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PubMed2003

Drug resistance in nematodes: a paper tiger or a real problem?

PURPOSE OF REVIEW: The purpose of this review is to illustrate where drug resistance in parasitic nematodes has become a major problem. The mechanisms underlying anthelmintic resistance, the possible reasons for the development of anthelmintic resistance, and recommendations to minimize the further development of anthelmintic resistance in humans will be addressed. RECENT FINDINGS: Resistance has developed to all drugs of the few anthelmintic classes currently available. Drug resistance has become a major threat to sheep production in Australia, New Zealand, Great Britain and South Africa. In addition, the treatment of nematode infections in horses has become insufficient because of anthelmintic resistance, whereas resistance in cattle has recently been found in New Zealand and southern America. In contrast, anthelmintic resistance to human helminths has only been reported anecdotally. The rate of development of anthelmintic resistance is determined by the resistance gene frequency and by selection pressure, as illustrated by the concept of 'worms in refugia' in ovine nematode infections. SUMMARY: Although anthelmintic resistance has become a major constraint in livestock production of small ruminants, drug resistance is currently not a major issue in the treatment of human nematode infections. However, if recent community treatment programmes are pursued injudiciously, the inevitable evolutionary consequence of anthelmintic resistance in humans might emerge sooner rather than later.

Anthelmintics↗
PubMed2003

A key mechanism of pathogenesis in sheep infected with the nematode Teladorsagia circumcincta.

Infection of sheep with the abomasal nematode Teladorsagia circumcincta can cause a relative protein deficiency and reduce growth rate in growing lambs. A key event appears to be the destruction of junctions between epithelial cells. If the infection is heavy or prolonged, this leads to increased mucus production, hyperplasia, decreased acid production, gastrinemia, inappetance and pepsinogenemia. The severity of the infection depends upon the extent of concurrent infection, the nutritional status of the host and genetically controlled variation in the ability to mount protective immune responses.

Abomasum↗
PubMed2005

Intron 1 of the interferon gamma gene: Its role in nematode resistance in Suffolk and Texel sheep breeds.

Genetic variation at intron 1 of the interferon gamma gene has recently been associated with variation in faecal egg count in Romney, Merino and Soay breeds of sheep. The Texel breed is more resistant to gastrointestinal nematode infection than the Suffolk breed, based on faecal egg count. Hence, the objective of this experiment was to characterise the polymorphisms of intron 1 of the interferon gammagene in Suffolk and Texel sheep, and to determine if the characterised haplotype variants were associated with faecal egg count variation in these breeds. Intron 1 haplotypes and faecal egg measurements were determined for Suffolks (n=113) and Texels (n=135). Four haplotypes were identified in Suffolks (A, B, C and D), two haplotypes as previously described, and two previously unknown haplotypes. However, there was no association between interferon gamma intron 1 haplotype and faecal egg count in Suffolks. In contrast, two previously identified haplotypes (A and B) were present in the Texel breed, and the B haplotype was associated with resistance to nematode infection (P=0.02). These results suggest that intron 1 of the interferon gamma gene has an important role in resistance to nematode infection in the Texel breed.

Animals↗
PubMed1998

Natural evolution of gastrointestinal nematodes in goats (Capra hircus) in the semi-arid ecosystem of the Paraíba backwoods, northeastern Brazil.

This study was conducted in Patos county, a semi-arid area with caatinga vegetation in Paraiba State, northeastern Brazil. Twenty-four male goats of mixed breeds were used. The animals were separated in age groups from 1-12 months, i. e., 1-2, 3-4, 5-6, 7-8, 9-10, 11-12 months, with four animals in each group. The animals were slaughtered and necropsied to recover and identify adult worms. The goats were exposed to nematode infection from the first month of life. The most prevalent nematodes in decreasing order were: Trichostrongylus colubriformis, Haemonchus contortus and Oesophagostomum columbianum. Age of the goats did not appear to be a factor in resistance to gastrointestinal nematode infection. Worm burdens of 11-12 month old animals were significantly (P<0.05) higher than in other age groups.

Age Factors↗
PubMed2004

Rapid age-related changes in infection behavior of entomopathogenic nematodes.

