Ascaris lumbricoides in neonate: evidence of congenital transmission of intestinal nematodes

Clinical and epidemiological study of a forty-days-old infant with a diarrheic condition and insufficient development led to the coprological diagnosis of ascariasis and possible congenital infection. Specific treatment with levamizole, resulted in clinical and parasitological cure, in addition to gain of weight up to normal levels. Maternal parasitism had been diagnosed two months before labor and proved beyond doubt during the ensuing epidemiological inquiry.

Intestinal nematodes and pulmonary tuberculosis

We report a significantly higher prevalence of intestinal nematodes in patients with pulmonary tuberculosis (TB) compared to a matched control group: 33/57 (57.8%) in patients with TB and 18/86 (20.9%) in the control group; OR=5.19; 95% CI= 2.33-11.69; p=0.000). When TB patients eosinophilia was also significantly higher among those with intestinal parasites (69.8%) compared to those without this condition (45.6%). We hypothesized that the immune modulation induced by nematodes is a factor that enhances TB infection/progression and that eosinophilia seen in TB patients is a consequence of helminth infection.

Prevalence of intestinal nematodes in alcoholic patients

We report the results of a retrospective study on the frequency of intestinal nematodes among 198 alcoholic and 440 nonalcoholic patients at the University Hospital Cassiano Antonio Moraes in Vitória, ES, Brazil. The control sample included 194 nonalcoholic patients matched according to age, sex and neighborhood and a random sample of 296 adults admitted at the same hospital. Stool examination by sedimentation method (three samples) was performed in all patients. There was a significantly higher frequency of intestinal nematodes in alcoholics than in controls (35.3% and 19.2%, respectively), due to a higher frequency of Strongyloides stercoralis (21.7% and 4.1%, respectively). Disregarding this parasite, the frequency of the other nematodes was similar in both groups. The higher frequency of S. stercoralis infection in alcoholics could be explained by immune modulation and/or by some alteration in corticosteroid metabolism induced by chronic ethanol ingestion. Corticosteroid metabolites would mimic the worm ecdisteroids, that would in turn increase the fecundity of females in duodenum and survival of larvae. Consequently, the higher frequency of Strongyloides larvae in stool of alcoholics does not necessarily reflect an increased frequency of infection rate, but only an increased chance to present a positive stool examination using sedimentation methods.

Interactions between nutrition and infections with Haemonchus contortus and related gastro-intestinal nematodes in small ruminants

Interactions between host nutrition and feeding behaviour are central to understanding the pathophysiological consequences of infections of the digestive tract with parasitic nematodes. The manipulation of host nutrition provides useful options to control gastrointestinal nematodes as a component of an integrated strategy. Focused mainly on the Hameonchus contortus infection model in small ruminants, this chapter (i) illustrates the relationship between quantitative (macro- and micro-nutrients) and qualitative (plant secondary metabolites) aspects of host nutrition and nematode infection, and (ii) shows how basic studies aimed at addressing some generic questions can help provide solutions, despite the considerable diversity of epidemiological situations and breeding systems.

Intestinal helminthes and/or Toxocara infection are unrelated to anti-HBs titers in seven-year-old children vaccinated at birth with recombinant hepatitis B vaccine

The aim of this investigation was to evaluate the possible effect of nematode infection on anti-HBs antibody levels in the serum of seven-year-old schoolchildren vaccinated at birth with the recombinant hepatitis B vaccine. Anti-HBs and anti HBc antibodies were evaluated in the sera of 100 schoolchildren with at least one intestinal nematode and/or a positive serological reaction for anti-Toxocara antibodies and in 95 schoolchildren without intestinal helminthiasis or serum anti-Toxocara antibodies. Both groups were from public elementary schools located on the urban periphery of Vitória, ES, Brazil. Among these 195 children, the median anti-HBs antibody titer was 31.3IU/ml and the frequency of titers less than 10IU/ml was 33.8% (95% CI: 27.1-40.4%). There were no significant differences between the medians of anti-HBs titers or the frequency of titers less than 10IU/ml between the groups with or without helminthes (29.5 and 32.9IU/ml and 33 and 34.7%, respectively; p>0.05). Even when the children with intestinal nematodes and/or anti-Toxocara antibodies and with blood eosinophil counts over 600/mm³ were compared with children without infection from intestinal nematodes and without anti-Toxocara antibodies, with blood eosinophil counts less than 400 eosinophils/mm³, these differences were not significant. None of the children presented anti-HBc antibodies. In conclusion, infections with intestinal nematodes and/or the presence of anti-Toxocara antibodies did not interfere with the anti-HBs antibody titers in seven-year-old children vaccinated at birth with the recombinant hepatitis B vaccine.

