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PubMed1979

Mebendazole.

The broad-spectrum of activity and safety of mebendazole remain, after 5 years of clinical experience, unique features of this anthelmintic. Through microtubular destruction, mebendazole kills helminths by inhibiting glucose uptake into susceptible parasites. The drug's poor absorption does not appear to affect clinical efficacy except, perhaps, in the treatment of systemic helminth infections. Mebendazole is generally considered the drug of choice for trichuriasis and has therapeutic advantages over other anthelmintics in the treatment of enterobiasis and hookworm infections. Although mebendazole is an effective agent against ascariasis, there are preferable alternatives. Among its nonapproved uses, mebendazole shows great promise in the treatment of capillariasis and hydatid disease. Further investigation is needed to establish its role in the treatment of taeniasis, Hymenolepsis nana, strongyloidiasis, trichinosis, and Dipetalonema perstans. Undoubtedly, mebendazole will find its greatest value in the treatment of patients with multiple helminth infections.

Ascariasis↗

PubMed1993

The in vivo role of stem cell factor (c-kit ligand) on mastocytosis and host protective immunity to the intestinal nematode Trichinella spiralis in mice.

The role of stem cell factor (SCF) in the generation of intestinal mast cell hyperplasia and host protective immunity following helminth infection was investigated using the Trichinella spiralis/mouse model. In vivo administration of a monoclonal antibody specific for the receptor for SCF (c-kit) was found to completely prevent the generation of intestinal mastocytosis normally observed following T. spiralis infection. This was reflected by markedly reduced intestinal mast cell protease (IMCP) levels in both tissue and serum. Moreover, animals treated with anti-c-kit antibody failed to show any evidence of worm expulsion from the gut. The data demonstrate for the first time, a critical role for the SCF in the generation of mucosal mastocytosis and host protective immunity following an intestinal helminth infection.

Animals↗

PubMed2006

The control of schistosomiasis and soil-transmitted helminths in East Africa.

As a result of support from the Bill and Melinda Gates Foundation, schistosomiasis and intestinal or soil-transmitted helminth infections have been the subject of national control programmes in three Eastern and Southern African countries: Uganda, the United Republic of Tanzania and Zambia. Here, we review the significant progress made in their control efforts and highlight the different approaches being adopted to ensure programme effectiveness and sustainability. Although a positive start has been made to reduce morbidity resulting from schistosomiasis and soil-transmitted helminth infections in these countries, it is imperative that support is identified to sustain the programmes until these infections are no longer a public health problem and children can therefore be given a healthy start to life.

Animals↗

PubMed2000

[A rare cause of asthma exacerbation: systemic anguilluliasis].

Strongyloides is an helminthic infection that may induce bronchospasm during systemic migration of larvae. We report a case of a 60 years old man originating from Caribbean who had corti-codependent asthma since 30 years. He was hospitalized for severe exacerbation that worsen when steroid dosage was increase. Sputum examination revealed the presence in great number of Larvae of Strongyloides stercoralis. A good clinical evolution was achieved after specific anti-helminthic treatment. Later on, it was even possible to stop completely steroid treatment. This clinical case demonstrates the interest to look for Strongyloides superinfection in asthmatic patients that worsen when receiving increasing dose of steroids. This is particularly important for patients who have resided, even many years earlier, in areas where intestinal helminthic infection are endemic.

Animals↗

PubMed2002

Sensitivity and specificity of ELISA and immunoblot for diagnosing neurocysticercosis.

