The American Journal of Tropical Medicine and Hygiene - Volume 10, Issue 3, May 1961

The honor of presenting the 25th Charles Franklin Craig Lecture is enhanced for me in two ways. For one, my subject, on account of Col. Craig's own concern with the immunological aspects of parasitic infections, would, I like to think, have had an unusual interest for him in depicting one of the directions in which wormhost relationships are now being so actively studied. For the other, it allows the list of topics of lectures given from the Craig rostrum to include another dealing with the helminths. The most recent was the 18th at Louisville in 1953 by Dr. H. E. Meleney on “Problems in the Control of Schistosomiasis.” Before that in the 9th at St. Louis in 1944, Dr. L. T. Coggeshall devoted half his lecture to “Filariasis in the Returning Service Man.” The 4th Craig Lecture in Memphis in 1939 by Dr. W. H. Taliaferro was on “The Mechanism of Acquired Immunity to Metazoan Parasites.”

At the annual meeting of the American Society of Tropical Medicine and Hygiene, held at Los Angeles, California, on Friday, November 4, 1960, in the presentation of the Walter Reed Medal in absentia to Sir Gordon Covell, Dr. Justin M. Andrews, * Member of the Walter Reed Medal Committee, said:

Mr. President, members, and guests of the American Society of Tropical Medicine and Hygiene:

The bestowal, at various appropriate intervals, of the Walter Reed Medal upon individuals widely known for their original researches in some aspect of tropical medicine was authorized by this Society in 1936. The Awards Committee was specified to consist of three past presidents of the Society. The present Committee is comprised of Dr. William Hays Taliaferro, Chairman; Dr. Frederick Brady; and me. Regrettably, neither of the other two members could be present at this meeting, so I am left with the pleasant responsibility of announcing our current choice of many potential candidates, and of presenting this award to him.

At the annual meeting of the American Society of Tropical Medicine and Hygiene, held at Los Angeles, California, on Friday, November 4, 1960, in the presentation of the Joseph Augustin LePrince Award, Mr. Lawrence B. Hall * said:

Mr. President, members, and guests of the American Society of Tropical Medicine and Hygiene:

The Joseph Augustin LePrince Award has become an established part of the meetings of the American Society of Tropical Medicine and Hygiene, but not all of the present membership had the opportunity of knowing the outstanding engineer, scientist, and great American in whose name this award was established. For those of us who had that opportunity, there will always remain the mental image of the tall, lanky figure, of the quick smile, of the simple and direct approach to complex problems.

Anopheles quadrimaculatus and A. freeborni mosquitoes which had acquired their infection from monkeys infected with Plasmodium cynomolgi bastianellii were allowed to bite 7 Negroes and 13 white inmate volunteers. No volunteer received less than 25 infected bites. Observations were as follows: (1) parasitemia of low density was demonstrable in 12 of the 13 white subjects; (2) the prepatent period ranged from 15 to 30 days with an incubation period of 15 to 23 days; and (3) parasitemia was not demonstrated in any of the Negroes, although 3 exhibited signs and symptoms referable to malaria.

Of the 20 volunteers, 16 exhibited clinical responses with oral temperatures over 100°F, enlarged tender liver or spleen and other symptoms graded from moderate to severe. Two exhibited temperatures under 100°F with mild symptoms, and two were asymptomatic. The most frequent symptom was headache followed in decreasing frequency by anorexia, abdominal pain, joint pain, nausea, myalgia, vomiting, chest pain, chills, and cramping. The most significant physical findings were splenomegaly and hepatomegaly which appeared early in the infection and were transitory. In general, this disease was more benign than that generally encountered in vivax although the severity of the symptoms appeared out of proportion to the parasitemia.

Man to man transfer of infection with P. c. bastianellii was accomplished by allowing A. freeborni infected on man to feed on two human subjects. Each subject developed symptoms referable to malaria and one developed patent parasitemia on day 107. On that day blood transferred to another volunteer and to an uninfected rhesus monkey resulted in an infection in each. Blood transferred to man and to monkeys prior to day 107 gave negative results.

The results reported in this paper show that P. c. bastianellii qualifies experimentally as a zoonosis. In addition, we have demonstrated that man-mosquito-man transfer can also occur. Whether these findings will be significant in terms of malaria eradication will only be determined by further investigations.

