Insects, people and disease: Adolpho Lutz and tropical medicine

Like Neiva, in 1909, he considered Galli-Valério's (1904) notification about the presence of oocysts of the malaria parasite in the walls of the stomach of specimens of Anopheles cited by Lutz. “Even a versed student of American mosquitoes would hesitate to positively identify such specimens, and I do not recall Galli-Valério before having given the slightest attention to American mosquitoes!”

Knab and Dyar issued Lutz a challenge: that whatever the true explanation was, “the burden of truth lies with the investigator … we have the right to wait for the proof to be complete or to reject the explanation provided.”

In Lutz's counter-rebuttal read by Howard in a session of the Entomological Society of Washington, Lutz (1913b), in a paragraph quoted above, refuted the assumption that mosquitoes that had never before been in contact with man could not transmit malaria, leaving open the chance that the infection of bromeliad mosquitoes could initially occur through contact with a non-human host that inhabited the forest.

Lutz then attacked the weakest links of the arguments against him made by the American entomologists.

I am accused of ignoring the fact that men are men, and it is

said that they must have slipped away at night, getting infected

elsewhere. I have already said that they lived in the forest some

many miles away and had no means of getting around except

by foot. Even if they had gotten out of control, they could not

have gone far enough away in one night for them to reach

anywhere where they could have found that which is suggested

they may have found, nor would this have helped, because

there was and there still is no malaria in those areas. If one

were to take such an argument further, one could also say that

the Italian sailors who contracted yellow fever on board the war

vessel anchored off Rio de Janeiro some distance from the

coast were attacked because they swam inland at night.

Lutz scoffed at the statement that Galli-Valério was not equipped to identify the Myzomyia lutzi, even though “it is an extremely characteristic species that can be differed from all others by a quick look at its scutum.” It was with justified disdain that he dealt with the accusation that he – as well as Chagas – had failed to note the presence of other anophelines in the areas where he made his studies, “even though Messrs Knab and Dyar can see them from Washington. Yet it was to be expected that Lutz and Chagas knew their anophelines, since they had worked with them for many years and had together identified most of the Brazilian species.”

But Adolpho Lutz made no comment about his adversaries’ demand that he provide proof that the mosquito from the forest in fact hosted the malaria parasite. He had not followed the protocol established by Manson in the study of filariasis transmission and replicated in the studies by Ross and the Italians about the transmission of bird malaria by Culex, and human malaria by Anopheles.

The study program that Lutz used was a combination of exhaustive study of habitats and the distribution of Myzomyia lutzi and the vegetation that hosted it with field studies into the cases of malaria in humans that occurred in the environments where forest and bromeliad mosquitoes lived in great numbers. It was a program that required the use of entomology, botany, epidemiology, and medicine, but which totally bypassed the wisdom of Ross, Grassi, and other investigators who had spent their time observing the evolution of the parasite in the organisms of its intermediate hosts. Though he had demonstrated his skills in this type of experimental procedure in the parasitology studies he had published in the 1880s, Lutz would not take the route indicated by his opponents. He concluded the matter, maintaining “entirely” the exactness of his observations and emphasizing the “practical interest” inherent to them.

This is why I oppose them … and reject the comment that most

likely the gentleman made a mistake, which seems to imply that

it is a habit of mine to commit errors when making scientific

observations. Being as I am in less of a hurry to communicate

my observations than many these days, I do not believe my

quota of errors to be unusually high.

These and other equally cutting remarks by Lutz, reintroduced into the present edition of his text, were suppressed by the editor of the Proceedings of the Entomological Society of Washington, which triggered a sharp protest by Frederick Knab. The letter he sent to W. D. Hunter on 24 January 1914 shows Adolpho Lutz's authority in that new field of knowledge -medical entomology – as well as the leading position he held among his peers in Brazil, especially the talented group of investigators at the Oswaldo Cruz Institute.

If we leave to one side the ethical question, the change in the

tone of the letter adds a completely different nature to the

controversy … placing Dr. Dyar and I in a very unpleasant

position. The researchers in Rio de Janeiro … will naturally draw

the conclusion that … we have made use of untoward means to

sidestep their forceful criticisms. I fear this procedure, however

trifling it may seem to you … may cause irreparable damage. It

may well have caused a rupture between us and the Rio

researchers that may never be repaired. I am most sorry about

this, as it will seriously affect my work. For some years it has

been my aim to cultivate friendly relations with these

researchers so that we may work in harmony and facilitate each

other's investigations, and I had found their response

encouraging. As you undoubtedly know, by far the most

important medical entomological work being done this side of

the Atlantic is by Lutz and his associates, and from a dipterology

standpoint, above all, it would be most desirable to maintain

contact with them.

In his reply dated 27 January, Hunter seemed surprised at their reaction. “The only alterations I made were to omit two sentences that in my view were too scathing to appear … In view of this, it seems to me that the publication of the letter … has served more to maintain an entente cordiale than to destroy it.”

The tone of the letter that Knab sent to Lutz two days later clearly

shows his desire to restore good feelings to their relationship, 112 which, to all intents and purposes, was sustained by a substantial, important scientific exchange for both parties. In 1911, Knab had published a detailed, complimentary criticism of two papers by Lutz (1909, 1910) about the Simuliidae of Brazil. In the American's view, it was

by far the most comprehensive study yet dedicated to this so

interesting, so economically important group of Diptera … it is

gratifying to see that Dr. Lutz does not adhere to the systems of

the old school, but rather approaches his subject from all

angles. He grants due importance to data obtained at initial

stages from biology, matches them with the characteristics of

the imagoes, while at the same time carefully considering any

potential sources of error.

