Intestinal Capillariasis

Transcription

1 CLINICAL MICROBIOLOGY REVIEWS, Apr. 1992, p /92/ $02.00/0 Copyright O 1992, American Society for Microbiology Vol. 5, No. 2 Intestinal Capillariasis JOHN H. CROSSt U.S. Naval Medical Research Unit No. 2, Manila, Philippines INTRODUCTION... DESCRIPTION OF THE PARASITE. HISTORY... LIFE CYCLE OF THE PARASITE... CLINICAL PICTURE... symptoms... Pathology Diagnosis Treatment EPIDEMIOLOGY Distribution and Prevalence Transmission Control.129 REFERENCES. INTRODUCTION Although more than 250 Capillaria species have been found in fish, amphibians, reptiles, birds, and mammals, only 4 species have been found in humans: Capillaria hepatica, C. aerophila (Eucoleus aerophilus), C. plica, and C. philippinensis. Reports of human infections with C. hepatica, C. aerophila, and C. plica are rare, but reports of C. philippinensis infections are increasing and appear to be spreading geographically. C. philippinensis has been involved in epidemics and has been responsible for the death of people in the Philippine Islands and Thailand. DESCRIPTION OF THE PARASITE Capillarids are closely related to Trichuris and Trichinella species; all are members of the superfamily Trichinelloidea. The group is characterized by having a filamentous thin anterior end and a slightly thicker, and sometimes shorter, posterior end. The esophagus consists of a short muscular portion surrounded by rows of secretory cells called stichocytes. The entire esophageal structure is called a stichosome. The male worms may or may not have a single sheathed spicule. In the female, the vulva is located at the junction of the anterior and posterior ends. Chitwood et al. (6) described C. philippinensis in specimens collected at autopsy from the first person known to have the infection and in material obtained from several subsequent autopsies. Additional specimens were examined by other investigators, and the initial findings were confirmed. The parasite is very small: males range in length from 1.5 to 3.9 mm and in width from 3 to 5,um at the head, 23 to 28,um at the stichosome, and 18,um at the cloaca. The male spicule is 230 to 300,um long, and the unspined spicular sheath may extend to 440 p.m. The anus is subterminal, and the tail has ventrolateral expansions containing two pairs of papillae. Females are much longer than males, 2.3 to 5.3 mm, with widths of 5 to 8 p.m at the head, 25 p.m at the t Present address: Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD IA 129 widest part of the stichosome, 28 to 36 p.m at the vulva, and 29 to 47 pum postvulva. The vulva is located behind the esophagus, is salient, and is without a flap. The anus is subterminal. Figures 1 and 2 illustrate male and female worms, respectively, showing some of the features mentioned above. The female uterus contains numerous thickshelled eggs (Fig. 2), thin-shelled eggs with or without embryos (Fig. 2), or larvae (Fig. 3). Eggs found in feces are peanut shaped with a striated shell and inconspicuous flattened bipolar plugs, and they measure 36 to 45 by 20 pum (Fig. 4). HISTORY Although a number of Capillaria species are known to inhabit the intestinal tract of lower animals, human intestinal capillariasis was unknown until Chitwood et al. presented the initial case report at the First International Congress of Parasitology in Rome in The patient was a 29-year-old male schoolteacher from Northern Luzon in the Philippines. He had an intractable diarrhea for 3 weeks prior to admission to the Philippine General Hospital, Manila. He suffered from chronic alcoholism, recurrent ascites, emaciation, and cachexia and died a week after hospitalization. At autopsy, a large number of worms were recovered from the intestines, but the parasite was not identified to species at the time. In late 1966, a Catholic missionary priest in Tagudin Ilocos Sur, Central Luzon, notified authorities of an unusually large number of deaths due to a chronic gastroenteritis that had been occurring since 1965 in a village called Pudoc West. This village is approximately 150 km south of the area where the first case was seen. Upon investigation the Philippine Department of Health established that C. philippinensis was responsible for the illnesses. The parasitosis soon spread to other villages and towns, and by the end of 1967, more than 1,000 people had become infected and 77 had died. The people in the village of Pudoc West were superstitious and believed that they were all destined to die of the mysterious disease because of a curse placed on them by a mystical river god. Against the advice of the public health authorities now working in the area, they hired two witch doctors to exorcise the village. The witch doctors were

