The American Journal of Tropical Medicine and Hygiene - Volume 4, Issue 4, 1955

Yellow fever virus has been isolated from the liver of each of seven naturally infected red howler monkeys found dead or dying in the forest. The pathological lesions in these livers were typical of yellow fever.

• 1.  Howling monkeys (Alouatta) died of histopathologically proven yellow fever in July and early August, 1954, on the coastal plain near La Masica, Honduras, in an ecological situation unlike that of epizootics experienced during the preceding five years in Panama and lower Central America. No naturally proven vector mosquitoes could be found on the coastal plain where the monkeys died.
• 2.  Small numbers of Haemagogus spegazzinii falco, a proven natural vector in South America, were taken on mountain slopes in the tropical rain forest some 10 to 20 kilometers or more from the place where the monkeys died, but no evidence could be obtained of monkey mortality there. The authors believe the north coast of Honduras to be at or near the northern limit of the range of H. spegazzinii falco.
• 3.  Haemagogus equinus, which has been shown to be capable of transmitting yellow fever in the laboratory, but from which virus has never been certainly recovered in the field, was the only Haemagogus species recovered at the place where the monkeys died near La Masica. This species which is widespread in Middle America has been taken by us in the Atlantic drainage as far north as the southwestern corner of the Mexican state of Tamaulipas which borders Texas on the Gulf Coast.
• 4.  Aside from the predominantly ground-level biting Psorophora and Mansonia, which are not considered to be involved in the yellow fever transmission, the commonest arboreal mosquito was Trichoprosopon magnus. The ability of this mosquito to transmit virus is unknown. Another sabethine mosquito whose status as a vector is also not known, Sabethes chloropterus, was present in moderate numbers. This species has been present at other recent yellow fever episodes in Panama and lower Central America.
• 5.  No human cases of yellow fever were recognized in the immediate area of the epizootic during, or in the months following the monkey fatalities.

Germfree, monocontaminated, and conventional (control) guinea pigs were maintained on identical sterilized rations and inoculated intracecally with E. histolytica derived from cultures of the ameba with T. cruzi. The results showed that none of 35 germfree animals developed amebic lesions. Furthermore, the longest observed period of survival of the ameba in the germfree intestine was five days, in one animal, and the amebae were few in numbers and in poor condition when observed in animals sacrificed beyond the second post-inoculation day. Of 37 conventional guinea pigs inoculated as controls for the germfree series, 34 developed acute ulcerative amebiasis, and the other three animals harbored the ameba when sacrificed on the 21st post-inoculation day. The results of similar studies with monocontaminated animals were in great contrast to those obtained in the germfree series. Acute ulcerative amebiasis was produced in guinea pigs of two experimental series which harbored E. coli and A. aerogenes, respectively, as monocontaminants. The results have shown that although E. histolytica is unquestionably the causative organism of intestinal amebiasis, the responsibility for the disease must be shared with other microorganisms, the activities of which contribute to the etiology, pathogenesis, and pathology. In the absence of such microbial associates, the ameba appeared to be a harmless microbe incapable of independent survival in the intestine.

Forty-five of 60 patients having hepatic involvement as a manifestation of systemic amebiasis were subjected to a variety of function tests and to clinical examination. Erythromycin stearate was employed orally in 15 mgm. per kilo doses daily for 10 to 14 days and cleared 14 of 15 patients with hepatic amebiasis; 14 of 19 were cleared by a combination of erythromycin plus fumagillin; while 8 of 11 were cleared with fumagillin alone. Of the 60 patients under study, 46 had demonstrable E. histolytica in their stools previous to therapy. Only two patients remained, after re-treatment with erythromycin or chloroquine, who still exhibited an abnormally high cephalin-cholesterol flocculation test; and two others who, though clinically improved, still exhibited hepatomegaly.

Ninety-eight patients with amebiasis were treated with the antibiotic, erythromycin (Ilotycin, Lilly). The results obtained in chronic amebiasis were highly satisfactory using a high initial dose (800 mg.), followed with a dose of 300 mg. every 6 hours, for 5 days, or a total of 6.5 gm. In all cases the stools containing E. histolytica cysts became negative. There was only one parasitological relapse in 36 patients thus treated. With smaller doses, the number of parasitological relapses was greater.

In acute amebiasis the results were spectacular. The acute symptoms of the disease disappeared promptly and the stools became negative in many cases by the third day, with clinical and parasitological cure in all of them at the end of the treatment. There was only one recurrence of symptoms and parasites among 28 patients treated with the above schedule. With smaller doses one observed the appearance of E. histolytica cysts in the stools after treatment in three out of eight patients with acute amebiasis.

The virulence of a strain of Trypanosoma gambiense was exalted to such an extent that it produced acute infection in mice (Mus musculus) which invariably terminated fatally within a week. Acute, always fatal Tr. gambiense infection in white mice was cured with adequate doses of nitrofurazone. A total dose of 50 mg./kg. body weight had only a suppressive effect. However, with an increase in total dosage from 150 mg./kg. to 450 mg./kg., divided into small doses and administered daily, cures were obtained in from 22 to 100 per cent of the cases. The curative results were approximately the same whether the drug was administered intraperitoneally or orally.

