Adolpho Lutz: febre amarela, malária e protozoologia

Jaime Larry Benchimol · Capítulo 8 de 56 · parte 1/9

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Adolpho Lutz: febre amarela, malária e protozoologia

Insects, people and disease: Adolpho Lutz and tropical medicine

Este capítulo é longo, por isso está dividido em 9 partes.

Insects, people, and disease: Adolpho

Lutz and tropical medicine

 

Jaime L. Benchimol; Magali Romero Sá

A dolpho Lutz spent seventeen years far from his family. Born in the Brazilian capital on 18 December 1855, the second of Gustav and Mathilde Oberteuffer Lutz's ten children, Adolpho was two when his parents returned to Switzerland in 1857, seven years after emigrating to Brazil. In 1864, they once again relocated to Rio, leaving their three eldest children to study in Basilea. Adolpho would only be reunited with his parents in 1881, when he went back to Rio with his medical degree in hand and a solid background in medicine and biology, acquired at German-speaking universities. While he was away, the city that had welcomed these Swiss immigrants had undergone remarkable changes.

When Adolpho Lutz's parents disembarked in Rio de Janeiro, in late 1849/early 1850, the forces that had in the previous decades resisted the Empires centralizing policies and Southeastern Brazil's escalating economic hegemony had been tamed.

Divided essentially into masters and slaves, the port city was thriving as the point of contact between an expanding coffee crop – tended by slaves in the Paraíba River Valley – and the world market. Its streets bustled with slaves hired out by their masters on a daily basis for work in a wide gamut of trades. The slaves received only a small portion of the money earned and applied it towards their own sustenance: food, drink, perhaps even a room in a tenement. But most of the earnings went to fatten the coffers of the richest slave holders or to guarantee the survival of the poorest among them, sometimes almost as poor as the working slaves themselves. Household slaves did the multiple tasks demanded by the natural economy buttressing residences based on slave labor. This meant they supplied their masters’ homes with water and removed sewage, duties soon transformed into profitable ‘public’ services in the hands of private companies.

 

Largo da Carioca, 1844. Watercolor on paper, by Eduard Hildebrand,

entitled “Brunnen in Rio de Janeiro” [fountains in Rio de Janeiro],

showing the Carioca Fountain, the Terceira da Penitência Hospital,

Saint Anthony's Church and Convent. Staatliche Museen zu Berlin

collection, Alemanha (Belluzo, 1994, v.3, p.106, fig. 481).

In the ensuing decades, the second industrial revolution – the revolution of iron and steel manufacturing, of capital goods, and of the construction of railways and steamboats – would consolidate England's world power, albeit other countries likewise revolutionized by big industry were emerging as serious competitors. Capital exports, in the form of public loans and direct investments, lent impetus to the modernization of peripheral economies like Brazil's, equipping them to respond to the new inflow of raw materials and industrialized goods.

In the time between Gustav and Mathilde Lutz's immigration to Brazil and young doctor Adolpho's return voyage, other processes helped to change the face of the Brazilian capital: abolition of the slave trade in 1850, the Paraguayan War (1864-70), demographic growth, and the gradual expansion of freed labor. In the 1870s, the Empire of Dom Pedro II and of the coffee barons seemed to be at the heyday of its grandeur and stability, and Brazil was living out its apparent destiny as a primarily agricultural nation. Rio de Janeiro was its most prosperous commercial and financial center. Matching the pace at which Paraíba Valley plantations absorbed the last contingent of Brazilian slaves through interprovincial trade, Rio made ample room for wage labor. The circulation of merchandise – basis of the urban economy – improved qualitatively thanks to these new labor relations. The production of important manufactures notwithstanding, the productive sector remained an appendix of import and export activities.

 

Rio de Janeiro's Providência Hill in 1866, then known as Gamboa Hill. Photograph by Augusto Malta (Museu Histórico Nacional, Rio de

Janeiro).

Replacing river and pack-mule transportation, the tracks of the Dom Pedro II and Leopoldina railways brought Rio de Janeiro closer to its rural rear guard. Likewise revolutionized by steam power, maritime transport increased alongside a complex of commercial and financial enterprises formed chiefly of British capital. The port itself saw its first reforms, like metal warehouses and steam-driven cranes on the Customs House pier, where cargo handling could now be done without slave labor.

In the 1860s through 1870s, foreign companies, along with some Brazilian ones, began setting up public services: gas lighting, household water and sewer, garbage disposal, urban transit, and so on. This helped eliminate the system under which slaves provided such services and also undermined the household economy responsible for the self-sufficiency of slave-run residences. Tramway companies spearheaded extension of the urban network beyond the former perimeter of the Old City and of Rio's latest development, the New City. Although new neighborhoods were springing up, critical problems became concentrated in downtown Rio, born of a growing incompatibility between the former material structure and the new capitalist economic relations taking root within this framework. Between rail station, docks, and the labyrinth of commerce, the center's narrow, winding streets became crowded with a greater inflow of men and merchandise, including large iron manufactures. The populous downtown was home to a wide assortment of edifices: offices and banks, stores, repair shops, waterfront warehouses, public buildings, private one- and two-story residences, grocery stores oft times servicing tenements and the like, old aristocratic mansions sliced up into tiny, dirty rooms that boarded entire working-class families. A heterogeneous, drifting multitude lived and labored in central Rio de Janeiro. In physical terms, the market where this now-freed labor force put itself up for sale was contiguous with the market where daily wages and uncertain earnings by workers were converted into the sustenance that ensured their survival.

Oil painting on canvas by C. J. Martin, entitled “View of Guanabara

Bay from Russel Beach,” in 1850. Sérgio Fadel Collection, Rio de

Janeiro, Brazil (Belluzo, 1994, v.3, p.154, fig. 525).5).

There, every year, more or less deadly epidemics broke out. Morbidity and mortality rates varied with the biological and social synergy of those who came into contact with each other during the course of each disease. Smallpox epidemics generally occurred in the winter. Cholera struck Rio de Janeiro in 1855-56, at the close of the 19th century's third major pandemic. In the nation's capital and in its provinces, tuberculosis, dysenteries, malaria, and fevers known by dozens of names raged like chronic scourges.

