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Parasitic diseases. Other roundworms. Trichuris, hookworm, and Strongyloides.

Trichuriasis may be asymptomatic or, in heavy infection, lead to profuse, bloody diarrhea and rectal prolapse. Diagnosis is made by finding the distinctive barrel shaped eggs in the stool or in the heavily infested patient, by anoscopy and identification of worms attached to reddened and ulcerated rectal mucosa. Mebendazole is the drug of choice in treatment. Capillariasis, a parasitic infection encountered mainly in the Philippine Islands, is of interest in that the eggs may be confused with the eggs of trichuris. Hookworm disease is generally asymptomatic, but in heavy infection, leads to iron deficiency and hypochromic, microcytic anemia. Diagnosis is made by finding the characteristic hookworm eggs on a examination of a direct fecal film. Accidental invasion of humans by dog and cat hookworm leads to cutaneous larva migrans, also known as "creeping eruption." Human hookworm is treated most effectively with mebendazole, while the rash produced by creeping eruption responds to topical thiabendazole. Strongyloides is fairly common in rural areas of the southeastern United States and may be seen in the urban setting among inmates of mental institutions, prisons, and in immigrants who formerly resided in endemic tropical regions. Because of its remarkable capacity for dissemination of larvae throughout the body, this parasite is now recognized as a serious problem for the patient who is immunocompromised. Diagnosis is made by finding larvae in the stool or by the Enterotest. All infected patients should be treated with thiabendazole. I consider the issue on Drugs For Parasitic Infections, published annually or biannually by The Medical Letter on Drugs and Therapeutics, to be the single best source of information on the treatment of parasitic diseases for primary care physicians.

Ancylostomatoidea↗

Inactivation of strongyloides stercoralis filariform larvae in vitro by six Jamaican plant extracts and three commercial anthelmintics.

In vitro bioassay of (a) aqueous methanol extracts (AME) of the green leaves of mimosa (Mimosa pudica), love weed (Cuscuta americana), vervine (Stachytarpheta jamaicensis), chicken weed (Salvia serotina) and breadfruit (Artocarpus altilis); (b) methanol-water fraction (MWF) of breadfruit leaves, and (c) commercially available drugs albendazole, thiabendazole and levamisole were assayed for nematode inactivating potential, using filariform larvae of Strongyloides stercoralis. Test larvae were obtained from a 10-day-old charcoal coproculture. Bioassays were conducted in Locke's solution, using 100 larvae in each of three replicates. Inactivation was recorded microscopically at 1, 3, 6 and 12 hours, then every 24 hours up to 5 days' incubation. It50 (time for inactivation of 50% of larvae) values read: levamisole and mimosa extract less than 1 hour; love weed extract, approximately 2 hours; breadfruit (MWF), 9.5 hours; chicken weed, 20 hours; albendazole, 35 hours; breadfruit (AME), 49 hours; thiabendazole, 74 hours and vervine extract, 81.5 hours. It95 values followed a similar, trend, and were approximately double the It50 measures. A potential role for locally available natural products in the treatment of strongyloidiasis is highlighted.

Animals↗

Recurrent massive upper gastrointestinal hemorrhage due to Strongyloides stercoralis infection.

A 29-yr-old black male immigrant from Africa presented with recurrent life-threatening upper gastrointestinal bleeding due to massive duodenal infection by Strongyloides stercoralis. The diagnosis was missed by repeated examinations of fresh stool specimens for ova and parasites and by an initial esophagogastroduodenoscopy. The diagnosis was made by pathologic examination of a duodenal biopsy and of a duodenal aspirate obtained at a second esophagogastroduodenoscopy. This has been previously reported as a cause of massive upper gastrointestinal hemorrhage in four cases. Patients with obscure gastrointestinal bleeding who have travelled or lived in an endemic area should have a duodenal aspiration performed at esophagogastroduodenoscopy.

Adult↗

Strongyloides infections in transplant recipients.