In a letter in January 1914, Knab respectfully consulted Adolpho Lutz about the habits and classification of two species of Ceratopogoninae he had been studying, and alluded to a comment previously made by his Brazilian colleague that he still had a lot of unpublished material about mosquitoes. “Why not publish it? It is hardly likely that your biological data at least will conflict with our book … Most of your observations will undoubtedly be original, and the rest, more comprehensive, thereby improving on what we have been able to present.”

 

Lutz's theory in limbo

Gadelha (1994) states that the decline of Adolpho Lutz's theory became more marked in the 1920s, when well-known malaria specialists produced work that seemed to invalidate it. He specifically refers to Darling and to Nelson Davis. The former had shown that no malaria vector came from bromeliads in Panama, thereby prompting cancellation of a costly project to eradicate these plants that had been launched in that country.

Davis investigated an epidemic in a mountain area of Angra dos Reis (Rio de Janeiro), where more than one railroad was built. Though he attributed most of the cases to relapses of chronic malaria, as Knab had about the cases examined by Lutz in the Santos mountains, Davis was forced to admit the existence of local transmission. This led him to study the infection capacity of forest malaria mosquitoes, which were now included in the genus

Kerteszia. 113 He obtained a very low frequency, and concluded that they were capable neither of setting off nor of maintaining an epidemic. Only when an epidemic was at its height, when there were numerous carriers of highly infected gametocytes, could the species perhaps contribute with some cases of transmission.

That very same year, Arthur Neiva (1925, p.4) produced a report for The Light and Power Company about the sanitary risks involved in introducing one of the Canadian company's projects in the Serra de Cubatão mountain range, the same area where Lutz had discovered forest malaria. The entomologist from the Oswaldo Cruz Institute, who had considerable experience working in campaigns to fight the disease, did not hesitate in stating that the main problem was the Myzomyia lutzi, which accounted for 40% of all the mosquitoes that lived in the bromeliads in that region. In his report, Neiva referred to the campaign he had led against that mosquito in Iguape, São Paulo, which had mainly consisted of deforesting the area that they planned to protect.

Gadelha (1994, p.136) finds it strange that the opposing viewpoints of Neiva and Davis should not have triggered a controversy. In his view, this was not only due to the limited circulation of the report written in Portuguese, but more importantly to the fact that “Davis's conclusions were based on lab work, while Neiva's were founded on generic entomologic and epidemiological observations.” Based on Deane (1986, p.7), Gadelha shows that the dissection of salivary glands to check for the presence of oocysts was a laborious, delicate technique, in which a small number of individuals were used to check infection rates in anopheles. With the introduction of a new technique at the end of the 1930s, it became possible for entomologists to examine hundreds or even thousands of salivary glands. It was then clear that Davis had been mistaken. In Gadelha's article, the reader will find a reliable analysis of the chain of events that granted forest malaria greater visibility as of the 1940s.

Lutz did not live to see this resurgence or the campaigns introduced by the National Malaria Service (1941) that caused the destruction of millions of bromeliads in southern Brazil.

In a paper published in 1903, he had considered it impracticable to deal with these plants. The use of chemicals to destroy the larvae sheltered in them had seemed to him “more theory than practice … Normally, the only thing that gets results against malaria in the wild is making clearings.” Malaria in wetland plains was more easily combated using a set of preventive measures. In a report written at

the turn of the 20 th 114 century, Lutz referred to studies performed in different parts of the world by English, German, and Italian committees, and stated that clear guidelines could now be established for fighting the disease that were very similar – as we shall see – to those that would soon be adopted to fight yellow fever. The director of the Bacteriological Institute stated:

1 – due to the habits of the parasites in the plasmodium

discovered by Laveran, of which there are many species,

malaria is only transmitted by mosquitoes of the genus

Anopheles, which serve as hosts during an essential phase of

their evolution; malaria only occurs where there is an

abundance of Anopheles; 2 – if it is to transmit the malady, the

Anopheles must bite people with malaria at an appropriate stage

in the development of the disease. Only after a certain period of

time, which varies between eight and fifteen days, will these

insects be capable of transmitting the malady to other

individuals by biting them.

Lutz believed malaria could be combated in any of three ways: by treating people with the disease to stop anophelines from infecting them; by destroying the mosquitoes, especially their larvae; by stopping infected mosquitoes from biting people by using mosquito nets, houses protected with screens, fumigation, and other such measures. “It is seen that these last means may stop groups of individuals who spend the hot months in areas where malaria is commonplace from being infected.”

In “Instruções sobre a profilaxia do impaludismo” (Instructions on the prevention of paludism), a previously unpublished text being released for the first time in the present volume of his Complete Works, Adolpho Lutz sets out in more detail what he calls “offensive,” “defensive,” and “specific” or “therapeutic” preventative measures.

Combatting Kerteszia. Tree full of bromeliads; arrows point at

workers knocking the plants down (Pinotti, 1947, p.22).

Worker fitted out to knock down bromeliads, breeding places for

 

Kerteszia (Pinotti, 1947, p.23).

 

Combatting Kerteszia. Clearing trees in the suburbs of Blumenau,

Santa Catarina state (Pinotti, 1947, p.24).

 

Yellow fever from microbes to mosquitoes Accountings of events have attributed the victory of scientific medicine over yellow fever either to the US or to Cuba, depending on the weight given two factors: Cuban doctor Carlos Juan Finlay's formulation of the theory of the diseases transmission by mosquitoes in 1880-81 and its experimental demonstration in Cuba by the U.S. team under Walter Reed in 1900.