2 VOL. 5, 1992 INTESTINAL CAPILLARIASIS 121 SC Sp FIG. 1. Adult male C. philippinensis indicating spicule (Sp), extended spicular sheath (Ss), and stichocyte (Sc). Magnification, x32. retained until one of them died of intestinal capillariasis. Other beliefs and superstitions emerged during the epidemic until a cure and means of transmission were established (15). A few years after the Pudoc West outbreak, it was determined that during 1963 to 1965 a number of people had died of a chronic gastroenteritis in the area of Northern Luzon where the first patient lived. In 1965, the disease began to be seen in Pudoc West, and in the ensuing years infections were found in villages along the western and northern coasts of Central and Northern Luzon. LIFE CYCLE OF THE PARASITE Since C. philippinensis was a new human parasite, it was essential to obtain knowledge about every aspect of the Vu I it,. (r? Tk,4e.. SC Lv Eg, UT parasitosis. Clinical management and treatment regimens were established, pathophysiologic studies were done, and epidemiologic information was gathered. One of the most complex challenges, however, was to determine the means of transmission of the parasite and its life cycle. First, attempts were made to determine possible reservoir hosts for adult and larval stages of the parasite. The Ilocano populations of Northern Luzon have unique dietary habits, unlike those of other Filipino populations. These eating habits were considered when searching for a source of infection. More than 150,000 specimens of animal life were examined, and although adult Capillana worms were found, none were C. philippinensis. Capillaria larvae were also found, but species determination was not possible (15). FIG. 2. Adult female C. philippinensis indicating stichocyte (Sc), salient vulva (Vu), uterus (Ut), eggs (Eg) in the uterus, and thin-shelled eggs with larvae (Lv). Magnification, x32.

3 122 CROSS CLIN. MICROBIOL. REV. Lv Vu FIG. 3. Adult female C. philippinensis indicating salient vulva (Vu) and uterus filled with larvae (Lv). Magnification, x 160. Massive stool surveys were undertaken to detect asymptomatic infections and to determine whether a relationship existed between C. philippinensis and other intestinal parasites. More than 7,000 stool samples from 23 village populations were examined, but there was no correlation between C. philippinensis infection and other parasitic infections. Most people (94%) had 1 and, more often, 2 to as many as 10 different parasites by a single stool examination. Only 2% were passing C. philippinensis eggs, compared with 83% passing Trichuris trichiura eggs (12). While the above studies were under way, investigations were conducted to establish the life cycle in the laboratory. At that time the life histories of only a few Capillaria species were known. Some species had a direct egg-to-egg cycle whereas others had indirect cycles involving an intermediate host. Eggs isolated from patients were found to embryonate at ambient temperatures in 5 to 10 days. The eggs were given orally to all types of animals, even human volunteers, but did not hatch (9). The experiments continued, and eventually eggs were found to hatch in the intestines of freshwater and brackish-water fish from the lagoons in the endemic area. The eggs hatched within a few hours after ingestion, and the larvae increased in size from ,um to ,um after 3 weeks (Fig. 5). Several species of fish in the Philippines (8, 10) and other species in Thailand (4) were found to be susceptible to infection. In further studies, one species of fish (Hypseleotris bipartita) was found naturally infected with the larval stage of the parasite, which was recovered from the intestine. Larvae from fish were subsequently fed to monkeys (Macaca spp.), and patent infections developed (8). Monkeys tolerated the infections well and never manifested symptoms. A few of these infections remained patent for as long as 14 months. Three to four months after being given 30 to 50 larvae from fish, some monkeys were killed and 10,000 to 30,000 worms were recovered from their intestines. This confirmed the suspicion that autoinfection was part of the life cycle because large numbers of worms in all stages of development were found at autopsy. In addition, female worms are larviparous. Many other laboratory and wild animals were experimentally infected with larvae from fish. Some wild rats (Rattus spp.) and multimammate rats (Mastomys natalensis) developed transient infections, but Mongolian gerbils (Meriones unguiculatus) developed patent infections and died of overwhelming infections after 6 to 7 weeks. A series of experi- FIG. 4. Two eggs of C. philippinensis, two-cell stage. Note the flattened bipolar plugs and striations in the eggshell; they measure 36 to 45 by 20 p.m. Magnification, x 160.

