The American Journal of Tropical Medicine and Hygiene - Volume 4, Issue 6, November 1955

Of a total population estimated at 2,788,122 more than 39,484 persons were examined of whom 70 per cent were school children, 2 per cent pre-school children and 28 per cent adults. The overall incidence of goiter was 38.5 per cent. Only one out of 22 departments had an incidence less than 20 per cent. One department had more than 60 per cent goiter, three between 51 and 60 per cent and the 17 remaining departments from 21 to 50 per cent. No differences in incidence of goiter were found between males and females in any age range, between Mestizos and Indians in the same locality nor persons living in department capitals and outlying villages. The average incidence of goiter increased with altitude. Endemic goiter is considered to be a serious public health problem in Guatemala and its prophylaxis through the iodization of all salt for human consumption has been approved by the government at a level between 1 part of iodine in 10,000 parts of salt and 1 part in 15,000. Because the salt used is crude and moist and distributed without special packaging, the use of potassium iodate is planned for this purpose.

A study of illnesses among 57 Americans living in Cairo, Egypt, as compared with previous health experience, showed a four-fold increase in sick days due to minor illness. This increase was due in major part to increased incidence of infectious diarrheal disease, communicable respiratory disease, and infections of the skin and eye. The incidence and duration of attacks of diarrheal disease were not greatly lessened during the months ensuing after arrival in Cairo. The health environment with respect to communicable disease incidence in Cairo is discussed.

Since age distribution analysis has shown that the prevalence of infection by Entamoeba histolytica reaches a maximum during school age and adolescence, the hypothesis that examinations of school children might yield evidence indicative of the prevalence of the infection in the community appeared justifiable. Such an investigation of a competent sample of the school population in Forsyth County, North Carolina revealed a prevalence of 6.1 per cent in the 1,934 school children examined. No significant differences in prevalence were observed with respect to racial distribution or residence. One group of infected urban children served as probands to the positive families and a second group of apparently uninfected urban children served as probands to the negative control families.

Examination of these two groups revealed a prevalence of E. histolytica of 20.7 per cent among members of the positive families and a prevalence of 0.6 per cent among the members of the negative control families.

These two comparable groups resided within the city limits of Winston-Salem, North Carolina. However, the observed prevalence of infection by E. histolytica was almost twice as great in the Negro families as in the white families. Since there is no evidence to indicate a special racial predilection to amebiasis among Negroes, this statistically significant difference may be attributable to greater exposure to infection and a poorer sanitary environment.

In preliminary trials of fumagillin and erythromycin in Louisiana and Mississippi, 45 patients were treated. Of fifteen patients with E. histolytica infection receiving fumagillin, four suffered recurrences. Eight persons with amebiasis treated with erythromycin 600 mg. every six hours were cured. Of sixteen individuals treated with 30 mg. per kilogram of body weight per day four suffered recurrences. Both drugs caused the temporary disappearance of nonpathogenic amebae from the stools.

One-hundred twenty Panamanian patients were treated for amebiasis with fumagillin, erythromycin or a combination of both drugs. There was failure or recurrence of infection within seven weeks in over 15 per cent of 39 treated with fumagillin, no failure or recurrence in 18 treated with erythromycin and only one recurrence out of 63 patients treated concurrently with both drugs. These differences were not statistically significant.

A definite effect upon nonpathogenic amebae was observed with each type of treatment but there was a high rate of recurrence. In the case of each species of amebae, Endolimax nana, Entamoeba coli, and Iodamoeba bütschlii there was a higher rate of recurrence with fumagillin treatment than with erythromycin or concurrent use of both drugs. These differences were not statistically significant.

Erythromycin provided rapid relief of amebic dysentery in three of four patients, fumagillin in one of two and combined therapy in three of three.

The amebicidal efficiency of certain antibiotic drugs has been established, but no single antibiotic agent has yet proved to be completely curative, nor have the therapeutic achievements even exceeded those attainable with nonantibiotic amebicides. With the introduction of each protozoicidal antibiotic drug, initial therapeutic acclamation has been enthusiastic. Time and further clinical experience have, in many instances, depreciated their status. The incidence of recurrences and objectionable side effects has prevented most antibiotic agents, when used alone, from being “ideal” amebicides.

