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Home , Ancylostoma braziliense, Ancylostoma caninum, Ascariasis, Ascaris lumbricoides, Capillaria hepatica, Cutaneous larva migrans

Visceral and Cutaneous Migrans PAUL C. BEAVER, Ph.D.

AMONG in general there is a In the development of our concepts of larva II. wide variety of parasitic in migrans there have been four major steps. The which larval stages migrate through and some¬ first, of course, was the discovery by Kirby- times later reside in the tissues of the with¬ Smith and his associates some 30 years ago of out developing into fully mature adults. When larvae in the of patients with such parasites are found in hosts, the creeping eruption in Jacksonville, Fla. (6). may be referred to as larva migrans This was followed immediately by experi¬ although definition of this term is becoming mental proof by numerous workers that the increasingly difficult. The organisms impli¬ larvae of A. braziliense readily penetrate the cated in infections of this type include certain human skin and produce severe, typical creep¬ of , , and nema¬ ing eruption. todes, but more especially the . From a practical point of view these demon¬ As generally used, the term larva migrans strations were perhaps too conclusive in that refers particularly to the migration of and they encouraged the impression that A. brazil¬ larvae in the human skin (cu¬ iense was the only cause of creeping eruption, taneous larva migrans or creeping eruption) and detracted from equally conclusive demon¬ and the migration of dog and cat ascarids in strations that other species of nematode larvae the viscera (). In a still have the ability to produce similarly the pro¬ more restricted sense, the terms cutaneous larva gressive linear lesions characteristic of creep¬ migrans and visceral larva migrans are some¬ ing eruption. While in the initial studies by times used to denote the formation, of lesions Kirby-Smith it was possible to demonstrate due to a particular species of larva known or larvae in 10 percent of the skin biopsies from in¬ presumed to be the one most commonly in¬ dividuals with creeping eruption, no sponta¬ volved: braziliense in the skin, neous case of has yet and in the viscera. This usage been given a specific etiological diagnosis; that of the terms is incorrect, however, since, as pre¬ is, no larvae have been identified in human skin. viously emphasized, the character and location For many years after it was shown that nema¬ of the lesions and the resultant symptoms are tode larvae cause creeping eruption it was as¬ unreliable clues in the specific identification of sumed that the apparently aimless migration the causative organisms (1). was due to abnormal host-parasite relationships and that the larvae eventually perished and of Development Concepts Dr. Beaver is professor of , department The various groups and species of in¬ of and public health, Tulane Uni¬ volved in the larva migrans type of infection, versity School of Medicine, New Orleans, La. This the clinical features of the caused by paper was presented at the Communicable them, and certain biological aspects of the host- Center's Conference for Teachers of Veterinary Pub¬ parasite relationships have been discussed in lic Health and Preventive Medicine, and Public a number of recent reports and reviews (2-5). Health Workers, Atlanta, Ga., June 12-18,1958.