Nonfeeding infective juvenile (IJ) entomopathogenic nematodes (EPNs) are used as biological agents to control soil-dwelling insects, but poor storage stability remains an obstacle to their widespread acceptance by distributors and growers as well as a frustration to researchers. Age is one factor contributing to variability in EPN efficacy. We hypothesized that age effects on the infectiousness of IJs would be evident within the length of time necessary for IJs to infect a host. The penetration behavior of "young" (<1-wk-old) and "old" (2- to 4-wk-old) Heterorhabditis bacteriophora (GPS 11 strain), Steinernema carpocapsae (All strain), and Steinernema feltiae (UK strain) IJs was evaluated during 5 "exposure periods" to the larvae of the wax moth, Galleria mellonella. Individual larvae were exposed to nematode-infested soil for exposure periods of 4, 8, 16, 32, and 64 hr. Cadavers were dissected after 72 hr, and the IJs that penetrated the larvae were counted. Larval mortality did not differ significantly between 72- and 144-hr "observation periods," or points at which larval mortality was noted, for any age class or species. However, age and species effects were noted in G. mellonella mortality and nematode penetration during shorter time periods. Initial mortality caused by S. carpocapsae and H. bacteriophora IJs declined with nematode age but increased with S. feltiae IJ age. Young S. carpocapsae IJs penetrated G. mellonella larvae at higher rates than old members of the species (27-45% vs. 1-4%). Conversely, old S. feltiae IJs had higher penetration rates than young IJs (approximately 8 to 57% vs. 4 to approximately 31%), whereas H. bacteriophora IJs had very low penetration rates regardless of age (3-5.6%). Our results show that the effect of age on IJ infectiousness can be detected in IJs aged only 2 wk by a 4-hr exposure period to G. mellonella. These results have important implications for storage and application of EPNs and suggest the possibility of shortening the time required to detect nematodes in the soil.

Animals↗
PubMed2004

Regulation of RELM/FIZZ isoform expression by Cdx2 in response to innate and adaptive immune stimulation in the intestine.

Host immune responses to commensal flora and enteric pathogens are known to influence gene expression in the intestinal epithelium. Although the Cdx family of caudal-related transcription factors represents critical regulators of gene expression in the intestinal epithelium, the effect of intestinal immune responses on Cdx expression and function has not been determined. We have shown that bacterial colonization and Th2 immune stimulation by intestinal nematode infection induce expression of the intestinal goblet cell-specific gene RELM beta. In this study, we investigated the transcriptional regulation of resistin-like molecule/found in inflammatory zone (RELM/FIZZ, RELM beta) and its isoforms RELM alpha and RELM gamma to ascertain the role of Cdx in modifying intestinal gene expression associated with innate and adaptive immune responses. Analysis of the RELM beta promoter showed that Cdx2 plays a critical role in basal gene activation in vitro. This was confirmed in vivo using transgenic mice, where ectopic gastric and hepatic expression of Cdx2 induces expression of RELM beta, but not RELM alpha or RELM gamma, exclusively in the stomach. Although there was no quantitative change in colonic Cdx2 mRNA expression, protein distribution, or phosphorylation of Cdx2, bacterial colonization induced expression of RELM beta, but not RELM alpha or RELM gamma. In contrast, parasitic nematode infections activated colonic expression of all three RELM isoforms without alteration in Cdx2 expression. These results demonstrated that Cdx2 participates in directing intestine-specific expression of RELM beta in the presence of commensal bacteria and that adaptive Th2 immune responses to intestinal nematode infections can activate intestinal goblet cell-specific gene expression independent of Cdx2.

Animals↗
PubMed1987

The physiology of infection with nematodes: the role of intracellular pH in the development of the early parasitic stage.

1. H2CO3, the host's signal which induced (less than 25 min) the Ca2+-dependent development of the first parasitic stage of Haemonchus contortus, produced a diphasic change in the pHi (less than 30 min), measured with 5,5-dimethyl-2,4-oxazolidinedione, in the infective stage. The intensity of the diphasic change was related to the [H2CO3] and so to the efficiency of the stimulus for development. 2. MES and HEPES buffers induced a rapid rise in pHi of infective stages in step with pHo. Ortho-and pyrophosphate induced greater changes in pHi. Such buffers did not initiate development. 3. These and other results suggest that the stimulus for development, H2CO3, induced an energy-dependent Ca2+/H+ exchange mediated by mitochondria of the infective stage, which initiated development of the parasitic stage.

Ammonium Chloride↗
PubMed1994

Nematodes and the spleen: an immunological relationship.

