February 15, 1916
Visit to the Oswaldo Cruz Institute
Demonstration of protozoology of Leishmaniasis cutanea, American trypanosomiasis (Molestia de Chagas), Ulcera granulosa pudendum and Yaws (Boba).
Dr. Chagas is a man of about 40 years of age, reserved, slight built, 64 inches high, blond and somewhat pale. His method of approaching his subject was direct and incisive and while very polite and agreeable he was not at all familiar. There was a distinct absence among all of the men of the institute of anything like ceremonious politeness and one is made to feel more at home than any place that I have yet been on account of the very evident genuineness of these gentlemen and their desire to share their scientific knowledge with those who have dedicated themselves to such studies.
Dr. Chagas first took up the subject of Trypanosomiasis tropica. He first showed the blood of an animal very heavily infected with the living Trypanosoma. The absence of a dark field made it difficult to distinguish the morphology of the organism. He then showed a stained specimen of blood taken from a case in the acute stage of the disease. He stated that it was rare to find them in the blood nave in the acute stage. The organism was exquisitely stained with Giensa. The blepharoplast was large and more intensely stained than the tropho-nucleus. The flagellum was seen to terminate posteriorly in the blepharoplast. The flagellum was not long and the undulating membrane could be easily made out and was not particularly folded.
He next showed a specimen of heart muscle which demonstrated very clearly the usual cause of death. The muscle cells were literally riddled with Leishmania-looking bodies. I could not distinguish them from Leishmania. The stain used was Van Gieson and they were beautifully clear. A muscle cell would have anywhere from 10 to 50 of these organisms and they were seen nowhere else.
Dr. Chagas remarked that the seriousness of the disease to him was its effect upon the heart, most fatal cases resulting from the myocarditis and degeneration of the heart muscle. He had a large number of organs which were invaded by these Leishmania-looking bodies which, as is well known, is a period in the schizogony of the parasite. This is what confers its fatality. The heart which he showed me, and which he said was typical, was that of a young man about 23 years of age; it was a true cor bovis and the preserving fluid had permitted the conservation of the colors, demonstrating very clearly that the entire heart muscle had been invaded. There was no lesion in the lining of the heart nor upon the valves.
Another organ I saw was the liver. It was also mottled with areas of degeneration. Hardly any part of either organ was normal but there were some apparently normal parts. He stated that he had large numbers of other organs including the nervous system and thyroid. I saw pictures of the goiter produced by this organism. He stated that all cases of American trypanosomiasis began in childhood, and that it was a very, very serious disease in those parts of Brazil affected, chiefly in Minas Gerais. The disease seems to be a chronic one but evidently must claim its victims with great regularity just as they reach adult life.
He next took from a large box a Conorrhinus, species megista, which he stated had been infected by feeding upon animals experimentally inoculated and containing large numbers of the trypanosomes in their blood. There must have been at least two hundred of these large bugs which crawled around quite unceremoniously upon the table and which he would casually pick up with his fingers when they would crawl too far. When one reflects that the bite of one of these bugs would confer a fatal and incurable disease and a moments indiscretion would cost one his life, I found myself looking in my pockets for one after his demonstration was concluded. The Conorrhinus megista seems to be mainly known by the absence of markings on its head, it being black and about one inch long by one-half inch wide, by three red lineal markings upon the back of its thorax and by a broad shield-like shell covering the abdominal cavity. He held the animals head with a pair of pincers while with very sharp, curved scissors he trimmed the edge of the posterior part of the elliptical shell, thus entering the coelomic cavity; then he cut directly across and lifted off the majority of the shell without opening the intestine. He stated that the infective forms were only found in the salivary glands; that they were then true trypanosomota; that they had only once been seen by him in the bug and that it was still a point of discussion as to whether these observations should be accepted or not, but that personally he was persuaded he was right.
The form found in the intestine is crithidial. He explained that in order to demonstrate this, one only need to tear away the posterior part of the gut and lay the mushy contents of the intestine upon a glass slide, cover it over and examine it with high power. He did this and I was able to see enormous numbers of rapidly moving, dart-like looking bodies, whose morphology I was unable to study because we did not have a dark field. This part of the intestine was simply filled with these organisms. He remarked that it was dangerous to net any of the trypanosomota from the glands as infection took place in that way; that once in taking the blood from a patient from a vein, some of it had flown into his eyes but he washed them out with bichloride of mercury and was relieved to find that he had not become infected some time later.
