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Interleukin (IL)-4-independent immunoglobulin class switch to immunoglobulin (Ig)E in the mouse.

Immunoglobulin (Ig) class switching in B cells is regulated by stimuli transduced by cytokines and cell-cell contact. Among these stimuli, interleukin (IL)-4 has been considered an absolute prerequisite for class switching to IgE in the mouse. Here we report that IL-4-deficient (IL-4-/-) and wildtype mice had comparably elevated serum IgE levels during the course of a murine retrovirus-induced immunodeficiency syndrome, MAIDS. IgE switching in IL-4-/- mice was also induced by injection of anti-IgD antibody. Treatment with anti-IgD induced germline epsilon (g epsilon) transcripts with comparable efficiency in IL-4-/- mice and controls, but the levels of productive epsilon transcripts (p epsilon) were lower by a factor of 200 and serum IgE levels were lower by a factor of 300 in IL-4-/- mice as compared with controls. Induction of g epsilon after anti-IgD treatment of IL-4-/- mice was unaffected by simultaneous treatment with monoclonal antibodies to IL-4 and IL-4 receptor alpha chain. Infection of IL-4-/- mice with Nippostrongylus brasiliensis, a potent stimulus for IgE production, resulted in induction of g epsilon transcripts; however, p epsilon transcripts were barely detectable and serum IgE was not detected. These findings establish a novel IL-4-independent pathway for IgE switching in the mouse that is strongly activated in retroviral infection but weakly in nematode infection. This pathway appears to be dependent on distinct factors that separately control induction of g epsilon transcription and switch recombination to p epsilon.

Animals↗

Occurrence of concurrent trypanosomosis, theileriosis, anaplasmosis and helminthosis in Friesian, Zebu and Sahiwal cattle in Uganda.

An epidemiological investigation was conducted on farms in Tororo and Soroti districts of Uganda from January to February 2000 to determine the cause of reported persistent mortality of cattle. Blood and faecal material of 98 cattle comprising of 33 Friesians, 58 Zebu and 7 Sahiwal were examined. Results revealed that seven (7.1 %) cattle had trypanosome infection, mainly due to Trypanosoma vivax and T. brucei, 17 (17.3%) Fasciola infection, 28 (28.6%) gastrointestinal nematode infection, 33 (33.7%) Theileria sp. infection and 13 (13.3%) Anaplasma marginale infection. Mixed infections were detected in 30%, 20.6% and 43 % of the Friesian, Zebu and Sahiwal cattle respectively. Anaemia (PCV < 25) was detected in 24%, 19% and 14% of the Friesian, Zebu and Sahiwal cattle respectively. Persistent mortality of cattle on these farms could have been due to either single or mixed parasitic infections probably exacerbated by malnutrition.

Anaplasmosis↗

Mast cell-independent impairment of host defense and muscle contraction in T. spiralis-infected W/W(V) mice.

In response to nematode infection, the host presumably attempts to create an unfavorable environment to prevent larval penetration of the host and to expedite parasite expulsion from the gut. In this study, we have used W/W(V) mice with or without mast cells after bone marrow reconstitution (BMR-W/W(V)) to examine the role of mast cells in the host response. W/W(V), BMR-W/W(V), and wild-type (+/+) mice were infected with Trichinella spiralis. Infected W/W(V) mice exhibited less tissue damage and experienced a delay in worm expulsion and a greater degree of larval penetration of the gut leading to encystment in skeletal muscle. Tissue injury was greater and worm expulsion was normalized in BMR-W/W(V) mice, but larval penetration remained unchanged. Spontaneous contractile activity of jejunal muscle was disrupted in W/W(V) mice, as was the contractile response to carbachol. These abnormalities were also present in BMR-W/W(V) mice. These results indicate that mast cells mediate tissue damage and contribute to the timely expulsion of nematodes from the gut during primary infection.