The enigmatic eosinophil: investigation of the biological role of eosinophils in parasitic helmint infection

In many helminth infected hosts the number of eosinophils increases dramatically, often without any concurrent increases in the number of other leukocytes, so that eosinophils become the dominant cell type. Many experimental investigations have shown that the eosinophilia is induced by interleukin-5 (IL-5) but its functional significance remains unclear. Mice genetically deficient in IL-5 (IL-5-/-) have been used to evaluate the functional consequences of the IL-5 dependent eosinophilia in helminth infected hosts. Host pathology and level of infection were determined in IL-5-/- and wild type mice infected with a range of species representative of each major group of helminths. The effects of IL-5 deficiency were very heterogeneous. Of the six species of helminth examined, IL-5 dependent immune responses had no detectable effect in infections with three species, namely the cestodes Mesocestoides corti and Hymenolepis diminuta and the trematode Fasciola hepatica. In contrast, IL-5 dependent immune responses were functionally important in mice infected with three species, notably all nematodes. Damage to the lungs caused by migrating larvae of Toxocara canis was reduced in IL-5-/- mice. Infections of the intestine by adult stages of either Strongyloides ratti or Heligmosomoides polygyrus were more severe in IL-5-/- mice. Adult intestinal nematodes were clearly deleteriously affected by IL-5 dependent processes since in its presence there were fewer worms which had reduced fecundity and longevity. The implications of these results for the viability of using inhibitors of IL-5 as a therapy for asthma are considered.

Nematode Infections Are Risk Factors for Staphylococcal Infection in Children

Nematode infection may be a risk factor for pyogenic liver abscess in children and we hypothesized that the immunomodulation induced by those parasites would be a risk factor for any staphylococcal infection in children. The present study was designed to compare, within the same hospital, the frequency of intestinal nematodes and Toxocara infection in children with and without staphylococcal infections. From October 1997 to February 1998, 80 children with staphylococcal infection and 110 children with other diseases were submitted to fecal examination, serology for Toxocara sp., evaluation of plasma immunoglobulin levels, and eosinophil counts. Mean age, gender distribution, birthplace, and socioeconomic conditions did not differ significantly between the two groups. Frequency of intestinal nematodes and positive serology for Toxocara, were remarkably higher in children with staphylococcal infections than in the non-staphylococcal group. There was a significant correlation between intestinal nematodes or Toxocara infection and staphylococcal infection in children, reinforced by higher eosinophil counts and higher IgE levels in these children than in the control group. One possible explanation for this association would be the enhancement of bacterial infection by the immunomodulation induced by helminth infections, due to strong activation of the Th2 subset of lymphocytes by antigens from larvae and adult worms.

In vitro and in vivo evaluation of the activity of pineapple (Ananas comosus) on Haemonchus contortus in Santa Inês sheep