The response to chloroquine of a strain of Plasmodium falciparum malaria from Colombia, South America, has been studied in seven patients. Six of these infections responded poorly to normal (0.6 gram, 1.5 grams) and above normal (2.1 grams) doses of the drug. The parasites were either not cleared from the blood stream or were eliminated slowly, after which they relapsed quickly. In two instances, 1.5 grams of chloroquine failed to eliminate the parasitemia; and, in two other instances, the parasites increased after a 600-mg single dose.

These findings indicate that this strain of malaria is resistant to the usual doses of chloroquine. The resistant quality was still present after mosquito passage.

Because of the widespread use of this drug for the suppression and cure of malaria and especially in malaria eradication programs, the occurrence of resistance by the parasites appears to be of considerable importance.

An enzyme system in the supernatant fraction of rabbit liver homogenate for the metabolism of chloroquine is described. Various compounds, including SKF 525-A (β-diethylaminoethyl diphenylpropylacetate·HCI) and a number of antimalarial drugs, constitute effective inhibitors in vitro to the metabolic transformation of chloroquine.

Plasma levels of chloroquine can also be prolonged in experimental animals with some of these compounds. The most effective drugs tested include amodiaquin, pamaquine, hydroxychloroquine and primaquine.

In a campaign of 7 years' duration to control malaria in Netherlands New Guinea, house spraying was combined with mass distributions of chloroquine and pyrimethamine.

In several moderately endemic areas, eradication was practically or almost achieved. Even in a holoendemic region, a point has been reached where eradication seems possible. However, in other areas, where people are of a roving disposition, results of house spraying and drug distribution were disappointing. The number of infections to which a population is exposed before control measures come into operation appears to be of major importance in relation to success or failure of eradication efforts. Aspects of holoendemic malaria, on which a new classification of malaria endemicity is based, are discussed. Changes in the ratio of the species of malaria parasites were not in accordance with expectations, falciparum showing an unexpected resurgence attributed to a more rapid loss of immunity to this species than to vivax. Future policy will be to continue residual spraying and drug distribution, supplemented by the use of medicated salt in problem areas and gradual bonification.

This study deals with the compound CI-423 [3-chloro-9(4-diethylamino-1-methylbutylamino) acridine, 10-oxide, dihydrochloride] as a potential non-staining, suppressive antimalarial drug.

Comparative testing by the drug-diet method against trophozoite-induced Plasmodium lophurae infections in chicks indicated CI-423 to be approximately 16 times as active as quinine, 4 times as active as quinacrine, and one-half as active as amodiaquin.

Comparisons on a single or multiple oral dose basis against trophozoite-induced Plasmodium cynomolgi infections in rhesus monkeys showed CI-423 to be distinctly more potent than either amodiaquin or quinacrine in rapidly suppressing the acute parasitemia and curing the animals.

In contrast to quinacrine, CI-423 did not induce visible staining of the skin of mice or rats when given for respective periods of 2 and 4 weeks.

Isosporosis in man is due to infection with Isospora belli and I. hominis, of which the former is the more prevalent form. Differential diagnosis is easily made on discovering the immature oöcysts of I. belli and the mature sporocysts of I. hominis in freshly evacuated stools.

Until 1935 there were only 200 known cases of human isosporosis in the world. At present at least 835 authentic cases have been diagnosed in the Americas, including isolated infections from many localities and endemic foci in São Paulo, Cali and Santiago. Examination of thousands of human stools, employing satisfactory concentration technics in addition to direct fecal smears, has indicated that the percentage rates of isosporosis in these three endemic centers are approximately 0.1, 1.0 and 1.8, respectively.

Although human isosporosis may become chronic, much more frequently it is only a temporary unstable infection in man and the dog. The one plausible explanation which we are able to suggest for the maintenance of I. belli and I. hominis endemically in a community is based on the resistance of the cysts to unfavorable environmental conditions, thus affording ample opportunity for human exposure.

Greater competence in the recognition of the stages of Isospora in the feces, use of a satisfactory concentration technic, and examination of thousands of fecal specimens are required to provide an accurate picture of isosporosis in a community.

Prolonged ether extraction of adult schistosomes removed 25 mg of non-specific ether soluble substances from each 100 mg of worms. The lipids were collected as five fractions, of which two fixed complement with syphilitic sera and two were anticomplementary. None of the lipid fractions fixed complement in the presence of schistosome antibody. A carbohydrate fraction isolated from Schistosoma mansoni worms was non-reactive in the complement fixation test.

Essentially all of the complement fixing activity of the saline extract from ether-treated adult schistosomes is present in the acid insoluble protein fraction. This fraction consists of one demonstrable electrophoretic component, and contains only one-third of the nitrogen and none of the carbohydrate present in the crude extract. The protein precipitates at 30% saturation with ammonium sulfate, but loss of some antigenicity results from this step.