4 VOL. S, 1992 INTESTINAL CAPILLARIASIS FIG. 5. Larva of C philippinensis from the intestines of a fish. Note the formation of stichocytes in the anterior end. Magnification, xloo. ments were subsequently carried out with the gerbil, and the unique life cycle of C. philippinensis was determined. When larvae from fish were administered by stomach tube to gerbils, the larvae developed into adult males and females in 10 to 11 days and female worms started to release first-stage larvae in 13 to 14 days. These larvae developed into adult males and females in 22 to 24 days, and the second-generation females began to release thick-shelled unembryonated eggs, which passed in the feces in 25 to 35 days postinfection. Most female worms at this time were oviparous, but a few female worms always produced larvae, an event that led to autoinfections and hyperinfections. In other studies only two larvae from fish were fed to gerbils, and on two occasions 2,520 and 5,353 worms in all stages were recovered from gerbils that died after 46 and 47 days. Other studies were done by administering three larvae from fish, and 852 to 5,253 worms were recovered (10). It was also established that female worms could switch from oviparous to larviparous reproduction when transferred from a necropsied infected gerbil to a clean gerbil. The larvae developed into adults and produced eggs that passed in the feces. In studies in Thailand (3) and Taiwan (11), fish-eating birds were infected with larvae from fish or were fed infected fish. It is now believed that fish-eating birds are natural hosts and that the cycle is a fish-bird life cycle. However, humans can become infected when they eat the tiny fish that are usually consumed by birds. One bird has been found naturally infected with the parasite in the Philippines. The proposed life cycle is presented in Fig. 6. CLINICAL PICTURE Few intestinal nematode infections actually cause disease that leads to death in their host. Most parasites live unmolested in the gut and at the same time do little to disturb their environment and the gracious host. C. philippinensis, however, is different; it always causes illness as far as we know, and, if the infection remains untreated, it leads to death. On numerous occasions we detected individuals passing eggs in their stools during surveys. Most were asymptomatic and would not report to the hospital for recommended treatment when told of their infections. Invariably, they developed symptoms as the worm population built up, and they then reported for treatment (17). Autointecton 3 weeks 4 FIG. 6. Proposed life cycle of C. philippinensis based on experimental infection in Mongolian gerbils. Reprinted from reference 14 with permission of the publisher. Symptoms The first patients seen in the endemic area with intestinal capillariasis had been suffering from abdominal pain, a gurgling stomach (borborygmus), and intermittent diarrhea for several weeks. They eventually had 8 to 10 voluminous stools daily and lost a considerable amount of body weight. Some suffered from malaise, anorexia, and vomiting. Studies by Whalen et al. (25) reported physical findings of muscle wasting and weakness, borborygmus, distant heart sounds, hypotension, gallop rhythm, pulsus alterans, abdominal distention and tenderness, edema, and hyporeflexia. There was no hepatosplenomegaly or jaundice. Laboratory findings showed severe protein-losing enteropathy, malabsorption of fats and sugars, decreased excretion of xylose, and low levels of potassium, sodium, calcium, carotene, and total protein in serum. There were usually high levels of immunoglobulin E (IgE) and diminished levels IgG, IgM, and IgA; several months after treatment, however, all immunoglobulin levels returned to normal (21). Patients ill for more than several months without treatment usually died either of the irreversible effects of the electrolyte loss resulting in heart failure or of septicemia due to a secondary bacterial infection. Patients seen in the endemic areas at present usually have mild symptoms of borborygmus, abdominal pain, diarrhea, and edema. After treatment, the symptoms disappear in a few days to a week and eggs and other stages of the parasite are no longer present in the stools. It is important that symptoms are recognized early and treatment initiated. One of the last patients to die of the infection had been misdiag-

