The American Journal of Tropical Medicine and Hygiene - Volume 4, Issue 3, 1955

It was supposed that the Program Committee had an ulterior motive in suggesting a symposium on schistosomiasis. With this in mind the panel's approach has been directed primarily toward the control of the disease. Since I recently had the opportunity to express my views on this problem (McMullen, in press), the introductory remarks will be brief so that the members of the panel will have as much time as possible.

Schistosomiasis, like yellow fever, typhus and malaria, is an extremely complicated bio-economic problem. At present, however, its control has not reached the same degree of proficiency. To attain this may require the efforts of experts in the fields of agriculture, biology, chemistry, ecology, education, engineering, epidemiology, malacology, medicine and public health. Statistically our best chance of success is to have representatives from each of these fields combining their efforts to solve this problem.

Each geographical region is characterized by schistosomes which infect man or lower animals, or both. In Africa and the Middle East, there are two categories of schistosomes, i.e., those of the S. haematobium-type producing terminally-spined eggs and those of the S. mansoni-type producing laterally-spined eggs. The parasite-host relationships of the schistosomes is not clearly understood at the present time. Representatives of the haematobium-complex, i.e., S. bovis, S. intercalatum, S. matthei and probably others occurring in livestock, are of greater concern in human schistosomiasis. Recent discoveries of schistosomes of the mansoni-complex, i.e. S. rodhaini and S. mansoni var rodentorum in rodents and other animals indicate unusual parasite-host relationships with the possibility of concern in the epidemiology of schistosome infections.

Schistosomiasis haematobia in Portugal is unique since the causative agent, S. haematobium, is morphologically similar to its counterpart in Africa but is restricted in its distribution and is transmitted by Planorbis dufourii.

Although a few autochthonous cases of schistosome infection in man have been reported, schistosomiasis in India at present is primarily a disease of livestock. The status of the schistosome problem in India may change with the recent discovery of an endemic focus of urinary schistosomiasis in the Bombay State.

In the Orient, S. japonicum is transmitted by several species of Oncomelania and infects man and a wide range of mammalian hosts over a large geographical area. Recent studies indicate the existence of geographical and physiologic strains of the parasite and its intermediate host. On Formosa, contrary to the situation in other areas of the Orient, S. japonicum is a parasite of lower mammals, man playing only a questionable role in its propagation. The Formosan schistosome has been designated as a “non-human” strain.

Geographical and physiologic strains of S. mansoni and its intermediate hosts in the Americas have been adequately demonstrated. Discovery of wild rodents infected with S. mansoni has altered the parasite-host relationships and epidemiological aspects of schistosomiasis in South America.

Schistosome dermatitis has not been differentiated from other types of dermal irritation in countries where the population is concerned with other more serious parasitic infections. In the Americas, however, schistosome dermatitis has received considerable recognition since it is widespread and occurs as a result of dermal invasion of man by animal schistosomes whose cercariae are present in fresh as well as marine waters.

Dr. Kuntz's presentation has made it very clear that the schistosome problem is much more complex and more widespread geographically than most of us realized. Failure to recognize this complexity results in part from the lack of a comprehensive review of the species of parasites and of the hosts involved, and of the areas where schistosomes occur. Most of us have been aware of no more than certain segments of the problem. We have not realized that in one aspect or another the schistosome problem is of concern to parasitologists and workers in the health sciences in most of the inhabited parts of the globe. We owe much to Dr. Kuntz for this presentation, which certainly has suffered because of the limitation of time.

Speaking as a taxonomist, the precise identification of the species of blood flukes and their snail hosts is a matter of utmost importance.

Schistosomiasis has long been recognized as a public health problem of the first magnitude. Nevertheless, it has gone essentially unchecked in most of the endemic areas. The schistosomes have not only been able to maintain themselves, but there is evidence that even now, while great strides are being made toward the control of many parasitic diseases, schistosomiasis is actually increasing in prevalence and spreading to new areas. In some areas schistosomiasis is now a more serious problem than it was some years ago. For instance, in a number of localities where schistosomiasis has long been endemic, the recent introduction of crop irrigation has been followed by increase in the prevalence of the disease (Khalil and Azim, 1935, 1938; Alcay et al., 1942; and Stephenson, 1947).

