The American Journal of Tropical Medicine and Hygiene - Volume s1-28, Issue 3, 1948

Food and Malaria have much in common. Both have plagued man down through the ages. The struggle for the one and against the other has sorely tried the wits and endurance of the human race. In every age and era, both have stayed the progress of generals in war and destroyed civilizations in peace. Today in this year of Our Lord nineteen hundred and forty seven, Malaria still ravages a large portion of our globe and the world-wide shortage of food is being forcibly brought to our attention.

Just previous to, and during the recent war, the world has been blessed with abundant crops and full granaries. It is to be regretted that we, in this country, who are technically competent, could not have stored during the years of plenty against the lean days ahead. What assurance do we have that we will be protected from prolonged years of drought or blight on our crops?

In an attempt to augment the knowledge currently available concerning the world distribution of members of the group, those Shigellae encountered in Japan during the summer of 1947 have been enumerated.

• 1.  A case of proven primary pneumonic plague, resulting from laboratory infection, has been reported.
• 2.  Recovery has taken place after a stormy and protracted course following combined therapy with sulfonamides and streptomycin.
• 3.  In vitro studies on the chemotherapeutic action of sulfadiazine and streptomycin on P. pestis have indicated that streptomycin is more efficacious and that there is some synergistic effect when the two drugs are used in combination.
• 4.  Transfusion malaria and jaundice (either homologous serum jaundice or infectious jaundice) have been observed in this case.
• 5.  Oral sulfadiazine has been used in the prophylaxis of contacts. No secondary case has appeared among them.

An incidence of amebiasis (E. histolytica) of 17 per cent among patients and personnel in a metropolitan hospital would suggest that this infection is more common than suspected fifteen years ago. The occurrence of trophozoites in more than half of the infected individuals, and a history of or symptoms of diarrhea or dysentery in more than one-third of the 42 cases of amebiasis, provide evidence of clinical significance. The greatest number of cases was among the housewife, food handler, and family groups. Many of the persons found infected were living in crowded dwellings in sections of the city where sanitary facilities were not always adequate. Memphis, and its surrounding areas, would appear to rank with other sections of the United States having a high incidence of amebiasis and similar community health problems. The need for adequate laboratory diagnostic facilities and personnel familiar with Heidenhain's iron-hematoxylin staining technic was apparent. The incidence of other protozoa was: Dientameba fragilis, 2.0 per cent; Giardia lamblia, 10.6 per cent; Endameba coli, 21.5 per cent; and Endolimax nana, 20.7 per cent among 246 people examined three or more times. There was a total of 2,061 stool specimens examined from 479 persons. All were inhabitants of the mid-south with the single exception of an ex-service-man.

Thioarsenites (C.C. No. 914 and No. 1037), the dithiocarboxymethyl and dithiocarboxyphenyl derivatives of carbarsone oxide (C.C. No. 606) (carbamidophenylarsenous oxide), which had shown in vitro and in vivo activities, in previous laboratory tests, superior to those of currently-used amebacides, were employed in 40 patients. Except for nausea and/or vomiting after initial doses of 100 to 200 mgm. in tablet form, no other untoward effects were noted, except transient diarrhea in one. Salol coating of tablets controlled gastric distress when marked (5 of 6 persons). Others continued their medication without difficulty. Laboratory tests of blood, urine, stool and function tests of the liver and kidneys, as well as electrocardiographic tracings did not show evidence of systemic toxicity. Total dose levels ranged from 3.0 to 7.2 gm. given orally over 7 to 24 days. In four cases of dysentery, rectal application was also given of from 3.0 to 6.0 gm. (Drug No. 1037) over six days. Return of leukocyte counts to average range and significant elevations in hemoglobin levels occurred. An average of 12 stool specimens was examined during the four months' follow-up. The majority of patients having diarrhea or dysentery were cleared of their symptoms. All but two of 40 patients treated were cleared of their amebas.

Fourteen individuals having giardiasis were given chloroquine, 2.2 mgm. per kilo orally, for seven days, with clearance of the flagellate in only three cases. There were five persons with pathogenic amebas who were not given the thioarsenites, and twelve others harboring giardia, who, without therapy, continued to show parasites during the follow-up period.

• 1.  Trypanosoma duttoni survived in experimentally infected Triatoma gerstaeckeri for about two to three days. During this period no multiplication occurred. The flagellates gradually became sluggish, motionless, and disintegrated; at the end of 72 hours no viable trypanosomes were found. Similar tests, performed on other rodent trypanosomes, yielded similar results.
• 2.  Triatoma, which had been experimentally infected with Tr. duttoni and which in three days and later were crushed and inoculated into normal mice (Mus musculus), invariably failed to produce infection.