Preliminary screening tests revealed also three other nitrofuran compounds effective against Tr. gambiense infection in mice. Nitrofuran No. 65 (5-nitro-2-furfurylidene amino biuret) produced a suppressive effect, while nitrofurans No. 60 (5-nitro-2-furaldehyde thiosemicarbazone) and No. 67 [5-nitro-2-furaldehyde 2-(2-hydroxyethyl semicarbazone)] were curative.

It is recommended that human cases of African trypanosomiasis, refractory to other known trypanocides, be treated orally with nitrofurazone.

These studies demonstrate that a diagnosis of malaria and even differentiation of species can be made from clotted blood under certain conditions. The age of the clot and the temperature at which they are stored influence the results. Because of alterations in specific characteristics and the poor staining of the organisms, identification of species is difficult or even impossible in many cases. Proper preparations from fresh blood are recommended for accurate laboratory diagnosis.

The problem of acute diarrheal disease is closely analogous to that of the weather. We've learned how to live with weather. In many cases we have found ways of protecting ourselves against weather and we are still actively exploring other possibilities for modifying ourselves and our environment so that we can develop coexistence to a high degree. Similarly, diarrheal diseases are progressively better understood and consequently we are better protected than ever before.

The group of papers is presented as one way of looking at the problem of those “diarrheal diseases other than amebiasis.” The papers themselves illustrate a stage in the acquisition of useful knowledge about particular disease agents. Two major groups of micro-organisms have been recognized as important agents for the production of these diseases in man: the genus “Shigella” and the genus “Salmonella,” respectively. In addition to these known parasites there is evidence which suggests to me that other bacteria and other viruses cause disease in man whose predominant symptom is diarrhea.

The relationship of some general environmental factors to the prevalence of Shigella infections and, more specifically, the effects of the availability of water for washing purposes on shigellosis rates were studied. The areas under observation were divided, either by city blocks, parts of blocks, or premises into groups with similar sanitational features. After each environmental grouping was completed, the infection rates for each of the groups was found.

Three conclusions which are applicable to diarrheal disease control were drawn from the results.

• 1.  Areas could be defined by using common sanitational standards to indicate potentials for spread of Shigella organisms.
• 2.  Infection rates of a neighborhood were found to vary with the proportion of poor housing in it.
• 3.  Infection rates were highest where water was least available for personal hygiene. Consequently, availability of water for washing purposes must be considered along with purity of water in any diarrheal disease control program.

Enteric infections of man, as cholera, shigellosis, Salmonella typhi and S. paratyphi A spread only from person to person. In contrast, the sources of most Salmonella other than the above types include a variety of lower animals and birds. Attention will be limited here to a consideration of modes of spread from sources other than man.

Historically there have been wide fluctuations in the attention given to the various possible sources and modes of spread of salmonellosis. Watt (1951) has commented “Rats and mice have been traditionally considered the main culprits in the spread of salmonellosis…. Too many investigators stop studying a Salmonella case as soon as they find a mouse pellet.” Recently attention has been directed to domestic fowl and particularly to the occurrence of Salmonella in powdered eggs. The problem is not to detect possible sources or modes of spread but rather to evaluate reliably their relative practical importance.

Multiplicity in etiology of diarrheal disease is illustrated sharply in the variety of subjects presented in this symposium. Nosologic entities based on clinical pictures long antedated bacteriological knowledge, yet with development of the latter it became clear that clinical definitions were not as sharply limited as had been thought (Watt, 1951). Gross relationship of certain bacteria to severe disease was appreciated early but refinements in bacteriological techniques have made more difficult the evaluation of clinical significance of many types of organisms. On the one hand it is apparent that supposedly highly pathogenic organisms like Shigella can be associated with mild illness. On the other it appears that under the best of circumstances a substantial portion of cases of diarrheal disease show no known pathogenic organisms, despite extensive search and excellent laboratory facilities (Wegman, 1951). It is only natural, therefore, that strong efforts be made to incriminate new or potential pathogens.

Of the identified or hypothetical viruses that occur in the feces, the agent or group of agents that induce so-called afebrile infectious nonbacterial gastroenteritis are the only ones known to cause watery diarrhea as a cardinal sign of illness. The rest of the clinical picture of this nonamebic nonbacillary diarrheal disease consists of anorexia, nausea, vomiting, and abdominal cramps, with little or no fever. It is a common syndrome of wide geographic distribution and is highly communicable, appearing in large epidemics as well as sporadically. While the disease is ordinarily self-limited, it can be incapacitating and is of importance because of its frequency.

Some epidemics of anorexia, nausea, and vomiting without diarrhea otherwise resemble outbreaks of afebrile nonbacterial gastroenteritis. Whether the respective causative agents are related is unknown. No recognized pathogen has been isolated from patients exhibiting either syndrome. Afebrile nonbacterial gastroenteritis with diarrhea can be transferred serially from one group of volunteers to another by feeding fecal ultrafiltrates. This is the chief evidence that one or more viruses may be the incitants.