According to Nancy Stepan (1978), the essential ingredients for elucidating the enigma of yellow fever had been present for some time, but social and political obstacles prevented an earlier victory over the disease. The conviction that the disease was entrenched in the Cuban soil, the Spanish metropolis’ lack of interest in science, Cuba's prolonged war of independence (which began in 1868 and resumed in 1895), and, finally, the island's occupation by the United States three years later all conspired toward this delay. The U.S. Yellow Fever Commission visited that island in 1879-80, and from it Finlay had picked up the hypothesis that yellow fever was caused by a germ that suffered a transformation outside the human body before infecting a susceptible person. A description of the intermediary host of the rust fungus (cereal disease), presented in a well-known botanical treatise by French scientist Philippe Edouard Léon Van Tieghem (1830-1914), led the Cuban doctor to conclude that the transmission of yellow fever was probably the work of an agent that existed independent of both the sick person and the microorganism of the disease. Entomological and epidemiological studies led him to verify that the female Culex (later denominated Stegomyia fasciata, currently Aedes aegipti) transported a live, infecting particle from a sick to a healthy person via its proboscide. Finlay first published his theory in Spanish (“El mosquito hipoteticamente considerado como agente de transmissiÓn de la fiebre amarilla,” 1881) and then in English (“Yellow fever: its transmission by means of the Culex mosquito,” Jul.-Oct. 1886). Stepan points out that knowing the precise species would have been sufficient for eradicating the mosquitoes and thereby controlling the disease, if there had been due interest.

Carlos Juan Finlay (1833-1915) (Olpp, 1932, S128).

 

Drawing of Stegomyia fasciata; on the right, the mosquito at rest,

feeding, in actual size (Kolle & Hetsch, 1918, Prancha 76)

On examining the events of 1900, we verify that the same

arguments that had previously seemed inconclusive, or even

implausible, had acquired great plausibility when the needs of

the military demanded a quick solution for the yellow fever

problem. The fact that the Reed commission needed only two

months to confirm Finlay's hypothesis, and that it committed

many of the mistakes attributed to him, suggests that it does not

suffice to blame his science to explain its inactivity … One

needs to examine the political and social context in which yellow

fever was perceived in the United States, and the reasons

behind such a drastic change in perception in 1900. (Stepan,

1978, p.402)

For François Delaporte (1989), Finlay and the North Americans diverged in their view of the mosquito: the first saw it as a mechanical medium of transmission and the second, as an intermediary host associated with a more complex biological process. Finlay's decision to make the mosquito an object of study, and the time that elapsed between the proposition and confirmation of his theory, were enigmas that would be explained by English tropical medicine, through the relations of conceptual kinship that linked the Cuban doctor to Patrick Manson, and Walter Reed to Ronald Ross. For Delaporte, Finlay's hypothesis remained in limbo for twenty years because this was the time necessary for establishing malaria's mode of transmission.

When Ross revealed the parasite cycle of bird malaria in the Culex mosquito in 1898, and Giovanni Grassi, Amico Bignami, and Giuseppe Bastinelli revealed the parasite cycle of human malaria in mosquitoes of the genus Anopheles the following year, it became inevitable to suppose that these insects played the same role in yellow fever – often confused with fevers caused by different species of Plasmodium during clinical diagnosis, as we have seen.

For Manson, the mosquito was important in that it was the host or nurturer of a parasite that completed part of the cycle necessary for its preservation as a species within the insect. Dealing with the transmission of an unknown germ, Finlay saw the mosquito bite in terms of the advantages that it brought to the insect. He verified that the female of the species engaged in not just one but frequent feedings of blood, and deduced that so much blood in such a small body could only serve to maintain optimal temperatures for maturing eggs. He concentrated on smaller-sized mosquitoes that needed several feedings and needed to lay eggs several times. A study of culicidian fauna in Cuba and its cross-comparison with yellow fever's geographic distribution led him to point to the small Culex as its agent of transmission. Under the light of this theory, he was able to explain a variety of intriguing epidemiological aspects of the illness (Delaporte, 1989).

 

The Reed commission's experiments in Havana

The U.S. medical commission nevertheless did not immediately accept Reed's theory. On 25 June 1900 in Cuba, tasks were assigned to team members according to the instructions of George Sternberg, Surgeon General for the U.S. Army and a man who had eyes only for the bacteriology of yellow fever. Investigations were brusquely redirected from the icteroid bacillus to Finlay's hypothesis after a meeting (which will be addressed further on) with English doctors from the recently created Liverpool School of Tropical Medicine. On 11 August, Jesse William Lazear (1866-1900) began his experiments with mosquitoes, while James Carrol (1854-1907) and Aristides Agramonte y Simoni (1868-1931) continued the bacteriological studies.

 

Jesse William Lazear (1866-1900) (Olpp, 1932, S227).

James Carrol (1854-1907) (Olpp, 1932, S62).

 

 

Aristides Agramonte y Simoni (1868-1931) (Olpp, 1932, S1).

The first two cases of positive infection by Culex were obtained toward the end of that month. On 25 September, Lazear suffered a tragic death due to an accidental mosquito bite. Walter Reed, who was in Washington finishing up the report of a commission on typhoid fever rushed back to Havana and hurriedly wrote the “Preliminary Note” presented at the 28 th Annual Meeting of the American Public Health Association in Indianapolis, held 2226 October 1900. Although he used mosquitoes born of larvae in captivity, Lazear had not established sufficient control over the inoculated individuals to rule out the possibility of other sources of infection. Reed, who until then had not taken part in the experiments,

took on himself the task of completing them.115

Three series of experiments were conducted between November 1900 and February 1901 at Lazear Field, in the vicinity of Quemados, Cuba, sheltered from the epidemics, at a place that had been drained, was sunny, and exposed to wind. Volunteers were recruited from among immigrants and U.S. soldiers, quarantined before being bitten by mosquitoes that had been previously infected by yellow fever sufferers. The aim of this first series was to confirm that the mosquito was the intermediary host of its ‘virus’. Of the six volunteers bitten, five showed symptoms of the disease. The commission reached the conclusion that twelve days were necessary after contamination of the mosquito for the germ to travel through its stomach, reach its salivary glands, and make it capable

of transmitting the infection. 116

The next experiment was set up in a room divided into two areas by a metal screen. Infected mosquitoes and a volunteer who let himself be bitten repeatedly were placed in one of the areas. Two witnesses remained many days in the other, protected area, without contracting the disease. The intention was to rule out the firmly entrenched notion that the air – vehicle for miasmas and germs – could transmit yellow fever. Reed wanted to demonstrate that a dwelling place

could only be dangerous if it contained infected mosquitoes.117

Walter Reed (1851-1902) (Olpp, 1932, S336).