Solid organ transplant recipients can experience serious disease and death from infection due to the parasitic roundworm Strongyloides stercoralis. This parasite lives in soil contaminated with human feces. Domestic dogs and cats may be another reservoir. Larvae can penetrate the skin, are carried hematogenously to the lungs, migrate up the bronchial tree, and then can be passed to the upper small intestine. Autoinfection occurs in the setting of immunosuppression when invasive larvae penetrate the gut wall and cause disseminated infection. Polymicrobial sepsis is sometimes seen due to enteric organisms adhering to the parasite. Transplant recipients are at highest risk during the first 3 months posttransplant. Many organ systems may be affected. Pulmonary symptoms include cough, wheezing, sputum production, dyspnea, hemoptysis, tachypneas, and pleuritic pain. Hyperinfection, an augmentation of the normal skin-lung-intestine life cycle, occurs in roughly two-thirds of infected transplant recipients, with dissemination in the remainder. Diagnosis is made primarily by examination of the stool or intestinal secretions for ova and parasites. Occasionally, parasites are noted in the sputum. New serologic tests show promise. The parasite may remain in the host for over 25 years before immunosuppression causes either dissemination or hyperinfection. Thiabendazole given for 3 to 7 days is the treatment of choice for organ transplant recipients. Repeat courses may be needed to eradicate infection.

Adult↗

Cryopreservation of first-stage and infective third-stage larvae of Strongyloides stercoralis.

Infective third-stage larvae of Strongyloides stercoralis were frozen over liquid nitrogen and remained infective to dogs when thawed. Successful cryopreservation depended on a 30-60-min incubation in a cryoprotectant (10% DMSO and 10% dextran) before freezing and thawing the frozen larvae into RPMI. First-stage larvae could also be frozen by this method. Thawed first-stage larvae remained viable and continued their development to third-stage larvae, which were shown to be infective to dogs.

Animals↗

Surface labelling of Strongyloides ratti: stage-specificity and cross-reactivity with S. stercoralis.

Various methods of radioiodination were compared for their efficacy in labelling the surface of Strongyloides ratti infective larvae and adult worms. The Iodogen method was chosen as the optimal technique for this parasite. The surface location of 125-iodine was confirmed with light microscope autoradiography of transverse sections of labelled worms. Stage-specific surface components were identified when the sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) profiles of infective larvae and adult worms were compared. Labelled surface molecules were solubilized with either the non-ionic detergent Triton-X-100, the anionic detergents sodium deoxycholate (DOC) or sodium dodecyl sulphate (SDS), or the cationic detergent cetyl trimethyl-ammonium bromide (CTAB). The CTAB extract yielded most labelled proteins that retained their antigenicity in an immunoprecipitation assay with hyperimmune mouse sera. Immunoprecipitation analysis with stage-specific mouse sera revealed that the surface of infective larvae is immunogenic and that there are no cross-reactions with adult worms. Adult worms resident in the intestine were not found to be immunogenic and showed a complete absence of reactivity. Antigenic determinants shared between S. ratti and S. stercoralis were identified. Patients infected with S. stercoralis precipitated bands with molecular weights 32 and 34 kD which were not reactive with normal sera. These reactions suggest the potential usefulness of the surface of S. ratti as a source of diagnostic antigens.

Animals↗

Strongyloides stercoralis: is there a canonical migratory route through the host?

It is generally accepted that the skin-penetrating larvae of Strongyloides stercoralis travel from the skin to the intestinal habitat of the adult stage by an obligatory migratory route that includes the blood, lungs, trachea, and upper gastrointestinal tract in sequence (the pulmonary route). It is assumed, furthermore, that following autoinfective invasion of the bowel wall, S. stercoralis larvae follow this same route to return to the small intestine where they mature. We reexamined the parasite's migratory behavior using a canine isolate of S. stercoralis, specific-pathogen-free pups, radiolabeled larvae, and compressed tissue autoradiography. Compartmental analysis of the number of larvae found in the organ sets examined revealed no reason to reject the simple idea that the pulmonary route was just one of several possible pathways to the duodenum. This was true whether the larvae began their journey in the subcutaneous tissue of the inguinal area or in the distal part of the ileum. Direct sampling of the larvae traversing the trachea indicated that the number of larvae reaching the duodenum by way of the presumptive pulmonary route was insufficient to account for the estimated absolute number actually found there.

Animals↗

Radiolabeling of infective third-stage larvae of Strongyloides stercoralis by feeding [75 Se]selenomethionine-labeled Escherichia coli to first- and second-stage larvae.