Analysis of the extremes in therapeutic achievement reveals variance in susceptibility of parasitic strain and in severity of the disease, as well as inconsistency in mode of administration and inadequacy and lack of uniformity in follow-up examinations. Acquired alteration in bacterial and amebic sensitivity may also be hypothesized. Critical comparative review suggests that the antibiotic drugs have not impressively reduced the rate of recurrence below that reported for nonantibiotic amebicides.

Entamoeba histolytica with its accompanying bacterial flora was cultured in vitro in a basal medium of inorganic salts and egg albumin plus rice starch, to which was added a variety of aliphatic amines and amino alcohols. In general, other simple substrates, including glucose and other alcohols, carboxylic acids, and certain amino acids failed to support the growth of the amebae.

Pyrimethamine (Daraprim) in doses of 25 mg. per adult, was administered weekly to 110 individuals living in a small malarial endemic village in Jordan. One hundred and twenty other individuals living in the same village who served as the control group received placebos. During the 18-week period of the study (June 20 to October 24, 1954), 25 of the control group developed malaria (P. vivax) whereas no cases of malaria occurred among the pyrimethamine treated individuals.

A flagellate encountered incidentally in Indian monkeys in the course of an investigation of experimental disseminated encephalomyelitis (Kabat et al. 1952) had been identified tentatively as Trypanosoma cruzi (Wolf et at. 1953). This was based upon the appearance of the micro-organism as a trypanosome having the morphological features of T. cruzi in the peripheral blood, its occurrence in the tissue in a leishmaniform stage, and upon the nature and distribution of the lesions produced by the flagellate in the monkey.

The present studies have shown that the trypanosome cultured from the skeletal muscle of a rhesus monkey imported from India is identical with T. cruzi of the Americas. This conclusion is based upon the following data: 1) the cultural characteristics of the Indian trypanosome are identical with those of Trypanosoma cruzi; 2) biologically, it passes through the leishmaniform, leptomonad, crithidia and trypanosome forms in the vertebrate and invertebrate host and in cultures; 3) serologically, it has the same agglutinins as two standard American T. cruzi strains (1114 and Lilly) and there is complete cross-absorption of agglutinins between it and these two strains of T. cruzi; 4) two species of triatomid bugs, Triatoma gerstaekeri and Rhodnius prolixus have been successfully infected with the Indian trypanosome; trypanosomes first appeared in the rectal discharges of the bugs 32 and 17 days respectively after the infective feeding.

Culex molestus was infected by feeding on suspensions of West Nile virus and the virus transmitted to susceptible animals. Strains of virus recently isolated from the blood of West Nile fever patients in Israel were used. When the titer of the suspension fed was 10-4.0 or more, virus was transmitted by mosquitoes to infant mice after an extrinsic incubation period of 7–28 days. When the titer was 10-2.0 or 10-2.8, transmission did not occur, even though virus was present in the mosquitoes. The percentage of mice infected by bite seemed to be a function of the length of the extrinsic incubation period.

The titer of virus in infected mosquitoes varied considerably in different experiments and fluctuated between 10-2.2 and 10-5.7 between the 9th and 28th day of the incubation period. It was found that an infected mosquito pool may be composed of individual mosquitoes having titers of virus ranging from less than 10-1.0 to 10-3.5. Though each mosquito feeding on a suspension having a titer of 10-5.0 or more became infected, only half of those infected were able to transmit the infection by bite after a suitable incubation period. The amount of virus injected into infant mice by the bite of infected mosquitoes was found to correspond to about 1000 ID50.

In broth cultures of 10 strains of Pasteurella pestis, 3,4-dimethyl-5-sulfanilamido-isoxazole (Gantrisin, sulfisoxazole) in concentrations of 8 to 16 times less than that of 2-sulfanilamidopyrimidine (sulfadiazine) produced a similar degree of bacteriostasis. Against the same strains of plague, chloramphenicol was 16 to 32 times more inhibitory than thiocymetin. Chloramphenicol exerted a marked antibacterial action at a concentration of 2.5 microgram/ml. as compared with about the same action for 1.3 mg./ml. of sulfisoxazole. Thus in vitro chloramphenicol was about 20 times more potent than thiocymetin, 500 times more than sulfisoxazole, and 5,000 times more than sulfadiazine. Since the mechanism of action of the synthetic antibiotics differs from that of the sulfonamides, the two types of drugs are not comparable. This difference is illustrated by the fact that sulfadiazine proved to be the most effective among these chemicals for experimental plague prophylaxis in laboratory mice, whereas chloramphenicol was the best therapeutic agent. The in vivo order of efficacy was chloramphenicol, sulfadiazine, thiocymetin, and sulfisoxazole. The lower therapeutic value of sulfisoxazole compared with sulfadiazine, and of thiocymetin compared with chloramphenicol is probably due to more rapid excretion by the kidneys.

