The American Journal of Tropical Medicine and Hygiene - Volume 10, Issue 4, 1961

Late in 1959, it became apparent that an independent appraisal of the status and prospects of the rapidly expanding global program for the eradication of malaria was needed to orient discussions of future United States participation. In December, the International Cooperation Administration (ICA) named a panel of twelve American experts to consider the future position of the United States with respect to malaria eradication. The ICA Expert Panel on Malaria met on four occasions between the first week in January and the last of April 1960.

At the opening session, Dr. Eugene P. Campbell, Director of the Office of Public Health, ICA, welcomed the Panel, and outlined the Panel's terms of reference.They were to (1) assess the progress of world-wide malaria eradication and consider the future l)oSition of the United States on malaria eradication; (2) estimate future program requirements in time, personnel, commodities and research and predict the future of malaria eradication;

The in vitro and in vivo amebicidal activities of eight new synthetic N,N′-bis(dichloroacetyl)diamines are reported. These compounds are amebicidal in vitro against Entamoeba histolytica in concentrations of 1 part in 1 million to as low as 1 part in 50 million. In vivo amebicidal activity was evaluated in hamsters spontaneously infected with Entamoeba criceti. The compounds discussed are highly amebicidal; their calculated ED50 values are in the range of 0.7 to 2.5 mg/kg/day when given for 4 days.

Radioactive tracer technics were used to study erythropoietic activity in dogs infected with Ancylostoma caninum. Uninfected animals served as controls. The erythropoietic response of these dogs was evaluated by means of the rate of removal of 59Fe from the plasma and its incorporation into the red blood cells. Results revealed that in infected animals erythropoiesis was either stimulated or remained within the upper limits of normal with the exception of one animal. Under the conditions of these experiments, there was no depression of bone marrow activity. Erythropoietic activity was stimulated to a degree that compensated for the blood loss due to the hookworms. Red cells were being lost from the infected animals by a process other than aging, but none of the animals became grossly anemic. The validity of this method of studying the causes of the anemia associated with hookworm infections is discussed.

Rabbits infected orally with 20, 5 and 1 third-stage larvae of Gnathostoma procyonis were bled weekly for a period of 11 months. The sera that were collected were tested by an indirect tannedcell hemagglutination test with 5 extracts of adult worms and 2 of larvae. The adult worm extracts were found to be either nonreactive or nonspecific in their reaction. An acid-insoluble extract of larvae was also found to be nonreactive, whereas the acid-soluble fraction of the same preparation was found to be a sensitive, as well as specific, substance. The time interval between infection and the first detection of antibodies, the rate of antibody production and the maximum antibody titer noted were found to depend on the size of the inoculum. In all of the infections high titers were found to persist throughout the observation period. In two rabbits infected by placing larvae subcutaneously, the antibody response and the titer maxima did not correspond to the infecting dose. Sera from humans infected with schistosomes, hookworms and Ascaris did not cross-react with the acidsoluble larval extract. Similarly, no cross-reaction was noted with sera from animals infected with filariae, Clonorchis or Paragonimus. However, cross-reactivity was noted with sera from rabbits infected with Ascaris or Toxocara as well as with sera from human cases of tropical eosinophilia and visceral larva migrans. Conversely, no reaction was noted when sera from hosts with any of the above heterologous infections were tested with gnathostome extracts. The results of the infections seem to confirm the similarity between Gnathostoma spinigerum and G. procyonis.

Trichlorophenol piperazine salt was given orally in tablet form to 53 persons with a total of 85 worm infections. The numbers of cases found negative on follow-up after treatment were: 7 of 8 with hookworm, 20 of 23 with Ascaris, 5 of 6 with Enterobius, 7 of 14 with Strongyloides, 6 of 26 with Trichuris and 2 of 8 with Hymenolepis nana. No side effects were reported by the individuals treated.

A study of three Puerto Rican communities, each in a different watershed, was made with respect to group culture, distance from stream, waste disposal, contact with water, snail populations, snail infections, and the manner in which these factors influenced schistosomiasis endemicity. During the course of a 2-year period, 289 identified children of both sexes, ranging in age from 1 through 16 years, were surveyed quarterly for schistosomiasis, ascariasis, trichocephaliasis, and necatoriasis. The communities selected for study included a low class rural culture, a low class suburban culture, and a lower middle class suburban culture. Over-all schistosome infection rates of 69, 26, and 18%, respectively, were found in the three areas. Only 1% of 10,514 snails tested were positive. Factors associated with high schistosomiasis infection rates were poor means of waste disposal, frequent use of infested streams, and relatively large numbers of infected snails.