5 124 CROSS CLIN. MICROBIOL. REV. FIG. 7. Human intestinal tissue at autopsy showing multiple histologic sections of C. philippinensis. Female worms with eggs in the uterus are visible. Magnification, x63. nosed at several hospitals as simply having gastroenteritis. By the time the correct diagnosis was made, it was too late to alter the course of his infection. Pathology Fewer than 15 autopsies have been done on Filipinos who died of intestinal capillariasis (5, 18). Their bodies were emaciated, dehydrated, and pale. Serous fluid was found in the peritoneal and pleural cavities. The heart weights were within normal limits with minimal pericardial fat. The lungs were congested. Bacteria (Micrococcus pyogenes [since renamed Streptococcus pyogenes] and Klebsiella pneumoniae) were cultured from the lungs of two patients. The splenic white pulp was conspicuous because of prominent malpighian corpuscles, and the livers were yellowish. The kidneys were reduced in weight, and there was cerebral vascular congestion. Most pathologic changes were found in the small intestine, especially the jejunum. Numerous C. philippinensis worms in all stages were found in the lumen (Fig. 7 through 9) and in the intestinal mucosa (Fig. 10 and 11). In 1 liter of bowel fluid from one autopsy an estimated 200,000 worms were recovered. Although most worms are found in the jejunum, some are found throughout the digestive tract, probably as a result of postmortem migration. The parasite was found once in extraintestinal tissue, in a section of liver (18). Histologic findings were fatty metamorphosis of the liver and vacuolization of the cytoplasm of renal proximal convoluted tubular lining cells. Hemoglobin pigments were also found in the tubules of some patients. Vacuolization of myocardial cells and concentrations of lipochrome pigment in the myocardium were also seen. In the intestines, the crypts of Lieberkuhn were atrophied and often contained parasites (Fig. 10 and 11) and cellular debris. The intestine FIG. 8. First-stage larva of C. philippinensis recovered from the human intestine at autopsy. Magnification, x 160.

6 VOL. 5, 1992 a *. ;>' ; * r t,. 't. -k'~ S k..**v 'Stp.;.A 41 INTESTINAL CAPILLARIASIS 125 W.h FIG. 9. Third-stage larva of C. philippinensis recovered from the human intestine at autopsy. Magnification, x63. also showed flattened denuded villi and dilated mucosal glands, and the lamina propria was infiltrated with plasma cells, lymphocytes, macrophages, and neutrophils. Electron micrographs of biopsied jejunal tissue showed loss of adhesion specialization and widespread separation of epithelial cells. In gerbil tissue taken at necropsy and studied by electron microscopy, the following changes were seen: (i) microulcers in the epithelium (Fig. 12), (ii) compressive degeneration and mechanical compression of cells, and (iii) homogeneous material at the anterior end of the worm (Fig. 13). These ulcerative and degenerative lesions in the intes- FIG. 10. Female Magnification, x63. x A S t.o Si tinal mucosa may account in part for the malabsorption with loss of fluids, protein, and electrolytes (23). Diagnosis Patients presenting with borborygmus, abdominal pain, diarrhea, and weight loss are usually passing eggs (Fig. 4), larvae (Fig. 8 and 9), and/or adult worms (Fig. 1 through 3) in their feces. Larvae found in the feces are in all stages of development and are difficult to identify as C. philippinensis (Fig. 8 and 9), but adult males and females have character-.;~~i5.:f4.;,.. r'- j.,,t*%g,asj ''/I t IY~~~~~~~~~~~~~~I -,'***-i '_. o5 phi:pien4 14 (Cp) in (n 0- C. philippinensis (Cp) in crypts (Cr) of human intestinal tissue at autopsy. Note the larva (Lv) in the uterus.

7 126 CROSS CLIN. MICROBIOL. REV. t) 4,~~~~~~~~0 +'ff!, *,' ;'I,- L 3 : t2 < W..: *s 44 i / S.~~~41b w iase' 2; -~~~~~~ ~~~~~a~w *Cp -. ' & i st i 9 > ' s ps s FIG. 11. Sections of C philippinensis (Cp) in human intestinal tissue at autopsy. Magnification, x 160. istic features (Fig. 1 through 3). An inexperienced observer may confuse the eggs with those of T. trichiura, which are larger (50 to 54 by 22 to 23,um) and barrel shaped, with prominent mucoid bipolar plugs. Figure 14 shows C. philippinensis and T. tnichiura eggs for comparison. Multiple stools may have to be examined in some patients. The parasite may also be found in material obtained by smallintestinal aspiration or biopsy. If intestinal capillariasis is suspected but not parasitologically confirmed, the patient should be given an anthelminthic agent. The parasite usually passes in the feces for a few days following treatment. Serologic tests have been evaluated but are considered unreliable (2, 16) and not necessary since eggs and worms are usually found in stool specimens. Treatment In the early days of the Philippine epidemic, all available anthelminthic agents were given to infected persons; however, thiabendazole in dosages of 25 mg/kg/day or 1 g/day for 30 days eventually became the drug of choice. Most patients responded well, but there were side effects and many relapses. In the second and third years of the epidemic, there were more relapse cases than new infections (22). One FIG. 12. Electron-microscopic view of a cross-section of C. philippinensis obtained from gerbil jejunum. Note the cuticular pore (CP) of the worm and dissolution of the plasma membrane and cytoplasmic organelles of the epithelial cell (arrow) opposite the cuticular pore. Magnification, x 12,500. Reprinted from reference 23 with permission of the publisher.