A technique is described for radiolabeling Strongyloides stercoralis larvae with [75Se]selenomethionine. Cultures of an auxotrophic methionine-dependent stain of Escherichia coli were grown in a medium containing Dulbecco's modified Eagle's medium supplemented with 5% nutrient broth, amino acids, and [75Se]selenomethionine. When the 75Se-labeled bacterial populations were in the stationary phase of growth, cultures were harvested and the bacteria dispersed on agar plates to serve as food for S. stercoralis larvae. Use of nondividing bacteria is important for successful labeling because the isotope is not diluted by cell division and death of larvae attributable to overgrowth by bacteria is prevented. First-stage S. stercoralis larvae were recovered from feces of infected dogs and reared in humid air at 30 C on agar plates seeded with bacteria. After 7 days, infective third-stage larvae were harvested. The mean specific activity of 6 different batches of larvae ranged from 75 to 330 counts per min/larva with 91.8 +/- 9.5% of the population labeled sufficiently to produce an autoradiographic focus during a practicable, 6-wk period of exposure. Labeled infective larvae penetrated the skin of 10-day-old puppies and migrated to the small intestine, where the developed to adulthood.

Animals↗

The effects of single and repeated inoculations of various larval doses on Strongyloides ratti burden and distribution in rats.

The changes in worm burden, distribution, length, and fecundity after and during single and repeated inoculations of 10, 50, or 500 larvae of Strongyloides ratti were examined in rats. Worm burden after a single inoculation of a higher larval dose reduced rapidly. Repeated inoculations of lower larval doses at weekly intervals led to a delayed peak and slower reduction of worm burden; the repeated inoculations of 10 larvae did not induce worm expulsion for at least 7 wk. In repeated inoculations at 3-wk intervals, a primary inoculation of 500 larvae induced strong resistance to reinfection at week 3, whereas no resistance was induced until week 6 in rats receiving repeated inoculations of 10 or 50 larvae. Similar dose-dependent reductions in worm length and fecundity were observed in single and repeated inoculations, and the reductions began earlier than worm expulsion. Intestinal migration of worms from the upper small intestine to the large intestine was observed during the course of single and repeated inoculations. Earlier and clearer migration was observed in rats receiving higher doses. These findings indicate that in S. ratti infection, the changes of worm burden, distribution, length, and fecundity are dependent on the inoculated larval dose.

Animals↗

Worm expulsion and mucosal mast cell response induced by repetitive IL-3 administration in Strongyloides ratti-infected nude mice.

After a primary infection of congenitally athymic nu/nu mice with Strongyloides ratti, worms were not expelled and the number of intestinal mucosal mast cells (MMC) remained at a low level. When S. ratti-infected nu/nu mice were treated by repetitive injections of semi-purified IL-3 from Day 5 to Day 10 post-infection (total 1.4 X 10(5) U), significant reduction of larval excretion in faeces (LPG) was observed on Day 13. The number of adult worms in the small intestine of IL-3-treated mice was significantly lower than that of untreated, infected nude mice. The higher dose of IL-3 treatment from Day 4 to Day 13 (total 5.8 X 10(5) U) caused more profound reduction of LPG as early as Day 9, although complete cessation of LPG was not observed until Day 13, the end of this series of experiments. By this higher dose of IL-3 treatment, adult worms were completely expelled from the small intestine, although a small number of residual worms, which could explain the persistent low level of LPG detected from Day 9 to Day 13, was found in the caecum. Histological examination revealed that the number of MMC, especially in the epithelium, of the small intestine of IL-3-treated mice was significantly higher than that of untreated mice.

Animals↗

Electron microscopical studies of Strongyloides ratti infective larvae: loss of the surface coat during skin penetration.

Previous indications using radiolabelled larvae that Strongyloides ratti free-living infective larvae lose a surface coat during penetration of the skin were further investigated by transmission electron microscopy of the cuticle of S. ratti infective larvae in the free-living stage, after penetration of mouse skin, and after migration to the lungs. These studies demonstrated the presence of a faint electron-dense surface coat external to the epicuticle on free-living worms which was absent from larvae recovered from the skin and lungs. When free-living infective larvae were incubated in 10% CO2 at 37 C and then examined with phase-contrast microscopy, worms were observed in the process of losing this coat. These observations confirm the hypothesis that S. ratti infective larvae lose a surface coat during penetration of the skin.

Animals↗

Unsuspected strongyloides coexisting with adenocarcinoma of the lung.

The findings in an unsuspected case of Strongyloides stercoralis infestation coexisting with adenocarcinoma of the lung are presented. The diagnosis of adenocarcinoma was confirmed histologically by lung biopsies; the parasitic infection was initially diagnosed by sputum cytology and then by bronchial washings. A stool specimen submitted to the microbiology laboratory confirmed the diagnosis of S. stercoralis infection. This case again suggests the possibility that neoplastic disease may play a role similar to that of immunosuppression in creating an immune deficiency, thus increasing the susceptibility to infectious diseases.