The most serious public health issue was without a doubt yellow fever, which ‘docked’ at the Imperial capital in the summer of 1849-50, just when Gustav and Mathilde Lutz first stepped on this new land, where signs seemed to promise a civilization similar to that

which had flourished in the Old World's temperate zones.1 Yellow fever and the beginning of Adolpho Lutz's

career

According to Bertha Lutz,2 her grandparents arrived in Rio de Janeiro in January of 1850. This would have been at the peak of the severe epidemic sweeping the Brazilian capital for the first time. Adolpho Lutz (1930, p.2), however, wrote that when his parents reached Rio, it was still free of the disease, which means they disembarked shortly before 28 December 1849, the date on which Robert Christian Berthold Avé-Lallement (1812-84), a physician from Lubeck, diagnosed the first cases at Santa Casa de Misericórdia Hospital (Franco, 1969, p.35; Chalhoub, 1996, p.61; Santos Filho, 1991, p.195).

Witnesses to the epidemic associated its outbreak with the arrival of a slave ship from New Orleans, which had made stopovers in Havana and Salvador before making harbor in Rio on 3 December 1849. Crew members took up lodging around the city, and ‘yellow jack’ erupted at one of the inns where they stayed, on Misericórdia Street. By February 1850, when the Imperial Academy of Medicine finally recognized that yellow fever held the city in its grip, the illness had already spread through the beaches of Mineiros, Peixe, Prainha, Saúde, and beyond. According to estimates by Dr. José Pereira Rego (1872, p.159), it struck 90,658 of Rio's 266,000 inhabitants, killing 4,160 according to official data or, according to extra-official sources, up to 15,000 (Chalhoub, 1999, p.61).

“Year for mangoes, year for yellow fever,” the locals said, expressing in colloquial language the relationship that doctors drew between heat, humidity, and epidemics. Except for the period between 1862 and 1869, the disease ‘grew’ as regularly as other seasonal fruit, always during the so-called muggy season, that long period of heat and rain running from about November till March or April. Analogies with the plant world didn't end there. It was assumed that yellow fever, like plants, took perfectly to coastal lowlands, especially port cities, where putrefying plant and animal matter provided them with ideal humus.

Writing about his parents and Rio de Janeiro's first epidemic, Adolpho Lutz said (1930):

In the subsequent period, they had many children, all of whom

ran the risk of yellow fever for varying but generally quite lengthy

periods of time. My mother, who lived in Rio for over thirty years,

never caught it, but my father and a brother of mine each came

down with it twice and another got sick during the first Santos

epidemic, that is, in 1879, meaning that family immunity can be

discarded. However, many more people in the family remained

free and today can be considered [to have been] protected by

this imperceptible process of immunization, whose existence is

as evident as its establishment is hard to accompany. Taking the

third generation into account, one can say that in my family the

morbidity rate of those exposed did not reach one-third, a

remarkable fact when one compares it with the general

morbidity rates during the first epidemics in different points

around the state of São Paulo.

When he came ashore in Rio de Janeiro in 1881 with his medical degree, at the age of 26, Adolpho Lutz took up residence at his parents’ home at 33 Princeza Imperial Street, in the neighborhood of Catete, a house large enough to accommodate his nine siblings and

the Girls’ School founded by his mother.3 His father's business was located at 44A Sabão Street. According to advertisements published in Almanak Laemmert (p.497, 512, 549), Lutz & C. was a company of “foreign businessmen” dealing in import and export, in the latter case in collaboration with J.R. Dietiker. They were publicized as “Consignees and Commission Houses for Import and Export Goods” and “Wholesale Stores of Imported Dry Goods.” Taking advantage of the process of urban modernization then underway, Lutz & C. acquired (4 Apr. 1872) control of the assets of an industry that produced “instantaneous tubular wells,” owned by Gustavo Adolpho Wierffbain, “civil engineer, born in Germany, and resident of the

Empire of Brazil.”4

As we saw in the first book of The Complete Works of Adolpho Lutz, one of the first things he did was to have his diploma recognized by the Rio de Janeiro School of Medicine. In an article published in Correspondenz-Blatt für Schweizer Aerzte in April 1882, Lutz described the bureaucracy entailed in this process and drew a portrait of medicine in the Brazilian Empire. He explained that the country's larger cities had their advantages, but that life was thrice as expensive as in Switzerland and, in the case of Rio de Janeiro, one could add the risk of yellow fever to the city's bothersome heat. This was one reason the young doctor decided to find a rural town where he could practice medicine. Besides enjoying the rewards of the “beauty of nature,” whoever set about building a reputable practice in such places could expect to make a small fortune, as in Europe. Income varied with the region, with less money to be earned in some places and substantial sums in others, like certain coffee-growing areas or some German settlements in southern Brazil.

Lutz remained in the capital of the Empire for eight months, waiting for his diploma to be recognized. In the first half of 1882, he tried opening an office in the nearby mountain town of Petrópolis but ended up settling in Limeira, site of a sizeable Swiss-German settlement where his sister Helena had just moved, shortly after her marriage to the German businessman Gottfried Wilhelm Luce.

Adolpho Lutz's results in general medicine, surgery and obstetrics,

after exams taken at the Rio de Janeiro Faculty of Medicine to

validate his degree in medicine, dated 21 December 1881 (BR. MN.

Fundo Adolpho Lutz).

Adolpho Lutz's registration at the Faculty of Medicine of Rio de

Janeiro, dated 27 October 1881, to take exams required to practice

the profession in Brazil (BR. MN. Fundo Adolpho Lutz).

From June 1882 to March 1885, Lutz resided in this vital center for coffee, sugarcane, and grain production in São Paulo province, its population then around 14,000.

He attended people from other settlements along the Paulista railway as well, which soon gave him a comprehensive view of the region's diseases. In late 1882, in a note published in the Swiss periodical mentioned earlier, he recounted his first impressions of rural São Paulo and listed the topics he might analyze in future articles. He underscored the contributions he could make to medical geography. Since he treated diverse ethnic groups, he could offer rich “observations concerning the influence of climate and of the human race on different diseases; in [his] work, [he] attended blacks, Brazilians, and German, Portuguese, and Italian immigrants, who thus provided most interesting comparative material” (Lutz, 1883, p.30).