In a second series of experiments analogous to the ones carried out a century earlier by the anti-contagionists, three volunteers were confined for twenty consecutive nights in a room full of objects covered with the vomit, feces, and urine of patients who had died of yellow fever. None of them contracted the disease, thus invalidating once again the notion of contagious fomites and the procedures that resulted from this belief: disinfection of clothes and objects

supposedly contaminated by contact with the sick.118

During September and October 1901, the U.S. commission carried out another series of experiments related to the yellow fever germ. Blood from a diseased person was injected into four volunteers, producing three positive cases; this proved that the disease was present in the circulatory system and that it could be transmitted by the prick of a needle. The next step was to verify if this was a filterable virus, a hypothesis that had been raised by the bacteriologist Frederick George Novy and suggested to Reed by his former professor, William Welsh. Serum was extracted from the blood of a diseased person, and its inoculation produced an experimental case. The serum was subsequently heated to 55° centigrade and inoculated, without producing any results. This procedure demonstrated that the virulence could not be attributed to a toxalbumin secreted by a bacillus. Finally, after passing it through Berkefeld and Chamberland filters, the serum was diluted and injected, provoking a clearly defined onset. It was understood then that yellow fever could be caused by such a minute microorganism that it could go through the most closely meshed filters and remain invisible to the most potent microscopes. Bacteriologists’ interest in this category of “ultra-microscopic” agents had been stirred by Friedrich LÖffler and Paul Frosch's March 1898 discovery that foot and mouth disease was induced by an agent of this kind. Ironically, Sanarelli had been one of the pioneers in studying “viruses” – a concept that was only just gaining shape in its modern sense – and had described the properties of the invisible agent responsible for myxomatosis in rabbits (Hughes, 1977).

 

Filter developed in 1884 by bacteriologist Charles Edouard

Chamberland (1851-1908). The liquid is pumped through a porcelain

filter component. Source:

www.gutenberg.org/dirs/1/1/7/3/11734/11734-h/illustrations/4a.png,

retrieved 22 June 2005.

On deciding to test this hypothesis, Reed and Carrol faced an environment that was already unfavorable to the use of ‘human guinea pigs’. The first experiments did not result in fatalities, but their reenactment by a Cuban team under the direction of José Guiteras in the summer of 1901 caused the death of three of the seven inoculated volunteers, leading to a great commotion among citizens of Havana and frightening off new candidates. Lõwy (1991) assures us that this kept the Reed commission from providing new and

conclusive proof that the yellow fever agent was a filterable virus.119

The anti-Culex campaign that U.S. military forces deployed in Cuba was a success. Diseased patients were isolated under mosquito nets, and mosquitoes and larvae were exterminated, breaking the disease's cycle of dissemination and bringing yellow fever under control in just six months. The experiments carried out by the Reed commission were then confirmed inside the walls of a few laboratories and in the open field, especially in some Brazilian cities, until being accepted as definitive at international scientific forums.

However, before we proceed to examine the developments mentioned above, let us examine one thread of the complex social and technical web in Cuba, since it is directly related to an event described earlier. The damning report that Adolpho Lutz wrote on Caldas’ serum did not mean the death of the invention by the doctor from Rio Grande do Sul. His greatest vulnerability was that the yellow fever microbe was unknown. On 28 April 1898, Felipe Caldas presented to the National Academy of Medicine yet another communication on the “transformation of the colibacillus into a

bacillus that produces yellow fever.” 120 Refuting Sanarelli, he then stated that it was a colibacillosis, in other words, a form of infection caused by the colon bacillus, which became malignant under the influence of biological and environmental factors. This saprophyte, normally present in the intestinal tract, would change its morphological characteristics in the presence of other microorganisms and become a terrible pathogenic agent. The theory was received respectfully at the New York weekly Medical News, whose editor commented:

Caldas’ communication is interesting because it represents a

serious and, at least in the eyes of its author, successful attempt

to prove in practice the interesting theory that bacilli can be

polymorphous, as so frequently discussed in recent bacteriology

– that is, that they can exist in different forms, each of which has

a unique virulence. This stands as an important contribution to

the question of whether or not a non-pathogenic virus may turn

into a pathogenic virus.121

 

Fraternidad Park, Havana, Cuba. Otoni Mesquita Post Card

Collection. UFF-Laboratório de História Oral e Imagem. Source:

www.historia.uff.br/labhoi/imagens/cpost032.jpg, retrieved 22 June

2005.

Caldas subsequently developed a vaccine for preventive use and made his last (or second-to-last) bid in favor of his inventions in Cuba, at a time when a successful battle was being waged against the disease, in light of Finlay's theory. He arrived in Havana in July 1901, along with his assistant, Dr. Bellinzaghi, as well as a commercial representative – “a businessman.” He proposed that his discovery be demonstrated to an official commission. When he was asked for letters of recommendation, he telegraphed the United States, and two weighty credentials arrived promptly at the desk of the Military Governor: one from the Secretary of War and the other from the Brazilian Consul General in New York. A commission was set up, the members being V. Havard, William Gorgas, Juan

Guiteras, Carlos Finlay, and a certain Dr. Albertini.122 It is probable that they performed their task at the same time that Gorgas and Guiteras tested another vaccine on human volunteers, at Finlay's suggestion, independently of the Reed commission's endeavors. As mentioned earlier, the death of three human guinea pigs would jeopardize these studies on the ultra-microscopic virus.