• 1.  Complement fixation tests were carried out in a group of 146 pigeons.
• 2.  Positive reactions were obtained in all pigeons with a microscopically diagnosed H. columbae infection and in the majority of latent chronic infections. The complement fixation tests particularly with P. gallinaceum antigen was found to be more reliable than direct blood examination for the diagnosis of H. columbae.
• 3.  Antigens prepared from P. gallinaceum and H. columbae gave specific and group reactions.
• 4.  The existence of serological cross reactions between the genus Plasmodium and the genus Haemoproteus was demonstrated.
• 5.  These results are significant in the light of recent findings of primary tissue forms in Plasmodium.

The plasma level of quinacrine during its administration for the suppression of malaria, and the rate of disappearance of the drug from the plasma after the treatment was stopped, were normal in patients with infectious hepatitis.

Quinacrine and quinine are well absorbed when given by mouth to patients with diarrhoea due to acute bacillary or non-specific dysentery.

• 1.  Ninety-nine patients with falciparum malaria were given the routine intensive quinacrine treatment used in the Southwest Pacific Theater (3.6 grams in 6 days), and the results of the therapy were compared with those found in a series of 104 patients treated with quinine (210 grains of hydrochloride in 6 days).
• 2.  Patients in both series responded rapidly to treatment. There was no difference observed in the rate of disappearance of fever and the rate of clearance of parasites in either of the series.
• 3.  Persons with intense infections responded as quickly as those with light infections.
• 4.  There was no statistically significant difference in gametocyte production in the two series.
• 5.  Six of the 99 patients treated with quinacrine showed transient manifestations of central nervous system irritation near the end of the course of treatment.
• 6.  Adequate plasma levels of quinacrine resulted from a less intensive treatment schedule of 3.2 grams in 6 days.

• 1.  In view of the absence of malaria transmission in the study area, no direct information was obtained as to the efficacy of chloroquine in suppressing malaria.
• 2.  Indirect evidence indicates that chloroquine (0.3 gram free base once weekly) is at least as effective in suppressing relapses of vivax malaria as a daily 0.1-gram dose of quinacrine.
• 3.  Approximately 350 men took chloroquine (0.3 gram free base once weekly) for varying lengths of time up to 20 weeks. Three men were forced to discontinue the drug because of gastro-intestinal reactions. Four men had mild gastrointestinal reactions which did not necessitate stopping the drug. Twelve men had headaches attributed to the drug. No occular symptoms were noted.

Introduction SN-11,437, a metanilamide (Fig. 1), was chosen for study of its pharmocological and antimalarial properties in Plasmodium vivax infections in man, because it is an effective prophylactic agent in Plasmodium gallinaceum infection in the chick, at one-fifteenth the dose needed to achieve prophylaxis with sulfadiazine, and because it has high activity in other avian malarias (1, 2). The unique efficacy of a few sulfonamides, notably sulfadiazine, in gallinaceum infections, which is characterized by an abundance of exo-erythrocytic parasites (3), has created special interest in related compounds since these forms of the parasite are refractory to quinacrine and quinine. Considerable indirect evidence also suggests that the persistence of pre-erythrocytic or tissue stages is responsible for relapses in vivax malaria. The marked qualitative superiority of SN-11,437 over sulfadiazine in avian infections led to the consideration that it might prove effective in vivax malaria, where sulfadiazine has only slight, if any, effect as a suppressive agent (4, 5) and does not lead to radical cure (5, 6).

• a.  Four different methods of malaria control were tested under field conditions in four separate towns in a tropical country where original incidence of malaria, as measured by splenic and blood findings, was highly comparable.
• b.  The incidence of malaria in all of the towns was severe to hyperendemic.
• c.  Meteorological factors were highly comparable in the towns, if they cannot be classified as identical. All towns were situated on the coastline within fifteen miles of one another.
• d.  Three surveys were performed in the towns over the period of nine months before any control was instituted, to serve, together with a comparison town, as a baseline from which to measure results.
• e.  All control was begun at the same time following the third survey of December 1945.
• f.  Subsequent surveys following the initiation of control procedures, were performed at the identical time of the year as those performed during the first nine months of observation.

Intercurrent infections occurred in nearly half of all hospitalized cases of Carrion's disease studied, and were responsible for the death in two-thirds of the fatal cases.