328 Public Health Reports were destroyed in the skin. Two significant mals have provided more interesting facts early observations argued against that view. about T. canis as a cause of the visceral type of Wright and Gold's finding of pulmonary infil¬ larva migrans than can be mentioned here. trations during or following the active phase Briefly, it has been established that infection of creeping eruption suggested that at least is acquired by ingesting previously con¬ some of the larvae succeeded in making the taminated by infected . passed in normal migration to the (7). It was also the , under favorable conditions in the soil, noted, however, that the pulmonary infiltra¬ become infective in 2 to 3 weeks, containing tions could have resulted from the larvae with¬ second-stage larvae which, when taken into the out their having left the skin. Evidence of a intestine of a child, erupt from the , pene¬ more convincing nature was provided by the re¬ trate the intestinal wall, and soon reach the port of an authenticated intestinal infection of . A majority of the larvae may remain in A. braziliense in a boy in Texas (8). If adults the liver but others pass on to the lungs and to could be found in the intestine, the larvae must other parts of the body. Larvae have been have migrated from the skin through the lungs found in nearly all organs. It is of chief inter¬ enroute to the intestine. That record is no est that a high proportion of them invade the longer accepted, however, and the reports of in¬ central nervous system and a considerable num¬ testinal infections of A. braziliense in man in ber have been found in the . The tragic other parts of the world have likewise been ren¬ consequence of invasion of the eye is the devel¬ dered doubtful by the observations that a mor¬ opment of a lesion which by its resemblance phologically very similar species, Ancylostoma to retinoblastoma prompts the unnecessary re¬ ceylonicum, formerly regarded as a synonym of moval of that vital . A. braziliense, is a valid species (9). An obser¬ Although most of the larvae eventually come vation by Muhleisen was, therefore, of special to rest in one location and stimulate fibrous en¬ significance (10). For a period of 24 days he capsulation, there is a period of at least several found large numbers of larvae in the sputum of weeks during which they move about in the tis¬ a man with severe and extensive skin lesions, sues of the visceral organs in much the same leaving no doubt about migration from the skin manner as hookworm larvae migrate in the to the lungs. Unfortunately the larvae were skin, leaving in their wake long trails of in¬ not identified, but it was determined without flammatory and eosinophilic granulomatous re¬ any doubt that a mature intestinal infection did actions. not develop in this case. Thus in comparison with their microscopic size the wandering larvae produce large and ex¬ tensive lesions that can be seen with the Second readily Step unaided eye in and on the surface of the liver The second major event in the study of larva and, at times, in other organs, especially the migrans came in 1952 with the discovery and brain. This is the type of infection now called identification of T. canis larvae in liver biopsies visceral larva migrans. Its most prominent from children with a common disease which up clinical feature is high, stable, and persistent, to that time had been given a number of dif¬ , not uncommonly reaching levels ferent names but was of unknown etiology suggestive of eosinophilic leukemia. Less out¬ (11). This was followed a year later by an standing and less constant features are enlarge¬ experimental demonstration of the etiological ment of the liver, hyperglobulinemia, intermit¬ role of T. canis (12) and by numerous confirm¬ tent , infiltrations of the lungs, neurologi¬ atory reports indicating that this common as- cal symptoms, and deviations in behavior. carid of dogs is responsible for much illness in Thus far T. canis is the only species of larva children here and in other parts of the world identified in cases of visceral larva migrans. and that it apparently is an occasional cause of However, there is a good experimental and epi¬ death (13). demiological basis for suspecting other species Biopsy and studies in children, and to be similarly involved. , as various types of studies in experimental ani¬ common or more so in as T. canis is in