On 9 August, the commission met with Caldas in the Las Animas Hospital and heard from him a description of the procedures employed in preparing his two immunizers. He explained that he first injected a dose of the serum to neutralize any strong reaction to the vaccine. The commission asked him to demonstrate the existence of the microbe and to describe the method used to isolate and culture it. Caldas refused to do so, alleging that he had made a pledge of secrecy to a company created to develop his discovery. Had they authorized him to vaccinate non-immune subjects, and if these people were bitten by infected mosquitoes without subsequently developing the disease, the causal relation between the microbe and

yellow fever would have been proven, indirectly. 123

After lengthy discussions, the inquirers reached an ambiguous decision: they would not take part in the experiments, since the Brazilian was withholding data crucial to addressing the issue scientifically, but they would allow him use of the necessary facilities and assume responsibility for checking results and reporting on them afterwards. Bellinzaghy hired four non-immune immigrants and had them sign a written agreement, as required by the commission, stipulating that they receive monetary compensation for the risks they were voluntarily assuming. Two were rejected due to a suspicion that they were immune. The other two – robust Spaniards who had recently arrived in Cuba – were admitted to the hospital and confined in mosquito-proof rooms; they were inoculated by Caldas himself. According to the Brazilian, immunization took four days. The commission thought it better to wait a week. On 22 August, two infected mosquitoes, whose history had been known from the very jar in which they were born, bit Paulino Alonso. Three days later, the signs of a typical and serious case of yellow fever developed. Caldas’ visits became more infrequent and when the commission met to establish a formal diagnosis, he was absent. He was a sore loser. Right to the very end, he denied that the disease was yellow fever, arguing instead that it was septicemia. According to Major Doctor Harvard, in charge of reporting the case, this statement put Caldas in a “strange and unenviable position,” since he believed

that the mosquitoes that bit [sic] the men with yellow fever could

only transmit septic infection and yet he proposed that these

mosquitoes would serve as proof of the value of his vaccine! …

The fact that he accepted the mosquitoes for the experiments

makes it doubtless that, had the results been negative, Caldas

would proclaim the triumph of his vaccine.124

On the right, the ambulance of Las Animas Hospital in Havana,

1900. Hench-Reed Collection, Claude Moore Health Sciences

Library, University of Virgínia. Source: www.med.virginia.edu/hs-

library/historical/yelfev/pan9.html, retrieved 22 June 2005.

 

The ‘Havana theory’ in Brazil

The experiments carried out in Cuba in 1900-01 have doubtlessly become a watershed in the history of yellow fever and, because of the disease's importance in Brazil, an equally distinct dividing line in the history of the nation's medicine and public health. The discovery of its mode of transmission made possible sanitary campaigns that were for some time able to neutralize epidemics in urban centers along the American coastline, silencing the controversy over the disease's etiology.

Ronald Ross's rise to fame as the “bold British successor to France's Pasteur and Germany's Koch” (Worboys, 1976, p.85, 90-1) was decisive in bringing to reality a project that Patrick Manson had defended in conferences at St. George's Hospital in October 1897: to invest in training medical doctors in what he termed “tropical medicine.” In June 1899, the Liverpool School of Tropical Diseases began its existence, and in October, the larger London School of Tropical Medicine was inaugurated.

It is worth mentioning that during the same period, Brazil also witnessed an attempt to establish a chair in tropical diseases at the Schools of Medicine in Bahia and Rio de Janeiro, with Francisco Fajardo being considered for the latter position. (The syllabus offered in Liverpool was published in Brazil-Medico, 1 Jul. 1900, p.220-1). The fourth Brazilian Congress of Medicine and Surgery (v.2, p.74) took place in the Brazilian capital in June 1900. Vitor Godinho and Carlos Seidl, representing O Brazil-Medico (22 May 1900, p.173-4) and Revista Médica de São Paulo proposed that the Legislature be asked to urgently create two new chairs at those schools, one in tropical pathology and medical practice, the other in clinical bacteriology and microscopy. The proposal was defeated by twenty-one votes to three at the 19 June session (Leão de Aquino, 1945, p.170-1).

Façade of the Liverpool School of Tropical Medicine (Miller, 1998,

p.32).

In 1900, Drs. Walter Myers and Herbert E. Durham, from the Liverpool School of Tropical Medicine, took off on an expedition to Brazil to investigate yellow fever. Their June encounter with the North Americans was a stopover that resulted in the establishment of a long-lasting experimental center of the English school in the Amazon. Myers would eventually die in Belém, on 29 January 1901,

a victim of the disease he had traveled to study.125 In Havana, they met with the members of the U.S. commission; with Major William Gorgas, who headed the Bureau of Inspection of Infectious Diseases; with Henry R. Carter, from the U.S. Marine Hospital Service; and also with Cuban doctors: Finlay, Guiteras (professor of the Havana School of Tropical Diseases), Bango, and Martinez. Durham and Myers (1900) brought with them a generic hypothesis – that a host insect transmitted yellow fever – and it gained consistency with the information gathered in Cuba. The article they published in September was skeptical of Sanarelli's bacillus, praised Finlay's ideas, and defined the unknowns that provided a glimpse of the contours of the hypothetical live vector. The feeling one gets from reading this article is that if the North Americans had not chosen to go down this path, his theory would have found its justification

through the hands of the Englishmen in northern Brazil. 126

 

Walter Myers, born 1872 in Great Britain, died 1901 in Belém, Pará,

of yellow fever (Olpp, 1932, S288).