In patients with neurocysticercosis (NCC), clinical manifestations and the results of neuroimaging procedures vary widely and often do not facilitate a definite diagnosis. In order to determine the value of immunodiagnosis for NCC, 222 serum and cerebrospinal fluid samples from patients with NCC and healthy subjects were examined. The samples represented patients from various endemic regions, those with other neurological disorders from an endemic area (Mexico), persons with various helminth infections other than NCC, and a group of healthy volunteers. All specimens were tested by enzyme-linked immunosorbent assay and immunoblot for the presence of Taenia solium-specific antibodies. The sensitivities of the enzyme-linked immunosorbent assay and the immunoblot test in NCC patients were almost identical (80% and 81.7%, respectively). For both tests, the sensitivity was higher when cerebrospinal fluid (86%) was tested compared with serum (75%). The overall specificity of enzyme-linked immunosorbent assay was only 75.3% because of frequent false-positive results in patients with other helminth infections, especially in those with echinococcosis. The specificity (99.4%) of the immunoblot test was clearly superior. It is concluded that enzyme-linked immunosorbent assay as a screening method and immunoblot as a confirmatory test contribute considerably to the diagnosis of NCC.

Animals↗

PubMedDate not supplied

Anti-filarial and total IgG4 and IgE antibody levels are correlated in mothers and their offspring.

In mothers who suffer from helminth infections or allergic diseases, prenatal sensitization with antigens/allergens is suspected to bias the immune system of the offspring towards a Th2-type response. To investigate this at the antibody level, we collected 113 blood samples on filter paper from a paediatric population aged 3 months to 10 years and their mothers, who resided in an area endemic for brugian filariasis in Indonesia. The results showed that antibody levels in children were strongly correlated with maternal antibody levels. However, for anti-filarial IgG4 and IgE this relationship was manifested directly after birth, whereas for total antibody levels a positive correlation could be detected only with children aged > or = 2 years. To investigate the influence of paternal antibody on progeny, specific IgG4 was determined in a different set of samples from 229 children and both of their parents. Interestingly, the influence of paternal IgG4 became apparent only after the age of 4 years. In contrast, maternal antibody levels were already correlated to levels produced by their offspring at a young age (3 months onwards). Taken together, it appears that children can become sensitized to parasite antigens in utero, allowing them to produce Th2-dependent specific IgG4 and IgE antibodies at a young age, whereas with increasing age, the influence of environmental factors, shared in households, such as filarial transmission and other helminth infections, becomes dominant.

Adult↗

PubMed2000

Single cell analysis reveals that IL-4 receptor/Stat6 signaling is not required for the in vivo or in vitro development of CD4+ lymphocytes with a Th2 cytokine profile.

The concept that IL-4 is the primary signal for Th2 lymphocyte differentiation has recently been put in doubt by studies in which the production of Th2-associated cytokines was detected in mice deficient in IL-4 synthesis or IL-4R triggering. In this study, we formally demonstrate by single cell analysis that CD4+ lymphocytes with a classical Th2 phenotype (IL-4+, IL-5+, IFN-gamma-, IL-2-) develop in significant numbers in helminth-infected mice deficient in either IL-4R alpha-chain or Stat6. While an expanded population of Th1 (IL-4-, IL-5-, IFN-gamma+, IL-2+) lymphocytes was observed in the same animals, surprisingly, cells with a mixed Th0 cytokine pattern were rare. The cytokine production phenotypes of the Th1 and Th2 subpopulations generated in infected Stat6-deficient mice were unaffected by in vitro neutralization of endogenous IL-4 or IFN-gamma. Nevertheless, while addition of exogenous rIL-12 resulted in transitory IFN-gamma production by Th2 lymphocytes from both wild-type and Stat6-deficient mice, IL-4 synthesis was preserved in the former, but temporarily ablated in the latter cells. Importantly, IL-4+ IFN-gamma- and IL-4- IFN-gamma+ populations similar to those arising in helminth-infected Stat6-deficient mice could also be generated in vitro by repetitive polyclonal stimulation of CD4+CD62Lhigh lymphocytes from uninfected mice of the same strain. Together, the results of these single cell analysis experiments demonstrate that IL-4R/Stat6 signaling, while influencing the final frequency of Th2 lymphocytes, is not essential for Th2 cell development, and suggest that this pathway has a previously unrecognized function in stabilizing Th2 populations once they have emerged.

Animals↗

PubMed2003

The intestinal parasite infection status of inhabitants in the Roxas city, The Philippines.