Vol. 74, No. 4, April 1959 329 dogs, should occasionally reach the tissues of may have acquired their ascarid and perhaps children. In one instance a larva in a child's some of their hookworm infections not directly liver has been questionably identified as T. from the soil but indirectly by eating other cati (H). mammals which by feeding on the ground had Greatest anticipation of early incrimination earlier picked up the infective stages, pre¬ is with . This is served or further incubated them in their tis¬ more common in dogs than T. canis, and occurs sues, and passed them on to their predators. in cats as well as dogs. Whereas T. canis is Experimentally, T. canis, T. cati, and A. cani¬ relatively uncommon in older dogs and is es¬ num can be transferred to their final host by pecially uncommon in sexually mature females, first inoculating mice or other small mammals A. caninum is found in both dogs and cats at all which are then after several days, weeks, or ages. Both parasites take full advantage of months fed to dogs or cats. The significance prenatal infection in maintaining a high level of such observations is immediately apparent. of endemicity and both are known to persist They point out that our previous interpreta¬ in the tissue of experimental animals for more tion of larva migrans caused by these species than a year. There is no apparent reason why was essentially incorrect. The migration and the larvae of A. caninum should not be found persistence without development in human tis¬ in the tissues of children along with the Toxo¬ sues are not, as we had supposed, basically due cara species. However, further studies may to an abnormal host relationship. We may still bring to light an explanation which is pres¬ regard man as an abnormal host for the adult ently not apparent. Larvae entering the body stage, and an unnatural host for the larvae in through the skin are less apt to be found in the that he provides no advantage for the parasite liver and it is probable that A. caninum larvae as a species, but the behavior of the larvae in are much less frequently ingested than the eggs man being the same as in natural transport of Toxocara and some of the other helminths. hosts apparently is not abnormal. It is then The searching of liver biopsies for Toxocara to be expected that any of the larval stages of larvae has in recent years uncovered three cases nematode parasites of wild or domesticated of hepatica which formerly was carnivorous animals adapted to the use of found only at autopsy and was thought to be mammalian intermediate or transport hosts may rare in man. It is hoped that when nematode grasp the opportunity to enter the tissues of larvae are encountered in the examination of human hosts and await, unsuccessfully of human tissues it will not be assumed on cir¬ course, the transfer to a predator final host. cumstantial evidence that they are any particu¬ It is obvious from these remarks that detailed lar species but rather will be identified on the studies on the life cycles of all worm parasites basis of characteristic morphology. of animals having contact with have great usefulness in the study of larva migrans Third Step and other zoonotic helminthiases. The third notable contribution to our knowl¬ Fourth Step edge of larva migrans came from a series of studies on the basic life cycle patterns among The fourth major advance in larva migrans the ascarids. Sprent (15) summarized these research was Nichols' demonstration of the studies and pointed out that while infections feasibility of identifying nematode larvae in by some and perhaps most of those species microsections of tissues (16,17). These classic adapted to carnivorous land mammals can be morphological studies, while limited to only a transferred from host to host in the same man¬ half dozen species considered most likely to be ner as lumbricoides, that is, by inges¬ encountered in human tissues, left no doubt that tion of infective eggs in contaminated soil, the descriptions of these and other species could be usual pattern under natural conditions,includes sufficiently detailed to permit reliable identifica¬ intermediate or transport hosts. tion often when only fragments of the larvae Originally our domesticated dogs and cats are available for study. The interpretation, 330 Public Health Reports prevention, and effective control of any para¬ Ehrenford has given at least a partial answer sitic disease are, of course, dependent upon the to one of the first and most significant questions accurate identification of the organism which asked about T. cards. Kecognizing that pups causes it. To make this possible, additional are more often infected than adult dogs the studies such as Nichols' are needed. question is often raised as to the actual risk with older Ehrenford's answer is that Research on Prevalence dogs. the risk depends upon the sex of the dog. Males Inasmuch as public health programs place are about as frequently infected as pups but the strong emphasis on the reliable determination incidence among females is lower at all ages of disease prevalence and on the development of and is markedly lower in the mature adult. In preventive measures, we should mention here Indiana and adjacent States less than 5 percent two additional phases of research in which re¬ of mature females were found to be infected, cent studies show promise of providing im¬ while almost a third of the mature males were portant, useful information. passing Toxocara eggs that might eventually Thus far it has not been possible to get a be the cause of illness in children. These data clear picture of either the extent or the prev¬ were obtained from stray, uncared for, un¬ alence of visceral larva migrans. Originally, wanted dogs, as has been the case in almost all diagnosis was based on liver biopsies taken by published surveys. laparotomy. This procedure is too hazardous Studies in New Orleans indicate that al¬ and expensive to be used routinely. Further¬ though the rate of infection among well cared more, no specific therapy is available, and usu¬ for dogs is relatively much lower, it still is ally when additional infection can be prevented, disturbingly high. Among 171 fresh dog stools the prognosis is favorable. It is understand¬ collected along the sidewalks in front of houses able, therefore, that a clinical diagnosis, un¬ of perhaps the most -minded, hy¬ confirmed by actual identification of the causa¬ giene-conscious, and economically most favored tive organism, is relied upon inthe management families in the city, 7 percent contained T. cams of most cases. It is equally understandable that eggs; hookworm eggs were found in 51 percent, unconfirmed clinical diagnoses are not really and in 25 percent. Almost all of these satisfactory. stools were judged to have come from adult In view of these circumstances, it is of great dogs. interest that promising and already somewhat Also in New Orleans, among 103 immature useful serologic techniques of diagnosis are and 222 mature dogs brought to veterinarians being developed by Sadun and associates (18), for various services, all relatively expensive Kagan (19), and Jung and Pacheco (20). The (indicating the owners' concern for their well- fault in serodiagnostic methods has been their being) , Toxocara was found in approximately lack of specificity due to cross-reacting - 15 percent of the young dogs and 3 percent of systems among related worms. By the older ones (23). Kelatively few of the fractionation and purification of , cross- dogs of either age group were presented spe¬ absorption of , and application of the cifically for treatment. Nearly recently developed hemagglutination and floc¬ half of them harbored and one- culation tests apparently reliable diagnoses are fifth had Trichuris infections. now being obtained. With the recognition that dog and cat para¬ Conclusion sites cause obscure, serious disease in humans, surveys to determine the geographic distribu¬ There is much needed information to be de¬ tion and prevalence of individual species have rived from good surveys and epidemiological taken on new significance. Among the first to studies of intestinal parasites of dogs and cats. recognize this and to carry out a thorough and To be of greatest usefulness such studies should meaningful survey of dog parasites were Don¬ .be carried out with the same careful prepara¬ aldson and his associates (21) and Ehrenford tion and epidemiological forethought and pur¬ (22). pose as would be acceptable in a study of hu-