The different intercurrent infections had varied prognosis according to the stage of the disease in which they developed. In cases with Bartonella bacilliformis anemia, intercurrent infections had a very severe prognosis due in most part to the decreased defenses of the host. Septicemias produced by enteric organisms proved to be fatal in almost every instance and accounted for half of the fatalities. The clinical picture in these infected cases consisted in a rise in temperature, diarrhea, splenomegaly, leukocytosis with marked shift to the left in the polymorphonuclear series, followed shortly by death. Amebic colitis greatly resembled the picture produced by salmonellosis and was fatal in three cases observed.

Malaria was the most frequent intercurrent infection occurring in approximately one-fourth of the cases. The immunological course of Carrion's disease is not significantly affected by intercurrent malaria infection, as no mortality was recorded in 28 cases. The clinical picture is most cases was very atypical for both diseases, the fever was usually irregular and without the characteristic periodicity of malaria, there was profuse sweating, enlargement of the spleen, anemia and a significant monocytosis. Intercurrent malaria was followed by prompt regression and thrombosis of the verrugae.

The host defenses against intercurrent infections did not appear to be decreased during the preeruptive or eruptive stages of Carrion's disease.

Wherever rabies is endemic among dogs, every physician in general practice will sooner or later be confronted with the problem of the management of human exposures, be they real or imaginary. Two responsibilities face him. One is the relatively simple procedure of administering antirabic vaccine to persons whose exposure is a definite break through the skin made by the teeth of a known or suspectedly rabid animal. The second far greater responsibility is the psychologic problem of rabiphobia whose victims far outnumber those actually in need of protection.

As very aptly stated by Denison (1), “there is no disease (other than rabies) about which the public is more misinformed. The fears, horrors and superstitions of exposed individuals, magnified by a superabundance of bad advice from well-meaning friends, often produce a state of mental panic before the physician can be reached.

Ever since the peoples of Europe, Africa and the Americas became conscious of the existence of yellow fever through the force of circumstances, they have sought to discover the origin of this scourge of tropical and subtropical countries; but it has remained unexplained.

As in other similar cases, each country has accused its neighbor. The recriminations of the “Gallic disease” were repeated here, just as a few centuries later were those of the “Spanish” influenza. America accused Africa and vice versa. The controversy narrowed as time went by and knowledge of the etiology of the disease increased. When objective information on aedine transmission replaced the miasmic theory, a new question arose: where was the first mosquito infected? Later, although the historical mystery was not solved, the discovery of a virus as the causative agent of the disease and the subsequent development of specific tests made it possible to limit inquiry to certain geographical areas.

The dispersion and flight range of forest mosquitoes were studied in a preliminary investigation to determine the role of these insects in the spread of the virus of jungle yellow fever over open country between forests. Sylvan mosquitoes were marked with bronzing powder and released in a small wooded area near Passos, Minas Gerais, Brazil. Recaptures were made after 12 hours, at the point of liberation and in neighboring forests, up to a distance of one kilometer. Nine per cent of the Haemagogus spegazzinii, 50 per cent of the Aëdes leucocelaenus and 16 per cent of the other marked species were recovered, the last specimen being taken on the twelfth day after release.

In another experiment, on flight range, Haemagogus spegazzini and Aëdes leucocelaenus were not available in large numbers, but an experimental vector of yellow fever, Aëdes scapularis was recovered at a distance of more than four kilometers, and 11 days after release in the forest. Other mosquitoes recaptured at distances of more than one kilometer from the point of liberation were Aëdes serratus, Psorophora ferox, Aëdes crinifer, Chagasia fajardoi and an anopheline.

A method is described for infecting groups of cotton rats with relatively constant numbers of the filarial worms, Litomosoides carinii, all of which are of the same age. The infections were produced by exposing the rats in metal tanks to counted numbers of mites whose percentage of infection had been determined. Such rats are superior for chemotherapeutic studies and for studies on immunity to wild caught rats with infections of various numbers of worms of mixed ages. Further improvement along this line is needed, however, and to indicate possible lines of procedure the factors in the variability observed in these experiments are analyzed.

Several kinds of tests have been employed in the selection of compounds effective as clothing treatments for protection of individuals against infestations of fleas and ticks. A number of the chemicals showed a high degree of protective value against both of the test species, and others were effective in repelling one of the two. The evaluation of these materials is being continued to determine the compounds most suitable for practical use.

In investigations of clothing treatments for protection against chigger mites, a number of effective materials were found to be more durable than benzyl benzoate, the present standard. Eighteen of these compounds were selected for impregnation into uniforms for rigid field testing in chigger-infested areas. Five that remained effective through 7 to 10 launderings were benzil, p-cresyl benzoate, 2-thenyl benzoate, diphenyl carbonate, and 2-thenyl salicylate. It is thought that all of them would be of value for large-scale practical use.