The serum proteins of 67 patients with chronic schistosomiasis and of 37 controls were studied by paper electrophoresis. Compared to the controls, slight but significant changes consisting of decrease of serum albumin and increase of gamma globulin were found in the infected group. The changes were more pronounced in patients with hepatosplenomegaly than in those without hepatosplenomegaly, but the differences were not significant. No significant relationship was found between the protein abnormalities and the hepatic functional impairment determined by the bromsulfalein retention test. The protein abnormalities had no relation to previous treatment with antimonial agents. The changes were significantly more marked in patients who had an abnormal cephalin flocculation test than in those whose cephalin flocculation test was normal. The gamma globulin was significantly higher in those sera that produced a large amount of precipitate (2+ to 4+) in the circumoval precipitation test than in those that produced either no or a small amount of precipitate (0 to 1+). However, no correlation between the circumoval precipitation test and the cephalin flocculation test was found.

These findings indicate that decrease of serum albumin and increase of serum gamma globulin represent a protein response by the human host to chronic infection with Schistosoma mansoni. In view of the known hepatic involvement which occurs in this disease it would seem reasonable to suspect that the protein changes result from this involvement. However, in the present study they could not be correlated at an acceptable level of confidence either with abnormal bromsulfalein retention or with hepatosplenomegaly. The evidence presented supports the view that these changes are due substantially to an immunologic mechanism. This mechanism probably produces a group of antibodies, one of which is the circumoval precipitin.

Complement fixation tests with a purified extract of adult Schistosoma mansoni were performed by a quantitative technique with the sera of 216 children (10 to 15 years of age) and 84 adults (20 to 40 years of age) passing eggs of S. mansoni in their stools. The test was positive in 88.9% of the children and 89.3% of the adults. The titers obtained for the two age groups did not differ significantly.

The efficacy of stibophen (Fusdin®) for killing mature Schistosoma mansoni was compared in mice on a standard commercial ration and in others on semi-synthetic diets. In several tests in which mice received intraperitoneally a dose of 100 mg/kg daily for 8 days, it was estimated that the drug was from 4 to 16 times more effective in eliminating the schistosomes in the animals on the semi-synthetic diets than in those on the crude commercial ration.

Tris(p-aminophenyl)carbonium chloride and pamoate, referred to as CI-403 chloride and CI-403 pamoate respectively, were administered to 64 patients with schistosomiasis in an endemic area in Nyasaland.

CI-403 chloride and CI-403 pamoate were given in respective total doses of 150 to 539 and 250 to 788 mg per kg during periods of 4 to 14 days. Stool and/or urine specimens were examined in about half of the patients a sufficient number of times during the first few weeks after treatment, for an indication of the effects of the drugs on egg excretion. CI-403 chloride appeared to suppress egg excretion in 12 of 13 patients infected with Schistosoma haematobium and in one of two infected with S. mansoni. CI-403 pamoate appeared to suppress egg excretion in 11 of 13 patients infected with S. haematobium and in each of the 5 patients infected with S. mansoni.

There were significantly more gastrointestinal reactions associated with CI-403 chloride than with CI-403 pamoate. The latter was tolerated well in this respect. Peripheral blood studies in 28 patients and urinalyses in 42 provided no indication of toxicity of either salt.

The salts, particularly CI-403 pamoate, seem to be worthy of further study as potentially practical antischistosomal drugs.

Haemogamasus liponyssoides hesperus Radovsky, a parasitic mite commonly taken from nests of meadow mice, was tested in the laboratory on the hypothesis that it might play a role in the maintenance of plague in nature. Techniques for forced feeding and external decontamination of the mites were developed. Mites fed well on healthy suckling mice and on heparinized blood from healthy mice, but fed poorly on suckling mice suffering a terminal bacteremia with Pasteurella pestis or on plague-bacteremic blood. Viable P. pestis were demonstrated to survive in the mites up to 23 but not to 24 hours following an infective blood meal. Bacterial culture of triturated mite suspensions proved less reliable in demonstrating the presence of viable P. pestis than did animal inoculation. Mites which had fed on an infectious blood source failed to transmit the infection by feeding upon suckling laboratory mice.

Results of the experiments do not support the hypothesis that the mite may be of significance in the maintenance of plague in nature.

