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PubMed2004

Human immunoglobulin G mediates protective immunity and identifies protective antigens against larval Strongyloides stercoralis in mice.

Protective immunity to larval Strongyloides stercoralis in mice has been shown to be dependent on antibody, complement, and granulocytes. The goals of the present study was to determine the following: (1) whether human serum could passively transfer immunity to mice, (2) the mechanism by which the serum mediated killing, and (3) whether the antigens (Ags) recognized by the protective human antibody could induce protective immunity in mice. Immunoglobulin G (IgG) from a S. stercoralis-seropositive individual passively transferred immunity to mice. The antibody required granulocytes, but not eosinophils, and complement activation to kill the larvae. Antibody-dependent cellular cytotoxicity was not required for larval killing. Immunization of mice with soluble larval Ags isolated by use of the protective immune IgG resulted in protective immunity. In conclusion, immunity could be transferred to mice by IgG from immune humans, and Ags identified by the immune human IgG induced protective immunity in mice, which thereby suggests their possible use in a vaccine against this infection.

Animals↗
PubMed1997

Strongyloides stercoralis infection in AIDS.

Strongyloides stercoralis infection in humans continues to be a subject that has frequently inspired reviews and papers. Within the AIDS epidemic, interest gathered momentum with the inclusion of this infection in the indicator diseases list, and its subsequent removal 5 years later by the CDC. These actions have prompted a debate as to whether this infection has special significance in patients with AIDS and whether its exclusion from the CDC criteria is justified. A detailed review of the world literature reveals an increased awareness and diagnosis of this infection in patients with AIDS which takes the form of dissemination, a rapid course, and a usually fatal outcome.

AIDS-Related Opportunistic Infections↗
PubMed1990

Zinc deprivation and zinc repletion: effect on the response of rats to infection with Strongyloides ratti.

The course of a subcutaneous weight-related infection with Strongyloides ratti was followed in rats fed diets containing either 3 mg Zn/kg diet [zinc deficient (Zn-)] or 40 mg Zn/kg diet [zinc adequate (Zn+)]. At 19 d postinfection (dpi) the proportions of larvae persisting in the intestines as adult worms were 52 +/- 2% (means +/- SEM) for Zn-, 39.5 +/- 2.5% for pair-fed Zn- (Zn-PF), and 31.6 +/- 3.2% for Zn+ (p less than 0.001, analysis of variance); some Zn- rats were then transferred to the zinc-adequate diet [This was the zinc-repleted group (ZnR).] Both groups retained a group of pair-fed controls (Zn-PF and ZnRPF). Between 19 and 28 dpi ZnR animals gained weight faster than did Zn- animals and had heavier thymuses relative to body weight. Zinc deficiency enhances the establishment of S ratti larvae in the intestine of rats and alters the characteristics of intestinal expulsion of the nematodes; however, spontaneous cure was achieved by 38 dpi in both Zn- and control groups.

Animals↗
PubMed1997

Effect of Strongyloides stercoralis infection and eosinophilia on age at onset and prognosis of adult T-cell leukemia.

Onset of adult T-cell leukemia (ATL) usually follows a long period of viral latency. Strongyloides stercoralis infection has been considered a cofactor of leukemogenesis. Hypereosinophilia (HE) is also observed and could be associated with either the presence of parasites or the leukemic process. In non-Hodgkin's lymphoma, eosinophilia may or may not affect prognosis. To determine whether infection with S stercoralis and therefore eosinophilia has a significant effect on the development of ATL, we studied two variables in 38 patients: age at onset and median survival rate. Infected (Ss+) patients (n = 19) were younger (P = .0002) and survived longer (P = .0006) than uninfected (Ss-) patients (n = 19) (median age, 39 vs 70 years; median survival, 167 vs 30 days). Mean survival of patients with hypereosinophilia (HE+) was not significantly different from that of patients without hypereosinophilia (HE-) (P = .57). However, overall survival was longer for Ss + HE + patients than for Ss-HE-patients (P = .01; 180 vs 30 days) or Ss-HE + patients (P = .03; 180 vs 45 days). Among patients with mean survival more than 180 days, Ss + HE + patients survived longer (P = .028). Our data confirm that cofactors related to the environment, such as S stercoralis and hypereosinophilia associated with S stercoralis or human T-cell leukemia virus, type 1 (HTLV-1) might be important in HTLV-1-associated leukemogenesis and suggest that hypereosinophilia affects the prognosis of HTLV-1-associated leukemia.

Adult↗
PubMed1993

Treatment of Strongyloides stercoralis hyperinfection syndrome with thiabendazole administered per rectum.