The development of resistance to anthelmintics has prompted research into alternative methods of controlling intestinal nematodes in ruminants. This study aimed to assess the activity of Ananas comosus on Haemonchus contortus in Santa Inês sheep. The aqueous extract of pineapple skin (AEPS), bromelain from pineapple stems (B4882) and residue from pineapple processing was evaluated in in vitro and in vivo tests. The enzymatic activity of substances was analyzed by the azocasein method. The egg hatch test (EHT) and larval development test (LDT) were performed using the Embrapa2010 isolate of H. contortus. In the in vivo test, 36 sheep artificially infected with H. contortus were divided into six groups: G1: 2g/kg BW of the aqueous extract administered for three days; G2: 2g/kg BW of the industrial pineapple residue for 60 days; G3: 180mg/animal of bromelain in a single dose; G4: negative control I; G5: positive control (levamisole phosphate); and G6: negative control II. The eggs per gram (EPG) in the feces were counted till 28 days after treatment. LC50 and LC90 were obtained by the probit procedure, while the in vivo test results were analyzed by GLM. The aqueous extract in the in vitro and in vivo test, the bromelain and industrial residue presented 0.102, 0.157, 1.864 and 0.048 enzyme units/mL, respectively. In the egg hatch test, the LC50 and LC90 were respectively 31 and 81mg/mL for the aqueous extract and 0.50 and 2mg/mL for bromelain. In the larval development test, the LC50 and LC90 were respectively 1.7 and 7.3mg/mL for the aqueous extract and 0.019 and 0.086mg/mL for bromelain. In the in vivo test, the general efficacies of the treatments in relation to the negative control were 22.6%, 42.2%, 3.65% and 89% for the aqueous extract, industrial pineapple residue, bromelain and positive control respectively. The transformed EPG values were 3.19±0.59, 3.32±0.25, 2.85±0.66, 3.44±0.50, 2.28±0.93 and 2.75±0.94 for the aqueous extract, industrial residue, bromelain, negative control I, positive control and negative control II respectively. The results for all the treated groups differed significantly (p<0.05) from the positive control, and although the residue presented efficacy of 42.2%, there was no statistical difference (p>0.05) in relation to the negative control. Therefore, both the aqueous extract and bromelain were effective in vitro, but showed reduced anthelmintic efficacy in vivo. For the pineapple residue, the 42.2% in vivo efficacy in reducing the EPG and the possibility of reducing environmental contamination through reuse of industrial residue indicate it can also be useful for control of this parasite. © 2013 Elsevier B.V.

Avaliação comparativa de duas formulações anti-helmínticas em caprinos naturalmente infectados

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Haemonchus contortus acetylcholine receptors of the DEG-3 subfamily and their role in sensitivity to monepantel

Gastro-intestinal nematodes in ruminants, especially Haemonchus contortus, are a global threat to sheep and cattle farming. The emergence of drug resistance, and even multi-drug resistance to the currently available classes of broad spectrum anthelmintics, further stresses the need for new drugs active against gastro-intestinal nematodes. A novel chemical class of synthetic anthelmintics, the Amino-Acetonitrile Derivatives (AADs), was recently discovered and the drug candidate AAD-1566 (monepantel) was chosen for further development. Studies with Caenorhabditis elegans suggested that the AADs act via nicotinic acetylcholine receptors (nAChR) of the nematode-specific DEG-3 subfamily. Here we identify nAChR genes of the DEG-3 subfamily from H. contortus and investigate their role in AAD sensitivity. Using a novel in vitro selection procedure, mutant H. contortus populations of reduced sensitivity to AAD-1566 were obtained. Sequencing of full-length nAChR coding sequences from AAD-susceptible H. contortus and their AAD-1566-mutant progeny revealed 2 genes to be affected. In the gene monepantel-1 (Hco-mptl-1, formerly named Hc-acr-23H), a panel of mutations was observed exclusively in the AAD-mutant nematodes, including deletions at intron-exon boundaries that result in mis-spliced transcripts and premature stop codons. In the gene Hco-des-2H, the same 135 bp insertion in the 5' UTR created additional, out of frame start codons in 2 independent H. contortus AAD-mutants. Furthermore, the AAD mutants exhibited altered expression levels of the DEG-3 subfamily nAChR genes Hco-mptl-1, Hco-des-2H and Hco-deg-3H as quantified by real-time PCR. These results indicate that Hco-MPTL-1 and other nAChR subunits of the DEG-3 subfamily constitute a target for AAD action against H. contortus and that loss-of-function mutations in the corresponding genes may reduce the sensitivity to AADs.

In vitro selection of Haemonchus contortus for benzimidazole resistance reveals a mutation at amino acid 198 of beta-tubulin

Benzimidazoles were the first broad-spectrum anthelmintics and are still in use today against gastro-intestinal nematodes of ruminants such as Haemonchus contortus. Benzimidazoles block the polymerization of nematode microtubules. However, their efficacy is jeopardized by the spread of drug-resistant parasites that carry point mutations in beta-tubulin. Here we use a novel in vitro selection-in vivo propagation protocol to breed drug-resistant H. contortus. After 8 generations of selection with thiabendazole an in vitro resistance factor of 1000 was reached that was also relevant in vivo in infected sheep. The same procedure carried out with ivermectin produced only a moderate resistance phenotype that was not apparent in sheep. Cloning and sequencing of the beta-tubulin genes from the thiabendazole-resistant H. contortus mutants revealed all of the isotype 1 alleles, and part of the isotype 2 alleles, to carry the mutation glutamate(198) to alanine (E198A). An allele-specific PCR was developed, which may be helpful in monitoring the prevalence of alanine(198) encoding alleles in the beta-tubulin isotype 1 gene pool of H. contortus in the field.