Despite being a major organ of the immune system, the spleen's role in resisting, controlling or simply ameliorating nematode infections has been neglected. A review of both filarial and gastrointestinal nematodes suggests that though it is difficult to fully assess or quantify the organ's importance in vivo, the spleen is prominent in acting against nematode parasites in mammals. One manifestation of this is that transfer of lymphocytes from the spleen of immunised individuals can protect recipients against the disease. Expansion of splenic lymphoid tissue also alludes to its activity during nematode infection. There is a considerable need for investigation of the spleen under natural conditions as well as much more rigorously controlled experiments even in mammals besides birds and other vertebrates.

Animals↗
PubMed1981

The heterologous protection of rats against a challenge with Fasciola hepatica by prior infection with the nematode Nippostrongylus brasiliensis.

Previous infection of rats with nippostrongylus brasiliensis was shown to result in protection against an oral challenge with Fasciola hepatica metacercariae but not against an intraperitoneal challenge with newly excysted juvenile (NEJ) flukes. The timing of the challenge was important and a double infection with the nematode gave more consistent results than a single. Resistance appeared to be associated with a prior induction of intestinal eosinophilia. Sera from these resistant rats, however, failed to induce eosinophil adherence to NEJ flukes in vitro.

Animals↗
PubMed1999

Persistent efficacy of doramectin pour-on against artificially induced infections of nematodes in cattle.

Two studies were conducted to determine the persistent efficacy of doramectin pour-on against an artificial, trickle challenge of mixed nematodes in calves. In each study, 42, 4-8 months old calves were randomly assigned into four groups of 10 animals each (T1-T4), plus two larval-viability monitor animals. All animals were treated with fenbendazole (10 mg kg(-1)) 14 days prior to the start of the study to clear any existing infection. Doramectin pour-on at 500 microg kg(-1) was used on each animal in Groups T2, T3, and T4 with intervals of 1 week (Day 0, 7, and 14, respectively). Calves in Group T1 were treated with saline solution on Day 0 and at the same volumetric rate (1 ml 10 kg(-1)) as the doramectin treated animals. All treatments were applied in a single passage along the midline of the back, from the withers to the tailhead. Subsequently, trickle inoculations with infective larvae were administered to all calves for 22 consecutive days (Days 14-35). Doramectin pour-on provided > or = 91.9% efficacy against challenge with Dictyocaulus viviparus, Haemonchus spp., and Ostertagia ostertagi for up to 35 days post-treatment and against challenge with Cooperia oncophora, Cooperia punctata, and Oesophagostomum radiatum for up to 28 days post-treatment.

Abomasum↗
PubMed2002

IL-4 dependent alternatively-activated macrophages have a distinctive in vivo gene expression phenotype.

BACKGROUND: "Alternatively-activated" macrophages are found in Th2-mediated inflammatory settings such as nematode infection and allergic pulmonary inflammation. Due in part to a lack of markers, these cells have not been well characterized in vivo and their function remains unknown. RESULTS: We have used murine macrophages elicited by nematode infection (NeM(phi)) as a source of in vivo derived alternatively activated macrophages. Using three distinct yet complementary molecular approaches we have established a gene expression profile of alternatively activated macrophages and identified macrophage genes that are regulated in vivo by IL-4. First, genes abundantly expressed were identified by an expressed sequence tag strategy. Second, an array of 1176 known mouse genes was screened for differential expression between NeM(phi) from wild type or IL-4 deficient mice. Third, a subtractive library was screened to identify novel IL-4 dependent macrophage genes. Differential expression was confirmed by real time RT-PCR analysis. CONCLUSIONS: Our data demonstrate that alternatively activated macrophages generated in vivo have a gene expression profile distinct from any macrophage population described to date. Several of the genes we identified, including those most abundantly expressed, have not previously been associated with macrophages and thus this study provides unique new information regarding the phenotype of macrophages found in Th2-mediated, chronic inflammatory settings. Our data also provide additional in vivo evidence for parallels between the inflammatory processes involved in nematode infection and allergy.

Animals↗
PubMed2006

A neutral protease from Bacillus nematocida, another potential virulence factor in the infection against nematodes.