There is a rising interest in Strongyloides stercoralis infection due to the expanding population of immunosuppressed patients. Currently the drug of choice for both enteric and tissue forms of infection with this organism is oral thiabendazole. We report a patient with a small bowel obstruction due to S. stercoralis hyperinfection who was unable to take thiabendazole orally. Thiabendazole was administered rectally, and the hyperinfection syndrome resolved. Peak serum concentrations of thiabendazole were achieved 4 hours after rectal administration, and drug levels were sustained longer than previously reported with oral dosing. In addition, elevated levels of thiabendazole metabolites in the patient's urine further confirmed significant absorption. Rectal administration of thiabendazole should be considered for patients unable to take the medication orally.

Administration, Rectal↗
PubMed2001

Sex determination in the parasitic nematode Strongyloides ratti.

The parasitic nematode Strongyloides ratti reproduces by both parthenogenesis and sexual reproduction, but its genetics are poorly understood. Cytological evidence suggests that sex determination is an XX/XO system. To investigate this genetically, we isolated a number of sex-linked DNA markers. One of these markers, Sr-mvP1, was shown to be single copy and present at a higher dose in free-living females than in free-living males. The inheritance of two alleles of Sr-mvP1 by RFLP analysis was consistent with XX female and XO male genotypes. Analysis of the results of sexual reproduction demonstrated that all progeny inherit the single paternal X chromosome and one of the two maternal X chromosomes. Therefore, all stages of the S. ratti life cycle, with the exception of the free-living males, are XX and genetically female. These findings are considered in relation to previous analyses of S. ratti and to other known sex determination systems.

Alleles↗
PubMed1989

Prominence of IgG4 antibodies in the human responses to Strongyloides stercoralis infection.

The participation of the four subclasses of IgG in the humoral response to Strongyloides stercoralis was assessed by analyzing total and parasite-specific responses of each IgG subclass in 20 patients with uncomplicated strongyloidiasis and 21 immunocompromised patients with extraintestinal disease. The total component of each subclass was normal in most patients. IgG4 antibodies (measured by ELISA) were the most prominent parasite-specific response in both groups. Specific IgG2 and IgG4 responses were significantly more elevated in immunocompetent than in immunosuppressed patients. When the reactivity of each IgG subclass was analyzed by immunoblotting on SDS-PAGE-separated larval antigens, IgG4 recognized more antigens than did any other subclass. No parasite antigens were selectively recognized by either clinical group. Thus the continuous antigenic stimulation of chronic strongyloidiasis may result in an enhanced IgG4 subclass response. However, no presence or absence of humoral responses specific for filariform larval antigens was associated with the extraintestinal dissemination of the parasite.

Adult↗
PubMed1993

Serum IgG reactivity with 41-, 31-, and 28-kDa larval proteins of Strongyloides stercoralis in individuals with strongyloidiasis.

Proteins from a deoxycholate-soluble extract of Strongyloides stercoralis infective larvae were separated by SDS-PAGE, blotted onto nitrocellulose paper, and reacted with sera from individuals with confirmed S. stercoralis infections (n = 100), suspected S. stercoralis infections in whom no larvae could be detected (n = 27), and other nematode infections (40 with Wuchereria bancrofti, 20 with Onchocerca volvulus, 20 with Necator americanus, and 20 with mixed Ascaris lumbricoides and Trichuris trichiura infections). Immunodominant proteins of approximately 41, 31, and 28 kDa were recognized by IgG in 91%, 88%, and 90%, respectively, of sera from those with confirmed strongyloidiasis; in 100%, 100%, and 93% of sera from those with suspected strongyloidiasis; and in 9%, 12%, and 14% of sera from those infected with other nematodes. IgG reactivity to each of these proteins was a more specific means of immunodiagnosis than the currently used indirect ELISA; the methods were equally sensitive.

Animals↗
PubMed1993

Strongyloides stercoralis: the first rodent model for uncomplicated and hyperinfective strongyloidiasis, the Mongolian gerbil (Meriones unguiculatus).

Strongyloidiasis is the most common endemic helminthiasis in several of the world's industrialized nations, yet relatively little is known about its basic biology and immunobiology because a practical rodent model for the investigation of this clinically important parasitism is lacking. This study reports such a model for use in the investigation of Strongyloides stercoralis infection. Normal male gerbils infected subcutaneously with 1000 infective filariform larvae harbored moderate numbers (83.6 +/- 27.6) of adult worms at 35 days after infection, and a low-grade infection persisted for at least 131 days mimicking the chronicity of human infections. Gerbils treated weekly with 2 mg of methylprednisolone acetate developed hyperinfective strongyloidiasis with up to 8000 autoinfective larvae occurring in these animals at postinfection day 21. Autoinfection never occurred in normal (untreated) gerbils.

Animals↗
PubMed1994

Immunoepidemiologic studies of Strongyloides stercoralis and human T lymphotropic virus type I infections in Jamaica.

