The American Journal of Tropical Medicine and Hygiene - Volume s1-31, Issue 2, March 1951

In 1946 (1) the final report of the Committee on the Teaching of Tropical Medicine of the Association of American Medical Colleges briefly outlined the future opportunities for study and research in the tropics. Meleney et al. stated that “No science can flourish or advance without opportunities for new discoveries.” One reason why tropical diseases have attracted so little interest in American medicine is that we have had little responsibility in the tropics, and too little exchange of ideas with medical scientists from tropical countries. In order to conserve the interest of those of us who have taught tropical medicine and parasitology during World War II and, in order to encourage the best talent to enter these fields, it is essential that opportunities be provided for medical personnel to study and conduct research in the tropics.This can best be accomplished by the establishment of research stations in tropical regions under friendly influence or control, and by a program of interchange of personnel between our universities and those of tropical countries.

The special prerogative of the President of the American Academy of Tropical Medicine consists in freedom to choose the subject of his valedictory address. He has given considerable thought and study to the material to be presented. He may have drafted his manuscript long in advance and rewritten it many times, or he may have prepared a long-hand copy only a few hours before the time of delivery. The subject matter may have been based on years of productive research; it may have dealt with the development of American tropical medicine; it may have been a constructive proposal for the Academy in fulfilling the aims and aspirations of the founders; it may have been educational or philosophical in its purpose, or it may have been a critique unrelated to tropical medicine. Each of these categories has been presented by one or more of our past presidents.

In the present instance it is proposed to be primarily analytical and introspective.

It is impossible to give a complete review of the numerous problems of nutrition in the tropics within half an hour. The speaker will limit himself, therefore, to those problems in which he himself was interested during the years he spent in the Far East, and to those which are of special importance to the Nutrition Division of the Food and Agriculture Organization of United Nations. The efforts of FAO have always been directed towards raising levels of nutrition, especially in underdeveloped, tropical countries, and these have received special emphasis in planning the Technical Assistance Program for Economic Development.

In what respects does “tropical” nutrition differ from “ordinary” nutrition in regions such as North America and Western Europe? As far as diet is concerned this might appear to be simple; rice, maize, and millet are the main foods in the tropics, whereas wheat is the main cereal in the northern countries.

• 1.  Serum protein levels cannot be used for the detection of mild to moderate degrees of protein deficiency in humans.
• 2.  Factors other than protein intake per se can bring about an increase in serum protein levels above normal averages even in the presence of mild to moderate protein deficiency as determined by diet interview or clinical examination.
• 3.  Neither racial differences, altitude differences, nor simple dehydration explain globulin fractions.
• 4.  The influence of endemic goiter and the high proportion of vegetable protein in the diet should be investigated in relation to it.
• 5.  The increase in serum proteins appears to be an increase in both albumin and globulin fractions.
• 6.  These phenomena of high serum protein values in the presence of mild to moderate protein deficiency are of special significance for tropical and subtropical regions.

An invitation to discuss nutrition in relation to resistance before a gathering of students of tropical medicine when proffered to one who has never before participated in tropical medical activities can, I think, be best explained by (1) a tolerant broad-mindedness of the program committee and (2) a recognition that the tap roots of tropical medicine run deep into the subsoil of theory which underlies infectious disease in general. Among these roots our mutual problems lie tangled among the aged, yet by no means fossilized concepts of virulence and avirulence, resistance and susceptibility. It is my thesis this afternoon that nutrition, in its relationship to these central issues, has not yet come to flower, but if we wish to see its growth, we must look to its roots as it penetrates ever deeper. This penetration can be expected to make two different kinds of contributions, the one practical and the other theoretical in its implications.

I am deeply appreciative of the honor accorded me by the invitation to deliver this, the fifteenth, Charles Franklin Craig Lecture. I have prepared it with an acute sense of my inadequacy to develop the subject in a fashion which would be fitting to honor the worker in whose name the lectureship was established.

I have taken a rather broad interpretation of the title, and shall review details of most recent developments in nutritional therapy only as they are illustrative of principles.

Medical treatment is almost never the therapy of a disease, but rather the understanding and treatment of a patient with one or more diseases. No group is more aware of the principle of considering the patient rather than the disease than are students of tropical medicine. This truth is illustrated by the frequently-heard statement that “tropical medicine” should be designated as “medicine in the tropics”—i.e. medicine as influenced by the total environmental conditions of the tropics.