Animals↗

Strategic control of gastrointestinal nematode and lungworm infections with eprinomectin at turnout and eight weeks later.

Two groups of 10 first-year grazing cattle were either left untreated as controls (group 1) or treated with eprinomectin as a pour-on application at turnout and eight weeks later (group 2). The control group developed a mild infection with gastrointestinal nematodes and lungworms during the season, whereas the treated animals remained healthy. The interval between the treatments allowed the establishment of adult worms, but the egg counts remained negligible. The total number of eggs shed by the treated cattle during the grazing season was significantly smaller than by the controls.

Animal Husbandry↗

Mucosal mast cell proliferation following normal and heterotopic infections of the nematode Nippostrongylus brasiliensis in rats.

Infections of intestinal nematodes induce the T cell-dependent proliferation of intestinal mucosal mast cells (MMC). To examine whether nematode-induced MMC proliferation is affected by the site of infestation, adult-stage nematode Nippostrongylus brasiliensis (NB) was transplanted into the normal infection site, the duodenum, or into heterotopic sites, the peritoneal cavity (i.p.) or subcutaneous tissue (s.c.), of rats. Two weeks after duodenal inoculation, MMC numbers in the small intestine had increased 6.5-fold. In contrast, i.p. and s.c. inoculation induced only slight increases of intestinal MMC. After i.p. inoculation, worm granulomas developed in the connective tissues adhering to stomach and duodenum, and large numbers of mast cells appeared around the granulomas. The majority of the latter mast cells showed histochemical features similar to MMC: they were formalin sensitive, berberine sulfate-, alcian blue+/safranine-, and rat mast cell protease (RMCP) II+. After s.c. inoculation, worm granulomas developed at the inoculation site, but the number of mast cells around the granulomas was not significantly increased. These results suggest that intense proliferation of MMC or MMC-like cells is induced only by the infections on mucosa or in mucosa-associated tissues.

Animals↗

The persistence of the efficacy of injectable or oral moxidectin against Teladorsagia, Haemonchus and Trichostrongylus species in experimentally infected sheep.

The persistence of the efficacy of moxidectin was evaluated against experimental gastrointestinal nematode infections in 55 lambs randomly allocated to 11 equal groups and infected on day 0. Moxidectin 1 per cent injectable solution was administered at a dose rate of 0.2 mg moxidectin/kg bodyweight to five of the groups on days -42, -35, -28, -21 and -14; five other groups were treated with moxidectin 0.1 per cent oral drench at the same dose rate on days -35, -28, -21, -14 and -7, and the 11th group remained untreated as a control. The lambs were infected experimentally with 8000 Teladorsagia circumcincta, 2000 Haemonchus contortus and 10,000 Trichostrongylus colubriformis infective larvae and killed three weeks later. Both formulations of moxidectin showed excellent activity against T circumcincta and H contortus with almost 100 per cent efficacy against the abomasal parasites for up to 35 days after treatment. The efficacy of moxidectin 1 per cent injectable against T colubriformis was much higher (> 99 per cent) than that of the oral drench and it was highly effective up to 21 days after treatment, and gave a moderate reduction in worm burden for up to 35 days after treatment. No adverse reactions to moxidectin were observed in any of the animals.

Administration, Oral↗

Gastrointestinal nematodes in indigenous Zebu cattle under pastoral and nomadic management systems in the lower plain of the southern highlands of Tanzania.