Studies by Ross, Grassi, and collaborators had also led to a change in the approach to yellow fever at the Bacteriological Institute of São Paulo, resulting in serious ruptures within the team. In 1898, Vital Brazil raised the first experimental objections to the icteroid bacillus, and Adolpho Lutz began his studies of the distribution of Culex and Anopheles across the nation. In February 1900, Arthur Vieira de Mendonça, another of Lutz's assistants, left the institute. “For the medical field, the mosquito bears ridicule on its wings” was his statement to the São Paulo newspapers (Antunes et. al., 1992, p.64, 67).

In the present volume, we reproduce three articles published in the Revista Médica de São Paulo, in which Lutz and Mendonça expound their now opposing views on the bacillus discovered by Giuseppe Sanarelli.

Headed by Walter Reed, the commission presented its findings at the Third Panamerican Medical Congress in Havana, in February 1901, at the same time William Gorgas began his campaign against the mosquito in that city (Reed, Carrol, and Agramonte, 1901). One month earlier, the sanitation commissions in the Brazilian cities of Sorocaba, Santos, and Campinas included as part of their routines the cleaning up of stagnant waters containing mosquito larvae. The battle against the mosquito played a bigger role in defining the measures adopted in São Simão. The outbreak of yellow fever began in that city in May 1902, but it was only in August that the commission appointed by Ribas was put into action; here, it also reconciled guidelines derived from the ‘Havana theory’ with disinfection measures. In Ribeirão Preto (1903), these guidelines were abandoned for good (Franco, 1969, p.64-6).

In a leaflet published in 1901, entitled “O mosquito como agente da propagação da febre amarela” (The mosquito as an agent of dissemination of yellow fever), Emílio Ribas endorsed the Reed commission's work publicly and without reservations. Although he recognized the need for “more experimental facts to conclude, positively and confidently, in favor of Finlay's theory,” he went on to say that

on the other hand everything leads us to believe that yellow

fever is a malady that disseminates itself through mosquitoes, in

the manner of paludism and filariasis … Among us, Dr. Adolfo

Lutz, director of the Bacteriological Institute, has been

concerned with the topic and continues his detailed research on

such an important question.

As a matter of fact, Lutz had been correlating the presence of mosquitoes to the yellow fever epidemics in the territory under his jurisdiction for quite some time, and therefore verification of the Cuban doctor's theory had not surprised him. São Paulo's Sanitation Service publication brought already, in the form of an inset, his first systematic observations on mosquitoes as agents of disease transmission.

Lutz's note concerned two species of mosquitoes of wide geographic distribution usually found in homes, only one of which, however, had been positively linked to the transmission of yellow fever. It is interesting to note that both Lutz and Theobald at first had trouble correctly identifying the species. In the first letter to his Brazilian

colleague, dated 28 April 1900, 127 the entomologist from the British Museum commented that their wide-ranging distribution and variety of local names raised significant obstacles to the identification of certain species, especially Culex taeniatus, even in older descriptions. Ficalbi's and Arribalzaga's works were cited as valuable resources in this endeavor. Lutz's answer to Theobald included a request for a sample of that Culex to compare with his own. A few months later, after receiving updated literature, he declared that he was already able to determine his species. In observations sent to Theobald on the material identified, he noted that C. taeniatus was commonly found in houses in coastal regions or inland, but not in the capital city of São Paulo. He had not yet postulated its relationship with yellow fever. It was only in a letter dated January 1901 that he informed Theobald that he had been paying particular attention to this species because its distribution coincided with that of the disease. His observations were published that same month by Ribas.

Terms such as ‘mosquito rajado’ (literally, striped mosquito) or ‘pernilongo’ (long-legged mosquito) – both colloquial names for Stegomyia fasciata – were commonly used to designate blood-sucking dipterous insects. Lutz had previously studied “a couple dozen species” in Brazil, most of which were only present in the wilds or in swamplands, the setting of the investigation he was finishing on the transmission of forest malaria. Only two species (Culex taeniatus and Culex fatigans) were frequent ‘tenants’ in human households. Although found in almost all regions offering the right climatic conditions, they were “extremely rare” species in uninhabited or uncultivated areas.

Letter to Adolpho Lutz from Frederick Vincent Theobald (1868-

1930), of the Zoology Department of the British Museum (Natural History), dated 28 April 1900 (BR. MN., Acervo Adolpho Lutz, pasta

267, maço 2).

The most widely scattered is Culex fatigans, our common night-

time mosquito, which is found almost everywhere since it is less

sensitive to the cold. It transmits filariasis and certain bird

haematozoa; I do not consider it a suspect in the case of yellow

fever. Culex taeniatus, on the other hand, is the only one that

can account for the distribution of yellow fever, because we

know that it has been described, under various names, in almost

all the places where yellow fever has reigned.

Lutz pointed out its occurrence in the United States, Cuba, Buenos Aires, on the south and west coasts of Africa, in Hawaii – in short, in all places where yellow fever had spread. He did not, however, associate it with Culex fasciatus, a species used in the experiments carried out by the Reed commission in Cuba. The Brazilian zoologist followed the classification proposed by Giles (1900) and the one

Theobald sent him in August 1900.128

Upon creating the genus Stegomyia in 1901, Theobald placed in it the Culex species related to yellow fever transmission, including C.

taeniatus 129 and many of the synonyms pointed out by Lutz. The species was then named Stegomyia fasciata. It was a mosquito that “had had 36 synonyms from 1762, when Linnaeus classified it as Culex aegipty, until 1926, when Silver renamed it Aedes aegypti, as it is currently known” (Franco, 1969, p.64).

Albuquerque (1950, p.11-2) most certainly falls into an anachronism when she states that already in 1889 in Campinas, Lutz would have had a “clear intuition of the truth” on the correlation between mosquitoes and yellow fever. Lutz himself is to blame since, in an article published in 1903 (“Yellow fever and the mosquito,” in Port.), and later in his Reminiscências (1930), he alluded to observations made in 1889; these, however, had not been published, most probably because they amounted to little more than suspicions as yet irreconcilable with the etiological theories of the day.

