The American Journal of Tropical Medicine and Hygiene - Volume s1-30, Issue 6, November 1950

Introduction

Within recent years the attention of various workers has been engaged in the consideration of oxidation-reduction potentials as an explanation for the dependency of Endamoeba histolytica on bacteria in vitro. The possibility that bacteria provide respiratory conditions required by E. histolytica in culture was suggested by failures to obtain growth of amoebae from micro-isolated cysts in sterile filtrates of cultures of bacteria which support the amoebae in vitro (1). It had also been found that cultures of amoebae developed in shorter time from micro-isolated cysts in the presence of bacteria when kept in an atmosphere of 15 percent CO2 than when incubated aerobically (1). Furthermore, the excystation of sterile amoeba cysts had been accomplished in the presence of a reducing agent, cysteine, by Snyder and Meleney (2). In addition to these observations, a considerable literature on oxidation-reduction potentials in bacteriology and protozoology had developed following the exposition of the theory by Clark (3).

• 1.  Acute amebiasis was produced in young guinea pigs by the inoculation of trophozoites of Endameba histolytic strain No. 200 directly into the cecum.
• 2.  The mortality rate varied from 40 to 75 per cent, depending on the diet. Animals fed a ration of rat pellets and fresh kale had almost twice the rate of fatal infection as those fed rabbit pellets and fresh kale.
• 3.  Eighty-four per cent of the animals that died had diarrhea and all had progressive weight loss.
• 4.  Amebic ulcers and other lesions were found at autopsy in the cecum and frequently in the colon of all of the 99 animals that died 3 to 29 days after inoculation and in only 3 of 57 survivors killed for study at 30 days. No amebic lesions were found in the liver or other organs.
• 5.  Histopathological studies were made on ulcerated lesions from 13 infected guinea pigs. In six animals the ulcers were confined to the mucosa, in three they extended into the submucosa, in three into the muscularis, and in one into the serosa; one animal showed a perforation. There is evidence that the amebae may reach the deeper layers by way of ulcerating glandular crypts which extend into lymphoid follicles lying in the submucosa.

An 18 year old white American solider, stationed in the Canal Zone, entered the hospital because of cellulitis of the left foot. After running a relapsing type of fever, he went into sudden shock on the 43d hospital day, expiring three days later. Laboratory work was non-contributory except for the heterophile antibody reaction performed on the 22d day of observation, which was positive to 1/1024 dilution. Absorption tests with boiled guinea pig kidney after death proved the antibodies to be of the Forssman type.

Autopsy disclosed a myocarditis associated with parasitization of the heart muscle by the leishmanial forms of the Trypanosoma cruzi. The immediate cause of death was congestive heart failure in acute Chagas' disease.

A study has been made of the response of some of the more common vertebrates of Brazil to yellow fever virus introduced by the bites of infected mosquitoes. The results obtained are summarized in Table 11.

Akodon arviculoides, Orzomys and Didelphis paraguayensis failed to circulate virus following such exposure; Metachirops opossum, Proechimys dimidiatus, Dasypus novemcinctus and Euphractus sexcinctus either circulated virus only occasionally or in too low concentrations to be epidemiologically significant. Metachirus nudicaudatus circulated virus with sufficient regularity and abundance to be a potential source of infection for blood-sucking arthropod vectors.

A. arviculoides, Oryzomys and D. paraguayensis fail to develop neutralizing antibodies following the bites of infected mosquitoes; in M. opossum, P. dimidiatus, D. novemcinctus and E. sexcinctus these antibodies appear irregularly or in barely demonstrable concentrations; furthermore, in the first two species mentioned they are not permanent. M. nudicaudatus produces neutralizing antibodies with regularity but they tend to disappear within a few months. Consequently, negative neutralization test results obtained in immunity surveys based on sera from any of these animals are of no value. Positive results obtained with sera from M. opossum or M. nudicaudatus would, if specific, indicate recent infections; positive results with sera from E. sexcinctus or D. novemcinctus might indicate either a recent or an old infection. Complement fixation tests are applicable only to sera from P. dimidiatus; a positive result with sera from this species indicates a recent infection.