One hundred and ten Swiss albino mice in three groups were experimentally infected with Schistosoma mansoni cercariae. In the first group the spleen weight was recorded from the 3rd to the 79th day after one exposure. The animals in the second group were reinfected weekly beginning 60 days after the primary infection, and the average spleen weight was recorded. The third group was reinfected daily, beginning 60 days after initial exposure.

The average spleen weight in the three groups, compared with that of a control group, increased (splenomegaly), markedly so in the daily reinfected animals. Histologically there was lymphatic and reticular hyperplasia which began on the 3rd day after infection (toxemic stage). In animals which survived from the 40th day on, the lesions were more evident, probably as a result of greater phagocytic activity due to the destruction of adult parasites and eggs in the tissues of the host. In animals reinfected weekly the splenic lesions were similar to those in the first group, but the hyperplasia was more intense. In the group of mice reinfected daily, the intensity of the lymphatic and reticular hyperplasia was even greater.

TWSb was employed in the treatment of 17 Egyptian children suffering from urinary bilharziasis. The drug was given daily, every other day or twice weekly. Observations on its effect on the electrocardiogram indicated that giving the drug is safer in twice weekly than in more frequent doses and is, moreover, equally effective.

A relatively small number of Marisa cornuarietis was introduced into a chain of five ponds containing well established Australorbis glabratus populations. During an 81-week observation period the Marisa effectively reduced the Australorbis population almost to extinction. The population has not recovered in one and a half years. Additional studies are indicated to determine if Marisa will work equally well in other Australorbis habitats.

The average number of surgical cases of hydatid disease per year among Lebanese during 1949 to 1959 was 63. The case rate was 3.82 per 100,000 population per year. The heaviest concentration of cases was in Beirut and environs. Case rates were much higher among Christians (5.00) than among Moslems (2.24) and among Armenians (8.18) than among the general population. Age specific rates for age at operation for patients from Beirut showed that operations were performed with equal frequency among individuals 20 to 60 years of age. An unusually high percentage of infected males were shoemakers.

The reactions noted in a series of 286 patients treated with Ciba-1906 for various dermatologic conditions were mild and subsided after the drug was discontinued. In one patient the eruption recurred promptly following a test dose. Nausea, diarrhea and a bad taste in the mouth were other reactions noted. Drug allergy should be considered when morbilliform eruptions appear in patients under Ciba-1906 therapy.

A virus strain (AR 2204) was isolated from a pool of 19 Mansonia (Mansonioides) uniformis (Theobald); another virus strain (AR 2211) was isolated from a pool of 278 Aedes (Neomelaniconion) circumluteolus (Theobald).

Serological studies utilizing CF and NT techniques have shown the two virus strains to be immunologically indistinguishable. Similar studies including also the HI technique indicate that the virus is not related to a wide spectrum of other arthropod-borne viruses. The agent has been named Ndumu virus after the locality where the mosquitoes were collected.

Ndumu virus is sensitive to the action of sodium desoxycholate. A vervet monkey was inoculated with Ndumu virus and the agent was detected in the serum on the 8th and 10th postinoculation days. Protection test surveys indicate that Ndumu virus has been active among human beings residing in widely scattered areas in southern Africa.

One hundred and ninety-five persons residing in a forested area of the Province of Darién in Panama near the Colombian border were tested for neutralizing antibodies against yellow fever, St. Louis encephalities (SLE) and Ilhéus viruses. Capacity to neutralize 2 or more logs of virus was observed in 8.4% against SLE, in 43.7% against Ilhéus and in 42% against yellow fever. The interpretation of these results is discussed.

Two hundred and forty-eight blood samples obtained from 139 mammals, 107 birds and 2 reptiles were tested for neutralizing antibodies against St. Louis encephalitis virus. Eleven, or 10.3%, of the avian specimens and two, or 1.4%, of the mammalian specimens neutralized this virus.

The first isolations of the virus of Ilhéus encephalitis in Panama are reported. The virus was recovered once from Haemagogus spegazzinii falco and once from mixed species of the genus Trichoprosopon.

The virus of Ilhéus encephalitis was isolated from the blood of two birds captured in March, 1960, in the Province of Bocas del Toro in Panama. Five of 62 birds obtained in Bocas and 2 of 68 birds obtained in Darién had neutralizing antibodies against this virus in their blood.