With the purpose of contributing to the knowledge of the epidemiology of pinta, a survey was made by interview and physical examination of the total population of a village called Apango, in the State of Guerrero, Mexico. This town is situated in a pinta-affected area.

Among the 2,110 inhabitants, 37.4% had pinta. The age specific morbidity rates per 100,000 population increased progressively from 1,900 in the age group 0 to 4 years to 75,500 in the 60 years and older group. The disease attacked all ages.

In the wives, as well as in the children, a marked relationship was found between the occupation of the head of the family, farmer or agricultural worker, and the prevalence of the disease. It was highest in the agricultural workers and their families. The presence of the disease in the parents was an important factor in the frequency of the disease in the children.

The data pointed to pinta as an infection contracted as a consequence of factors intimately related to the familial household and to the presence of pintous adults in the family.

A rat ectoparasite survey of the City of San Juan, Puerto Rico, was made from 7 December 1956 to 31 December 1960. Data obtained from 964 rats collected from 15 April 1957 to 4 May 1958, 747 rats collected in 1958–59, and 573 in 1959–60 were compared with similar data obtained in 1946–47 and 1954–55. In 1946–47 54% of the rats were infested with Xenopsylla cheopis; in 1954–55, 16%; in 1957–58, 6.0%; in 1958–59, 3.3%; and 1959–60, 2.6%. Other common rat ectoparasites, Laelaps nuttalli, Ornithonyssus bacoti, Listrophoroides expansus, and Polyplax spinulosa increased in abundance. In particular, L. nuttalli showed marked increases. Ornithodoros puertoricensis which affected 26.8% of the rats in 1946–47 infested only 5.4% in 1959–60. Designed rat flea insecticidal control measures have never been applied in Puerto Rico. The rat population has always been high. Fleas were uncommon in poorly sanitated areas and more often found in well sanitated places subject to other pest control activities. Weather Bureau records indicated that precipitation, humidity or temperature could not account for the rat flea reduction. Of 998 rat sera subjected to the complement fixation test with U. S. Army group specific typhus antigen at 1:10 dilution, 804 were negative and 194 were anticomplementary. In 1954 and succeeding years including 1960 there were no cases of murine typhus fever reported from the City of San Juan and in 1958, 1959, and 1960 none in Puerto Rico as a whole. Since a great reduction in rat flea population occurred and no infection in rats was found, there is no reason to doubt the reported morbidity or to postulate that the use of antibiotics had anything to do with the rate. It was concluded that investigations on the ecological circumstances of the association of arthropods, particularly mites, with rat fleas are necessary, if the question of why the rat flea population was decimated is to be answered.

The isolation and laboratory studies of a new virus isolated from a human fever case in Trinidad, West Indies, are described. The virus has been named Oropouche virus after the region from which it was obtained. Oropouche virus has been found to be related to Simbu virus, an agent isolated in South Africa. Neutralizing antibodies were found in the blood of a few forest workers, 8 of 26 native cebus monkeys in the Nariva Swamp and 9 of 26 howler monkeys widely distributed over the island.

Sera collected from 152 healthy young inhabitants of the island of St. Vincent (population, about 80,000) were assayed for antibody against all three types of poliovirus. Results showed that, in spite of the fact that the island has never had an outbreak of poliomyelitis, a significant part of the population develops antibodies to each of the three types of poliovirus by the age of 5 years, and this increases to involve 86 to 95% of the young adult population. Evidence indicates that at present St. Vincent is part of a Caribbean zone of poliomyelitis endemicity. But as clinical poliomyelitis is appearing with increasing frequency in other parts of this zone, vaccination of susceptible young children on St. Vincent should be considered in order to anticipate, and prevent, a shift to the epidemic situation.

From January, 1956, through April, 1960, 171,210 culicine mosquitoes from Ndumu, Natal, Union of South Africa, were inoculated into mice in 2,325 lots for attempted virus isolation. Fifty-nine recoveries of viruses were effected.

The viral isolates, including nine identified viral types, were recovered from nine species of mosquito, but among these the only ones principally concerned were Aedes (Neomelaniconion) circumluteolus (Theobald), Culex (Culex) univittatus Theobald, Mansonia (Mansonioides) africana (Theobald) and Mansonia (Mansonioides) uniformis (Theobald), in the order named.