In other areas there is evidence that the disease is spreading. In Brazil, a focus of the disease has appeared at Forlandia in the Amazon Basin (Machado and Martins, 1951; Sioli, 1953).

Before commenting on technical aspects of Dr. Olivier's paper, I would like to emphasize some points made in the Introduction. In view of our mutual experiences, two concepts need especially to be stressed: (1) that schistosomiasis is spreading rapidly; and (2) that there is an urgent need for obtaining better knowledge of the biology (in its broadest sense) of the vector snails.

With regard to the spread of schistosomiasis, three countries in another part of the world (Egypt, Sudan, and Iraq) will be mentioned. It is important to note that in Egypt more than half of the population, or an estimated 15 million people, have intestinal or vesicular schistosomiasis or both. Under present conditions of sanitation, education and medical treatment, the only hope of alleviating this serious situation lies in the control of the vector snails. It must be remembered that Egypt is overpopulated and in order to feed the growing population the country is forced to bring more and more of the Nile Valley into perennial irrigation.

Apparent limitations of molluscicides against Oncomelania snails, imposed by environmental conditions, have prompted increased emphasis on fundamental studies of snail biology (McMullen, 1952; McMullen et al., 1953). It is possible that derived information, when properly integrated with agricultural practices, engineering pursuits and methods of applying molluscicides, will suggest more effective control of schistosomiasis japonica.

Extensive investigations on morphology, bionomics, reproduction and control of Oncomelania are currently being undertaken by several agencies. 1 The nature and results of these, which are presently available only as progress reports or personal communications, will be incorporated with a general review of the literature.

Biologic Studies of Oncomelania. Morphology. Morphologic studies, such as those of Li (1934) and Abbott (1948), are being reviewed and extended at the 406 MGL as a basis for determining pathogenesis elicited by molluscicides.

Dr. Ritchie is to be congratulated for his paper on the biology and control of the oncomelanian snails. We, the Oriental people, are especially thankful for his own painstaking studies on this problem in Japan. In the Orient there are about 33 million persons suffering from schistosomiasis japonica. It is, therefore, one of the major medical problems in that part of the world.

His review of the subject is so complete that it is difficult to add anything to it. For some time, however, the distribution of the snail vectors has puzzled me. As you know, in Japan the distribution of O. nosophora is confined to only five small areas. When I visited these areas I was impressed by the fact that snails were further restricted to small, isolated habitats. For many years, although the Japanese have not succeeded in eliminating the vectors in an endemic area, the mollusks have not spread into adjacent areas.

• 1.  Antibody studies in the sera from human subjects infected with Schistosoma mansoni have revealed the presence of cercarial precipitins, cercarial agglutinins, and circumoval precipitins. Adult precipitins were also detected, but in low titers and in a small per cent of the sera tested.
• 2.  There were differences observed in the concentration of these antibodies as related to the duration of infection. In early infections (40 to 240 days after exposure to cercariae) cercarial precipitins and agglutinins have high titers but become low or negative in infections of long duration (10 years and over). Circumoval precipitins are present in both recent and old infections but become more active in older infections.
• 3.  The adult, cercarial, and egg antibodies as produced by artificial immunization of the rabbit are stage specific. Treatment of rabbit anti-serum with lyophilized adult or cercarial material results in the absorption of the homologous but not of the heterologous antibodies. Treatment of anti-adult, anti-cercarial, and anti-egg sera with egg material absorbs only the homologous and the cercarial antibodies. This postulates a cercarial factor in the egg.
• 4.  No circumoval precipitins were detected in the sera from mice with single sex infections. This provides further evidence confirming stage specificity of the circumoval antibody which only develops in the presence of eggs.
• 5.  Successful Fuadin therapy as determined by repeated negative stools and rectal biopsy reduces the circumoval activity of sera. This effect was observed within a year after therapy. The reduction in circumoval precipitin content of serum may be used as a test to determine the therapeutic effect of Fuadin or other anti-schistosome drugs. The circumoval precipitin test, therefore, is both of diagnostic and prognostic value.
• 6.  Intradermal response to egg antigen differs from that elicited against adult and cercarial antigens in that a negative reaction is observed in active cases. The skin response becomes positive after treatment of infection.
• 7.  Knowledge of stage-specific antibodies, and the time during the course of infection when their concentrations are highest, is of great importance in the serological diagnosis of schistosomiasis. Stage-specific antibodies are also of great interest in the study of the mechanism of acquired immunity to schistosomiasis.