Adenocarcinoma↗

Larval distribution and histopathology of experimental Strongyloides ransomi infection in young swine.

Necropsy at various intervals of three week old pigs following experimental infection with larvae of Strongyloides ransomi showed distribution of the larvae through the body during the first 24 hours. Quiescent larvae at the 24 hour necropsy, as indicated by higher recovery before and after this period may be an indication of physiological changes preceding a moult. Whether or not a moult occurs in the lung prior to migration of the larvae to the intestine has not been determined. At the 72 hour necropsy, larvae were largely confined to the lung and juvenile worms were beginning to appear in the small intestine. Migration to the small intestine was completed by the 96 hour necropsy. Lesions were observed in the skin and lungs up to the 96 hour necropsy, and lymphocytic accumulations were observed in the skin and lungs to this point and lymphocytic accumulations were observed in the liver to the 72 hour necropsy. At 28 days post-application lung lesions were still evident and the duodenum and jejunum were heavily parasitized. Egg passage began on the sixth day post-application and peaked on the 12th day.

Animals↗

Specific allergic sensitization to Strongyloides antigens in human strongyloidiasis.

Reaginic antibodies to antigens from the human parasite Strongyloides stercoralis were studied by histamine release from basophils in 15 patients with chronic uncomplicated strongyloidiasis and in 12 controls (six North Americans with no evidence of parasitic diseases, two patients with Schistosoma mansoni, two with hookworm, one with Ascaris lumbricoides, and one with Onchocerca volvulus). All of the patients had antibodies to the somatic larval antigens, and 14 of 15 patients also had antibodies to the excretory/secretory products of S. stercoralis larvae. None of the controls had a positive response to any of the antigens tested. These findings indicate that patients with chronic strongyloidiasis have parasite-specific IgE antibodies and that S. stercoralis larval allergens may have a potential role in the immunodiagnosis of strongyloidiasis.

Antigens↗

Shedding of antibody complexes by Strongyloides ratti (Nematoda) larvae.

Antigens on the epicuticular surface of Strongyloides ratti infective third-stage larvae (L3) could be demonstrated by an indirect fluorescent antibody technique under certain conditions. Infective L3 shed anti-antibody complexes at room temperature, but not at 4 C or in the presence of sodium azide or colchicine. Shedding of antibody did not appear to involve epicuticular antigens, and only occurred when anti-rat IgG was complexed to rat anti-larval antibody. However, parasitic L3 removed from rats did not exhibit this shedding reaction, suggesting that an important developmental change in cuticle physiology occurs during the transition from a free-living existence to a parasitic mode. The ability to shed foreign objects from the epicuticle of free-living infective L3 may be a defensive or protective response to soil microorganisms.

Animals↗

Strongyloides stercoralis.

Strongyloides stercoralis, a nematode not well known to many Canadian physicians, infects 35% of some tropical populations. Larvae can be isolated from the stools in 25% of cases and from duodenal aspirates in 95%. Treatment is with thiabendazole given twice daily in a dose of 25 mg/kg up to a maximum of 1.5 g/d. Frenquently an individual with a previously asymptomatic infection presents with hyperinfection and death rapidly ensues, but usually classical symptoms are present. Such a case is described. Immunosuppression is frequently associated with the hyperinfective state.

Canada↗

Loss of surface coat by Strongyloides ratti infective larvae during skin penetration: evidence using larvae radiolabelled with 67gallium.

The optimal conditions for labelling infective larvae of Strongyloides ratti with 67gallium citrate were determined. Radiolabelled larvae were injected s.c. into normal and previously infected rats. The distribution of radioactivity in these animals was compared with that in rats infected subcutaneously with a similar dose of free 67Ga by using a gamma camera linked to a computer system. Whereas free 67Ga was distributed throughout the body and excreted via the hepatobiliary system, the bulk of radioactivity in rats injected with radiolabelled larvae remained at the injection sites. Direct microscopical examination of these sites, however, revealed only minimal numbers of worms. When rats were infected percutaneously with radiolabelled larvae, it was found that most radioactivity remained at the surface, despite penetration of worms. When infective larvae were exposed to CO2 in vitro and examined carefully by light microscopy, loss of an outer coat was observed. It was concluded that infective larvae lose an outer coat on skin penetration.

Animals↗