In Limeira, Adolpho Lutz did important investigations into both clinical practice and the helminthology of domestic animals and man. It was then that he undertook his research on worms, broadening the repertoire of pathologies under study by the Bahian tropicalist school and likewise opening the door to the investigation of animal diseases in Brazil. As we saw in the second book of this collection (Benchimol and Sá, 2004), Adolpho Lutz's interest in leprosy led him to Hamburg in March 1885, where he worked about a year at the clinic founded by Paul Gerson Unna. Under the latters guidance, he ventured into the territory of bacteriology, focusing on the morphology of germs linked to a number of dermatological diseases.

Adolpho Lutz's sister, Helena Lutz Luce, with her son Gottfried

Wilhem Luce, Born 24 August 1884. They lived in Limeira, São

Paulo, near Campinas. The photograph was taken at Photographia

Rozén, Nickelsen & Ferreira, on 20 June 1886 (Margareta Luce

collection).

When he returned to Brazil in mid-1886, Lutz resumed his medical practice, this time in the city of São Paulo, while continuing to publish articles in German periodicals not only on dermatology but on

helminths too. 5 A Portuguese translation of Lutz's work on ancylostomiasis, originally released in Volkman's collection of lessons from medical practice (Leipzig, 1885), then came out in O Brazil-Medico, Gazeta Médica in Bahia (188789), and shortly thereafter in book form (1888), all of which made Lutz's name more familiar to his Brazilian peers. In Limeira and then later in the city of São Paulo, he also explored the life cycles of Ascaris lumbricoides and Rhabdonema strongyloides. In 1888, he published a series of articles in the prestigious Centralblatt für Bakterologie, Parasitenkunde und Infektionskrankheiten on infestations of intestinal nematodes in man -ancylostomiasis, oxyuriasis, ascaridiasis, and trichocephalosis. He emphasized the role of the soil and feces in spreading these diseases and drew correlations between them and the immigrant population's living and eating habits; he further called his peers’ attention to how often domiciliary

infestations and family epidemics occurred. 6

 

Two-story house where Adolpho Lutz lived in Limeira, São Paulo.

Photograph by Eduardo Cruz, taken in April 1986, just before the

house was torn down (Instituto Adolfo Lutz).

 

Amoebae, bacilli, and dysenteries Intestinal diseases were a preponderant component of public health problems in Brazilian cities, which were to greater or lesser degrees then experiencing population booms and witnessing the decline of living conditions as a counterpart to the development of capitalism. Lutz started studying these diseases while practicing medicine in Limeira, and in 1891 he published a vital study on the subject, likewise in Centralblatt für Bakterologie, Parasitenkunde und Infektionskrankheiten (1891, p.241-8).

The etiology of dysenteries was quite unclear back then. Amoebae had been located in the corpses of people who had succumbed to a variety of intestinal syndromes, but no one had been able to demonstrate a cause-and-effect relation with these protozoans.

When Lutz began exploring the question, existing notions about dysentery were quite ill-defined and the topic one of great controversy. Physicians searching for the cause of this malady found various microorganisms in patients’ feces and body organs, and each one believed that whatever they found played the role of specific etiological agent.

Dopter (1909, p.1-2) pinpoints 1859 as the year these studies began, when Vilem Dusan Lambl (1824-95), a Bohemian physician who had obtained his medical degree in Prague and who worked at a

children's hospital there (Franz-Josefs-Kinder-Spitale), 7 observed the presence of amoebae in the feces and, more importantly, in the intestines of a child stricken with dysentery.

According to Martinez-Palomo (1996), in an article published ten years earlier in the bulletin of Moscow's Imperial Society of Naturalists under the title “Fragments d'helmintologie et fisiologie microscopique,” the Russian doctor G. Gros had demonstrated that organisms he called Amoeba gengivalis parasitized humans.

As stated by British biologist Clifford Dobell (1919), it was the surgeon Timothy Richards Lewis who in 1870 first observed that amoebae could be present as parasites in the human intestine.

Lewis was then member of a commission formed to investigate cholera in colonial India.

 

Various forms assumed by the degenerating liver-cells; for the

purpose of comparison an amoeba is represented in the lowest

figure (Harris, 1898, fig. 5).

“Today we know,” Martinez-Palomo explained, “that two types of intestinal amoebae are present in man: one non-pathogenic, observed by Lewis (Entamoeba coli), and one pathogenic (Entamoeba histolytica), defined by Lõsch. It took decades to establish this differentiation.”

This author credits Fedor Aleksandrovich Lõsch, a physician and microscopist from Saint Petersburg, with discovery of the causative agent of amoebiasis.

In 1873, a young peasant named J. Markow, who was suffering

from heavy diarrhea and a rectal malady, began undergoing

treatment (initially successful) with quinine sulfate (and other

drugs) … Lõsch provided a precise description of the amoebae

found in the patients feces, which he christened Amoeba coli

(most of the ulcerations were in the colon), but since … the

inoculation of dogs with these amoebae had no effect, he dared

not categorically affirm that they were responsible for the

infection.8

The Russian doctor presumed the amoebae would merely exacerbate intestinal inflammation through direct mechanical irritation (Dopter, 1909, p.2). Perhaps the physician's doubts also derived from his reading of a paper published by Basch shortly before (1869), in which the latter had observed non-characterized spherical elements and filaments suggestive of a bacterium of the group Leptothrix in slices of dysenteric intestines. A short time later (1875), Rajewsky was to describe colonies of cocci and bacteria in the lymphatic vessels of the submucous membrane.

 

Microscopical section of liver abcess, showing Entamoeba hystolitica

at margin of abcess cavity surrounded by necrotic liver cells

(Manson-Bahr, 1940, p.548, fig. 62).

 

Entamoeba coli. X 2,500: 1 – Cyst with eight nuclei. 2 – Active

Amoeboid stage with ingested food material (Manson-Bahr, 1940,

p.859, fig. 190).

In subsequent years, Sonsino, Perroncito, Grassi, Calandruccio, and Blanchard corroborated the presence of amoebae in dysenteric feces, but their role remained an issue since Grassi found them in healthy individuals too, and Cunningham and Lewis, in patients suffering from cholera.