A neutral protease (npr) (designated Bae16) toxic to nematodes was purified to homogeneity from the strain Bacillus nematocida. The purified protease showed a molecular mass of approximately 40 kDa and displayed optimal activity at 55 degrees C, pH 6.5. Bioassay experiments demonstrated that this purified protease could destroy the nematode cuticle and its hydrolytic substrates included gelatin and collagen. The gene encoding Bae16 was cloned, and the deduced amino acid sequence showed 94% sequence identity with npr gene from B. amyloliquefaciens, but had low similarity (13-43%) with the previously reported virulence serine proteases from fungi or bacteria, which reflected their differences. Recombinant mature Bae16 (rm-Bae16) was expressed in Escherichia coli BL21 using pET30 vector system, and its nematicidal activity confirmed that Bae16 could be involved in the infection process. Our present study revealed that the npr besides the known alkaline serine protease could serve as a potential virulence factor in the infection against nematodes, furthermore, the two proteases with different characteristics produced by the same strain co-ordinated efforts to kill nematodes. These data helped to understand the interaction between this bacterial pathogen and its host.

Animals↗
PubMed1998

The processes influencing the distribution of parasitic nematodes among naturally infected lambs.

The impact of mixed, nematode infection upon a group of animals will depend upon the number of nematodes present, how they are distributed among hosts and whether individuals that are heavily parasitized with one species are more likely to be heavily parasitized with other species. A survey of over 500 six-month-old, Scottish Blackface lambs from a single farm in Southwest Strathclyde identified 7 different categories of nematodes in the abomasum and small intestine. There were considerable differences among years and among nematodes in the prevalence and mean intensity of infection. Ostertagia circumcincta was present in nearly all lambs and judged by prevalence and intensity is one of the most successful of all parasitic nematodes. Each category of nematodes had a skewed distribution; most animals had relatively few worms but a small proportion had many worms. The variance of the number of nematodes in each category were approximately equal to the square of the mean. The counts of adult O. circumcincta followed a negative binomial distribution, but the negative binomial distribution did not provide a good description of the observed values for the other species. These other species had a lower prevalence and possibly some sheep were not exposed to infection. There was no significant genetic variation among lambs in the number of nematodes present and therefore the differences among these lambs were unlikely to be a consequence of genetic differences in host susceptibility. Lambs with increased numbers of one species were more likely to be have increased numbers of the other species, but the correlations were weak and may reflect covariation in exposure to different parasites.

Abomasum↗
PubMed2004

Biochemical changes in Glomus fasciculatum colonized roots of Lycopersicon esculentum in presence of Meloidogyne incognita.

Glasshouse experiments were conducted to elicit biochemical substantiation for the observed difference in resistance to nematode infection in roots colonized by mycorrhiza, and susceptibility of the fresh flush of roots of the same plant that escaped mycorrhizal colonization. Tomato roots were assayed for their biochemical profiles with respect to total proteins, total phenols, indole acetic acid, activities of polyphenol oxidase, phenylalanine ammonia lyase and indole acetic acid oxidase. The roots of the same plant (one set) received Glomus fasciculatum and G. fasciculatum plus juveniles of Meloidogyne incognita separately; and half the roots of second set of plants received G. fasciculatum while the other half of roots did not receive any treatment. Roots colonized by G. fasciculatum recorded maximum contents of proteins and phenols followed by that of the roots that received G. fasciculatum plus M. incognita. However, IAA content was lowest in the roots that received mycorrhiza or mycorrhiza plus juveniles of root-knot nematode and correspondingly. Roots that received juveniles of root-knot nematode recorded maximum IAA content and per cent increase over healthy check and mycorrhiza-inoculated roots. The comparative assay on the activities of PPO, PAL and IAA oxidase enzymes in treated and healthy roots of tomato, indicated that PAL and IAA oxidase activities were maximum in G. fasciculatum colonized roots followed by the roots that received mycorrhiza plus juveniles of root-knot nematode, while the activity of PPO was minimum in these roots. The roots that received juveniles of root-knot nematode recorded minimum PAL and IAA oxidase activities and maximum PPO activity. Since the roots of same plant that received mycorrhiza and that did not receive mycorrhiza; and the plant that received nematode alone and mycorrhiza plus nematode recorded differential biochemical contents of proteins, total phenols and IAA, and differential activities of enzymes under study, it was evident that the biochemical defense response to mycorrhizal colonization against root-knot nematodes was localized and not systemic. This explained for the response of plant that differed in root galling due to nematode infection in presence of mycorrhizal colonization. The new or fresh roots which missed mycorrhizal colonization, got infected by nematodes and developed root galls.

Animals↗
PubMed1999

Can prevalence of infection in school-aged children be used as an index for assessing community prevalence?

