Yellow fever in Brazil: an unfinished history
Oswaldo Cruz Foundation – by Jaime L Benchimol
Yellow fever was Brazil’s biggest public health challenge in the 19th and 20th centuries. The virus still circulates in rural woodlands and knocks at doors in cities infested with the urban vector Aedes aegypti – but there have been no outbreaks in these environments, where dengue (a disease propelled by the same main vector) now rules. In October 1958, the 15th Pan American Sanitary Conference declared much of the Americas free of A. aegypti. And while yellow fever recovered lost territory after reappearing in the northern state of Pará in 1967, raising fresh fears, it is dengue that has made headlines since summer 1986. The transition from one disease to the other is an enigma we still do not fully understand.
Hygiene became an important consideration of government policy owing to the 1849 yellow fever epidemic in Rio de Janeiro, capital of Brazil’s slave-owning Empire. A vast arsenal of initiatives was advocated for reforming city landscapes as well as the human habits and creations associated with the miasmas polluting urban life.
In the summer of 1879–80, Domingos Freire announced the discovery of Cryptococcus xanthogenicus, supposedly the cause of yellow fever, and then gave abolitionists and republicans a vaccine that became widely used. Other fungi and algae were blamed as well, while bacilli became the prime culprit the following decade. In 1892, in hopes of wrenching the fever from Rio’s soil, the President of the newly born Republic considered hiring Edmund Alexander Parkes, author of the Manual of Practical Hygiene, which systematised experiences in British and Indian cities.
Those years saw much speculation about insects’ role in disease transmission, including yellow fever. These creatures (especially the flies buzzing through the miasma-filled air) were primarily seen as mechanical agents that transmitted microorganisms. New living links were fitted into the constructs designed to explain the extracorporeal transformation of the yellow fever microbe. Entwining soil, water, air, food, ships and housing, the outdoors was a composite urban–coastal agent, hot and humid, where fungi, algae or bacilli spent part of their cycles before infecting people, exclusively in certain seasons and geographical zones.
In June 1900, one year after the creation of the Liverpool School of Tropical Diseases and shortly after the deciphering of malaria transmission, Herbert Edward Durham and Walter Myers headed to the Amazon armed with Finlay’s hypothesis of yellow fever transmission via mosquitoes. They stopped in Havana to observe the Walter Reed commission at work. Their September 1900 article leaves the impression that the Americans had not embraced the mosquito theory; the British instead would find its justification in northern Brazil.
In August 1900, Lazear began experiments with the Culex Finlay had identified, while Carrol and Agramonte advanced their priority studies on the alleged yellow fever bacillus. After Lazear’s death, Reed initiated better-controlled experiments to prove that Culex fasciatus was host of the yellow fever ‘parasite’.
Liverpool School researchers were busy with their work when this turnabout occurred, with Myers dying of yellow fever in January 1901. Their investigations soon slipped into the cauldron of conflicting bacteriological theories abounding in the medical field. The explanation lies in Durham and Myers’s prior experiences, which led to a figure who unexpectedly ties Belém to Liverpool. When invited to take that journey, they were at Cambridge doing research related to that of Alfredo Antunes Kanthack, their recently deceased professor of pathology and bacteriology.
A prominent figure within the small group of pathologists who devoted themselves full-time to the microbial world, Kanthack had headed a team associated with David Bruce’s research on nagana. Kanthack, Durham and Blandford had confirmed that the haematozoan identified by Bruce belonged to the genus Trypanosoma, about which little was known. They had studied its symptoms and lesions, especially the site of inoculation by the tsetse fly.
While in Cuba, Durham and Myers helped promote an alternative framing of yellow fever from the perspective of new discoveries about malaria, yet their involvement with immunology and serum therapy and the then understanding of tsetse disease may explain their falling back on the bacteriological approach during their time in Belém.
In April 1905, Wolferstan Thomas and Anton Breinl disembarked in Manaus to study yellow fever in the Amazon. Between the Liverpool School’s fourth expedition and this one (its 15th), extremely dynamic processes were at play within tropical medicine. In Gambia, Dutton had demonstrated the presence of a trypanosome in the blood of humans with sleeping sickness. In 1903, Thomas became head of the Runcorn Research Laboratory, shortly before the School’s 12th expedition left for Congo to conduct further research on trypanosomiases. With the collaboration of Breinl, Thomas showed these could be treated with atoxyl. Ehrlich was to visit Runcorn, and in 1910 his own research with atoxyl would lead him to Salvarsan, the first effective drug for treating syphilis.
It is somewhat intriguing that scientists investigating trypanosomiases were sent to Brazil right when this research was at its peak. Britain’s commercial interest in the Amazon clearly played a role but I suggest a hypothesis that links the Manaus laboratory with this advanced frontier in tropical medicine.
In 1905, Schaudinn and Hoffmann announced the discovery of Treponema pallidum, which causes syphilis. Biomedical institutions worldwide dedicated their work to this and other spirochaetes. Analogies drawn between malaria and yellow fever led many researchers to believe the yellow fever agent was also a filterable, ultramicroscopic protozoan, a hypothesis defended by Finlay himself. Schaudinn suggested that a spirochaete might be the yellow fever agent, since it was then thought that this organism and trypanosomes were related protozoans that crossed bacterial filters during certain phases of their cycles.
This hypothesis guided Otto and Neumann’s research in Rio, at the height of the yellow fever campaign led by Oswaldo Cruz. In 1907, Stimson found Spirochaeta interrogans in a yellow fever victim. Schaudinn’s theory gained much ground after the Japanese named a spirochaete as agent of haemorrhagic jaundice (leptospirosis). Disentangling this knot, we come to the Rockefeller Foundation’s post-World War I campaign, partially based on Leptospira icteroides as the alleged yellow fever agent discovered by Noguchi.
The discrepancies that emerged as efforts were made to extend the campaign to Africa resulted in identification of the disease’s viral aetiology in 1928. In Brazil, in 1932, Soper and collaborators found yellow fever in areas near woodlands devoid of Aedes aegypti, confirming the existence of other transmitters and hosts. A vast research programme on both sides of the Atlantic soon revealed the complex dynamics between urban and sylvatic yellow fever.
There are several hypotheses for why the disease has not spread in cities teeming with the mosquito that proved a fine host for its virus in the past, but none excludes the possibility that it will eventually spread. When people consider this frightening possibility, they are reminded of the 19th and 20th centuries’ terrible epidemics. This affords us an opportunity to rethink questions that by their very nature demand a meeting of the biological and human sciences.
Jaime L Benchimol is a Researcher and Professor in the Postgraduate Programme in the History of Sciences and Health, Oswaldo Cruz Foundation.