We carried out a small-scale survey to investigate the status of intestinal protozoa and helminthes infection of inhabitants in Roxas city, Mindoro, the Philippines. Total 301 stool samples were subjected to the formalin-ether concentration method for the detection of helminth ova and protozoan cysts. The overall positive rate was 64.5%, and that of male and female were 56.6% and 72.5%, respectively. The highest infected helminth was Ascaris lumbricoudes (51.2%), followed by Trichuris trichiura (27.6%), hookworm (8.0%) and Enterobius vermicularis (0.3%). The protozoa infection status revealed that Entamoeba coli was the most frequent (15.0%). Iodoamoeba buetschlii and E. histolytica were found but few. The multiple infection more than two parasites was 29.6%, and double infection with A. lumbricoides and T. trichiura was most common. The intestinal helminth infections were highly prevalent in this area, according to this result, and we concluded that anthelminthic drugs should be given to inhabitants, especially to children of 1 to 15 years-old.

Adolescent↗

PubMed2006

[Tissue helminthoses].

Helminthic infections affecting host organs/tissues belong to the most important parasitic infections. In the Czech Republic, an increase in the travelers to and immigrants from endemic countries has been noted. Except for larval toxocarosis, however, the total number of patients with schistosomiasis, hydatid disease, cysticercosis and filariases does not exceed 15 cases per year till present. It remains to be solved whether this situation reflects manners of a Czech tourist in endemic areas or the diseases are neglected during routine practice. The presented paper, therefore, focuses on some diagnostically important features accompanying helminthic infections. And, clinical symptoms and signs of the infections are analysed in relation to the patient history and laboratory findings.

Czech Republic↗

PubMed1981

IgE antibodies in human onchocerciasis. Application of a newly developed radioallergosorbent test (RAST).

A radioallergosorbent test (RAST) was developed to detect IgE antibodies against adult Onchocerca volvulus antigens coupled to CnBr-activated Sepharose. Twenty-four out of 25 (96%) onchocerciasis sera were reactive. The lower limit of sensitivity was estimated to be at approx. 3 ng/ml IgE antibodies. Tests of sera from patients with non-filarial helminth infections showed much less cross-reactivity with RAST than with an enzyme-linked immunosorbent assay (ELISA) detecting IgG and IgM antibodies against the same antigen preparation. At a specificity comparable to that of RAST, the sensitivity of ELISA was only 61%. A heterologous antigen, prepared from female Dipetalonema viteae worms, was comparatively evaluated with O. volvulus. In RAST and ELISA, onchocerciasis sera were less reactive than against the O. volvulus antigen. Since sera from patients with non-filarial helminth infections were more reactive in RAST and almost equally reactive in ELISA using the D. viteae antigen, sensitivity was 83% for RAST and only 22% for ELISA (compared at the specificity identical to that of the O. volvulus RAST).

Animals↗

PubMed1997

[Control of gastrointestinal helminthiasis in pasture-reared lambs].

Two sheep herds kept in different geographic conditions with spring lambing by the end of March and April (herd No. 1: 400 ewes, 600 metres above sea level; herd No. 2: 450 ewes, 300 metres above sea level) were examined. The dynamics of gastrointestinal nematode and Moniezia spp. cestode egg counts in samples taken regularly every 4 to 5 weeks was studied during the year 1995 with the intention to verify the system of effective control of these helminth infections under pasture conditions of lamb rearing. In ewes a significant rise in gastrointestinal nematode egg counts was proved during the lambing season, "spring rise phenomenon", and during the summer pasture until autumn months with maximum EPG values reaching 150 (Figs. 1 and 2). In lambs that started grazing at 1 to 4 weeks of age, the excretion steeply rose to maximum EPG values 350 and 290, respectively, after 4 to 5 weeks of grazing (Figs. 1 and 2). In order to control these rising infections, ewes were treated with antihelmintic albendazol by the end of February (herd No. 1) and in March (herd No. 2) and lambs during the first or third decade of July. This anthelmintic treatment significantly lowered egg excretion to EPG values lower than 30 in ewes and 50 or 60, respectively, in lambs. Later, during the summer and autumn months, a mild rise of egg counts was found in lambs. These maxima were liquidated anthelmintis treatment in both herds in late autumn months and it also lowered helminth infections to minimum during winter months (EPG values lower than 50). The excretion of Moniezia spp. eggs had the same dynamics as that gastrointestinal nematodes. Values of lamb infection prevalence reached 21% in herd No. 1 and 29% in herd No. 2. Anthelmintic treatment during July controlled cestode findings in lambs. Albendazol (Vermitan susp. 2.5%), dosed 5 mg/kg of body weight, proved highly effective in the control of gastrointestinal nematodes and Moniezia spp. cestodes.