“At that time, all the elements for explaining this mode of transmission were lacking,” reads an excerpt from the first article. Even so, when that coffee-growing center was devastated by yellow fever, Lutz had noted “an extraordinary abundance of the ‘striped mosquitoes’ that [he] knew so well from Rio de Janeiro, but that [he] had never observed in the interior during five years of practice in a region not too far from Campinas.” Lutz at that time correlated the “plague of the Stegomyias with tanks of still waters in the gardens of houses that had been abandoned by their owners. They were such a nuisance that he used a mosquito net every night and sometimes even in the daytime “so that [he] could read in peace; naturally that did not stop [him] from being bitten on several occasions” (Lutz, 1930).

It is, however, true that his first speculations on the role bloodsuckers played in spreading disease predate this event. They are found in his “Studies on leprosy,” written in 1885-86 and published in Monatshefte für Praktische Dermatologie (1887). On describing primary lesions of the nervous form, which could act as “the entryway for infection,” he considered it “impressive that its first locus of manifestation … is almost always in the parts of the body that are left uncovered and exposed to insect bites and other trauma” (1887, p.549). Lutz had already observed that each new case of infection required a pre-existing case within a defined area, but that the necessary conditions were of such complexity and peculiarity (much like yellow fever, we might add), that one could exclude direct person-toperson contagion. To explain transmission of Hansen's disease, Lutz admitted, albeit hypothetically, that blood or excretions from the patient's mucus that contained the infectious agent might require “maturation” in an external medium, or “direct inoculation that generates vulnerability (for example, through insect bites).”

This documented speculation leads us to give credit to the statement made in 1903 that the notion of mosquito transmission of yellow fever had been “always attractive” to Lutz after Campinas. “As a doctor and naturalist, I have always paid attention to these mosquitoes,” Lutz wrote, “and I knew that they were very common in Rio de Janeiro and in Santos, although much scarcer in rural São Paulo, where on rare occasions they did become a nuisance to me in the places I knew and lived in.”

In the 1903 article, he traced doubts about this hypothesis to the realm of entomology itself; his main objection concerned the epidemics of yellow fever along the Mediterranean and African coastlines, since it was believed that the Stegomyia fasciata existed only on the American continent. “It was with great surprise that, a few months later, I observed the same mosquito in the Sandwich Islands, and not only in the capital but even in far-removed plantations … I then understood that [S. fasciata] was scattered about by seafaring vessels and that it must be found in other warm countries, although I was unaware of its presence in southern Europe. Theobald was to demonstrate this in the early 20 th century.

As we have shown in the previous volume of the Collected Works of Adolpho Lutz, it was in Hawaii, where he lived from 1889 to mid-1892, that Lutz became convinced that mosquitoes transmitted leprosy. According to Albuquerque (1950, p.13-4):

Although he had never avoided direct contact with lepers, he did

not contract the disease … and among the sick who entered the

leper colony, some had never seen another leper. There had

been a time, and not so long before, when neither leprosy nor

mosquitoes existed in Hawaii. The native language did not have

words for either leprosy or mosquitoes, and nicknamed leprosy

‘Chinese sickness’, since it had appeared only after the Chinese

arrived and began raising rice. They cultivated rice, as is

customary, in continuously irrigated ditches where mosquitoes,

similarly of alien origin, found an excellent micro-habitat.

We thus find reasons to believe that the following statement from Lutz's Reminiscências (1930) is legitimate:

Had I not made the previously mentioned observations on

mosquitoes in Campinas, it would not have been possible for

me – much later, and as soon as I received a letter with the first The certainties that had been upheld inflexibly during Gorgas, Ribas, and Cruz's times came crashing down in 1932-33 in the valley of Canaã, in rural Espírito Santo, when sanitarians from the Rockefeller Foundation, led by Fred Soper, confirmed the suspicion that yellow fever had one or more undetermined vectors, and that it was connected with the work of men who became infected while in the forests.

news of the demonstrative experiences carried out in Havana —

to name the guilty mosquito among us without hesitation, a

mosquito that did not exist in the city of São Paulo. It seemed

probable to me that we were dealing with the same species,

although I did not call it by the name the Americans used; only

later was the species identified, having already been given a

variety of names. I immediately informed the director of

Sanitation Services, who accepted my guidance when I insisted

on the importance of the verifications made in Cuba. After

publishing the necessary instructions, we verified a coincidence

of yellow fever epidemics with an abundance of Stegomyias in

many places.

This discussion is related to the important role that Adolpho Lutz played at the turn of the 20th century in changes in how yellow fever was perceived and in the drastic change in direction taken by Brazilian public health. There is, however, another important issue underlying the text of Reminiscências, written in 1928-29. The paradigm that guided the campaigns of William Gorgas, Emílio Ribas, and Oswaldo Cruz began to fall apart at the seams, a paradigm that had led the Rockefeller Foundation to strive for the complete eradication of the disease by combating its transmitter in a few ‘key foci’ along the American and African coastlines following World War I.

For doctors at the turn of the century, yellow fever was an illness associated with ships, European immigrants, port cities, and the warm and humid coastal lowlands, which created the habitat for miasmas, then for fungi, algae, and the bacillus, and, lastly, for Stegomyia fasciata. The reinfestation of many coastal Brazilian cities in the 1920s prompted the recognition of anomalies in a paradigm that had been considered irreproachable. When yellow fever reappeared in Rio de Janeiro in 192829, it became clear that its ‘place’ had shifted to poor inland settlements, from which native migrants now brought the disease to the periphery of the great coastal cities.

