cases in rural areas.
There were scattered reports of yellow fever in rural areas of northeast Brazil in autumn of 1927, but Dr. Michael Connor, head of the Yellow Fever Commission, rejected the diagnoses, and planned to stop yellow fever control efforts in one state (Ceará) to test for complete eradication. In January 1928, Connor predicted that if no new yellow fever cases were reported by March, he could consider the disease gone from the western hemisphere.
In March, however, sporadic cases were reported. Though Connor again rejected the diagnoses, post-mortem samples of liver tissue were taken from one case, and these tested positive for yellow fever virus. They also showed the characteristic tissue lesions that had been described by Henrique da Rocha Lima at a Congress of Hygiene two months earlier. Rocha Lima had published his observations on the characteristic patterns of liver necrosis found in yellow fever victims much earlier (1912), but these attracted little attention from epidemiologists at the time. Pathologic diagnosis of yellow fever would soon become a standard part of Soper's campaign against the disease.
In May 1928 yellow fever broke out in Rio de Janeiro--which had been free of the disease for 20 years--and subsequently in many other parts of Brazil. The Cooperative Yellow Fever Service (CYFS), combining efforts of local, federal, and RF health teams, was formed in early 1929. Soper (as Rockefeller Foundation representative) and Dr. Clementino Fraga, Director of Brazil's National Department of Public Health, directed the new agency.
From 1930 to1934, Soper reorganized the yellow fever campaign to include more detailed and uniform records of field-work, careful checking by supervisors, routine oiling of water containers and meticulous house searches for adult mosquitoes and larvae. He literally "wrote the book" on effective eradication procedures and personnel management; the Yellow Fever Service manual of operations became the standard handbook for this effort, and a model for subsequent malaria eradication campaigns. Soper also instituted routine viscerotomies (post-mortem collection of liver tissue) in all suspected yellow fever deaths, and had the samples examined at the newly established yellow fever laboratory, to confirm the diagnosis. This allowed a much more accurate assessment of the disease. Within two years, routine viscerotomies revealed the presence of endemic rural yellow fever in several Brazilian states.
Viscerotomies also helped confirm the existence of an alternative yellow fever pattern, later called "jungle yellow fever." Between 1929 and 1932, the CYFS had succeeded in tracking and controlling yellow fever in northeast Brazil, and was cautiously optimistic that by continuing to kill off the Aedes aegypti mosquito, the disease could be eradicated. But several isolated epidemics occurred in Brazil and neighboring countries during those same years, and while viscerotomies showed the characteristic yellow fever damage, inspectors could find no Aedes aegypti mosquitoes anywhere within range. By 1935 investigations proved that humans were not, after all, the sole hosts of the disease: monkeys in some jungle border regions could be infected with yellow fever, and mosquitoes other than Aedes aegypti could transmit it to humans.
Fortunately, a yellow fever vaccine was developed by Rockefeller Institute researchers in 1937, and this was rapidly added to yellow fever control programs in South America. During 1938 alone, the CYFS teams vaccinated over 800,000 Brazilians.
While Soper and the CYFS were advancing both control and understanding of yellow fever, another serious disease threat appeared in northeastern Brazil. Anopheles gambiae mosquitoes, the most efficient malaria vectors, were indigenous to Africa. But in 1930, Raymond Shannon, a Rockefeller Foundation entomologist, discovered that gambiae (apparently recently arrived from Africa) were breeding in Natal, Brazil. Three weeks later, a severe outbreak of malaria was underway there. Soper urged Brazilian authorities, including the President, to eradicate the gambiae while their numbers were still small, but nothing was done immediately. In 1931, the CYFS was asked to help with eradication efforts in Natal; these efforts were successful by 1932, but the campaign was not carried inland. Meanwhile, yellow fever eradication kept everyone busy, including Soper, and no serious outbreaks of malaria were reported.
As Soper later wrote, the Brazilian authorities and the CYFS directors misjudged badly when they failed to follow up their successes in 1932. Epidemic malaria appeared in Ceará in April 1938, and a gambiae survey begun in October showed that the mosquitoes had become established far into the interior. In January 1939, the Malaria Service of the Northeast (MSNE) was established by Brazil's government, with Rockefeller Foundation contracted to administer the program, and freely share personnel and resources with the CYFS. Soper was chief of both services. The effective organization of CYFS, and improved procedures for applying the Paris green larvicide to rural areas, along with increased funding from both Brazil's government and the Rockefeller Foundation, allowed the MSNE to finish its mission by June 1942. The invading mosquitoes were stopped and finally eradicated from the known infested areas in less than two years.