Epidemiologic investigations of Strongyloides stercoralis and human T lymphotropic virus type I (HTLV-I) infections were conducted. Of 312 persons contacted, 209 (67%) provided blood and stool samples. Prevalences of S. stercoralis and HTLV-I antibodies were 26.8% and 8.1% (n = 198), respectively, and S. stercoralis larvae were detected in 4%. HTLV-I antibodies were significantly more common in persons positive for S. stercoralis larvae (10 [58.8%] of 17) compared with seropositive larva-negative (4 [8.9%] of 45) or seronegative persons (9 [6.2%] of 145) (P < .002). IgE levels increased with age in S. stercoralis-seropositive persons who were HTLV-I negative (P < .002). However, there was an age-related depression of serum IgE in HTLV-I-positive positive persons (P < .003) that was sufficient to annul the IgE level-raising effect of S. stercoralis seropositivity. The data provide evidence that HTLV-I infection is associated with increased frequency of larvae in the stool of S. stercoralis-infected persons and suggest that the mechanism may involve suppression of the IgE response.

Adult↗
PubMed1988

Efficacy of albendazole against Strongyloides ratti and S. stercoralis in vitro, in mice, and in normal and immunosuppressed dogs.

In view of conflicting clinical reports, the effects of albendazole on Strongyloides were examined in vitro and in experimentally-infected animals. Albendazole inhibited the hatching and moulting of S. ratti eggs and larvae and prevented the development in vitro of S. stercoralis first-stage larvae. Pre-exposure to the drug did not impair the infectivity of either S. ratti or S. stercoralis third-stage larvae. Albendazole had a dose-dependent inhibitory effect on S. ratti migrating larvae in mice when measured in terms of the numbers of larvae recovered from the skin or lungs or the subsequent development of a patent infection. Likewise, killing of adult S. ratti in the gut and eradication of S. stercoralis third-stage larvae from the muscles of mice were dose-dependent. Albendazole in a dose of 100 mg twice daily for three days given at the time of infection with S. stercoralis of immunocompetent dogs prevented completely the subsequent development of patent infection. When the drug was given in the same dosage to immunosuppressed dogs with patent infections, the larvae disappeared from the stools transiently; when the animals were killed seven weeks after treatment, small numbers of adult worms and rhabditiform larvae were found in the gut. It is concluded that albendazole may be effective treatment for strongyloidiasis if it is given in sufficiently large doses.

Albendazole↗
PubMed2004

Chronic Strongyloides stercoralis infection in former British Far East prisoners of war.

BACKGROUND: Chronic infections with the nematode worm Strongyloides stercoralis can occur in former WWII Far East prisoners of war (FEPOWs). The condition may be asymptomatic, but frequently causes a characteristic urticarial 'larva currens' rash. Under conditions of immunosuppression (particularly systemic corticosteroid treatment) potentially fatal dissemination of larvae ('hyperinfection') may occur. AIM: To review our total experience of strongyloidiasis in former FEPOWs, and investigate its prevalence, characteristics and risk factors. DESIGN: Retrospective case series. METHODS: We reviewed 2072 records of all FEPOWs seen at the Liverpool School of Tropical Medicine, 1968-2002. Cases with strongyloidiasis were compared with non-infected controls. RESULTS: There were 248 (12%) with strongyloidiasis. Diagnostic features included larva currens rash (70%), eosinophilia (66%), positive faecal culture (30%), positive faecal microscopy (26%), and positive serology (64%). Mean (+/-SD) age of cases was 65 +/- 7 years, and as expected, their blood eosinophil counts were significantly higher than controls (775 vs. 238 x 10(6)/l, p < 0.001). Captivity on the Thai-Burma Railway (vs. elsewhere) was significantly associated with strongyloidiasis (78% cases vs. 40% controls, OR 4.19, CI 2.70-6.81, p < 0.001). In terms of prevalence, strongyloidiasis occurred in 166/1032 men imprisoned on the Burma Railway (16.1%). Malaria (88% vs. 69%, p < 0.001) and tropical ulcer (53% vs. 42%, p < 0.02) were more common amongst cases than controls, probably because these diseases were very common on the Burma Railway. DISCUSSION: S. stercoralis infection is common amongst ex-FEPOWs, particularly those from the Thai-Burma Railway project. It is usually characterized by a 'larva currens' rash and marked eosinophilia. The condition is eminently treatable, and continued diagnostic surveillance is needed, if cases of potentially fatal hyperinfection are to be avoided.

Aged↗
PubMed1999

Exudative eosinophilic pleural effusion due to Strongyloides stercoralis in a diabetic man.

A 61-year-old diabetic man had fever and a significant exudative type of eosinophilic pleural effusion. Microscopic examination of stained specimens of bronchial washings revealed filariform larvae of Strongyloides stercoralis. This intestinal nematode is endemic in some areas of the world. Pulmonary symptoms are usually mild, though severe pulmonary involvement may be occasionally seen. Although serohemorrhagic pleural effusion has been well reported in the literature, we found no report of such an unusual case of significant exudative eosinophilic pleural effusion due to strongyloidiasis.