This study aimed to determine the prevalence and intensity of gastrointestinal nematode infections in indigenous Zebu cattle in the lower plain (lowland zone) of the southern highlands of Tanzania. Gastrointestinal tracts were randomly purchased at the Iringa regional abattoir and at Kihesa and Ipogolo slaughter slabs in different seasons of the year. The contents of the abomasum, small intestine and large intestine were processed separately to recover the worms. The results indicated that 140 out of 144 (97.2%) of the examined animals were infected. The mean (+/-SE) total worm burden was 1284 +/- 183 (range 10-12,600) worms per animal and most infected animals contained more than one nematode species. The nematode species present, their prevalence and mean burden were as follows: Haemonchus placei, 84.7%, 316; H. similis, 5.6%, 1; Oesophagostomum radiatum, 79.2%, 66; Cooperia pectinata, 55.6%, 713; C. punctata, 44.4%, 157; Bunostomum phlebotomum, 5.6%, 5; Trichuris globulosa, 5.6%, 2; and Trichostrongylus colubriformis, 1.4%, 24. The burdens were mainly composed of Cooperia pectinata (55.5%), Haemonchus placei (24.6%), Cooperia punctata (12.3%) and Oesophagostomum radiatum (5.1%). The highest burdens occurred at the end of the rainy/early dry season, while the lowest burdens were found at the end of the dry/early rainy season. There was no difference in the burdens between male and female animals. Immature cattle (< 3 years) had significantly higher worm burdens than mature cattle (p < 0.01). A poor grade for a live animal was associated with higher worm burdens only in immature cattle and then especially during the dry season (r = 0.456, p < 0.001). Anthelmintic treatments in the late rainy/early dry season and early rainy season are recommended in order to prevent outbreaks of helminthosis during the dry season and to reduce carryover of infection into the next rainy season. An additional wet season treatment is advisable in immature cattle, but may not be needed for mature cattle owing to the availability of plenty of mature, good quality pasture.

Abomasum↗

RELMbeta/FIZZ2 is a goblet cell-specific immune-effector molecule in the gastrointestinal tract.

Gastrointestinal (GI) nematode infections are an important public health and economic concern. Experimental studies have shown that resistance to infection requires CD4(+) T helper type 2 (Th2) cytokine responses characterized by the production of IL-4 and IL-13. However, despite >30 years of research, it is unclear how the immune system mediates the expulsion of worms from the GI tract. Here, we demonstrate that a recently described intestinal goblet cell-specific protein, RELMbeta/FIZZ2, is induced after exposure to three phylogenetically distinct GI nematode pathogens. Maximal expression of RELMbeta was coincident with the production of Th2 cytokines and host protective immunity, whereas production of the Th1 cytokine, IFN-gamma, inhibited RELMbeta expression and led to chronic infection. Furthermore, whereas induction of RELMbeta was equivalent in nematode-infected wild-type and IL-4-deficient mice, IL-4 receptor-deficient mice showed minimal RELMbeta induction and developed persistent infections, demonstrating a direct role for IL-13 in optimal expression of RELMbeta. Finally, we show that RELMbeta binds to components of the nematode chemosensory apparatus and inhibits chemotaxic function of a parasitic nematode in vitro. Together, these results suggest that intestinal goblet cell-derived RELMbeta may be a novel Th2 cytokine-induced immune-effector molecule in resistance to GI nematode infection.

Animals↗

Efficacy of morantel against nematode populations in calves exposed on a pasture stocked for two years with morantel sustained-release bolus-treated calves.

Two groups of 10 parasite-free calves were maintained either for 2 weeks on a pasture grazed by nonmedicated cattle (pasture A) or for 3 weeks on a pasture grazed by morantel sustained-release bolus-treated cattle (pasture B) for the preceding 2 years. After a 4-week holding period to allow for maturation of acquired gastrointestinal nematodes, 5 calves from each group were administered a therapeutic dose (10 mg/kg of body weight) of morantel tartrate. All calves were necropsied 1 week later, and the abomasal and small intestinal nematodes were isolated, identified, and enumerated. A comparison of efficacies between nonmedicated and morantel tartrate-treated calves of each pasture demonstrated that morantel was equally effective against the gastrointestinal nematode infections, regardless of infection source (ie, pasture A vs pasture B). The overall nematode reductions due to morantel tartrate treatment of calves that grazed pastures A and B were 98% and 96%, respectively. It was concluded that the sensitivity of gastrointestinal nematodes to morantel tartrate was not diminished in calves maintained on pasture B, which had been stocked with morantel sustained-release bolus-treated calves for the preceding 2 grazing seasons.