8 VOL. S, 1992 INTESTINAL CAPILLARIASIS 127 FIG. 13. Electron-microscopic view of the penetrating site of the parasite (P) in gerbil jejunal epithelium. Note the electron-dense homogeneous material (arrow) at the anterior end of the parasite in connection with two large vesicles (V) at both sides of the worm. The basal lamina (BL) below the oral tip of the nematode appears deteriorated. Epithelial cells (EC) at the right side are compressed with increased compactness of the cytoplasmic organelles. A lymphocyte (L) is seen between the cells. Magnification, x 7,500. Reprinted from reference 23 with permission of the publisher. - ; >, r* 4F ffb VI W3-a-ok 1%.-l- i " -( patient had 15 relapses in a 12-year period (1). Patients with severe disease are given electrolyte replacement therapy, an antidiarrheal agent, and a high-protein diet. Mebendazole at 400 mg/day in two divided doses for 20 days soon replaced thiabendazole. In patients with relapses the drug was given for 30 days and there were few subsequent relapses. Albendazole is presently the drug of choice in a dose similar to that for mebendazole, but is administered only for 10 days. Treatment for less than 10 days has resulted in relapses in some patients. It is believed that relapses result from the inability of thiabendazole and mebendazole to affect the larval stages. The adults are affected, and as the larvae mature, they are susceptible to the drugs. Albendazole, on the other hand, appears to act on the larvae as well as the adults. After therapy with most drugs the parasites are not found in the feces after 4 days. If treatment stops at this time, the parasite and eggs will reappear after 20 to 30 days. EPIDEMIOLOGY Distribution and Prevalence From 1967 to the end of 1990, 1,884 confirmed cases of intestinal capillariasis were documented and 110 people died (Fig. 15). Through the years, twice as many males, mostly middle-aged, as females have become infected (Fig. 16). A few infections were reported elsewhere, and in the early 1980s a new endemic area was identified in Southern Leyte 0 i-t.1 i, *,J.l I I b- Ar. 40k4 11 'O -t- a W. ICp.> a 11 p Cp FIG. 14. Eggs of C. philippinensis (Cp) compared with an egg of T. trichiura (Tt). Magnification, x 160.

9 128 CROSS CLIN. MICROBIOL. REV U 1000 Cl) C) Z 100 IL I 60- co D 30- Z YEAR FIG Intestinal capillariasis cases (total, 1,884) and deaths (total, 110) recorded in Northern Luzon in the Philippines from 1967 through in the Central Philippines. In a preliminary stool survey, 14% of 362 specimens contained C. philippinensis eggs, larvae, and adults (13). As far as we know, intestinal capillariasis was first reported from Bacarra, Ilocos Norte, in the Philippines. The first epidemic occurred in Pudoc West in Ilocos Sur, and infections were subsequently seen in persons from provinces up and down the Philippine coast along the South China Sea. A focus of infection was found near a U.S. Naval Base in Zambalas (24), and the subsequent epidemic occurred in Southern Leyte. Only sporadic cases are seen today in Northern Luzon. Capillariasis philippinensis was first recognized in Thailand in 1973 (20), and additional cases were reported thereafter. The disease seems to be widespread in Thailand, with cases being seen at many medical centers in the north and northwest and around Bangkok. No effort is being made to document the infections, however. An epidemic is known to have occurred in 1981; more than 100 persons acquired the disease and 9 died of the parasitosis (15). C. philippinensis infections are now being seen in Japan, with three cases reported, followed recently by a fourth (la) % Northem Luzon, Philippines February December 1990 X 300- LU 14% U 1334 Males 250- (70%) E 550 Females (30%) C ) = LLL 11%. LL % Northern Luzon, Philippines February December F11 Cases Deaths LI L[HUH WII Iran and Taiwan have each had one case (7), and Egyptian workers have documented two cases (19). Transmission The eating habits of people are responsible for the transmission of human