• 1.  The mixed bacterial flora accompanying our culture of the NRS strain of E. histolytica was analyzed into its components: Escherichia coli communior (NRS-I), E. coli anaerogenes (NRS-IA), and an unnamed paracolon bacillus (NRS-II).
• 2.  A series of monobacterial cultures were established by chemical treatment of cysts with 1:50,000 mercuric chloride for 90 minutes at 4°C.
• 3.  E. histolytica was established separately with the following bacteria in aqueous eggyolk infusion: NRS-II, NRS-I, Aerobacter aerogenes, E. coli communis, Proteus vulgaris, Aerobacter cloacae, Kurthia zenkeri, Streptococcus equinus, S. faecalis, and S. liquefaciens.
• 4.  Populations of bacteria and amebas were plotted in the form of growth curves for the first six types listed above, with the relative growth response of the amebas in the same order as the above list. No correlation could be observed between the relative ranking of bacterial and amebic growth, and within rather wide limits no controlling influence of inoculum could be determined.
• 5.  The highest growth response of the amebas was obtained with the original mixed flora.

• 1.  The in vitro effect of aureomycin on a strain of E. histolytica growing with Clostridium perfringens and Bacterioides necrophorus was studied.
• 2.  The addition of the drug to the ameba cultures resulted in failure of the amebae to appear (complete inhibition) or in evidences of amebastasis which increased directly with the concentration of the drug.
• 3.  The inhibition of amebic growth was associated with temporary inhibition of bacterial growth.
• 4.  Resumption of amebic growth usually followed recovery of bacterial growth from the inhibitory effects of aureomycin but occurred less frequently as the dose of aureomycin increased.
• 5.  The treatment of ameba cultures with aureomycin for one hour and the subsequent transfer of the treated inocula to media containing an actively growing bacterial flora resulted in greater amebastasis as the concentration of aureomycin was increased.
• 6.  It was concluded that aureomycin affected the growth of E. histolytica in vitro by inhibiting the bacterial flora and by a direct anti-amebic action.

• 1.  247 patients with malaria were treated with Camoquin. There were 156 patients in the vivax infection group, 86 patients in the falciparum infection group, and 5 patients in the malariae infection group.
• 2.  There were 19 readmissions to the hospital in the vivax group, of these 19 patients four patients had two or more readmissions. There were no readmissions in the falciparum or malariae group.
• 3.  Clinical symptoms were controlled within 24 to 48 hours.
• 4.  There were no toxic reactions to the drug.

• 1.  Strains of trypanosomes are to be found in the French Cameroun which are resistant to tryparsamide only, or in addition to tryparsamide, to one, or several drugs of the group tartar emetic, orsanine, amidines, moranyl.
• 2.  Ninety seven per cent out of 394 tryparsamide resistant patients responded favorably to treatments with Mel B; three per cent were Mel B resistant.
• 3.  Mel B resistance occurs in the French Cameroun under two circumstances: (a) linked to tryparsamide resistance as an inherent character of certain strains of trypanosomes; (b) developed in the organism of infested humans, in the wake of an insufficient treatment with a compound containing the same phenylmelaminyl radical, as Mel B.

Chloromycetin was inactive against filariasis in the cotton rat (1), was mildly active in Borrelia novyi infection in mice (2), and had a curative effect in experimental syphilis in the rabbit (3). The chemotherapeutic action against trypanosomiasis is shown herewith.

Albino rats, weighing 108 to 140 grams, were inoculated intraperitoneally with a suspension of Typanosoma equiperdum in physiological saline. The infected animals showed a mean parasitemia of 39 trypanosomes per 1000 red blood cells in forty-eight hours. At this time, Chloromycetin was administered to groups of five animals each in single intravenous doses of 20, 40, 60, 80, or 100 mgs./kg., of 1.0 per cent concentration in 60 per cent propylene glycol-water solution. In the subsequent twenty-four hours a number of animals were dead or dying. Those living showed increased trypanosome counts in blood while the dead animals showed positive liver smear preparations. All animals were dead forty-eight hours after treatment (Table 1).