Importance of immunoglobulin E (IgE) in the protective mechanism against gastrointestinal nematode infection: looking at the intestinal mucosae

This review discusses experimental evidences that indicate the IgE participation on the effector mechanisms that leads to gastrointestinal nematode elimination. Data discussed here showed that, for most experimental models, the immune response involved in nematode elimination is regulated by Th-2 type cytokines (especially IL-4). However, the mechanism(s) that result in worm elimination is not clear and might be distinct in different nematode species. Parasite specific IgE production, especially the IgE produced by the intestinal mucosae or associated lymphoid organs could participate in the intestinal elimination of Trichinella spiralis from infected rats. Intestinal IgE may also be important to the protective mechanism developed against other gastrointestinal nematodes that penetrate the murine duodenum mucosa tissue, such as Strongyloides venezuelensis and Heligmosomoides polygyrus. At least in Trichinella spiralis infected rats, the results indicated that intestinal IgE might work independently from mast cell degranulation for worm elimination.

Intestinal helminths of capybaras, Hydrochoerus hydrochaeris, from Venezuela

Quantitative parameters of intestinal helminth species and their potential relations to host characteristics in a population of capybaras (Hydrochoerus hydrochaeris) from Venezuela are reported for the first time. The intestines of 40 capybaras were collected during the 1992-annual harvest at Hato El Cedral. Six helminth species were found: 2 cestodes (Monoecocestus macrobursatum, M. hagmanni), 2 nematodes (Viannella hydrochoeri, Protozoophaga obesa), and 2 trematodes (Hippocrepis hippocrepis, Taxorchis schistocotyle). This is the first report for M. macrobursatum in Venezuela. Helminth abundance did not differ between sexes or age classes. Although patterns of distribution for all helminth species were overdispersed, the high prevalence found for all species (over 70%) and the high abundance observed for nematodes made it difficult to assess the effect that these helminths may produce on capybaras. Nevertheless, the negative associations found between the body condition of capybaras and helminth intensity for M. macrobursatum and V. hydrochoeri, might be pointing out potential host population regulatory role for these parasites which require further research.

Intestinal parasitic infections and eosinophilia in an human immunedeficiency virus positive population in Honduras

The occurrence of intestinal parasites, their regional distribution and their relations to eosinophilia were studied in 133 human immunodeficiency virus (HIV) positive individuals from Honduras. After signing an informed consent, participants answered a socio-demographic and risk factor questionnaire, a complete physical examination, medical history, and a series of laboratory tests. All participants were HIV positive but not acquired immunodeficiency syndrome positive. Of them, 67% were co-infected with pathogen and non pathogen parasites. Overall occurrence of nematodes was: 44.3% for Trichuris trichiura, 24% for Ascaris lumbricoides, 12% for Hookworm and 7.5% for Strongyloides stercoralis. No cases of Giardia lamblia, acute amebiasis or cryptosporidiasis were diagnosed. Mean eosinophil percents for participants were consistently and significantly higher in infected than in non infected individuals: 22% for Hookworm vs 7.2% (p < 0.001), 11% for Trichuris compared to 5.2% (p < 0.001), 13.2% compared to 7.5% for S. stercoralis (p < 0.05), and 12% compared to 6% for Ascaris cases (p < 0.05). Helminths and non pathogenic protozoa, as single or mixed infections, occurred among the participants. There was a strong correlation between eosinophilia and helminthiasis infections; however, none was identified between CD4 levels and eosinophilia. Because parasitic infections aggravate malnutrition and promote a disbalanced Th2 response in a potentially immuno-compromised host, their effect on HIV disease progression needs further study, mainly in countries were HIV and parasitic infections are highly prevalent.