Reinoculation experiments in volunteers indicate that following an attack of afebrile nonbacterial gastroenteritis specific active immunity develops, and that it may last for a year or longer. Since cases recur at yearly intervals in families and communities, it is necessary to postulate that there may be more than one antigenic type. The afebrile disease can be differentiated from a febrile, non-diarrheal entity by their different incubation periods, different clinical manifestations, and lack of cross-immunity.

The results of the first human volunteer experiments, reported by Reimann and his colleagues, indicated that a filterable agent could induce diarrheal disease when it was administered via the respiratory route. Some epidemiologic observations are consistent with these findings but several subsequent attempts to confirm experimental respiratory transmission in volunteers have failed. Respiratory symptoms and signs are conspicuously absent in experimentally induced attacks of afebrile nonbacterial gastroenteritis. At present the possibility that their occurrence in epidemic cases is adventitious must be strongly considered.

Further characterization of the nonamebic, nonbacillary diarrheal diseases awaits comparative studies of the agents now known and the detection of new ones. This will be difficult until practicable methods of laboratory propagation and immunologic identification are discovered.

There are presented here the results of periodic egg counts in the course of an experimental infection with Necator americanus, from the beginning of the patent period to the natural cessation of infection 15 years later. The infection was originally induced with an undetermined number of cultured larvae in a healthy 21-year old white male in order to study the daily egg output during the early patent period. The results of the first 151 days of study have been reported (Palmer, 1941). An attempt was then made to eradicate the infection, first with tetrachlorethylene and then carbon tetrachloride. Only two females and one male were recovered, and egg counts were not affected by treatment. At that time it was decided to continue following the infection until egg-laying had ceased, presumably marking the point at which all females had been shed from the intestine.

It is believed with assurance that hyperinfection did not occur during the 15 years of observation.

Parathion-impregnated cords, 3/16″ and 3/32″ in diameter were installed at premises in two separate rural areas of approximately 6 square miles each near Savannah, Georgia. Reductions of house fly populations to low density levels were obtained in both areas for the major portion of the season. Treatment with either size of cord markedly reduced the incidence of flies in kitchens of unscreened residences as compared with those in the untreated zone. The cost of the cord treatment was comparable to that of a standard DDT residual application.

Latrodectus tredecimguttatus antivenin produced in Yugoslavia proved effective in protecting 20-gram white mice from lethal doses of venoms of L. mactans and L. hasseltii. In all potency tests intraperitoneal injections of venom were followed in 30 minutes by intraperitoneal injections of antivenin. Test animals were observed for a 24 hour period, after which time results were recorded. Death and survival were regarded as endpoints. Amounts of venom were expressed as portions of the contents of one venom gland. One-fourth the contents of one venom gland constituted the minimum certain lethal dose of L. mactans venom for white mice. Complete protection against effects of two certain lethal doses of mactans venom was afforded by amounts of antivenin as low as 0.1 cc. of a 1:1 dilution.

The first part of the World-Atlas of Epidemic Diseases is an imposing volume of portfolio sise, solidly bound with the aid of brass book-screws so that maps and text-pages are changeable as well as readable side by side. It contains, besides 12 “basic” (geographical) maps of the various parts of the world, those dealing respectively with (a) epidemics caused by bacteria (15); (b) spirochetal diseases (4); (c) virus-caused diseases (7); (d) louse-borne typhus (2); (e) protozoan and metazoan diseases (5); and 7 maps illustrating observations on climatology and population distribution. While most of the maps depict epidemic situations met with in Europe, there are some noteworthy exceptions. For instance, one interesting map shows the pandemic spread of cholera during the period 1863–68 and another still more valuable map, the global distribution of leptospirosis 1915–1950.

This is the 14th edition of the first important text on Tropical Diseases which for almost six decades has been a classic in this field. When Sir Patrick Manson discontinued his editorial activities, Sir Philip Manson-Bahr assumed responsibility of subsequent revisions. Innumerable students and workers in the tropics cannot but express a debt of gratitude to “the father of Tropical Medicine” for having originated the text and to Sir Philip for having supervised the last eight editions.

A wealth of pertinent information and detailed knowledge is contained in this volume and the reader is stimulated by the fact that the author often finds opportunity to express his own opinions following a review of the literature; e.g., on certain phases of filariasis in which subject he has been especially active.

The volume is in reality two books in one, the text and the appendix.

A World Health Organisation meeting for the South-East Asia region dealing with problems of rabies and its control was held at the Pasteur Institute of Southern India, Coonoor, India, in July 1952. Medical and Veterinary officials from 23 different countries participated. WHO consultants on rabies arranged demonstrations and laboratory courses and prepared laboratory instructions for use in the training course. The WHO Expert Committee on Rabies at its second session in Rome, September 1953, recommended that the laboratory instructions and lecture material prepared for the Coonoor meeting be expanded and revised for publication.

This technical manual covers five phases of laboratory work with rabies virus. Part I describes the rapid diagnosis of rabies by demonstration of Negri bodies, the mouse inoculation test for the isolation of rabies virus and the identification of rabies virus by the serumvirus neutralization test.