It is a pleasure to discuss Dr. Oliver-González' paper on serological responses to schistosomiasis. Several observers have found, when studying this disease under natural conditions, that there is a decrease in the percentage of individuals who have eggs in their stools as the age of the individuals increases. Presumably, these people are still exposed to infection and many believe that the worms live for an indefinite period of time in the host. Also, the percentage of individuals with enlarged livers decreases with age. This has encouraged the idea that some kind of immunity following repeated infection operates in these hyperendemic areas.

A number of workers, including several within this audience, have developed techniques for studying this problem. They have shown that there is a moderate reduction in the number of worms which developed in animals on reinfection as compared to those receiving the first infection.

For the past 35 years the principal and most widely used drugs in the treatment of schistosomiasis have been two antimony compounds: tartar emetic introduced by Christopherson (1918) and stibophen (Fuadin) a sulfonated catechol-antimony complex introduced by Khalil et al. (1929). Literally tons of these drugs have been used, largely empirically, in the treatment of this infection. The literature dealing with the subject is indeed voluminous, and as one reviews it, one cannot escape the recurring theme of pessimism in relation to the alleged shortcomings of these drugs, and one notes the oft repeated expression of hope for better drugs. The chemists and other laboratory investigators are repeatedly urged to provide such drugs, yet there are few examples of critical stock-taking on the part of the clinicans relative to the actual efficiency of the antimony compounds already available as therapeutic agents.

The use of tartar emetic (antimony and potassium tartrate) in preference to Fuadin has been emphasized properly, in combatting schistosomal infections. Of the clinical forms mentioned, S. japonicum infections are most resistant to therapy, and also are not infrequently overlooked in differential diagnosis. Four deaths have occurred fairly recently in San Francisco in personnel returned from overseas (personal communication from Dr. H. G. Johnstone).

Not all physicians using tartar emetic are aware, I believe, of the need for beginning with very small doses and after some tolerance to antimony has developed, build up the dose to much higher levels than originally possible. This technic is based on sound pharmacologic evidence in animals.

Dr. C. Pak (now Surgeon General of the Korean Navy), when working in Shanghai (before the Japanese-American conflict) at the Henry Lester Institute for Medical Research, found that rats or mice, given a dose equivalent to ⅓ of the lethal amount of an antimonial, within 5 to 48 hours can be given a surely fatal dose of the same antimonial without harm.

The Occident is making rapid advances in the field of food preservation. We have been inclined however to overlook the contribution which peoples of the past in other areas have made in this field. These early discoveries, largely unconscious and possibly the result of blind experiment, should not be overlooked.

Early agricultural man was limited in his choice of food materials, but he made a number of food choices which we now realize were rather intelligent ones. While there is little evidence that instinct plays a significant role in human nutrition, it does seem that the dietary developed by agricultural man was just about as good as could be expected under the circumstances. The early accomplishments in food preservation quite probably are part of his striving toward an effective diet.

Man found it necessary for example to store food materials till the next harvest furnished a new supply.