Albendazole↗

PubMed1994

Purified excretory-secretory component of filarial parasite enhances Fc epsilon RII/CD23 expression on human splenic B and T cells and IgE synthesis while potentiating T-helper type 2-related cytokine generation from T cells.

The CD23-bearing cells are known to be involved in multiple biological activities, including IgE synthesis and IgE-dependent cytotoxicity to parasites. The factors that regulate interleukin-4 (IL-4)-induced IgE synthesis in helminthic infection were analysed by using an excretory-secretory component (ESC) of Dirofilaria immitis (DI). Human splenic B and T cells significantly enhanced the expression of low-affinity Fc receptors for IgE (Fc epsilon RII/CD23) by stimulation with ESC, either acting alone or in synergy with IL-4. On B cells, ESC potentiated the CD23 expression in synergy with IL-4, whereas ESC alone was unable to modulate CD23 expression. In contrast, ESC directly induced CD23 expression on T cells by acting alone and no further enhancement was observed in the presence of IL-4. Furthermore, IL-4-induced IgE synthesis by splenic mononuclear cells (SMNC) was greatly enhanced in the presence of ESC. Of particular interest, T cells primed by ESC significantly produced a set of cytokines including IL-3, IL-4, IL-5 and IL-6. Inasmuch, IL-4-induced IgE synthesis in helminthic infection may be selectively modulated by parasite protein(s) acting on the generation of T-helper type 2 (Th2)-related cytokines.

Animals↗

PubMed2006

Schistosoma japonicum egg antigens stimulate CD4 CD25 T cells and modulate airway inflammation in a murine model of asthma.

A number of epidemiological and clinical studies have suggested an inverse association between allergy and helminth infection, such as Schistosomiasis. Therefore, we hypothesize that Schistosoma japonicum egg antigens, a type of native antigen, can induce production of CD4(+) CD25(+) T cells with regulatory activity, modulating airway inflammation and inhibiting asthma development. The frequency of CD4(+) CD25(+) T cells was determined by flow cytometry for mice treated with ovalbumin (OVA), CD25(+) depletion/OVA, schistosome egg antigens, schistosome egg antigens/OVA and for control mice. The ability of CD25(+) T cells from these mice to suppress T-cell proliferation and cytokine production was investigated both in vivo and in vitro. Results showed that the CD4(+) CD25(+) T cells of OVA-treated mice exhibited impaired control of dysregulated mucosal T helper 2 responses compared to the controls (P < 0.05). Depletion of CD25(+) cells accelerated OVA-induced airway inflammation and increased the expression of interleukin (IL)-5 and IL-4. Treatment with schistosome egg antigens increased the number and suppressive activity of CD4(+) CD25(+) T cells, which made IL-10, but little IL-4. In a murine model of asthma, S. japonicum egg antigens decreased the expression of Th2 cytokines, relieved antigen-induced airway inflammation, and inhibited asthma development. Thus, we provided evidence that S. japonicum egg antigens induced the production of CD4(+) CD25(+) T cells, resulting in constitutive immunosuppressive activity and inhibition of asthma development. These results reveal a novel form of protection against asthma and suggest a mechanistic explanation for the protective effect of helminth infection on the development of allergy.

Animals↗

PubMed2004

CD200 receptor family members represent novel DAP12-associated activating receptors on basophils and mast cells.