Animals↗
PubMed2026

Recent advances in Strongyloides screening, diagnostics, therapeutics, and management.

PURPOSE OF REVIEW: Strongyloidiasis affects an estimated 30-100 million people globally and can have life-threatening consequences in immunocompromised hosts, yet it remains underdiagnosed due to limited access and performance of available diagnostics. Novel assays and anthelmintics may reshape screening, diagnosis, treatment, and prevention for at-risk populations. RECENT FINDINGS: Advances in molecular diagnostics coupled with robust stool extraction methods have supplanted traditional parasitologic methods in settings where nucleic acid amplification is feasible. Transition from standard immunoglobulin G (IgG)-based immunoassays to the new IgG- and IgG4-based rapid diagnostic tests using recombinant Strongyloides stercoralis nematode immunodominant E antigen (NIE) and/or S. stercoralis immunoreactive antigen (SsIR) has facilitated serologic screening at the point of care. The World Health Organization now conditionally recommends community-wide ivermectin mass drug administration in highly endemic settings. Regarding new treatment options, moxidectin is noninferior to ivermectin with 93-94% cure rates and a longer half-life, while emodepside shows 80-90% predicted cure rates in early trials and offers a mechanistically distinct option. Understanding of immunosuppressed populations at risk for hyperinfection has expanded, prompting updated screening recommendations. SUMMARY: Serologic and molecular tools are improving screening and diagnosis, and moxidectin and emodepside may broaden treatment options, but data in severe disease and special populations remain limited. Priorities include harmonized screening algorithms and prospective studies in high-risk groups.

Humans↗
PubMed1993

Mating in the nematode parasite Strongyloides ratti: proof of genetic exchange.

Strongyloides, a parasitic nematode, has a complex life cycle that represents a transition between free-living and purely parasitic ways of life. By using minisatellite DNA fingerprinting, we have detected a large number of polymorphic loci in cloned lines of S. ratti. In controlled crosses between free-living adults of S. ratti, we show that genetic exchange, consistent with normal sexual reproduction, occurs. This is in contrast to earlier cytological studies which claimed that reproduction in this organism was by pseudogamy, and thus that inheritance was maternal only.

Animals↗
PubMed1996

Developmental switching in the parasitic nematode Strongyloides ratti.

Strongyloides ratti is a nematode parasite of rats. It is able to undergo two types of development outside the host: heterogonic (free-living adults and sexual reproduction) and homogonic (direct larval development). Homogonic development has a number of similarities with the development of the dauer stage of free-living nematodes, including Caenorhabditis elegans. Using isofemale lines of the parasite, factors that control this developmental choice have been investigated. Isofemale lines can be selected for both heterogonic and homogonic development, but are still able to respond to environmental conditions. By using temperature shift experiments it has been possible to determine when larvae become developmentally committed. All larvae are developmentally committed after 24 h at 19 degrees C.

Animals↗
PubMed1998

The population genetic structure of the facultatively sexual parasitic nematode Strongyloides ratti in wild rats.

We have investigated the population genetic structure of the parasitic nematode Strongyloides ratti in wild rats. In the UK, S. ratti reproduces predominantly by mitotic parthenogenesis, with sexual forms present at a rate of less than 1%. S. ratti was found to be a prevalent parasite and substantial genetic diversity was detected. Most rats were infected with a genotypic mixture of parasites. A hierarchical analysis of the genetic variation found in S. ratti sampled across Britain and Germany showed that 73.3% was explained by variation between parasites within individual hosts and 25.3% by variation between rats within sample sites. Only a small proportion (1.4%) of the total genetic variation was attributable to genetic subdivision between sample sites, suggesting that there is substantial gene flow between these sites. Most parasites sampled were found to exist in Hardy-Weinberg equilibrium and this population genetic structure is discussed in view of the virtual absence of sexual reproduction.

Animals↗
PubMed2000

The control of morph development in the parasitic nematode Strongyloides ratti.

The parasitic nematode Strongyloides ratti has a complex life cycle. The progeny of the parasitic females can develop into three distinct morphs, namely directly developing infective third-stage larvae (iL3s), free-living adult males and free-living adult females. We have analysed of the effect of host immune status (an intra-host factor), environmental temperature (an extra-host factor) and their interaction on the proportion of larvae that develop into these three morphs. The results are consistent with the developmental decision of larvae being controlled by at least two discrete developmental switches. One is a sex-determination event that is affected by host immune status and the other is a switch between alternative female morphs that is affected by both host immune status and environmental temperature. These findings clarify the basis of the life cycle of S. ratti and demonstrate how such complex life cycles can result from a combination of simple developmental switches.

Animals↗