In 1883, while studying the disease in Egypt, Koch recognized that amoebae could play a specific pathogenic role, after having found them not just in human stool but also in slices of dysenteric

intestines, deep within the intestinal walls. 9 Kartulis, his disciple, confirmed these observations after examining many sick people in Alexandria and in Greece. He had found amoebae in their stools and intestines and in abscesses of the liver as well (Dopter, 1909, p.2-3), but he could not erase doubts about their pathogenic role, since experimental inoculation in laboratory animals had been inconclusive; nor could he demonstrate a relationship between the ‘tropical’ dysentery he was studying and the cases described in

Europe by doctors who saw no relation with the amoebae.10

From then on, the number of papers published on the topic grew steadily, some confirming and others refuting Koch and Kartulis’ hypothesis.

In Prague, in 1886, Jaroslav Hlava presented the results of a study

of sixty cases. 11 He had managed to reproduce the disease by inoculating dysenteric material in different animals, but he had isolated not only amoebae but nineteen different bacteria too. He did state that only the first were specific. The following year, however, Theodor Albrecht Edwin Klebs (1887) incriminated a bacillus isolated from the intestinal walls. Chantemesse and Widal reached a similar conclusion (1888).

At Lõsch's clinic in Kiev, Massiutin examined the stools of five patients: one with chronic dysentery, two with ‘chronic intestinal catarrh’, one with typhoid fever, and the last with ‘acute intestinal catarrh’. All presented amoebae. In an article published in 1889, Massiutin concluded that these were not responsible for the dysentery; they had penetrated the intestinal canal through water, and their development there had been favored by existing ulcerations, which those protozoans merely exacerbated (Councilman and Lafleur, 1891, p.400-1; Dopter, p.4).

 

Edoardo Perroncito (1847-1936) in Turin (Emile Brumpt Fund,

Institut Pasteur). He and Lutz corresponded frequently from 1883

onwards.

 

Giovanni Battista Grassi (1854-1925) (Howard, 1930, fig. 49).

Towards the end of that year, Adolpho Lutz passed through Baltimore, in the United States, on his way to the Kingdom of Hawaii, where he was to accept a post as the Government Physician for the Study and Treatment of Leprosy. In this east coast city, then a heavily-populated junction of roads linking north and south, one of the most modern hospitals in the world had just been inaugurated: the Johns Hopkins. While there, Lutz talked about his unpublished investigation into amoebae with the head of medical services, the

pathologist William Osler (1849-1919).12

Johns Hopkins (1795-1873), the hospitals founder and patron, had been president of Merchants Bank and a director of the Baltimore and Ohio Railroad. Unmarried and a Quaker, Johns Hopkins had decided to invest part of his huge fortune in the establishment of a university and hospital for medical education and research, serving mainly the region's indigents. John S. Billings (1838-1913) was hired to supervise construction; he was an Army doctor familiar with the Civil War's ‘barrack hospitals’. The guiding principle behind these – prevention of contagion – was the same one underlying the hospital project, which was composed of isolated pavilions subject to rigorous standards when it came to the arrangement of spaces, beds, and services. The complex comprised seventeen pavilions connected by nearly 600 meters of hallways; construction stretched from 1877 until the institute's inauguration on 7 May 1889. In early 1886, William H. Welch had already begun teaching microbiology and pathological histology; that same year William Thomas Councilman (1854-1933)

joined the pathology laboratory headed by Welch.13 After Osler was made head of the hospital's medical services, he put together a team of assistant physicians who resided there, dedicated full-time to teaching and research. Henry A. Lafleur was one of them from 1889 to 1891, when he transferred to McGill University in Canada, where he had earned his degree.

Adolpho Lutz began his 1891 paper (published in Germany) with a mention of his visit to this hospital, thereby underscoring that in 1889 no studies on amoebiasis had as yet been conducted at the Baltimore establishment. In 1890, quick as can be, Osler had described a case of hepatic abscess involving the presence of amoebae, making no reference to the Brazilian scientist, which provoked the following resentful comment: “the priority of observations concerning the New World falls … to me, whereas Osler should present these [observations] only in relation to North America.” Lutz alleged that he had delayed publication of his investigations “in the (unfortunately vain) hopes of being able to complete them with a greater abundance of material.”

Lutz's article was based on only three cases, but it was comprehensive and precise. He provided an overview of the fragmentary facts recorded in different countries to that date and postulated a theory that could reconcile the divergent viewpoints regarding dysenteries. In one of the first compendia later published on this syndrome (then associated with a number of reasonably well-established etiologies), Lutz's work was characterized as “quite singular, since the ideas laid out by the author are those currently considered definitive regarding the etiology of dysentery.” Lutz believed the pathogenic role of amoebae to be “unquestionable” but he presumed that, in addition to this dysentery,

 

Johns Hopkins Hospital at the beginning of 20th Century. Source:

mdhsimage.mdhs.org/Library/Images/Mellon%20

Images/Z24access/z24-00250.jpg, retrieved 22 June 2005.

Johns Hopkins Hospital, Baltimore, MD. Post card whose caption

reads: “A world-fames institution, located at Broadway and

Monument Street, occupying more than four city blocks. It began

operation in 1889” (Author's collection).

whose evolution is chronic, with the alternatives of a passing

cure or exacerbations, frequently complicated by liver

abscesses, there is room for another dysentery, epidemic,

acute, causing diphtherial lesions in the intestines, and without

ever occasioning liver abscesses. In a word, at that time Lutz

had already foreglimpsed the now-recognized distinction

between bacillary and amoebic dysentery. (Dopter, 1909, p.4)

The São Paulo doctor sent these observations to the Centralblatt für Bakteriologie und Parasitenkunde while in Hawaii serving as head of medical services at the Molokai leprosarium. He had in effect demonstrated that two morbid entities were being confused, and he established criteria for differentiating them. He showed that pathological changes known by such diverse names as ‘acute (or chronic) intestinal catarrh’, ulcerous enteritis, hepatic abscesses, and chronic or tropical dysentery all fit into the profile of morbidity caused by amoebae. He called this “enteritis with bloody stool” to distinguish it from dysentery itself, which manifested as an acute infectious disease capable of spreading across wide areas. This distinction would be proven in 1898 when the Japanese bacteriologist Shiga Kiyoshi (1870-1957) isolated the agent of bacillary dysentery (Shigella dysenteriae).