A single stool specimen from each of 125 individuals in Jerusalem and 300 in Amman was examined for the purpose of determining the type and incidence of intestinal parasitism.

The percentage prevalence of the most important pathogenic parasites was: Entamoeba histolytica, 12.0 per cent in Jerusalem and 20.3 per cent in Amman; Ascaris lumbricoides, 77.6 per cent in Jerusalem and 51.3 per cent in Amman; Trichuris trichiura, 78 per cent in Jerusalem and 44.3 per cent in Amman. The indicated incidence of infection between these two cities is not considered comparable because the survey in Jerusalem was conducted during the cooler months of the year, and in Amman during the warmer months when chance of parasite transmission is probably greater.

Considering the prevalence of unsanitary conditions, abundance of houseflies during the summer months, and the close association of the population, the incidence of intestinal parasitism in these areas is considered to be comparatively low. Intense sunlight, drought, and dryness of the soil are probably important factors in the destruction of many eggs and cysts of parasites.

The incidence of S. japonicum in the molluscan intermediate host, and in various wild and domestic mammals was known to be relatively high in the endemic area in Formosa. The apparent absence of schistosome infection in the human population needed further study. Stool examinations by the sedimentation method were done in seven villages in the Changhua endemic area. An examination of 12,591 stools from 4,197 persons did not reveal a definite positive case of S. japonicum infection. The intradermal test for schistosomiasis japonica on 2,562 persons in six villages where stool examinations had been done showed 8.4 per cent of positive reactors. The incidence of positive reactions was significantly less for women than for men. It was also significantly less for the age group 3 through 12 than for the higher age groups but there was no significant difference among the higher age groups.

Three stools were obtained from each person giving a positive reaction (214 persons) and re-examined for S. japonicum infection by the sedimentation, acidether, and hatching methods. No positive cases were found in examination of these stools. An explanation has been given for the apparent discrepancy in the results obtained from stool examinations and intradermal tests. All the evidence obtained in this study indicates that S. japonicum in Formosa is a non-human, zoophilic strain.

• (1)  A total of 207 adult males, infected with Schistosoma haematobium but livingin a schistosome-free area, were treated with intramuscular injections of stibophen; 114 of these could be studied post-treatment for six months.
• (2)  Five different treatment schedules were tested with total drug dosages ranging from 21 cc. to 40 cc., and administered over periods of three to twenty days.
• (3)  Untoward reactions included anorexia, nausea, vomiting and a skin rash. Some patients also complained of weakness and generalized body pain. The severity and frequency of untoward reactions was positively correlated with the size and frequency of the individual doses, but not necessarily with total drug dosage.
• (4)  Cure rates, based on the clearance of all schistosome eggs from the urine by the sixth month post-treatment, ranged from 50 to 79 per cent. With adequate total dosage, the more intensive treatment regimes gave the higher cure rates.
• (5)  Concentrated treatment was followed by earlier relapse as shown by the re-appearance of living eggs, but degenerate eggs may also indicate unsuccessful treatment after an extended course with low dosages.

Polyps of the rectosigmoid colon are common complications of intestinal schistosomiasis and found present in 17–20 per cent of our cases. Schistosomiasis was found present in 26.5 per cent of our series of autopsy cases of persons over 5 years of age.

Patients with polyp formation of the rectosigmoid colon associated with schistosomiasis, ranged from 19–40 years of age, and presented complaints referable to the rectum and colon. The most frequent symptoms in our series were rectal bleeding and tenesmus.

Clinical and autopsy studies indicated that the polyps are primarily limited to the rectosigmoid portion of the bowel.

The gross and microscopic findings have been described in detail.

The majority (74.8%) of the 159 polyps contained eggs of the mansoni type whereas 30.2 per cent contained the S. haematobium type.

The combination of S. mansoni and S. haematobium was present in 17.6 per cent of the polyps. Worms were found in less than 2 per cent of the polyps.

Studies in regard to pathogenesis, mucosal changes, and relationship to neoplasia are in progress and are to be reported in the future.