C. philippinensis. Populations in the Philippines where intestinal capillariasis occurs have unique eating habits in that they prefer to eat a variety of foods uncooked. The Ilocanos of Northern Luzon relish raw animal organs, and intestinal juices from animals are used to season rice and other foodstuffs. They also eat raw crabs, snails, clams, shrimp, squid, goat, and water buffalo meat and a variety of small freshwater and brackish-water fish abundant in lagoons along the coast. The fish are too small to eviscerate and so are eaten whole. The people especially like to eat female bagsit (Hypseleotris bipartita) (Fig. 17) when filled with roe. Thai populations also enjoy eating small freshwater fish and crabs uncooked. In other countries reporting the infections, consumption of raw fish has been associated with most infections. Since a number of species of freshwater fish have been experimentally infected with C. philippinensis and some fish in the Philippines were found naturally infected with larval forms of the parasite (15), it is believed that the means of MpII-, % AGE GROUP COMBINED 7%o 14% 23% 19% 17% 12%h 6% 1% 1% FIG. 16. Intestinal capillariasis cases (1,884) reported in Northern Luzon in the Philippines by age and sex from 1967 through FIG. 17. Bagsit (H. bipartita), a fish often eaten uncooked, especially when gravid, by Ilocano populations of Northern Luzon in the Philippines. The fish is usually only 2 to 3 in. (5.1 to 7.6 cm) in length. This species was found naturally infected. When these fish were fed to Mongolian gerbils, patent infections developed and the gerbils died.

10 VOL. 5, 1992 transmission of capillariasis philippinensis is by eating uncooked fish. The parasite has not been found in any area where the populations do not eat raw fish. Several species of fish-eating birds have now been experimentally infected with the parasite (3, 11), and one bird (Ixobrychus spp.) has been found naturally infected in the Philippines. Birds, especially migratory fish-eating birds, are considered potential natural hosts, and their migratory habits are considered responsible for dissemination of the parasite to widely separated parts of the world (7). Bird droppings along the flyways could easily disperse the eggs into water bodies, where fish become infected. Birds, as well as humans, eating such fish would subsequently become infected. Control Sanitation in rural areas of the Philippines and Thailand is considered poor. There is indiscriminate defecation, and although indoor toilet facilities may be available, they may not be fully used. During the epidemic in Pudoc West in the Philippines, bed sheets soiled with feces from patients were usually washed in the lagoons, thus depositing eggs into the water and exposing the fish to infection. This practice may be the reason for more than 200 cases of intestinal capillariasis occurring in the village. Drinking water comes from wells and other natural sources and is rarely boiled or chemically treated. The people like to eat animals raw, and when asked why they do it, they explain that their ancestors did it, that it is a habit, and that in their opinion raw food is more nutritious. Control of this parasitosis is simple; it consists of not eating raw fish. This habit is difficult to end when it has been practiced for generations. Educational programs warning of the dangers associated with eating raw fish have been of little help. Cooking the fish for a short time would be sufficient to kill larvae in the intestines, but most people prefer the fish raw. Early diagnosis and treatment are recommended to prevent serious disease and death. Early treatment with mebendazole or albendazole has been very effective, and deaths are now rare. Infections continue to be reported sporadically in the Philippines and Thailand, and in the future the disease will very probably continue to be reported from Japan and Egypt and possibly other areas of the world. REFERENCES 1. Alcantara, A. K., C. V. Uylangco, and J. H. Cross An obstinate case of intestinal capillariasis. Southeast Asian J. Trop. Med. Public Health 16: la.ando, K Personal communication. 