Lutz showed that amoebae were “true parasites” that lived inside and outside the human body but could tolerate only a limited temperature range. This was precisely one of the main problems in studying them. Once immobilized by the cold, they resembled other cells, especially in the feces, so rich in microorganisms. In order to observe amoebae at length, Lutz devised an apparatus that kept the microscope stage heated to a constant temperature (Lutz and Lutz, 1943). This enabled him to uncover their mechanisms for adaptation to human hosts, their prolonged persistence inside hepatic abscesses, and the presence of elements supplied by the host organism, especially red blood cells.

Despite both the prestige of the German periodical that published Lutz's paper and its broad readership, many authors passed over the study, as Dopter noted in surprise (1909, p.4).

Quicker on the draw, Osler was in fact the first in the United States to describe amoebae, but involving only one case of chronic dysentery. The patient was a 29-year-old physician who had contracted the illness in Panama many years earlier and had suffered numerous attacks, consisting of fever, general malaise, and pain in the liver region. Although Osler observed numerous amoebae in the pus of a liver abscess and in the man's feces, he concluded it was still early to incriminate these protozoans as the disease's causative agent

with any real certainty. 14

Phylum Rhizopoda, Amoeba. (Brusca & Brusca, 2003, p.121, fig.5.1-

C).

Microscope similar to the one Lutz developed in the 1880s to study

protozoans, helminths and insects. It is attached to an apparatus that

keeps amoebas warm (Instituto Adolfo Lutz).

It was actually Councilman who first detected amoebae in Osler's patient. Together with Lafleur, Councilman then studied another fourteen cases. The paper they published in 1891 likewise failed to mention Lutz, although his article had already come out. These authors knew German well, and their omission is even more startling given the pains they took to conduct a thoroughgoing inventory of the state of the art in that particular area of medical investigations.

The pathologists at Johns Hopkins Hospital endeavored to isolate and distinguish the microorganisms present in patients’ stools and intestinal tissue slices and also analyzed the tissue lesions produced by the parasitic amoebae. Based on clinical and pathogenic characteristics, they drew distinctions between dysenteries, differentiating the amoebic variety from the inflammatory and diphtherial varieties (Dopter, 1909, p.4-5).

Based on our current knowledge of protozoans, we do not have

the same ability to classify and recognize the distinct species of

amoebae as we have for bacilli. It is therefore impossible to

state whether the amoebae found in fecal matter under certain

conditions are or are not members of the same species.

We use the name Amæba dysenterice to refer to the

microorganism first described by Lõsch as Amoeba coli, since

the latter term does not seem very characteristic, given that a

good number of amoebae of various species may exist and that

… they are not located specifically in the colon. (Councilman &

Lafleur, 1891, p.405)

In addition to suggesting that the human host contained different species of amoebae, some pathogenic and others not, these authors showed that amoebiasis was a disease characterized by “well-defined anatomical lesions displaying a degree of homogeneity.” They declared there to be no similarity between changes to tissues produced by bacteria or by amoebae. The latter reached the large intestine when a person ingested food or drink; they had no affect on the stomach or small intestine since conditions there were not favorable to their development (owing, for example, to the environment's alkalinity). Ulcerations were believed to be caused by invasion of the mucous membrane. They detected amoebae in the lymphatic and blood vessels, leaving the impression that these reached the liver via such channels. They also often found amoebae in the veins of the liver and lungs “but there was no evidence that they [reached] these organs via the blood stream.” They further stated that “other organs do not suffer metastasis, which should occur were the amoebae to pass through the blood stream” (ibid, p.509, 512-4).

Following publication of Councilman and Lafleur's paper – which Cox considers the most complete of all those produced in the late 19th century dysentery became a topic of note in the United States, and many doctors published reports on cases found in the areas where

they worked. One of these was H. Harris, 15 professor of pathology at Jefferson Medical College. In a paper dated 1898 (p.385-6), he cited Adolpho Lutz, recognizing that the latter had lodged “fair criticisms against our imprecise classifications of intestinal diseases.”

Other authors assumed a stance similar to Councilman and

Lafleur's. Dopter (1903, p.4-8) cites a long list of names, 16 including one Brazilian, Francisco Fajardo, who – as we will see – had a close relationship with Adolpho Lutz in other realms of protozoology. The papers published by these authors would make a vital contribution to our understanding of the life cycle of the amoeba and its parasitism, but it would take some years for the differentiation between pathogenic and non-offensive forms to firmly establish itself.

 

Amoebae and cell from the margin of a liver abscess, stained and

fixed by different techniques (Harris, 1898, fig. 11).

Cycle of the Entamoeba hystolytica: fig.16 – trophozoites in the

 

feces; fig. 17 – precystic stage; fig. 18 – mature cyst; fig. 19 –

excystation (Storer & Usinger, 1979, p.291, fig. 16 a 19).

During an investigation conducted in Egypt in 1894, Kruse and Pasquale raised the hypothesis that “hot countries” were home to a kind of dysentery caused by a pathogenic species, Amoeba dysenteriae, which differed from other varieties found in the intestines of healthy individuals (Dopter, 1909, p.6-7). The German scientists Heinrich Iranaus Quincke and Ernst Roos (1893) reached

the same conclusion. 17 Although unable to correctly differentiate the amoebae (Martinez-Palomo, 1996), in a 1903 paper the protozoologist Fritz Schaudinn established the name of the pathogenic species that is still used today: Entamoeba histolytica. But it would be another ten years before Walker and Sellards distinguished it unequivocally from free-living amoebae in water, which did not produce dysentery (Entamoeba coli) (Faust, et al., 1975, p.85). Schaudinn conducted his experiments on prisoners at the Bilibid penitentiary in Manila, in the Philippines. Of the twenty men who ingested eggs of that species, seventeen became infected but none developed the disease. On the other hand, of the twenty volunteers who received capsules containing Entamoeba histolytica eggs, seventeen were infected by the first dose whereas it took one of them three inoculations. Only four of the eighteen who had the parasite got sick. The experiment showed that the organism could be pathogenic in some people and not produce symptoms in others. It further showed that asymptomatic carriers could transmit the pathogenic parasite to healthy people (Martinez-Palomo, 1996). Following publication of Adolpho Lutz's papers, other authors endeavored to draw a relationship between dysentery and bacteria, assigning amoebae a secondary, meaningless, or sometimes even beneficial role. One who took this line was Maggiora; he attributed the disease to the pyocyanic bacillus and to a colibacillus displaying an abnormal level of virulence. Laveran also incriminated colibacilli. In 1895, based on case studies from Rome, Tivoli, Sienna, and even Alexandria, Celli and Fiocca concluded that a variety of this microorganism, which they called Bacterium coli dysenteriae, was responsible for dysentery. According to Bertrand and Baucher, dysentery was a polymicrobial infection associated with a number of different germs (septic Vibrio, pyocyanic bacilli, staphylococci, and colibacillus). In Saigon, Calmete incriminated the pyocyanic bacillus