The observations presented indicate that the incidence of protozoan infections was lower on the floor of the Kofu Valley, Yamanashi Prefecture, Japan, where drinking water was obtainable from open wells, than in secondary valleys of surrounding mountains where the primary source of water was either a river or an irrigation stream. For Endamoeba histolytica the incidence tended to increase from upper to lower levels of the valley, in agreement with an expected increase in fecal pollution. Fluctuations in the incidence of E. coli and E. nana which were irrespective of valley levels, and a disproportionate increase in the rate of E. histolytica in the hill communities prompt the speculation that the several modes of protozoan transmission may not be equally effective for E. histolytica and the other amebas. Since cyst drying has been shown to be less damaging to E. coli and E. histolytica, the latter may be more dependent on water transmission. Although other factors such as direct and food handler transmission and flies may have contributed to the increased incidence of protozoa in hill villages, it is believed that water was the major factor of difference.

• 1.  Four hundred and twelve fecal specimens from two surveys were used to evaluate (a) the effect of adding antibiotics to the culture medium employed in the diagnosis of intestinal amebae and (b) cultivation as a diagnostic technique in comparison with other procedures performed on the same specimen. The cultivation routine included the examination of permanently stained films prepared from culture sediments preserved in PVA-fixative. This type of examination facilitated the identification of organisms and increased the number of infections found.
• 2.  The addition of small amounts of penicillin G sodium and streptomycin sulfate to LER medium significantly increased the number of infections of intestinal amebae found in both old, normally passed specimens (Survey I) and fresh, post-cathartic specimens (Survey II). In general, the individual species reacted similarly to the addition of the antibiotics.
• 3.  As a diagnostic technique, cultivation was ineffective with old, normally-passed specimens, but superior to the other techniques used (concentration and stained smears) when fresh, post-cathartic specimens were examined. These results indicate that cultivation would not be a worthwhile routine technique for laboratories that usually receive mailed specimens (for example, public health laboratories), but would be advisable in clinics and hospitals. When fresh specimens are available, it is believed that a good routine consists of a cultivation technique (including stained preparations) for the identification of trophozoites and a concentration technique for the recovery of cysts.

Examinations of wet mounts and iron hematoxylin stained sediments preserved in PVA-fixative from 878 diagnostic fecal cultures were made, and the results compared. Of a total of 391 infections found by the two examinations, 366 infections (or 94 per cent) were identified in the stained films as compared to 212 (or 56 per cent) identified in the wet mounts of the same cultures. The increased number was due (a) to the addition of infections found only in the stained films and (b) to the identification of infections seen but not identified in the wet mounts. The numbers of infections of all five species of amebae were increased to varying degrees.

The sediment from routine diagnostic fecal cultures for amebae can be fixed with PVA-fixative and stained by permanent staining techniques with good results. In order to reduce the work involved in the cultivation procedure, it is suggested that the preparation of stained smears be reserved for those cultures in which organisms are observed in wet mounts. In this study 94 per cent of the infections would have been identified by this limited number of examinations of stained slides (250 slides rather than 878).

Reviewing the history of the epidemics of dengue and yellow fever, little or no evidence can be found that these diseases coexist freely. In their history dengue and yellow fever seemed to display a tendency toward mutual exclusiveness, consistent with the geographical and experimental evidence.

A serologic study of twenty leptospiral isolates from Malaya, North Borneo and Thailand is reported. Initial serologic typing of these strains by means of the cross agglutination-lysis reactions revealed the presence of seven distinct antigenic leptospiral types. Subsequent antigenic analysis of representative strains indicated the presence in Malaya of L. pyrogenes, Salinem (4 human), L. mankarso (1 human), and an “incomplete” biotype of L. wolffi (2 human, 3 rodent), a “complete” biotype of L. grippotyphosa (1 rodent), L. schüffneri (1 rodent) and a new serotype strain (1 human). In addition L. mankarso was isolated from R. whiteheadi trapped in North Borneo, and L. autumnalis AB was isolated from the six members of the rodent genus Bandicoota, trapped in Thailand.