Immunity surveys based on the immunological examination of sera from captured wild animals are valid only when it is well established that animals of the species under consideration are capable of forming antibodies with regularity following the bites of infected insect vectors. Consideration must also be given to the length of time during which these antibodies, if formed, persist in a demonstrable concentration in the serum of the infected animal.

Azotemia that may develop during the course of cholera may be:

• 1.  Uremia with the classical symptoms and signs of renal failure, or
• 2.  Extrarenal azotemia with elevation of blood urea, normal kidney function, normal urinary output and absence of abnormal findings in the urine. All these cases recover.

Cholera vaccines containing organisms killed with streptomycin, aureomycin and neomycin were tested and found effective in small groups of mice. Neomycinkilled vaccine in large-scale experiments in mice was at least as effective as the routinely used formolized and phenolized vaccines.

Five hundred patients were tested intradermally with histoplasmin, tuberculin and coccidioidin on the wards of Colon Hospital, Panama Canal Zone. Histoplasmin (1:100) produced induration five or more millimeters in diameter in 190 (38.0 per cent). Two separate sources of antigen were used; results were entirely comparable. A total of 302 patients (60.4 per cent) reacted to test injections of 0.0005 milligram of P. P. D., of whom 142 were also histoplasmin-positive. Coccidioidin (1:100) produced reactions in only two patients; two separate sources of material were employed, these patients giving responses to both. These tests provided adequate control.

There was no evidence that sex, race or geographic background influenced the incidence of histoplasmin sensitivity. Age was a significant factor; culmulative curves started at zero (newborn infants) and rose sharply during the second, third and fourth decades with gradual leveling off thereafter.

There is an obvious discrepancy between the finding that 38.0 per cent of the patients tested reacted to histoplasmin and the fact that there has been no recognized case of human histoplasmosis proven on the Isthmus of Panama since 1906. Further studies are in progress to determine whether the high incidence of histoplasmin sensitivity is due to cross reactions in patients who have had infections with antigenically related fungi, to direct exposure to H. capsulatum, or to the operation of both factors.

In 1949, Edelman and Spingarn (1) reported clonorchiasis in four Caucasians living in New York City. It is highly probable that these are the first cases of this disease among the white race to be observed in this country, if not the first such cases to be reported from the entire Western Hemisphere. Within the past ten months we have observed three additional cases of clonorchiasis in Caucasians living in Greater Boston.

The present three cases are male patients, aged 37, 40, and 46 years, respectively. They were born and raised in Germany. About ten years prior to their residence in the United States they left Germany as refugees and moved to Shanghai, China, where they lived from eight to nine and one-half years. The diagnosis of clonorchiasis was established upon the finding of eggs of Clonorchis sinensis in stool specimens.

In our first report (11, 23) we stated the following beliefs: 1) Among troops quartered in native villages in Samoa, Wallis and Funafuti, there were many whose skins were penetrated by filarial larvae; 2) the clinical entity to which Buxton had applied the Samoan term mumu was common among these troops; 3) this entity was of filarial origin, as Buxton (7) had believed, and the pathogenesis probably involved allergic sensitization, as O'Connor (33) had suggested. It is of interest to review these assertions with reference to the experience of the past five years.

That experience has alleviated the prognostic uncertainty which some of us felt. Permanent tissue damage has proved extremely unusual (48). Much has been written about the psychiatric aspects of the problem (37, 41, 53). The disease had all the terror of novelty, and at first there was natural dread of the possibility of elephantiasis.