A very interesting remark followed my question "Do you consider Atoxylemetic a means of cure of this disease?" "No, there is no cure known for this disease." He seems to be very doubtful about the efficacy of emetic, which was proven by his statement that a doctor working with him in the laboratory had become infected and was at present dying in Rio de Janeiro but that he had not believed it proper to even use emetic, so evidently he had very little faith in it. When I asked him how the doctor was coming on, he said "Oh! Well, it has now reached his heart and you know what that means."
He first showed me some Leishmania from a sear made from the sore, which he said was an exceptionally good specimen because there were so many Leishmania. As a matter of fact, it took him a long time to find every one that he showed me and I asked him if it were an easy diagnosis to make. He smiled and said, "Well, if you have a fresh specimen you may find them sometimes rather easily but usually you have to look in the smear, best of scrapings, for a long time, and he mentioned two or three hours for each case as being not uncommon, with a considerable percentage of failures even then.
The books stated that Leishmania is usually found in the cells, generally of endothelial type, but I saw several lying in the perfectly free serum. These bodies are exceedingly difficult to distinguish without practice. In the first place, whether the preparation I saw was an old one or whatsoever might be the reason, the body of the cell was so faintly stained as to require imagination to look for it but then it might be confirmed more or less securely by an expert.
Another very important point is that we are at times not able to get a proper angle at which to view at one time the tropho-nucleus, and the kineto were also more irregular and apparently less abundant, although this seems to be a matter of chance. He also remarked that clinically Buba was never known to affect mucous membranes as was syphilis. He made a beautiful observation which I have never seen written in any book to the effect that the localization of the syphilis organism was well down in the derm, lying well below the papillae and inaccessible to caustics and local treatment, but that the organism of Yaws was always found in the papillae and rarely if ever in the derm and was very easily accessible to local treatment. He states that whereas it is well known that salvarsan will cure Yaws more quickly and more completely than syphilis, it is also true that the spontaneous cure of Yaws, which normally occurs in time, and their more ready response to local treatment depend upon this localization of the organism.
I was now taken in hand by dr. H. de Souza Araujo, a young man of very pleasant appearance, nephew of dr. Oswaldo Cruz. He demonstrated to me the newly discovered organism of Gaspar Vianna, the causative actor in producing the loathsome Ulcera granulosa pudendum. This organism in many ways looks like the capsulated diplococcus of Friedlander. That it is the cause of the disease seems to be very well accepted here and, as has been already seen, the specific cause for the disease is antimony. While I did not measure the organism it appeared to be a little smaller than Leishmania, capsule and all being stained. It is extremely abundant and in pure culture in the tissues, where it causes an abundant infiltration. It is inoculable in animals causing their death by septicemia in a few hours, but the most curious feature is that while in animals the organism stained by Giemsa shows the capsule always, the organism in the tissues of man practically never shows this capsule although sometimes he says it may be seen. Its appearance is generally, when the capsule is present, similar to a half of a coffee bean, the central depression representing the rod-like body of this parasite and the flare, the capsule. It has a tendency to occur two by two but long chains are often seen. In fact the tissues I saw were arranged like long log rafts, two logs wide. The capsule stains red, the central body blue. There are four principal forms to this central body. The first and simplest is the perfectly round red capsule with a central blue dot; the next is the ovoid body of the capsule with its central bacillus; the next is the same except that the bacillus has become drawn out at its two extremities and is connected only by a very fine hair-like bridge, and the fourth form is that of an ovoid containing two polar blue dots. These organisms are very abundant in all smears and in tissues and are easy to find. I should think they would be very easily confused, however, unless the clinical side of the case were known, with capsulated bacteria. He states that cultures can be easily made, the hard part being to get the culture pure. For this reason he uses a Sabouraud agar slant and after getting a growth by transfer, which is free of bacteria not growing on so acid a medium, it is possible to transfer to most of the laboratory media in pure culture. The culture looks like tubercular sputum, with a large amount of liquid saliva and very little color except where it is thick and collects at the bottom. He gave me a recent work on this disease, a section of tissue containing the organism and four or five Giemsa stained smears, and is also growing for me some cultures to take back with me. This terminated my seance in the laboratory for the day.
