Leishmaniases of the New World in a Historical and Global Perspective

 

 

My research project deals mainly with theories and practices concerning the leishmaniases of the New World in a historical perspective, without losing sight of the dynamics of the leishmaniases of the Old World. They are the only neglected tropical disease which are still growing, and Brazil is the country in the Americas with the most cases of the three forms of the disease: cutaneous, mucocutaneous, and visceral.

In India, medical records of visceral leishmaniasis (also known as kala-azar) date back to the nineteenth century. This disease was initially associated with malaria or ancylostomiasis, and joined the leishmaniasis group at the turn of the twentieth century, at the same time as dermatological diseases known in the Old World under a wide range of local names. Starting in 1909, physicians from Central and South America began to stand out in the international scientific arena for their work on the unique manifestations of leishmaniasis in the skin and mucous membranes. In the Americas, the disease had another unique characteristic: unlike in the Old World, it was only acquired in forest zones. In the 1930s, this leishmaniasis was generally recognized as “American tegumentary leishmaniasis,” indicating the foothold gained by Latin American researchers in the field of tropical medicine.

A very promising addition to the sources with which I have been working was made at the Center for the History of Medicine, located in the Francis A. Countway Library of Medicine, at Harvard University, Boston. There I found a precious documentation pertaining to the scientific expedition made by Richard P. Strong, professor of Tropical Medicine at Harvard University, to the Amazon region in the 1920’s. 

Visceral leishmaniasis was at the time virtually absent in the Americas.  It erupted as a public health problem in 1934, amidst a routine pertaining to another disease. The Yellow Fever Service had recently established a laboratory in Bahia to analyze liver samples sent by hundreds of viscerotomy stations scattered across the country, taken from persons who had died from suspicious fevers. In slides from material collected in the north and northeast of Brazil which tested negative for yellow fever, the pathologist Henrique Penna identified Leishmania. As a result, 41 deaths were suddenly linked to visceral leishmaniasis.

Carlos Chagas, the director of the Oswaldo Cruz Institute, charged his eldest son and director of the Institute’s hospital, Evandro Chagas, with investigating the new medical and scientific problem. Using the records from cases diagnosed post-mortem, he found the first living Brazilian patient in the Northeast of Brazil. In a note published in March of 1936, Evandro Chagas referred to Brazilian visceral leishmaniasis as possibly differing from the disease observed in the Old World, although it was impossible to morphologically differentiate the Leishmania found in Brazil from L. donavani, the agent of kala-azar in India and other parts of Asia and Africa or L. infantum, the parasite incriminated by Charles Nicolle as the cause of infantile visceral leishmaniasis in the Mediterranean.

In June 1936, the Commission for the Study of American Visceral Leishmaniasis was created under the leadership of Evandro Chagas, with financial and logistic support of the Rockefeller Foundation. The documents I examined at the Rockefeller Archive Center will allow me to have a much more precise view of the emergence of visceral leishmaniasis not only as a public health problem in Brazil but as a new research subject for the International Health Division specialists and the Yellow Fever Service workers. These documents though light on how the relation between Evandro Chagas and the Yellow Fever Service evolved, in the same years that a laboratory was establish in Instituto Oswaldo Cruz to produce a yellow fever vaccine and to investigate the many controversial aspects of the jungle form of the disease. To my surprise, the Phlebotomus sandflies were investigated as possible vectors of both kala-azar and yellow fever.

In Pará, as in the northeast, Evandro Chagas and his staff continued to navigate using the reports from the pathologists of the Yellow Fever Service to guide them. They would make great efforts to demonstrate the theory of the alleged autochthony and specificity of American visceral leishmaniasis.

Evandro Chagas followed the example of Gaspar de Oliveira Vianna, a pathologist at the Oswaldo Cruz Institute who in 1911 had described Leishmania braziliensis,[1] one of the many explanations offered for the unique characteristics of cutaneous and mucocutaneous leishmaniasis in the Americas. Vianna’s theory was bolstered by archaeological findings from ancient pottery vessels on the pre-Colombian origins of mucocutaneous leishmaniasis, alongside the inclusion of nationalist ideologies in the medical debate, since an autochthonous protozoan species added to the symbolic capital of Latin American researchers within the international scientific network of tropical medicine.