The incidence of viral isolates in time and space at Ndumu indicates the possibility of the following assumptions having some basis in fact: (a) host specificity of most of the viruses concerned is not strict among genera of the tribe Culicini; (b) the virus types occurring in the Ndumu region may have undetected local cryptic cycles, their episodic reappearances being accounted for less by foreign reintroduction than by the occasional conjunction of ecological conditions that permits them to enter mosquito cycles detectable by current methods of investigation.

Sera of 947 members of 169 southern Louisiana households and of 995 Peruvian Indians from the Andean highlands were examined for the presence of encephalomyocarditis (EMC) virus neutralizing antibodies. Of the sera from Louisiana 3.5% showed antibodies; of those from Peru, 9.6%. In both populations it was found that boys and girls had equal prevalence rates but that adult females had higher rates than did adult males. The data suggest an association between very poor hygienic household conditions and probability of infection. No familial pattern in the occurrence of antibodies was found. The possibility that man becomes infected by the contamination of skin wounds with infective rodent excreta was mentioned.

Melanesians of the Highlands of New Guinea are best considered a single geographic breeding unit whose distant origins can no longer be traced. Cultural and environmental factors have contributed to situations of extreme isolation of cleavage communities which has resulted in a condition ideal for the operation of random genetic drift and consequent development of markedly diverse small groups, each with its own genetic constitution.

Wurm's classification of Highland languages into the East New Guinea Highland Stock and Phylum and his glottochronological calculations with respect to the languages in this Stock are used cautiously as one means of demonstrating probable long isolation and independent evolution of the Fore people.

Intermarriage across language borders and migrations of smaller and larger groups across such boundaries have probably played a major role in determining the current pattern of kuru incidence and distribution. However, the central nucleus of kuru, with the current highest prevalence and mortality, is found in the Purosa and Atigina native areas of the South Fore, and the kuru mutation most probably first arose in a direct ancestor of these peoples.

Detailed analysis of the pattern of kuru incidence of 961 kuru cases studied since the beginning of 1957 is presented with prevalence and mortality figures for the entire kuru region. This is believed to represent an essentially complete coverage of all kuru cases that have occurred in the 4 years 1957 through 1960.

Distortions in the male to female sex ratio in the kuru region are marked, with a preponderance of males, particularly in those regions of highest kuru prevalence and mortality. Presumably, the disproportionately high toll of females among kuru victims has contributed to this pattern. Thus, the extent of departure from normal Highland sex ratios in populations in the kuru region may reflect the extent and the duration of kuru involvement in the various communities.

An intensive study of the Moke community of North Fore natives, carried out in 1957 and 1958, and continued less intensively since then, has failed to suggest any change in kuru prevalence or mortality over the past decade. The still primitive living conditions of the first half of the period, 1951 to 1955, contrast markedly with the rapid acculturation of civilized society of the second half of the decade; and yet, no alterations in the kuru pattern can be detected over these years.

Sixty-three cases of kuru have been recorded for the Moke complex of hamlets with a total population of about 240. Of these, twelve cases have been studied since the onset of investigations in 1957 and the remainder were recorded from the memories of natives by direct inquiries or coincident with the collection of genealogies. The pattern of distribution of the grounds inhabited by the kuru patients at the time of onset, of the places of death and of garden sources of food used by kuru victims, in no way suggests association between the cases or common exposure in time or place to any particular sub-ecology of the region.

A blood group genetical survey has been carried out in the kuru region of the Eastern Highlands and other parts of Papua-New Guinea. A total of 2,853 blood specimens has been tested and gene frequencies are presented for the ABO, MNSs and Rh blood groups. Results are also presented for the blood groups P, Lea, Fya, K, Lua, Wra, Jka, Dia, Jsa, and V. A few S.C.T. and P.T.C. tests were also made. The extensive blood group genetic data for natives of New Guinea (Papua, New Guinea and Netherlands New Guinea) have been tabulated, and comparisons made of frequencies found in various linguistic groups in different parts of New Guinea.

It is considered that the apparent phenotypic heterogeneity of the natives of New Guinea is largely the result of differentiation developing from a small, reasonably homogeneous population which spread gradually to many relatively isolated regions, and that over the centuries diverse types have evolved which show variations both in physical characteristics and in blood group gene frequencies.

No evidence of the blood antigen Dia, a possible Mongoloid marker, was found in New Guinea. No evidence of the blood antigens Jsa and V, or S.C.T., possible Negro markers, was found. The absence of subgroup A2 (except in one family) and the low frequency of the gene Ro do not offer any support for earlier suggestions that a Negro component is present in New Guinea natives.