The epidemiological map that began to take shape between 1930 and 1937 ultimately changed the terms of the equation that had prevailed in the previous decades. Jungle yellow fever seemed to form not only great endemic stains that interlinked regions and nations but also waves that would from time to time, and by way of unknown mechanisms, sweep through vast regions, advancing dangerously from the wilds and forests to coastal cities. It seemed to be the common form of the disease, and the urban one, simply an abnormal manifestation that would tend to extinguish itself either when the mass of non-immune individuals had been consumed or when Aedes aegypti itself had been eradicated (Benchimol, 2001).

Map of the state of Espírito Santo, highlighting the municipality of

Santa Teresa, where the first suspected cases of sylvatic yellow

fever were registered at the end of 1930 (Benchimol, 2001, p.144).

Lõwy (Nov. 1998/Feb. 1999) rightly holds that the dogma of exclusive transmission via Aedis aegypti would never have been defeated had there not been tools that magnified the presence of the virus: histological analysis of the livers of the deceased and protection tests on blood drawn from the living. One must add that this change in point of view was also due to the growing skepticism of Brazilian doctors, who rebelled against the dogma maintained by the directors of the Rockefeller Foundation in the 1920s. The flames of escalating doubts were fanned when Adolpho Lutz published his Reminiscências.

As early as 1903, he admitted to the possibility that other mosquitoes were able to transmit yellow fever. “It is probable that this property belongs to the entire Stegomyia genus and not solely to one species. I know two more species that belong to our fauna that could probably be included in this genus, but fortunately they are wild species, are not abundant, and could only produce small disseminated foci.”

In his 1930 publication, Lutz brought attention to the importance of two foci he had observed at the end of the 19 th century, foci that bore no relation to the railways or riverboats that carried Stegomyia fasciata and yellow fever inland. At these foci, disease transmission was attributed to

probably … woodland mosquitoes from the wilds, more or less

related. One of the cases [I] only have information on involves a

village of native Indians from Verde River. The other, which I

investigated personally, was indeed yellow fever, which

appeared in a few ranches built in the middle of a forest and

inhabited by workers. They cut down the vegetation to prepare

for building a railroad that was to link Funil to Campinas. I

examined a number of the ranches from which cases of yellow

fever had appeared, and found no trace of larvae or adult

Stegomyia, there being no shortage, however, of forest

mosquitoes. This fact proves even more interesting since

transmission of the disease by mosquitoes other than our own

domestic Stegomyia has recently been verified in Africa. Among

us, this species will always play the most important role, while

transmission by other species must be rare and the exception,

but the problem of identifying other species able to transmit the

virus is nevertheless interesting.

In the note published in 1901, Lutz was already certain that Culex taeniatus was found in Rio de Janeiro, Santos, Campinas, Casa Branca, and Sorocaba. In the capital city of São Paulo, considered exempt from yellow fever, he had never spotted it in the houses where he had lived, but he had recently sighted it:

Ferro Carril Agrícola Funilense railway, known as “A Funilense,” that

linked Fazenda Funil in the Campos Salles Settlement (Cosmópolis),

to Campinas. Source: www.cosmopolisemrede.com.br, retrieved 22

June 2005.

even quite abundantly, in circumscribed points about town,

which should explain certain outbreaks limited to a few streets.

Although all those who lived [on these streets] would fall ill,

there were no examples of contagion by the tramway personnel

who continuously travel those streets. Simple pedestrians were

not affected, but it was sometimes enough to spend but a few

hours in the infected houses, be it by day or night, to contract

the disease … One should not, however, suppose that the

incidence or scarcity of the species in a specific place should

stand as a definitive and absolute cause. Quite the contrary, it

may vary greatly, according to the season and the ease of

procreation. [The species] can also be introduced into a place

that was previously immune, as occurred in the Sandwich

Islands on a recent, well-known date.

 

Lutz's and Ribas’ experiments in São Paulo Towards the end of that year, the President of the State, Francisco de Paula Rodrigues Alves, authorized the directors of the Bacteriological Institute and the Sanitation Service of São Paulo to reproduce locally the experiments carried out by North Americans in Cuba. The objective then was to neutralize reactions to the ‘Havana Theory’, reactions that were voiced most especially by doctors who were supporters of the Sanarelli bacillus and other microbes.

Before starting, Adolpho Lutz traveled to Rio de Janeiro more than once to obtain mosquitoes and have them bite people with mild cases of yellow fever. He would stay at 36 Mariz e Barros Street, at the school his sisters ran. In a letter to Emilio Ribas, dated 25 June 1902, he complained about the rain, the heat, and the time he lost traversing great distances by streetcar. This included the trip to São Sebastião Hospital, in the neighborhood of Cajú, where he kept track of three patients “from whom [he] obtained a few mosquitoes that had sucked. Two of them were doing regularly well and one was very badly off.” The epidemic that broke out in December 1901 continued its death toll, and “serious cases” kept on arriving. It had been a year of many mosquitoes in Rio de Janeiro but, Lutz wrote, “now they are rarer and the larvae develop slowly.” He might have been referring to a batch of mosquitoes being raised in a pavilion of Sebastião Hospital by the French medical mission (to which we will soon return), but it is not very likely, since he was not able to meet with one of its members, Paul-Louis Simond, “because of two holidays.” It is more likely that these mosquitoes were being raised by Lutz himself in the bacteriological laboratory at the General Directorship of Public Health, which operated at 56 Visconde do Rio Branco Street under the direction of Emílio Gomes. This was where Lutz's assistant Carlos Meyer was supposed to send specimens of Stegomyia fasciata being bred at the Bacteriological Institute of São Paulo. “We are in sore need of more mosquitoes,” Lutz wrote. He was going to visit Manguinhos in the company of Oswaldo Cruz that same day, and was to stay at the federal capital “until Monday of the following week” — in other words, five more days, since the letter was written on a Wednesday.