Evandro Chagas's political connections resulted in the creation of the Northern Pathology Institute (IPEN) in Belém, Pará as a home for his studies. His most prestigious international ally was Saul Adler, a Belorus-born physician educated in England who started his work at Hebrew University in Jerusalem in 1923. With the entomologist Oskar Theodor, he studied recognized or disputed species of Leishmania, developed ingenious serological methods to differentiate them, and investigated the known and alleged vectors of the parasite and zoogeography of leishmaniasis in the Mediterranean region. Following the examples of the Sergent brothers from the Pasteur Institute of Algeria, and of Henrique Aragão from the Oswaldo Cruz Institute, Adler and Theodor were able to transmit L. infantum to humans via Phlebotomus papatasi, but neither the Europeans who studied leishmaniasis in the Mediterranean region nor the British and Indians investigating kala-azar in Asia were able to experimentally transmit the parasite to human volunteers through the bite of flies previously fed on patients with the disease (the decisive proof).

The documents I found at the Rockefeller Archive Center will allow me to enrich the analysis of this international framework. I have now very interesting data regarding a mission sent by the China Medical Board of the Rockefeller Foundation to China in the 1920’s to study kala-azar. The mission comprised, among others, Charles W. Young, Marshall Hertig and his brother, Arthur Hertig. In the Harvard-Yenching Library, in Boston, I found an interesting photographic documentation produced by the Hertig brothers during their stay in China.

In September 1939, Adler sent Evandro Chagas an article that was published in the journal of Instituto Oswaldo Cruz.[2] "So far it has been impossible to distinguish L. chagasi from L. infantum by any laboratory test," wrote Adler (1940, p. 177), but he proposed other arguments to justify this distinction, among them this one, that I quote: "Up to the present there have been no proved instances of the formation of new foci of L. infantum even in the Old World itself where the disease is remarkably static in its distribution"  (1940, p. 178).

On November 8, 1940, Evandro Chagas died in a plane crash in Guanabara Bay. Studies on visceral leishmaniasis slowed down in Brazil, but the first major epidemiological survey on American tegumentary leishmaniasis was begun by Samuel Barnsley Pessôa, parasitologist in the recently inaugurated University of São Paulo.

During the post-war period, developmentalist nationalism was embraced by many teachers and researchers in the traditional medical schools or those which were being created around Brazil, as well as by sanitarians, who found promising professional prospects in the health services created after the 1930 revolution which brought Getúlio Vargas to power. Mário Pinotti, the head of the National Malaria Service, led the team responsible for the health program of Juscelino Kubitschek, elected president in 1956 on the promise of "50 years of progress in 5 years of government." The living conditions of rural workers were expected to improve with eradication or control of endemic diseases in the interior of the country.

While diagnoses of tegumentary leishmaniasis increased in number, there were few in vivo cases of visceral leishmaniasis. Since the first diagnosis in 1912, only 35 cases had been recognized in living patients in in the Americas. But in 1953, an epidemic broke out in northeastern Brazil that dramatically changed this situation. In only five years (1953 to 1957), the total number of in vivo cases jumped from 34 to 1,832, the majority (81.38%) in the state of Ceará. In the Americas the number rose to 2,179, but more than 98% of the total were found in northeastern Brazil.

At that time a devastating drought punished the region, and thousands of people left in search of food, shelter, and work. Contemporary investigations showed that “calazar” had gone unnoticed for quite some time. A campaign against the disease began in Ceará and its leaders took as an important example the China experience. Until now I had only indirect and precarious information regarding the work done against Kala-azar in China before and after the revolution. But at the Francis A. Countway Library of Medicine I had access to a series of articles on kala-azar published by the China Medical Journal from the 1920’s to the 1960’s. It will be very interesting to compare the lines of action taken by the Brazilian and Chinese workers regarding the vectors, the human and animal hosts (domestic and sylvatic). With the sources I brought from Boston I hope to verify various aspects of the campaigns against kala-azar: did DDT have in China the same importance it had in Brazil? Is it true, as a veterinarian I interviewed told me, that only in China the elimination of dogs was as extensive as in Brazil? What were the policies regarding the victims of the disease and the mobilization of workers to fight it.

In the 1950’s and 1960’s activities against rural endemic diseases rolled out throughout Brazil. Studies at that time showed that the emigration of people from the northeast increased the incidence of the leishmaniases in other regions of the country.

The epidemiological surveys done in those years were made possible by the transformation in the public health apparatus at the federal and state levels, and by the strengthening of the institutional network to house studies on the leishmaniases and other rural endemics. Medical schools in the Southeast and Northeast of Brazil and the Oswaldo Cruz Institute in Rio de Janeiro were the main centers for this network. The Belém do Pará Institute, which was renamed the Evandro Chagas Institute, also played an important role, along with three research centers created in 1950’s in the capitals of Bahia, Minas Gerais, and Pernambuco, which today are branches of the Oswaldo Cruz Foundation.