Modulation by balancing activating and inhibitory receptors constitutes an important mechanism for regulating lymphocyte and myeloid cell effector responses. Using a microarray screen during parasitic helminth infection, we identified CD200 receptor-like 3 as a transcript highly expressed in basophils. Novel splice variants were present that generated proteins that differed in surface expression. The second immunoglobulin-like domain, encoded by exon 4, was required for cell surface expression and recruitment of DAP12 to the cell surface. Splice variants also generated unique cytoplasmic domains, which contributed to efficient pairing with DAP12. Despite expression on basophils and mast cells, which are integral components of allergic immunity, the absence of DAP12 did not alter effector cell recruitment or the host response elicited by helminth infection with Nippostrongylus brasiliensis.

Adaptor Proteins, Signal Transducing↗

PubMed1997

Helminth surveillance as a prerequisite for anthelmintic treatment in intensive sow herds.

Helminth prevalences in pigs in intensive production systems are often very low due to housing and management factors, and the present study was carried out to examine whether routine anthelmintic treatment in such herds can be replaced by coprological surveillance of the helminth status combined with anthelmintic treatment when necessary. After an initial examination, 25 out of 28 large herds of Danish sows (> or = 50 sows, production of fatteners) were found to have such light helminth infections that routine deworming could be replaced experimentally by coprological examination every 6 months of 10 weaners (10-12 weeks old), 10 fatteners (5-6 months old), 10 dry sows and 10 lactating sows. This coprological surveillance continued in 21 herds of the selected 25 herds for a 3-year period, while it was stopped immediately in one herd due to increasing Ascaris suum prevalences, and ceased after one year in three herds due to other reasons. A. suum was found in all but one of the 25 herds. The most heavily infected age group was the sows, in which the A. suum prevalence was consistently low in approximately half of the herds, while it increased slowly or rapidly in the other half. When this happened, treatment of the breeding stock was recommended which resulted in low prevalences for varying periods of time. Few farmers neglected the recommendations for some time or for all 3 years, which resulted in consistently high prevalences in the sows (e.g. 40-60%). The fatteners were in general more lightly infected with A. suum than the sows, and in approximately 3/4 of the herds the prevalence remained at a low level, while it fluctuated in the remaining herds. No weaners were ever found to excrete eggs, most likely due to unfavourable conditions for egg development in the farrowing pens. Throughout the study Oesophagostomum sp. eggs were found sporadically in the sows of two herds, and in a third herd, Oesophagostomum sp. was introduced after 2 years, probably due to close contact with a neighbour herd. Oesophagostomum sp. was not found in the remaining herds. Eggs of Trichuris sp. were found sporadically. In conclusion, it is recommended that veterinarian advisers evaluate the production systems before suggesting an anthelmintic routine. If helminth infections may be controlled by intensive management and housing alone, coprological surveillance combined with anthelmintic treatment when necessary may replace routine use of anthelmintics. If the surveillance reveals that the infection levels continue to be low unnecessary medication is avoided, and if the infection levels increase, the coprological data obtained can be used to optimize the anthelmintic strategy.

Animal Husbandry↗

PubMed1991

The mast cell-committed progenitor. In vitro generation of committed progenitors from bone marrow.

Mast cell-committed progenitors are detected in the unique microenvironment of the mesenteric lymph node (MLN) of Nippostrongylus brasiliensis-infected mice but not in naive bone marrow. We have determined that MLN cells, after infection, produce high levels of IL-3, IL-4, and IgE, presumably in the form of immune complexes with antigens produced by the infecting helminth. After N. brasiliensis infection, peak production of these factors occurs several days before the peak appearance of mast cell-committed progenitors in the MLN. To determine if these factors play a role in mast cell commitment, we recreated these conditions, in vitro. Naive bone marrow cells were cultured with combinations of IL-3, IL-4, and IgE immune complexes, or on IgE-coated plates, and then assayed for acquisition of the ability to form mast cell colonies when supplemented with fibroblast-conditioned medium alone. IL-3 and IgE immune complexes, and, unexpectedly, IgE immune complexes alone were found to be capable of producing mast cell-committed progenitors, i.e., cells responsive to fibroblast-conditioned medium alone, from bone marrow, whereas IL-4 did not enhance production of mast cell-committed progenitors from bone marrow. Production of IFN-gamma peaked at the same time point as committed progenitor activity and may be responsible for down regulating the response.