• 1.  Thirty-nine male Puerto Rican veterans ranging in age from twenty-four to fifty-nine years, and suffering from schistosomiasis mansoni were treated with a trivalent antimony compound, antimony lithium thiomalate, better known as Anthiomaline. The patients were hospitalized during treatment and for follow-up study. Thirty-eight individuals received the same amount of the drug, that is, 3 cc. of the solution (30 mgs. of antimony, every other day for a total of ten injections, containing 300 milligrams of antimony). One other case received a total of 60 cc. Anthiomaline, divided in two courses of 30 cc. each, the second course being administered five months after the first.
• 2.  In twenty-two patients the stools were free of ova prior to the completion of treatment. Dead ova were detected in the stools at the end of therapy in three other cases. Stool examination remained negative for ova in thirty-eight of the thirty-nine individuals studied, during a period of one to three weeks following completion of treatment.
• 3.  Follow-up studies beginning one month and extending to seventeen months after completion of treatment were performed in thirty cases. Twenty of these (66.6 per cent) had positive stools for Schistosoma ova and in ten other cases (33.3 per cent) no ova were detected. Ten patients complained of recurrence of gastrointestinal disturbances one to seventeen months after treatment.
• 4.  Toxic manifestations occurred in fifteen of the thirty-nine individuals treated. These were never severe and in no instance they warranted interruption of treatment.
• 5.  We wish to emphasize the importance of follow-up examination of the stools at frequent intervals in the final evaluation of any drug employed in the treatment of schistosomiasis mansoni.
• 6.  Anthiomaline, when given in one course of 30 cc. to thirty-eight individuals, and in the amount of 60 cc. to another case, is not a very efficient drug in the treatment of mild, asymptomatic or moderately severe chronic infections with Schistosoma mansoni, as determined by the presence of ova in the stools.

• 1.  Schistosoma mansoni eggs in gradually diluted liver, fecal or intestinal cultures at 23° to 25°C. continued to hatch until the end of the second day after setting up the apparatus. A few eggs in the intestinal cultures hatched as late as the third day. Thus, under these conditions, eggs of S. mansoni remained viable for a relatively long period.
• 2.  When exposed to miracidia, an empty snail shell as well as fine gravel appeared to be attacked as readily as was a live snail, apparently indicating that attack is confined not merely to the live snail but may include other objects encountered by the miracidia during random movement.
• 3.  A total of 254 laboratory-reared Egyptian snails, Biomphalaria boissyi, belonging to well-determined age groups remained uninfected when exposed to miracidia of the Puerto Rican strain of S. mansoni. However, some of these snails became infected when re-exposed to the Egyptian strain of the parasite. Thus, exposing them to the Puerto Rican strain did not give them immunity against infection with the Egyptian strain of S. mansoni, to which they are the known intermediate host.
• 4.  These experiments strongly support the view that S. mansoni endemic in one area may be physiologically distinct from the S. mansoni endemic in another region.
• 5.  Biomphalaria boissyi snails were susceptible to infection with the Egyptian strain of S. mansoni at all ages ranging from two weeks to five months. Differences were slight between the number of snails that shed cercariae at the various ages; hence, apparently the age of the snails has little or no influence on their susceptibility to infection.
• 6.  Dwarfed specimens of B. boissyi produced by overcrowded conditions in the aquaria showed considerably less susceptibility to infection with S. mansoni; also, the incubation period of the parasite in the snail was increased to 49–51 days as compared to 28–34 days among normal individuals.

Four cases of filariasis are described, two with L. loa and two with W. bancrofti, in which the pathology was restricted to severe psychoneurotic changes with apparent involvement of the central nervous system. After the surgical removal of adult L. loa, and treatment of the W. bancrofti cases with Hetrazan, the patients were relived completely of their symptoms.

• 1.  Latrodectus geometricus Koch is for the first time reported from the Philippine Islands. Specimens were collected at Clark Air Force Base, Camp O'Donnell, and Ft. Wm. McKinley, all on Luzon Island.
• 2.  This spider is a common house-infesting species at Clark Air Force Base, where its habits are similar to those of L. mactans Fabr. in the United States. Observations on longevity, habits, and egg sack production are based upon study of a colony of spiders maintained in the laboratory.
• 3.  Effects of venom on mice, guinea pigs, and cats were similar to those reported by other workers using venoms of L. mactans and L. hasseltii, but indicate a lower degree of toxicity for laboratory animals. Pathological findings included necrosis and fatty infiltration of the liver, and hemorrhage in the liver, lungs, and pericardium.
• 4.  There are no records of humans bitten by geometricus on Luzon. However, demonstrated toxicity of geometricus venom, combined with close resemblance of this spider to mactans and hasseltii, suggests the possibility that some of the bites credited to those species may have been caused by geometricus, which occurs in the ranges of both species.
• 5.  DDT in spray, aerosol, and powder form is effective in destroying both adult and juvenile spiders. Egg sacks and spiders found in living quarters may be easily swept down and crushed. Natural enemies of Luzon include unidentified predacious wasps, and the egg sack parasite, Eurytoma arachnovora Hesse, never before reported from the Philippine Islands.