The names of several compounds are given, which as clothing treatments were effective and long-lasting repellents to salt-marsh mosquitoes. As repellents applied to the skin, dimethyl phthalate and N,N-ethyl succinamate appeared to be the best of a series of compounds tested against subarctic species of Aedes and Simulium.

One of the new compounds, parathion (O,O-diethyl O-p-nitrophenyl thiophosphate), has shown a high degree of toxicity to several species of insects. In laboratory tests it was indicated to be several times as toxic as chlordane to cockroaches, and about 10 times as toxic as DDT to anopheline larvae. Field results against anophelines, however, were not so striking. In a residue type of application against house flies and mosquitoes it compared very favorably with DDT. It also appeared to be a promising insecticide for the area control of chigger mites. Since this compound is quite toxic to warm-blooded animals, special attention must be given to the maximum concentration that can be safely used under different conditions.

Methoxychlor (methoxy analog of DDT) and two “DDT byproduct oils” appeared, from laboratory tests, to be of possible usefulness as residue treatments. Chlordane and benzene hexachloride were effective for this purpose for a short time after application, but did not show the long-lasting qualities of DDT.

A strain of DDT-resistant flies developed in the laboratory proved to be resistant also to other insecticidal sprays. With chlordane, pyrethrins, or chlorinated camphene, as well as DDT, about twice as much material was required to cause mortality equal to that obtained with flies from a normal colony. A subculture from the special strain lost most of its resistance when reared for 12 to 15 generations without further exposure to DDT.

In tests of cockroach dusts, several of the newer compounds were equal to Lethane 384, and better than benzene hexachloride, in speed of knock-down.

DDT, chlordane, and chlorinated camphene were about equally effective in the area control of the lone star tick, when applied as sprays at rates of 1 and 2 pounds of the toxicant per acre. Thorough treatment of the infested ground litter was necessary to produce good results. Heavier dosages of the materials in dust form were required to insure effective control. In one large-scale dusting test an application of DDT at about 4 pounds per acre gave a high degree of control over an extended period of time. Against adults of the American dog tick treatments with the same three materials, as dusts, at rates of 2 and 3 pounds per acre gave better than 90 per cent control.

Chlordane and chlorinated camphene as emulsions gave good results in the control of chigger mites at dosages of 2 pounds per acre. Benzene hexachloride had about equal immediate, but less residual, effectiveness. Parathion showed distinct promise for use against these mites.

The prehatching, or preflooding, treatment of mosquito breeding places was indicated to be an important method of control of salt-marsh and other floodwater species of Aedes. DDT gave the best results of any of the materials tested.

TDE was highly effective as a black fly larvicide when applied to infested streams at a dosage of 0.2 p.p.m. over a period of 10 minutes. This dosage is believed to be well below the tolerance limit for fish.

Body lice (Pediculus humanus corporis Deg.) were reared successfully for 25 generations on certain common domesticated rabbits. The individual rabbits differed considerably in their suitability as hosts, and of 97 tested only 7 proved to be favorable. Additional favorable individuals were found among the off-spring of mated favorable pairs. The longevity and fecundity of the lice on these hosts and of the lice in the original colony maintained on man appeared to be nearly equal.

After 10 generations on favorable rabbits, newly hatched nymphs were transferred to unfavorable rabbits and a second colony was successfully established on them. Within a few generations longevity and egg production had reached a satisfactory level. Although egg production was about a third lower than the average for lice fed on favorable hosts, it was sufficient to maintain a vigorous colony.

Lice collected from a naturally infested man were reared for three generations on favorable rabbits and appeared to be doing as well as those from the inbred laboratory colony.

When lice were compared for their susceptibility to pyrethrum and DDT, no marked differences were found between those reared on man and those reared on either favorable or unfavorable rabbits.

The second edition of this monograph brings the subject up-to-date in an excellent manner. One finds condensed here all the important literature relating to allergy from the clinical and scientific standpoints. A careful perusal of this work demonstrates systematic, practical, concise yet adequate discussions of the various classes of allergy with a clarification of the old ideas stressed. A chapter on vascular allergy has been included in this new addition.

The rather exhaustive bibliography makes a compendious expository source of information relative to allergic disorders readily available. As in the first edition the most generally accepted viewpoints are given with the author's interpretations expressed on controversial matters. The space alloted to each aspect of clinical allergy is proportional to its importance with emphasis being placed on practical therapeutic methods. Introduction and usage of the recent drugs, such as demerol, antihistaminics, etc. are discussed authoritatively under the various allergic manifestations in which they can be of some efficacious value.