In the Rockefeller Archive Center, I found documents which bear witness to the support given by the Rockefeller Foundation to these medical schools, stimulating certain specialties or changes in their curricula. Chairs and laboratories that undertook studies on rural endemic diseases were also benefited by grants and material support.

A landmark in the consolidation of this research network was the Kala-Azar Seminar held in Salvador, the capital of Bahia, in 1960. On the opening day of the event, the Brazilian Society of Tropical Medicine was founded. Tropical medicine also gained renewed importance internationally, because the traditional diseases in this category began to appear as significant obstacles (and byproducts) to development policies targeting countries like Brazil to lift them out of their 'underdeveloped' status and more notably to prevent them from breaking loose of their orbits in the capitalist world by force of popular rebellion propitiated by poverty and disease.

In 1962, the year of the Cuban missile crisis and exacerbation of the Cold War, a comprehensive study on tropical diseases and the resources for their study and control was completed in the United States.[3] The study, which was sponsored by the National Academy of Sciences and the National Research Council, had support from the Rockefeller Foundation. Its Consultant Committee  brought together heavyweights of health, industry, and business. The arguments justifying the relevance of the study clearly show concern with preserving a power with imperial ambitions from the dangers that threatened it: decolonization movements, revolutions, and communism.

Rockefeller Foundation programs related to the revaluation of tropical medicine and tropical diseases after World War II and, later, the so-called Neglected Diseases originated precious documents I have found in the Rockefeller Archive Center. They will be of great value for the understanding of the dynamics of tropical medicine in the post-war period.

To analyze the state of the art in relation to leishmaniasis, Leonidas Deane of the University of São Paulo was consulted, along with Marshall Hertig of the Gorgas Memorial Laboratories (Panama) and Philip Edmund Clinton Manson-Bahr, a British physician connected to the Department of Health in Nairobi, Kenya. One notable aspect of their reports is the contrast between the fixed epidemiological scenario described by Adler in the 1930s and its fluidity in the 1960s. 

This researcher and Percy Cyril Claude Garnham, a professor at the London School of Hygiene and Tropical Medicine, were key players in constructing a new international network addressing this complex of diseases, linking mostly isolated teams in the Old and New Worlds with the support of WHO, PAHO, and organizations such as the Wellcome Trust. I am studying this network from the viewpoint of the New World leishmaniases, which received more exposure after research conducted by British scientists in Central America and then Brazil. After the 1964 military coup, large-scale public works in the interior of Brazil transformed American tegumentary leishmaniasis into an extremely serious problem in the Amazon region. In 1965 at the Evandro Chagas Institute, Ralph Lainson (recently deceased) and Jeffrey Shaw founded the Wellcome Parasitology Unit. They showed that populations of parasites, with their respective vectors and vertebrate hosts, were much more heterogeneous than had been imagined. Philip Marsden began his work in Brazil in 1967, as a professor of tropical medicine at the University of Brasilia. There he became a leading authority in controlling the leishmaniases until his death, in 1997. Toby Barrett worked at the National Institute of Amazonian Research (INPA).

           

At the end of the twentieth century, in Brazil and in other countries, all forms of leishmaniasis emerged or reemerged in urban and rural areas due to environmental changes, human migrations, chaotic urban growth, and other socioeconomic processes underway in large expanses of these countries. Visceral leishmaniasis acquired severe forms when occurring concomitantly with other infections, such as AIDS.

The leishmaniases were classified as neglected tropical diseases. Although they are in fact overlooked by public policies and affect neglected populations, they mobilize vigorous research communities. This is partly due to the fact that many uncertainties still remain about transmission mechanisms, diagnostic techniques, treatment, and prevention. At the same time, investigations on leishmaniasis were reframed by molecular biology. This discipline has had a major impact on knowledge production about all forms of the disease, including the development of therapeutics and vaccines.

For my research, a valuable resource to disentangle this process are the documents found at the Rockefeller Archive Center regarding research projects on Leishmania and/or leishmaniasis sponsored by the Rockefeller Foundation since the 1970’s, in cooperation with other institutions or agencies which were investing in the study of neglected diseases.

Thanks to the Consortium for History of Science, Technology and
Medicine, in New York I interviewed the leader of one of the projects funded by The Rockefeller Foundation. John R. David, Richard Pearson Strong Professor Emeritus of Harvard T.H. Chan School of Public Health, conducted important research in Brazil, in cooperation with the Federal University of Ceará, the Fundação Oswaldo Cruz and the Tropical Medicine Foundation of Manaus.

I am immensely grateful for the warm welcome I received in the archives and libraries I visited in March-April 2019. I owe this fruitful journey to the Consortium for History of Science, Technology and Medicine, a brilliant idea for people like me, and so I extend my words of gratitude to those who conceived and who run this program.