At the lunch table with me were seated drs. Oswaldo Cruz, Chagas, and Lutz, the assistants eating at other tables. Dr. Oswaldo Cruz asked me what I would like to do while my companions were away. I said
It is my desire to go into the interior with some members of the institute and make a first-hand study, principally of hookworm disease and incidentally of such other diseases as may present themselves. The expedition was sent here purely to acquaint the Rockefeller Foundation with the medical situation as regards disease in Brazil, with especial regard to the prevalence of hookworm disease; that the Rockefeller Foundation was composed of serious-minded men who had no thought at all of writing popular articles or allowing them to be written; that their idea was to acquaint themselves with the distribution of these diseases so that in case the government of Brazil should desire their cooperation in combating these diseases they (the Rockefeller Foundation) might have an intelligent idea of where they existed, on how great a scale, how much inefficiency they might cause for labor, and what means there were here of combating them at present in order to prevent duplication of material and personnel.
I emphasized the fact that this particular medical commission had the strictest orders to confine their statements as to conditions to a report to the Rockefeller Foundation only and was not authorized to make any general remarks to laymen, either here or in the United States. I stated that I did not think it unlikely that if any real scientific war on prevalent diseases in the open country should be desired here that the Rockefeller Foundation would not only take an intelligent interest in such work but might materially assist it, always remembering, however, that heretofore its work had been performed entirely through the administration of existing local government agencies; that no independent work was contemplated in any part of our own country or abroad; that in such a vast territory as is Brazil it had seemed to me worthwhile, after having made the usual visits to available parts of the country within reach of Rio, in the time at our disposal; that we should come prepared to make an intensive study, under country conditions, of current diseases which might fairly represent similar regions in the vicinity and which might give us quite a clear first-hand understanding of these conditions; that acting upon this idea the director general of the Rockefeller Foundation International Health Commission, dr. Wickliffe Rose, had authorized me to submit a list of articles for the equipment of a portable dispensary provided with all of the medicines and even some instruments and dressings, and certain clinical laboratory material for the purpose above described; that to that end I had selected two light, portable houses, one 12x16 feet, the other 12x24 feet, well screened against mosquitoes; that we had all of the medicines, dressings and laboratory supplies that I had found useful in making similar surveys in Puerto Rico and in such form as to be easily administered and transported; that owing to lack of time these things had not all yet arrived but would be here in about a week.
Gentlemen, now you know exactly what we hope to be able to do. Our Commission does not urge that this survey be made in this way if you believe that it can be made better in another way, but we have come prepared in order that you might not be put to the bother of assisting us to equip down here with very little time at our disposal and at yours, a matter which would undoubtedly disturb the equanimity of the Institute; so the equipment is at your disposal and the plan is for your consideration, recognizing that we will be guided entirely by your judgment and that we and our equipment are under your direction.
It was very evident to see that everything that had been said was thoroughly understood. I spoke in Spanish, which they understood perfectly and in such form as to leave not the slightest ambiguity. I asked dr. Oswaldo Cruz if he understood. He smiled and said, "Yes, it looks good to me." He said, "Where do you want to go and who do you want to take." I said, "Now that is just precisely what I want to leave to you." He said, "Very well, I will select one of the professors of the institute to accompany you, and a young assistant and will make the proper arrangements to go as soon as your equipment arrives. In the meantime I understand that you wish to examine the hospitals and medical institutions of Rio and I shall be glad to give you someone from this Institute who will accompany you." I thanked him and said that I thought it would be better if he would simply send one of the staff to introduce me or let me have a letter of introduction to the authorities of the institutions inasmuch as it would seem manifestly improper that the available time of the investigating staff of the institute should be taken up in such a manner. It is perfectly clear that this conversation and the conclusions drawn therefrom were highly satisfactory to dr. Oswaldo Cruz and his assistant. I can see no reason for any delay or any unusual difficulty.
There was, however, one point upon which they were all very firm and that was the inadvisability of rambling about in the yellow fever regions as they said that infection might be possible. They naturally did not want to say that yellow fever existed but it was perfectly clear that they regarded it seriously when I spoke of Bahia. Not that I was led to believe that there were many cases but I was given to understand that these places were beyond their control and that this was a disease not to be fooled with unless by an immune. I shall, however, try to go to Bahia.
Before leaving, professor Lutz read over some of his own previous work and once again demonstrated to me the wonderful influence he has had upon all scientific matters connected with his profession in Brazil, as he is an accurate observer and wonderfully versed in entomology.
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06 Jan 2004
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