(Dopter, 1909, p.5-9).18

The absence of amoebae in typical cases of dysentery, combined with their presence in healthy individuals or people with other diseases – facts pointed out by a number of authors – simply added to the confusion in this area of pathology.

As stated earlier, unification of these two lines of interpretation as proposed by Lutz in 1891 was justified nine years later by Shiga Kiyoshi (1898). He was a member of the new generation of bacteriologists who had recently joined the Institute for the Study of Infectious Diseases, inaugurated in Japan in 1892 under the direction of Kitasato Shibasaburo (18521931); he was also a brilliant investigator who had been one of the pillars of Koch's group, alongside Friedrich A.J. Lõffler (1852-1915), Georg T.A. Gaffky, and Emil von Behring (1854-1917). Kitasato transformed the new institute, known by the Japanese as Denken, into the main force behind transformation of medicine and public health in his country (Yoichiro, 1997).

In purifying feces from victims of a dysentery epidemic, Shiga isolated a bacillus similar to the coli and typhoid bacilli, one which did not ferment saccharides. Diagnostic tools then recently developed for use in bacteriology enabled him to recognize another important property of the microorganism: it was bound by the sera of dysentery patients but not by the sera of those suffering from other infections (Dopter, 1909, p.10-1).

 

Shiga Kiyoshi (1870-1957), who discovered the dysentery bacillus

(Yoichiro, 1997).

Kruse (1900), in Germany, and Flexner (1901), in the United States, soon confirmed Shiga's discovery, and dysenteries were differentiated in terms of etiology. There was one that took an acute, epidemic form, sweeping especially through temperate countries, and another, an amoebic form, chronic in nature and endemic to the tropics. New differentiations soon followed; the form of dysentery caused by Balantidium coli as well as the one caused by spirilli were described (Le Dantec). The term ‘dysentery’ came to refer to a syndrome with various etiologies. “Thus the opinion formulated by Lutz, Councilman, and Lafleur in 1891-92 has now been proven,” wrote Dopter in 1909 (p.10-2), in one of the first treatises on this subject.

 

Adolpho Lutz and yellow fever

It is possible that Lutz had come into contact with yellow fever patients or individuals suspected of having the disease while practicing medicine in Limeira and in the city of São Paulo, but no such traces can be found in the documentation with which we have worked. His first documented contact with the disease took place in early 1889, in Campinas, when the city fell victim to a major epidemic that had serious impact not only on its citizens but also on public opinion around the country.

Campinas was one of the principal urban centers of Southeastern Brazil. “It competed and in many regards was actually tied with São Paulo, the capital,” in the words of Santos Filho and Novaes (1996, p.9), authors of the most thoroughgoing study on this yellow fever epidemic, which “destroyed [the city's] vigor, paralyzed development, and crushed the city.”

Over the previous three decades, coffee had replaced the region's sugarcane plantations, and Campinas had prospered as a dynamic commercial and financial center. Its plantation owners and businessmen held a good share of the wealth in the province of São Paulo, and they invested it in railway lines that encouraged the expansion of crops and of new urban centers in western São Paulo state, an expanding frontier for the country's principal economic activity. Armed with a capitalist mentality that contrasted with the mentality of plantation owners in the decaying areas of the Paraíba Valley, Campinas coffee growers and businessmen invested capital in companies that provided public services and outfitted the city with the same improvements that had been transforming urban life in the capitals of the Empire and the provinces: gas lighting (1875), animal-powered tramlines (1879), and telephone lines (1884). Water and sewer services came only later, in 1891-92, largely in response to yellow fever.

Campinas became the hub of western São Paulo thanks to two railroads: the Companhia Paulista de Vias Férreas e Fluviais, founded in 1868, and the Companhia Mogiana de Estradas de Ferro. The first company inaugurated a line between Jundiaí and Campinas on 11 August 1872, four months after the second company had been founded (30 Mar. 1872). On 27 August 1875, Dom Pedro II and his entourage were aboard the train that opened the track connecting Campinas to Moji-Mirim, owned by the Mogiana (Santos Filho and Novaes, p.13-4).

The Brazilian census of 1872 informs us that 31,377 people resided in Campinas’ two parishes, Nossa Senhora da Conceição and Santa Cruz. Another source estimated that in 1871 the urban population was 10,000, while another 32,000 resided in the surrounding rural

areas, 12,000 being freedmen and 20,000, slaves.19

Santos Filho and Novaes (p.13-6) provide a detailed description of the companies, urban facilities, and personalities that made Campinas “the main center of São Paulo's rural aristocracy.” They write of the opulent mansions of the coffee barons, who even questioned whether São Paulo should remain the capital of the province. They name the retail and wholesale businesses that supplied the entire western part of the province, with such products as iron and bronze castings, agricultural machinery, ornamental goods, and locally made construction materials.

 

Inauguration of Companhia Paulista, in Campinas, on 11 August

1872. Lithograph by Jules Martin (Walker & Braz, 2001, p.80). Campinas had a cathedral, theaters, a skating rink, a hippodrome, clubs, and three large hotels: the Europa, the França, and the Grande Hotel Campineiro. It also boasted six schools (including one called Culto à Ciência, or Homage to Science) that drew students from a broad region of influence and where some important

proponents of the Republic taught.20 The Gazeta de Campinas (1869) was the major newspaper but others in circulation included Sensitiva (1873), Mocidade (1874), Diário de Campinas (1875), and Correio de Campinas (1885).