• 1.  One hundred consecutive admissions, consisting of Egyptian males of the Cairo and Delta region, admitted usually for brucellosis or amebiasis, were subjected to rectal biopsy.
• 2.  There were no complications to the procedure. Sixty-one cases were found to have schistosome eggs; sixty, S. haematobium; one, S. mansoni; and eight had both S. haematobium and S. mansoni present.
• 3.  An average of 3.4 twenty-four hour urine examinations for schistosome eggs were done per patient. A total of 33 patients were found to have eggs by this method.
• 4.  In 32 patients the rectal biopsy was positive when examination of 24-hour urine specimens had been negative. Conversely, in only 3 patients were eggs discovered in concentrated urine specimens in patients in whom a rectal biopsy had been negative.
• 5.  Rectal biopsy is the method of choice in establishing the diagnosis of vesical schistosomiasis.

The livers of mice infected with S. mansoni showed a reduced ability to oxidize succinic acid despite the fact that endogenous respiration was little affected. The effect on the succinoxidase activity is possibly, in part, attributable to the incorporation within the liver of extra-hepatic tissues, but the existence of a toxic influence by the infection was not ignored. The total nitrogen of infected liver was slightly higher than that of normal liver and an increase in liver collagen accompanied the present infections. No effect of preliminary extracts of infected liver and adult worm were obtained on the succinoxidase system of normal mouse liver. Tyrosinase activity of mouse liver was unaffected by the infection but the glycolytic mechanism was somewhat reduced in activity.

In the study of the effect of oral administration of quinacrine hydrochloride and chloroquine phosphate on Opisthorchis infection, 65 patients were treated in Northeast Thailand.

Quinacrine in the amounts used and over the periods tested failed to have any appreciable effect on the infection. On the other hand, among the patients treated with chloroquine, a marked reduction in the egg laying capacity of the worms was frequently observed as a result of treatment. In 30 out of 32 patients treated with chloroquine for 16 consecutive days or longer there was a decrease or a disappearance of Opisthorchis eggs in the stools. Observations of 23 patients up to 90 days after treatment was discontinued seem to indicate that, in most cases, the reduction in egg production is not just a temporary phenomenon due to stunning or to transient sterilization of the adult flukes. Significant toxicity was not observed during this study.

Ninety-five Honduran laborers with multiple intestinal worm infections were treated with piperazine citrate liquid or capsules. Eighty (94 per cent) of 85 men with Ascaris lumbricoides infections were cured, many of them on only 2.0 grams in a single daily dose for 3 days. The drug seemed to have little effect against Trichuris trichiuris in the dosages employed, and no effect against Necator americanus. No toxicity was observed.

The current and proposed plan of development of the Damodar Valley Corporation, often referred to as India's T. V. A., is outlined. Malaria survey results are reported for the pre-development stage. Recommendations which were made toward malaria prevention in the vicinities of six artificial impoundments and in a million acre area to be irrigated are described. The malariogenic importance of the irrigation development is considered to be far greater than that of the reservoirs. Two conflicting opinions as to the measures which should be undertaken to curb “irrigation malaria” in this particular area, are presented, and a proposal for field research in anopheline ecology is described. The objectives of this research are to evaluate the potential problem and to provide a basis for developing appropriate counter-measures.

Previous observations in an East African village had revealed that Anopheles gambiae and A. funestus were almost completely anthropophilic, and that only 5 per cent of the biting population was known to rest outside after feeding. Spray-catching in all the houses in the village was therefore used to ascertain the total size of the biting population. From this figure the total numbers at all stages of ovarian development were estimated.

Spray catches in 119 houses yielded over 27,000 mosquitoes. The total number of A. gambiae and A. funestus was estimated at about 15,000 females of each species. As the area of the investigation totalled 380 acres, the spatial density was calculated to be of the order of 40 females per acre of each species. The outside resting population was estimated at 14–15 females per acre of each species. The annual range of fluctuation in density was estimated from observations on the biting population in an experimental hut, in which catches were made throughout the year. The density of A. gambiae at different seasons was estimated to vary between 2 and 48 females per acre and of A. funestus between 0.5 and 78 females per acre.

These results indicate that the very high rate of malaria transmission in the area is maintained by relatively small numbers of anopheles, and that factors influencing the association of the mosquito with man, and the longevity of the mosquitoes, are of primary epidemiological importance.