Classification of the leptospiral isolates based on a modified adoption of the proposed scheme of Wolff and Broom (1954) disclosed the presence of three hitherto undescribed antigenic types, a new serotype designated as L. malaya, an “incomplete” biotype of L. wolffi, designated as L. wolffi A, and a “complete” biotype of L. grippotyphosa designated as L. grippotyphosa AB.

The results of agglutinin absorption studies with the members of the pyrogenes, icterohemorrhagiae, hebdomidis, and grippotyphosa serogroups were consistent with the findings of other investigators on the inter-relationships among the serotype members of these respective groups.

Each of 19 patients undergoing the acute febrile phase of Carrión's disease received, in divided doses, approximately 17.0 gm. oral chloramphenicol in five days. After initial dosage with chloramphenicol, temperature usually returned to normal within 24 hours. A reticulocyte response averaging nine per cent (varying between 6.8% and 36%) was evident shortly after the beginning of chloramphenicol therapy. Although some coccoid forms of the bartonellae remained in the red cells, the bacillary form disappeared in 24 hours. Red cell count and red cell size were reestablished. Relapse was infrequent; when it occurred, further administration of chloramphenicol resulted in recovery.

Three of the patients were also infected with Salmonella; one of these died, the other two made a gradual recovery. Since Carrión's disease and a Salmonella infection are likely to co-exist, chloramphenicol is suggested as the drug of choice to combat both the bartonellosis and the complicating salmonellosis. Large doses of chloramphenicol had no depressing influence on blood formation.

A serological survey of antibodies to all three types of poliomyelitis virus has been carried out in an urban and semiurban population in French Morocco. The rates at which neutralizing antibodies and complement-fixing antibodies have been acquired by this population according to different age groups are herein reported.

Heavy infection and a rapid development of antibodies at an early age characterize the pattern obtained. The results indicate the presence of actively acquired neutralizing antibodies, and presumably immunity, to all three types of poliomyelitis virus in about 80 per cent of the population by the time children have reached 5 years of age. The percentages persist in all older age groups. Complement-fixing antibodies, on the other hand, are present largely in the juvenile population, and fall to low levels in those over 10 years of age. Since the complement fixing antibody in poliomyelitis is a transient one, this suggests that active infection is occurring only in young children in the Moroccan population.

As a control disease, presumably spread by human association, mumps was selected, and antibody patterns to mumps virus were determined. Results indicate that mumps infection also comes early to this population but in so far as a comparison is warranted, apparently not as early as does poliomyelitis virus infection.

The findings differ sharply from those which might be expected from a United States city studied at about the same latitude. Their interpretation has some bearing on the relationship between antibody and immunity in the infant, pointing to a close relationship between the two. The results also point to the fact that living conditions in this population are apparently particularly conducive to the spread of infantile infections with both poliomyelitis and mumps but particularly the former.

Collections of forest mosquitoes totaling 72,211 individuals were made on the ground and in the canopy during the rainy season of 1950 at 18 localities throughout the length of Panama and into Costa Rica, in seeking an explanation for the failure of sylvan yellow fever to appear west of the Canal Zone prior to that time.

It was found that the known South American vectors of the disease, Haemagogus spegazzinii falco and Aedes leucocelaenus clarki occurred sparingly west into Costa Rica, but the only station at which they were present in substantial numbers was one located in the well developed tropical rain forest of the Atlantic slope.

The vertical stratification of the mosquitoes taken in the forest is summarized for each species of which more than 15 individuals were taken. These data are of importance in assessing the possible role of each species in terms of its contact with the arboreal mammals which are the intermediate hosts of the yellow fever virus.

It is suggested that physiographic and meteorologic conditions in central Panama and the Canal Zone area produce a forest cover which is intermediate between tropical rain forest favorable for the production of substantial numbers of tree hole breeding vector mosquitoes, and tropical deciduous forest in which conditions are less favorable. It is further suggested that since conditions are marginal in this critical area, it would take a particularly favorable rainfall pattern to produce the mosquito population necessary to carry the virus across into the Atlantic side rain forest of western Panama as happened in 1949 and 1950.