Animals↗

PubMedDate not supplied

Analysis of gamma4 germline transcription in human B cells.

BACKGROUND: Allergic reactions occur rarely in patients with chronic helminth infections, although FcepsilonRI-bearing cells are sensitized with anti-parasite IgE and are exposed to antigen. The inhibition of allergic reactivity is due to 'blocking antibodies', predominantly IgG4. IgG4 antibodies represent 50-95% of anti-filarial IgG, and have blocking activity because they compete with cell-bound IgE for allergen binding. Blocking IgG4 antibodies have also been detected in patients treated with immunotherapy. However, the molecular mechanisms of IgG4 regulation have remained unexplored. We address this issue starting with the IL-4-dependent induction of gamma4 germline transcription, an essential step in the commitment to isotype switching. RESULTS: gamma4 germline transcripts were cloned and shown to contain Igamma4 spliced to the 5' portion of Cgamma4 using the splice donor site shared by gamma1 and gamma3 germline transcripts. Sequence analysis located the human Igamma4 exon thick approximate0.6 kb upstream of the Sgamma4 region. Four major transcription start sites located 547-583 bp upstream of the Igamma4 splice donor site were identified by primer extension analysis. A HindIII/NaeI construct (-413/+466) had the highest activity in reporter assays. Transcription was induced 4.6-fold by IL-4, 2.1-fold by CD40 engagement, and 14.5-fold by a combination of the two signals. Thus CD40 crosslinking enhanced IL-4-dependent transcription by 3.1-fold, showing that the two stimuli act synergistically. CONCLUSION: As we understand more about IgG4 regulation, our hope is to apply to allergy the lesson we learnt from helminth infections.

Antibodies, Blocking↗

PubMedDate not supplied

Pathology of pyogenic liver abscess in children.

Little is known about preexisting lesions in livers of children with pyogenic liver abscess (PLA). Study of these lesions may elucidate possible predisposing factors for the disease. In Vitória, state of Espirito Santo, Brazil, PLA in children is frequently associated with helminthic infections and eosinophilia. We hypothesize that nematode infection with larvae migrating through the liver is a predisposing factor for PLA, because the infection induces immunomodulation and likely trapping of bacteria in liver granulomas. In this report, we describe observations of 22 cases of PLA in children studied at autopsy (16 cases) or in surgical biopsies (6 cases), including 17 boys and 5 girls ranging in age from 1 to 13 years (mean 4.6 years, median 3.5 years). Multiple abscesses in both lobes were found in 13 cases and a single abscess was found in the right lobe in 10 cases. All cases showed histologically classical pyogenic inflammation without morphological evidence of amoebiasis. In six cases there were granulomas similar to those caused by larva migrans visceralis (from Toxocara or other nematodes) in liver tissue not affected by the abscess. Nematode antigens in central areas of necrosis of granuloma in all six cases and fragments of a larva, possibly of Toxocara, were found on samples immunohistochemically stained with polyclonal anti-Toxocara antibodies. There were numerous eosinophils in abscesses with Charcot-Leyden crystals. Eosinophils were found frequently in portal triads far from the abscess wall. In four cases, in which bile duct ascariasis was found, worms were noted in the bile ducts, and eggs were found in liver parenchyma surrounding the abscess in two cases. Foreign-body granulomas were found in one case in which penetrating trauma was the cause of abscess. In one case there was one histiocytic granuloma whose origin was not determined. The observation of six cases of granuloma similar to larva migrans visceralis (or produced by other nematode larva) in liver tissue not directly affected by the abscess supports the hypothesis that helminth infections with larva migrating through the liver are a predisposing factor for pyogenic hepatic abscess in children.

Adolescent↗