The North American distribution of the mosquito Culex tarsalis Coq. is presented in detail and it compares well with the range of the severe 1941 epizootic of the Western equine encephalomyelitis virus in horses. This mosquito has been found to be naturally infected with this virus in six widely distributed areas over its range which extends throughout the great plains, prairies, and western irrigated areas.

During the war period 1942–1946 the known distribution of C. tarsalis was extended 500 miles eastward to South Carolina. The species may have been discovered in this area due to more intensive collecting during that time, or the species may have been introduced due to increased airplane and vehicular traffic in that area. The mosquito is most abundant in the western states and becomes less common eastward. The peak of adult abundance in the western United States is in July and August, and eastward the population maximum occurs progressively later until in the southeast, adults are found only in late fall and winter.

The main hosts are wild and domestic animals which are attacked at dusk and night. Human beings are not important hosts. The larvae breed in a large variety of habitats and under a wide range of conditions

In the course of recent studies on murine typhus fever at Tampa, Florida, it was necessary to maintain a culture of oriental rat fleas, Xenopsylla cheopis. White mice, Mus musculus, were used as hosts to these ectoparasites, according to a technique modified from one in use at the Bureau of Entomology and Plant Quarantine at Orlando. The relationships between flea and mouse were observed over a two-year period.

During the same time it was frequently desired to feed fleas on roof rats, Rattus rattus, and comparable observations were made. Laboratory personnel, responsible for these routine operations, reported a divergence of flea behavior with respect to the two species of host. Subsequent observations have repeatedly confirmed their findings. These later observations are here reported since they may have bearing, as a side light, on the epidemiology of murine typhus fever and other diseases of commensal rodents in which ectoparasites serve as vectors.

• 1.  Consideration of the diet of natives in Fiji (South-West Pacific) shows that it is not adequate and complete. The traditional foodstuffs of Fiji are very rich in concentrated carbohydrates, comparatively poor in protein content and definitely lacking in Vitamin B complex.
• 2.  The staple foods of the native population in Fiji are roots, tubers and leafy plants. Unfortunately very little is known about the Vitamin B content of the plants grown in Fiji. However as the plants are generally boiled and the water discarded, their value as a source of Vitamin B supply is doubtful.
• 3.  Between July 1948 and October 1949, 14 cases of typical pellagra and 16 cases of pellagra-like dermatitis were seen. The pellagra-like dermatitis responded very well to specific treatment with nicotinamide alone or in combination with riboflavin, and, therefore, should be considered as mild pellagrous manifestation.
• 4.  Three cases of typical pellagra and four cases of pellagra-like dermatitis were observed amongst Europeans. These cases of pellagra amongst the white population in Fiji are believed to be the first recorded. It is of interest to notice that two European patients with typical pellagra were born in Fiji and are permanent residents in the colony.
• 5.  Consideration of 16 cases of pellagra-like dermatitis show that in 5 cases the lesions were symmetrical, and in 7 were accompanied with edema of the lips, ears and eyebrows. The lesions are usually found on exposed portions. The main clinical symptoms are extreme itching and feeling of heat around the affected areas. They become red and swollen in from 24 to 48 hours after the onset. Small vesicles usually appear at this time. Later on the skin becomes dry, less red, thick and scaly, surrounded by a narrow zone of hyperpigmentation, better seen on the white skin. It has a “dirty” appearance on a dark skin, and grey-brownish on a white one.
• 6.  The 14 cases of typical pellagra all had symmetrical dermatitis; 12, angular stomatitis; 8, edema of lips, ears and eyebrows; 7, glossitis; and 4, mental disturbances (the cases over 5 years duration). As a rule the patients, when untreated, showed some improvement during the rainy season, and relapsed with the advance of dry weather.
• 7.  It has been found that the addition of riboflavin to nicotinamide is beneficial in the treatment of typical pellagra and pellagra-like dermatitis. This combination of vitamins produces a dramatic improvement in all patients in whom edema of lips, ears and eyebrows is well marked. The intravenous use of Vitamin B Complex in injectable form shortens the course of treatment.
• 8.  A careful analysis of the diet of each patient is essential, as without strict adherence to a well balanced diet, even properly treated cases, are liable to relapse.