Community data on the prevalence of helminth infections is important for guiding health policy, but expensive to collect. As a result most surveys focus on school-aged children, frequently using schools as a sentinel population. Since there already exists a vast amount of data on infection levels in school-aged children, but limited community-based data, we undertook a literature search on age-stratified infection data for intestinal nematode infections and schistosomiasis in Africa, to investigate whether estimates of the prevalence of infection in school-aged children could provide an index for determining community prevalence. The observed data on prevalence of infection in infants, school-aged children and adults were fitted using linear and logistic regression models which take into account variation in sample prevalences. Despite the wide variation in study sites, the observed relationship between community prevalence and school-aged prevalence was remarkably consistent for each parasite species. The prevalence of infection in school-aged children alone was shown to be higher than the predicted prevalence in the community, but the degree of overestimation was dependent on the parasite species and the level of infection. The results suggest that the prevalence of infection in school-aged children could provide a cost-effective predictive tool which can be used at a district/national level to identify target areas for control and to evaluate the numbers at risk of infection.

Adolescent↗
PubMedDate not supplied

In vitro activity of Brazilian strains of the predatory fungi Arthrobotrys spp. on free-living nematodes and infective larvae of Haemonchus placei.

In vitro tests were carried out to assess the activity of 26 Brazilian isolates of predatory fungi of the genus Arthrobotrys on a free-living nematode (Panagrellus sp.) and on infective larvae of Haemonchus placei, a parasitic gastrointestinal nematode of cattle. The results showed that the free-living nematode Panagrellus sp. was the most preyed upon, compared to H. placei, for all the fungal treatments. Also, variable predatory capacity was observed for different fungal isolates belonging to the same genus when applied to different nematode species.

Animals↗
PubMed2001

Assessment of genetic variability of resistance to gastrointestinal nematode parasites in Creole goats in the humid tropics.

Goat production is widespread in the tropics. Goats are very susceptible to gastrointestinal nematode infection, but there is less evidence of their genetic resistance. Genetic resistance of Creole goats to gastrointestinal nematodes has been studied at Guadeloupe in the French West Indies since 1995. The objective of this research was to investigate genetic variation for resistance to gastrointestinal nematode infection, in order to introduce this trait into breeding schemes. Genetic variability was assessed within a Creole experimental flock. Forty-nine sire groups were characterized at weaning and 55 during fattening after weaning. Kids were naturally infected, mainly by Haemonchus contortus and Trichostrongylus colubriformis. Fecal egg counts were determined once at weaning and every 6 and 7 wk after drenching during fattening. Blood samples were collected every 7 wk during fattening for determination of packed cell volume. Live weights were recorded at weaning and at the beginning and middle of every infection period during fattening. Genetic parameters were estimated using the REML for multivariate animal models. The heritability estimate for transformed fecal egg count was 0.37+/-0.06 at weaning. During fattening, it increased from 0.14+/-0.05 at 4 mo to 0.33+/-0.06 at 10 mo. Heritabilities of packed cell volume ranged from 0.10 to 0.33. At weaning, maternal heritability of fecal egg count reached 0.26 and direct heritability 0.20. After 6 mo of age, maternal effects were found to be unimportant for fecal egg count and packed cell volume. Live weights presented significant genetic variability. Genetic relationships between fecal egg counts and live weight in infected pastures were never significant. Genetic correlations between packed cell volume and live weight decreased from 0.47 to 0.10 from weaning to 10 mo of age. These results demonstrated the feasibility of breeding for improved resistance to nematodes in Creole kids.

Animals↗
PubMed2006

The mast cell and gut nematodes: damage and defence.

Gut nematode infection induces a dominant type 2 immune response, crypt hyperplasia and mucosal mastocytosis. Despite their strong association with nematode infection, the role of mast cells in the mechanism of worm expulsion is yet to be fully defined. Recent work suggests that they contribute to resistance, aiding the effector mechanisms which ultimately result in worm expulsion. Although it is widely accepted that both connective and mucosal mast cells arise from a common progenitor, it is clear that mucosal mastocytosis is dependent on the presence of type 2 cytokines such as interleukin 4 (IL-4), IL-9, IL-10 and IL-13. Importantly, it is now evident that mucosal mast cells can amplify this protective response, as well as contributing to intestinal pathology. Here we discuss current areas of interest in this field, including the potentially conflicting role that mast cells play in intestinal inflammation. We also highlight the significance of these responses to current ideas relating to parasite infection and allergy.

Animals↗