In experiments in which cockroaches, Periplaneta americana, were fed a single meal containing a member of the Coxsackie group of viruses, the results proved that the test roaches excreted daily over a period of as many as 15 days sufficient virus to paralyze and kill test mice. Control experiments and other tests showed that the lethal effect was due to infection by the Coxsackie virus and not from extraneous bacterial or viral infection.

The significance of these experiments in relation to the natural transmission and dissemination of the Coxsackie group of viruses remains to be determined.

In recent years the hemagglutination test has been used as an aid in the diagnosis of various diseases (9–19). This test is based upon the specific agglutination by homologous immune serum of erythrocytes which have been sensitized with bacterial filtrates or carbohydrate fractions (32).

It has long been recognized that rickettsiae possess a non-specific antigen in common with certain strains of Proteus, making possible the Weil-Felix Reaction (1–8, 20–30).

This study deals with the application of the hemagglutination test to epidemic and murine typhus fever, using as antigen sheep erythrocytes which have been sensitized with extracts from Proteus OX19.

MATERIALS AND METHODS A Proteus OX19 culture, No. 7484 of the American Type Culture Collection, was used in this study.

The various antigens were prepared in the following manner:

• 1.  W-antigen. 200 ml. of a 10 per cent suspension of Proteus in distilled water was shaken for one-half hour and the bacterial debris removed by centrifugation.

Laboratory tests were conducted with 620 insecticides to evaluate their effectiveness in dusts against the cat flea, Ctenocephalides felis (Bouché) and the oriental rat flea, Xenopsylla cheopis (Rothsch.). Recrystallized DDT was used as a standard of comparison. At a concentration of 0.5 per cent, 29 compounds were more effective than DDT, 24 were within the range of effectiveness of DDT, and 566 were less effective than DDT.

The outstanding toxicants were heptachlor, dieldrin (compound 497), aldrin (compound 118), and benzene hexachloride (95 per cent gamma isomer). Chlordane and parathion were more effective than DDT at concentrations of 0.5 and 0.05 per cent, and toxaphene and pyrethrum extract plus piperonyl butoxide at 0.5 per cent only. Methoxychlor and other analogs were about equal to DDT.

Thirty-three compounds were more toxic to cat fleas than to rat fleas, whereas only two, benzene hexachloride and pyrethrum extract plus piperonyl butoxide, were more toxic to rat fleas.

Dusts of 13 of the better toxicants showed no evidence of deterioration after 10 to 12 months of storage, and with 3 others the evidence was not conclusive.

The eye gnats, or Hippelates flies (Diptera, Chloropidae), have been attracting increasing attention in recent years in connection with investigations of the epidemiology of yaws and of various eye diseases. Unfortunately, virtually all medical, parasitological and entomological works are continuing to cite several important species under incorrect names. The nomenclature of these species was revised by Sabrosky (1941), but current editions of various texts have overlooked that paper or, in a few cases, were published earlier. The purpose of this note is to call attention to the information in that publication, which also contains a key for the identification of species of the United States.

On the basis of the work of Kumm and others in Jamaica, Hippelates pallipes Loew is regularly cited as being, or suspected of being, the vector of yaws in Jamaica, the West Indies, or the Neotropical Region in general (Séguy, 1940; Belding, 1942; Matheson, 1944, 1950.

• 1.  Investigations were made on effects of acetic acid and some other chemical compounds on larvae of the dog and cat hookworm, Ancylostoma caninum, in fecal-soil cultures.
• 2.  The sources of hookworm eggs were worms in two young cats which were inoculated subcutaneously with larvae from a dog infection. Larvae were recovered from fecal-soil cultures with the aid of a Baermann apparatus.
• 3.  Results of effects of chemicals on hookworm larvae introduced into soil cultures demonstrated that all the compounds tested, acetic acid in particular, acted to some extent upon the larvae.
• 4.  Applications of five or 10 per cent concentrations of acetic acid to cat fecal-soil cultures for 24 hours after the larvae appeared at the surface of the culture killed over 98 per cent of the larvae in the cultures as determined by the number of surviving larvae in the control cultures.
• 5.  Application of 10 per cent acetic acid to newly-made cat fecal-soil cultures inhibited hatching of hookworm eggs for two days, and limited hookworm survival to 2.1 larvae per gram of fecal material during the first five days of treatment.
• 6.  The following 10 chemical compounds tested for the first time on hookworm or other strongyle larvae exhibited some lethal action: trichloroacetic acid, lactic acid, tartaric acid, citric acid, sodium acetate, calcium lactate, lead acetate, ferric acetate, manganese chloride and amyl acetate.
• 7.  The order of highest effectiveness of eight of the chemicals tested against hookworm larvae was acetic acid, trichloroacetic acid, oxalic acid, citric acid, lactic acid, tartaric acid, ammonium sulfate and sodium hydrogen phosphate.