Dr. Mark F. Boyd, Editor

American Journal of Tropical Medicine,

615 East Sixth Avenue

Tallahassee, Florida

Dear Dr. Boyd:

As you may know Doctor R. E. Dyer will soon reach retirement age and will leave the National Institutes of Health where he has been Director for eight years. He has accepted a position with Emory University as Director of Research in the Robert Winship Clinic.

Many of his friends both in and out of the Government service have discussed informally the establishment in his honor of a lectureship to be known as the R. E. Dyer Lectureship of the National Institutes of Health, financed by contributions of his friends throughout the country.

We, who join as co-signers of this very informal letter, feel that you would like to have this matter brought to your attention to give you the opportunity to bring it to the attention of those of your colleagues who may know Doctor Dyer and his many splendid contributions to the medical field.

Note: Books received for editorial consideration will be intermittently listed. This acknowledgment must be regarded as an adequate expression of appreciation for the courtesy of the author or publisher. Selections will be made for review in the interest of our readers.

John W. Field and Yap Loy Fong. The Microscopic Diagnosis of Human Malaria. Part I. A Short Descriptive Atlas of Thick-Film Diagnosis. Pp. vi plus 117, Figs. 67, Plates XIV (1 in color) 4°, clo. Studies from the Institute for Medical Research, No. 23, Kuala Lumpur, Federation of Malaya, 1948.

J. R. Andy. A Summary Topographical Account of Scrub Typhus, 1908–1946. P. vi plus 84. Figs. 25, 4°, wrap. Bull. 1 of 1949. Kuala Lumpur, Institute for Medical Research, Federation of Malaya, 1949.

John W. Field and J. F. B. Edeson. A Malaria Parasite of the Malayan Squirrel. Pp. iv plus 24. Plates VII. 4°, wrap. Bull. 2 of 1949.

This useful work which merits a wide distribution, attempts by drawings, diagrams and description to show the appearance of stained parasites in lysed blood smears, and to define the critera by which species may be identified, and, in addition describes techniques for the preparation of satisfactory blood smears, with their staining, either by Giemsa's stain or the quick buffered Romanowsky method known by the author's name.

This volume presents the papers contributed to a symposium in viral diseases organised by the Section on Microbiology of the New York Academy of Medicine, in December, 1948. The participants are all distinguished by their important contributions to this special field.

Included are more general papers: (1) R. E. Shope on “The Spread of Viruses from Infected to Susceptible Hosts” (2) C. J. Buddingh on “The Culture and Effects of Viruses in Chick Embryo Cells”; (3) G. Dalldorf on “The Relationships of Viruses and Cells, with Particular Reference to the Interference Phenomenon”; (4) T. F. Anderson on “The Activators of Viruses by Absorption Cofactors”; (5) R. W. G. Wyckoff on “The Electron Microscopic Study of Virus Growth”.

Another series of papers treat of pathology, thus (6) Scott, Blank, Corriell and Crouse discuss Variola, Vaccinia, Herpes Simplex, Herpes Zoster and Varicella; (7) Ash deals with Yellow Fever; (8) Lillie with Lymphatic Choriomeningitis; (9) Wolf with Viral Encephalitides.