2. Banzon, T. C., R. M. Lewert, and M. G. Yogore Serology of Capillaria philippinensis infection: reactivity of human sera to antigens prepared from Capillaria obsignata and other helminths. Am. J. Trop. Med. Hyg. 24: Bhaibulaya, M., and S. Indra-Ngarm Amaurornis phoenicurus and Ardeola bacchus as experimental definitive hosts for Capillaria philippinensis in Thailand. Int. J. Parasitol. 9: Bhaibulaya, M., S. Indra-Ngarm, and M. Anathapruit Freshwater fishes of Thailand as experimental intermediate host for Capillaria philippinensis. Int. J. Parasitol. 9: Canlas, B. C., B. D. Cabrera, and U. Davis Human INTESTINAL CAPILLARIASIS 129 intestinal capillariasis. II. Pathological features. Acta Med. Philipp. 4: Chitwood, M. B., C. Valasquez, and N. G. Salazar Capillaria philippinensis sp. n. (Nematoda: Trichinellida) from intestine of man in the Philippines. J. Parasitol. 54: Cross, J. H Intestinal capillariasis. Parasitol. Today 6: Cross, J. H., T. C. Banzon, M. D. Clarke, V. Basaca-Sevilla, R. H. Watten, and J. J. Dizon Studies on the experimental transmission of Capillaria philippinensis in monkeys. Trans. R. Soc. Trop. Med. Hyg. 66: Cross, J. H., T. C. Banzon, K. D. Murrell, R. H. Watten, and J. H. Dizon A new epidemic diarrheal disease caused by the nematode, Capillariaphilippinensis. Ind. Trop. Health 7: Cross, J. H., T. C. Banzon, and C. M. Singson Further studies on Capillaniaphilippinensis: development of the parasite in the Mongolian gerbil. J. Parasitol. 64: Cross, J. H., and V. Basaca-Sevilla Experimental transmission of Capillania philippinensis to birds. Trans. R. Soc. Trop. Med. Hyg. 77: Cross, J. H., and V. Basaca-Sevilla Biomedical surveys in the Philippines. NAMRU-2 SP47: Cross, J. H., and V. Basaca-Sevilla Intestinal capillariasis-current concepts, laboratory diagnosis and treatment. Asian J. Clin. Sci. 7: Cross, J. H., and V. Basaca-Sevilla Intestinal capillariasis. Prog. Clin. Parasitol. 1: Cross, J. H., and M. Bhaibulaya Intestinal capillariasis in the Philippines and Thailand, pp In N. Croll and J. H. Cross (ed.), Human ecology and infectious diseases. Academic Press, Inc., New York. 16. Cross, J. H., and J. C. H. Chi The ELISA test in the detection of antibodies to some parasitic diseases in Asia, p In Current concepts in the diagnosis and treatment of parasitic and other tropical diseases in Southeast Asia. Proc. 18th SEAMEO TROPMED Semin., Kuala Lumpur, 2 to 5 August Detels, R., L. Gutman, J. Jaramillo, E. Zerrudo, T. Banzon, J. Valera, K. D. Murrell, J. H. Cross, and J. J. Dizon An epidemic of human intestinal capillariasis: a study in a barrio in North Luzon. Am. J. Trop. Med. Hyg. 18: Fresh, J. W., J. H. Cross, V. Reyes, G. E. Whalen, C. V. Uylangco, and J. J. Dizon Necropsy findings in intestinal capillariasis. Am. J. Trop. Med. Hyg. 21: Mansour, N. S., M. H. Anis, and E. M. Mikhail Human intestinal capillariasis in Egypt. Trans. R. Soc. Med. Hyg. 84: Pradatsundarasar, A., K. Pecharanond, C. Chintanawongs, and P. Ungthavorn The first case of intestinal capillariasis in Thailand. Southeast Asian J. Trop. Med. Public Health 4: Rosenberg, E. B., G. E. Whalen, H. Bennich, and S. G. 0. Johansson Increased circulating IgE in a new parasitic disease-human intestinal capillariasis. N. Engl. J. Med. 283: Singson, C. N Recurrences in human intestinal capillariasis. Philipp. J. Microbiol. Infect. Dis. 3: Sun, S. C., J. H. Cross, H. S. Berg, S. L. Kau, C. Singson, T. Banzon, and R. H. Watten Ultrastructural studies of intestinal capillariasis Capillana philippinensis in human and gerbil hosts. Southeast Asian J. Trop. Med. Public Health 5: Tidball, J. S., J. P. Aguas, and J. W. Aldis A new concentration of human intestinal capillariasis on western Luzon. Southeast Asian J. Trop. Med. Public Health 9: Whalen, G. E., E. B. Rosenberg, G. T. Strickland, R. A. Gutman, J. H. Cross, R. N. Watten, C. Uylangco, and J. J. Dizon Intestinal capillariasis-a new disease in man. Lancet i:13-16.