A contributor to the field of tropical and parasitic diseases for a full half-century, Charles Franklin Craig probably made a more distinctive impress on students of American tropical medicine than any of his colleagues and associates. Born in Danbury, Connecticut, the son of a country physician and educated at Yale, he received his medical degree from that institution in 1894 when laboratory medicine was relatively young. In 1898 he became a contract assistant surgeon with the United States Army, first at Sternberg General Hospital (Chicamauga Park, Georgia), then successively at Simpson General Hospital (Fortress Monroe, Virginia), Camp Columbia Hospital (Havana, Cuba) and the Army General Hospital (Presidio, California). During the last of these assignments, in 1903, he began his long service as a regular Army officer, starting as 1st lieutenant and receiving regular promotions until he attained the rank of colonel in 1918.

Craig's tours of duty were fortunate ones for American tropical medicine: in Manila (1906–07) with the Army Board for the Study of Tropical Diseases, at El Paso (1916–17),in Hawaii (1922–26),at Ft. Leavenworth (1907–09,1913–16 and 1917–18),and in Washington with the Army Medical Museum and the Army Medical School (1909–13,1919–22)and later, as Director of the Army Medical School (1926–30) and Assistant Commandant of the Army Medical Center (1930–31)

Note: Books received for editorial consideration will be intermittently listed. This acknowledgement 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.

George R. Herrmann. Methods in Medicine. The Manual of the Medical Service of George Dock (in honor of his 90th birthday). A Comprehensive Outline for Clinical Investigation, Management and Treatment of Patients with Various Medical Disorders. Second Edition completely revised. Pp. 488 Cloth. St. Louis: The C. V. Mosby Co. 1950. Price $7.50.

Ch. Joyeux et A. Sicé. Précis de Médecine des Pays Chauds. Fourth edition entirely revised. Pp. viii + 1072; 332 figs. Cloth or paper. Paris: Masson et Cie., 120 Boul. St-Germain. 1950. Price, paper 2800 frs., cloth, 3300 frs.

American Public Health Association, Ed. Diagnostic Procedures and Reagents. Technics for the Laboratory Diagnosis and Control of the Communicable Diseases.

Here is a vivid book written by a crusader, about life and death. Even the dedication, to eleven men eminent in the field of tropical medicine, is a revelation of the wide extent of the author's interests and friendships. He has known fighters for health everywhere.

How sick is the world, he asks; and leads us on to grasp the nature of the health crisis everywhere. He is concerned, not only with the countries around the Equator, but with America, where he reports 540 counties without health provision of any sort.

But he shows how much worse off other parts of the world are. The author well reminds us that the great continent of Africa, so little developed, so underpopulated, “is a gigantic incubator for many diseases that menace the world. Sleeping sickness, just one example, is communicable, and a potential threat to millions of peoples beyond African boundaries.”Hundreds of millions in three continents go hungry because of the devastation caused in Africa by sleeping sickness alone.

This text is presented in four parts. Each part is rather complete within itself. Thus, its appeal will reach those of varied interest in the general subject of the serology of syphilis. This of course leads to some repetition for those who view the book as a whole. Except for the very excellent chapter on the history of the Wassermann and early flocculation tests, this book deals chiefly with the author's experience in the development of the various Kahn test procedures over a period of the last 25 years.

In Part I, his new concept of the universal reaction is presented and illustrated with charts, diagrams and tables. He states that some of his previous conclusions were in error and shows that the capacity of serum to react with tissue extract antigen is not limited to syphilis but that non-syphilitic serum possesses this same capacity.The author stresses that there exists a biologically universal tendency for serum, whether human or animal,to give serologic reactions with lipid antigen.