Vol. 74, No. 4, April 1959 331 man disease. In fact such studies can be distribution of Tococoara larvae in the tissues regarded as being directly concerned with hu- of children and mice. Pediatrics 12: 491 (1953). man disease. We are only beginning to appre- (13) Dent, J., Nichols, R., Beaver, P., Carrera, G., and ciate the importance of including household Staggers, R.: Visceral larva migrans: with a pets in the total picture of the family's and case report. Am. J. Path. 32: 777 (1956). the public's health. (14) Karpinski, F. E:., Everts-Suarez, E. A., and Sawitz, W. G.: Larval granulomatosis (visceral larva migrans). Am. J. Dis. Child. 92: 34 REFERENCES (1956). (1) Beaver, P.: Larva migrans. A review. Exp. (15) Sprent, J. F. A.: The life cycles of nematodes Parasitol. 5: 587 (1956). in the family Blanchard 1896. J. (2) Beaver, P.: Parasitic diseases of animals and Parasitol. 40: 608 (1954). their relation to public health. Vet. Med. 49: (16) Nichols, R. L.: The etiology of visceral larva mi- 199 (1954). grans. I. Diagnostic morphology of infective (8) Beaver, P.: Wandering nematodes as a cause of second-stage Toxocara larvae. J. Parasitol. disability and diseases. Am. J. Trop. Med. & 42: 349 (1956). Hyg. 6: 433 (1957). (17) Nichols, R. L.: The etiology of visceral larva (4) Beaver, P.: parasites and human dis- migrans. II. Comparative larval morphology eases. Pediatrics 22: 380 (1958). of Ascari8 lumbricoide8, Necator amerioanus, (5) Platou, R. V., and Beaver, P.: Visceral larva Strongyloides 8tercoralis and Aaneyo8toma migrans. Acta. Paediat. 46: 64 (1957). caninum. J. Parasitol. 42: 363 (1956). (6) Kirby-Smith, J. L., Dove, W., and White, G. F.: (18) Sadun, E. H., Norman, L., and Allain, D.: The Creeping eruption. Arch. Dermat. & Syph. 13: detection of antibodies to infection with the 137 (1926). nematode, ToGcocara cani8, a causative agent of (7) Wright, D. O., and Gold, E. M.: LUfflers syndrome visceral larva migrans. Am. J. Trop. Med. & associated with creeping eruption (cutaneous Hyg. 6: 562 (1957). ). Report of 26 cases. Arch. (19) Kagan, I. G.: Serum-agar double diffusion studies Int. Med. 78: 303 (1946). with ascaris antigen. J. Infect. Dis. 101: 11 (8) Dove, W. E.: An intestinal infection of Ancylos- (1957). toma brazilien8e in a boy and skin lesions pro- (20) Jung, R. C., and Pacheco, G.: Relationship of duced with larvae from this strain. J. Para- clinical features to immunologic reactions in sitol. 15: 136 (1928). visceral larva migrans (abstract). Am. J. (9) Beaver, P.: The record of Ancylostoma brazi- Trop. Med. & Hyg. 7: 256 (1958). liense as an intestinal parasite of man in North (21) Donaldson, A., Steele, J., and Scatterday, J.: America. Am. J. Trop. Med. & Hyg. 5: 587 Creeping eruption in the Southeastern United (1956). States. Am. Vet. M. A., Proc. 87th Ann. Meet., (10) Muhleisen, J. P.: Demonstration of pulmonary p. 83, 1950. migration of the causative organism of creep- (22) Ehrenford, F. A.: Canine as a source ing eruption. Ann. Int. Med. 38: 395 (1953). of visceral larva migrans, a . Am. J. (11) Beaver, P., Snyder, H., Carrera, G., Dent, J., and Trop. Med. & Hyg. 6: 166 (1957). Lafferty, J.: Chronic eosinophilia due to vis- (23) Vaughn, J. B.: The prevalence of Tococara canis ceral larva migrans; report of three cases. infection in dogs admitted to four veterinary Pediatrics 9: 7 (1952). hospitals in New Orleans, Louisiana. In (12) Smith, M. H. D., and Beaver, P.: Persistence and press.

Second National Conference on World Health The Second National Conference on World Health will be held in Washing- ton, D.C., May 7-9, 1959, under the sponsorship of the National Citizens Com- mittee for the World Health Organization. Conference chairman will be Dr. Milton S. Eisenhower, president of the Johns Hopkins University. Topics in- clude prospects for the International Health Year; health and population changes; health and the American image abroad; and training and exchange programs for public health personnel.

332 Public Health Reports