Santa Casa de Misericórdia Hospital was inaugurated in 1876; two years later, Beneficiência Portuguesa Hospital was founded. Santos Filho and Novaes (p.21) also write of hospitals for smallpox victims and lepers, both funded by the Municipal Chamber. During the crisis of 1889, special infirmaries or lazarettos would be hastily created to isolate those stricken with yellow fever.

The conviction that this disease “could not move into the mountains” (Lutz, 1930) and that its sole habitat was the overcrowded urban centers of the hot and humid coastal plains had been shot down in 1876, when Dr. Valentin José da Silveira Lopes, future Viscount of São Valentin, had diagnosed two Portuguese with yellow fever, both having just arrived from Rio de Janeiro. They had checked into a small hospital of which Lopes was one of the owners. The event had no major repercussions because these were imported cases, but two months later (30 Apr. 1876), Lopes stated to the Gazeta de Campinas that another eight people had come down with yellow fever. Since all of them lived near the Companhia Paulista de Vias Férreas e Fluviais railroad station, in houses contiguous with land where train cars filled with coal and merchandise from the port of Santos stood parked, Lopes presumed these wagons had brought the germs from infected ships. His diagnosis alarmed the population and incited much controversy not only in Campinas but likewise among physicians, politicians, and journalists from the capitals of the province and of the Empire, since very few believed yellow fever could manifest itself so far from the coast (Santos Filho and Novaes, p.23-4).

Arms of the city of Campinas. Founded in the first half of 18th

century it was called Mato Grosso until 1842, when it was given its

current name. Source: www.ngw.nl/int/bra/images/campinas,

retrieved 22 June 2005.

Lopes submitted a special communication about this to the Imperial Academy of Medicine; in its 5 June 1876 session, the note was read and commented on by Antônio Correia de Sousa Costa (1834-89), professor of hygiene at Rio's School of Medicine and president of the Central Board of Public Hygiene. His expert opinion was that the cases verified in Campinas were indeed yellow fever, and this was published in the Anais Brasilienses de Medicina (“Treatise on yellow fever in Campinas” [in Port.]). Lopes was elected a corresponding

member of the Academy on 28 August 1876.21

Dr. Valentin José da Silveira Lopes’ viewpoint was endorsed by Antônio Felício dos Santos (1843-1931), Júlio Rodrigues de Moura (1839-92), João Vicente Torres Homem (1837-87) – one of the most renowned clinicians in the city of Rio de Janeiro and professor of medical practice at its School of Medicine – and Carlos Ferreira de Souza Fernandes (1829-88), author of “Yellow fever in Campinas” [in Port.] (Anais Brasilienses de Medicina, v.28, p.1876-7). Another ally was Augusto César de Miranda Azevedo (18511907), future deputy for São Paulo to the constitutional assembly (1891) and then a resident of Rio de Janeiro.

But the hypothesis that yellow fever was present in Campinas was contested by a number of professors from the Rio de Janeiro School of Medicine. Among these was José Martins da Cruz Jobim (1802-78), for many years the school's director, professor of forensic medicine, one of the founders of the Academy of Medicine, and also a senator of the Empire. His ideas concerning the etiology of the disease underpinned the position taken by Antônio de Souza Campos (1845-1918), the first native of Campinas to earn his medical degree (1872): the latter argued that it would be impossible to transport the element which produced the disease (that is, the “infected” air of Santos, which impregnated train cargos), since the trip across the highlands would be through the mountains’ cold, healthier air (Santos Filho and Novaes, p.26).

The controversy did not dissuade rural inhabitants from their illusion that they were safe from yellow fever, “until the facts came to prove the contrary,” as Adolpho Lutz would later state (1930), having believed Lopes’ diagnosis to be correct in 1876.

The 1889 epidemic, the first to sweep through Campinas, hit the population hard and had national repercussions.

When it broke out, the population was terrified and whoever could, fled.

The plantation owners … moved to their rural landholdings or to

São Paulo … Entire families abandoned their homes and their

belongings. Those who couldn't get their hands on a carriage or

a horse went by foot, seeking refuge at nearby farms or cities.

Houses, shops, grocery stores, workshops, hotels were closed

… Pharmacies could not keep up with the dispatch of

prescriptions” (ibid., p.36-7).

The physician José Maria Teixeira (1854-95), about whom we will speak shortly, author of A epidemia de Campinas em 1889 (Rio de Janeiro, 1889), was to register these words: “The city was abandoned and almost deserted! Long, straight streets with hundreds of houses closed up and not a single passerby” (cited in Simões, 1897, p.23). The remaining residents rushed to the church every day to “pray publicly adpetendampluviam” according to another witness to the crisis (ibid.), in hopes that God's tears would wash away the sinister miasma hanging over the city.

According to a report published in the Freie Presse: Zeitung für Deutsche in Brasilien (Free press: a newspaper for Germans in Brazil), the “business of thieves” became quite profitable in this ghost town. One of those who fled, Mr. Felipe José, discovered upon his return that neither gold, nor silk, nor watches remained in his shop. Another businessman who had sought refuge in São Paulo came back to find his store stripped clean. “Many robberies of this type will undoubtedly come to light as the fugitives of the epidemic return to Campinas.”

In Reminiscências (1930), Lutz makes mention of the general opinion that three-quarters of the city's 20,000 inhabitants had abandoned it, “leaving behind mostly men who held jobs; however, many people returned too soon and ended up contracting the infection. Of those who were not immune and lived inside the city, almost all were infected.”

According to Santos Filho and Novaes (1996) and Simões (1897), the person who carried the disease to Campinas was the Swiss woman Rosa Beck, unmarried, 24 years old, having recently arrived in Brazil with the intention of finding employment as a French teacher. It is not clear where she disembarked nor where she caught the disease – Santos or, more likely, Rio de Janeiro. She died at 2:00 a.m. on 10 February 1889. She had taken up lodging with compatriots of hers, in the same building where they ran a bakery called Padaria Suíça. From there yellow fever spread through the rest of the town. The second death was a nine-year-old boy who shopped at the bakery. Two days prior to the boy's death, the attending physician, Eduardo Guimarães, “for the good of the public health,” published the news that he was caring for a patient with a critical case of yellow fever. Such was the incredulity that he summoned “eleven distinguished colleagues” to corroborate his diagnosis (Correio de Campinas, 23 Feb. 1889, cited in Santos Filho and Novaes, p.41). The fact that the victim was from Campinas and had never left the city was frightening: some as yet unknown local cause was responsible for his yellow fever. “Like olive oil spilled on a blotter” (Simões, 1897, p.21), the disease spread during March; it then let up for a few days, worsened in April (the “month of horror”), subsided again, and in early May intensified once more, from then

on waning until dying out in late June. 22

According to Adolpho Lutz (1930), overall mortality was estimated at about 2,000, “including those who were infected and passed away in other places.” The physician Ângelo Simões (1897) says that yellow fever attacked “over 2,000 people out of a population of 3,000 (since that is how many remained in the city, at most), resulting in 1,200 deaths, a number which I have most carefully verified.”

The wealthier people, who could afford to leave the city, were less affected. Most of the victims were Brazilians with no immunity to the disease, followed by Italians, Portuguese, and immigrants of other nationalities.

 

Adolpho Lutz in Campinas

In March 1889, the Municipal Chamber converted into lazarettos some residences in the neighborhood of Guanabara, then located a distance away from downtown. Special infirmaries for yellow fever patients were likewise set up in the Circolo Italiani Uniti's building, at the Correia de Melo municipal school, at the headquarters of the Sociedade Portuguesa de Beneficiência, and also at Santa Casa de Misericórdia Hospital. In 1890, the Lazareto do Fundão would be inaugurated in the vicinity of the cemetery; it was later transformed into an isolation hospital, with two wooden pavilions for patients, lodgings for the physician and caretaker, and facilities for a pharmacy, sterilizer, and so on (Lapa, 1996, p.261).

Santos Filho and Novaes (p.44-6) described the hygiene measures

adopted by the Chamber:23

Public thoroughfares were coated with pitch and watered down

almost every evening, while barrels of tar burned day and night

on the corners of the main streets. Bonfires of fragrant herbs

were lit. It was believed that the smoke … would clean the air of

harmful miasmas … All furniture and objects found in the rooms

of those who perished from the fever were destroyed and

burned … To keep the city's inhabitants safe from contagion, the

corpses were buried at night.24

Since it was mostly the poor who had remained in town, the Chamber enacted measures to help this population, vulnerable not just to the disease but also to hunger and neglect. It paid for public vehicles to transport doctors who made house calls for free, distributed food and clothing, and authorized pharmacies to provide medicine at the expense of the Municipal Chamber, whose president, José Paulino Nogueira (1853-1915), fell sick with yellow fever too.

In early April, when the situation worsened, Nogueira telegraphed the president of the province, Pedro Vicente de Azevedo (1844-

1902),25 requesting that doctors be sent urgently since most of them who lived in the town – about twenty – had left with their families,

and the few who remained were stretched thin.26 In Santos on assignment to the government of São Paulo, Dr. Francisco Marques de Araújo Góis headed to Campinas. He arrived on 5 April. Astonished by the extent of the crisis and the precarious aid provided to its victims, he endorsed the request for medical reinforcements. Towards the end of that month, he returned to Campinas as head of the Provincial Aid Commission, which comprised some thirty-five people, including physicians, fifth-and sixth-year students from the Rio de Janeiro School of Medicine, pharmacists, disinfectors, and staff who would provide other

services.27

Adolpho Lutz was a member of the commission, together with Drs. Claro Marcondes Homem de Melo (1866-1924), Irineu de Sousa Brito Junior, Aristides Franco de Meireles, Bráulio Gomes, and Luis Felipe Jardim (the last two came down with yellow fever but survived). In Reminiscências (p.128), Lutz recalls the weeks he spent in that city:

In 1889, when I was urgently called from São Paulo to

Campinas, where there were no more doctors, I encountered a

pandemic rightfully said to be yellow fever … After four to five

weeks, colleagues had arrived from Rio de Janeiro, and the

epidemic was waning in Campinas.

Lutz makes mention of two other medical commissions, one sent by the Ministry of the Empire and the other by the Comissão de Imprensa Fluminense (Rio de Janeiro State Press Commission), the latter comprising several Rio de Janeiro newspapers (Gazeta de Noticias, O Paiz, and Jornal do Commercio, among others).

Cartoons by Angelo Agostini show yellow fever epidemics in

Campinas and Santos and refer to the Republic, then being founded.

“They seem like two cities abandoned by God and by men! The press, seeing that the government does not take the necessary

measures, has decided to beg on behalf of the poor inhabitants of Campinas and Santos” (Revista Illustrada, year 14, n.545, 1889, p.4-

5; Arquivo Geral da Cidade do Rio de Janeiro).

The commission sent by the central government, then under the control of the Conservative Party, was headed by Dr. José Maria Teixeira (185495), mentioned earlier, who was professor at the Rio de Janeiro School of Medicine in medical subjects and pharmacy. It seems the first members of the group reached Campinas on 7 April, bearing 100 beds and an “ambulance” for which the pharmacist Joaquim T. Soares da Câmara was responsible. Besides Teixeira, other members included the physicians Eufrásio José da Cunha,

Francisco Custório Pereira de Barros, 28 Francisco Corrêa Dutra, João de Deus da Cunha Pinto, Fernando de Barros, and Luís Manuel Pinto Neto (Santos Filho and Novaes, p.54-5). The Imprensa Fluminense sent the physicians Clemente Miguel da Cunha Ferreira (18571947), as head, and João Batista da Mota de Azevedo Correia (1854-?). They arrived in Campinas on 20 April, bringing with them a substantial quantity of medicine, clothing, and foodstuffs that had been donated to the victims of the Campinas epidemic at events held in Rio de Janeiro, including a charity party, a horse race, and a concert. They stayed in town until 28 May, when the epidemic was already on the ebb. In addition to the physicians on assignment, Drs. Baltasar Vieira de Melo and Domingos José Freire Júnior came to Campinas of their own accord, the first having signed two death certificates (Santos Filho and Novaes, p.58-9, 61, 63).

Continuar: parte 2 de 9