Animals↗

The relation between the number of parasites/host and host age: population dynamic causes and maximum likelihood estimation.

We examined dynamical factors that shape the distribution of the number of parasites/host in constant or temporally varying environments, and with or without host-age dependent variation in host susceptibility and parasite mortality. We predict properties of the parasite distribution in the absence of density-dependent factors such as density-dependent mortality of recruitment and parasite-induced host mortality. These properties provide a criterion for the detection of density dependence in temporally variable systems with host-age dependent interactions. We have then introduced methods to estimate and statistically evaluate the effects of host age or size on the distribution of parasites/host. The methods are based on a maximum likelihood protocol for linear and non-linear regression when data are negatively binomially distributed. We have illustrated the use of the theoretical results and statistical methods by re-analysing the data of Halvorsen & Andersen (1984) on cestode infections in Norwegian arctic charr and by analysing new data on nematode infections in Caribbean Anolis lizards.

Age Factors↗

Human infections due to nematode helminths nowadays: epidemiology and diagnostic tools.

An update on the epidemiology of intestinal and tissue roundworms, in the world as well as in Italy, is presented. This analysis indicates that the most important changes happened in developed countries, where two main phenomena have been registered. The improvements occurred in social, economic, hygienic and sanitary conditions resulted in decrease of intestinal geohelminth prevalence but, besides, the changes happened at level of other factors, like environment, climate and human behaviour, promote more and more the opportunity for infections due to animal nematode species, which in people induce tissue syndromes. Therefore, the easier circulation of zoonoses among humans constitutes the main remark, which has to be strongly taken into account in countries like Italy, in that it is an emerging sanitary problem, important both for the number of people involved, and for the difficulties induced by their diagnosis. The general trend of "traditional" and "new" nematode infections that can affect humans is analysed, changes in the distribution patterns are tentatively explained, and available diagnostic tools are summarised.

Adult↗

Pathophysiology of infection with gastrointestinal nematodes in domestic ruminants: recent developments.

Infection with gastrointestinal nematodes, particularly Ostertagia species in domestic ruminants, continues to represent an important cause of impaired productivity in temperate parts of the world. The mechanisms responsible for such losses include changes in feed intake, gastrointestinal function, protein, energy and mineral metabolism, and body composition, and were described in detail at the last Ostertagia Workshop (Fox, M.T. 1993. Pathophysiology of infection with Ostertagia ostertagi in cattle. Vet. Parasitol. 46, 143-158). Since then, research into the pathophysiology of infection has focused on three main areas: mechanisms of appetite depression; changes in gastrointestinal function; and alterations in protein metabolism. Studies on the mechanisms responsible for appetite depression in Ostertagia-infected cattle have continued to support a close association between impaired feed intake and elevated blood gastrin concentrations. Alternative explanations will have to be sought, however, to account for the drop in feed intake associated with intestinal parasitism in which blood gastrin levels normally remain unaltered. Such work in sheep, and more recently in laboratory animals, has shown that central satiety signals are associated with inappetance accompanying intestinal infections, rather than changes in peripheral peptide levels. Changes in gastrointestinal function have also attracted attention, particularly the mechanisms responsible for increases in certain gut secretions, notably pepsinogen and gastrin. Elegant experimental studies have established that the gradient in pepsinogen concentration between abomasal mucosa and local capillaries could alone account for the increase in blood concentrations seen in Type 1 ostertagiosis. Additional factors, such as increases in capillary permeability and in surface area, probably contribute to such responses in cases of Type 2 disease. The increase in blood gastrin concentrations that accompanies Ostertagia infections in cattle is associated with the concurrent rise in abomasal pH. However, in sheep, additional factors appear to contribute to the hypergastrinaemia which may occur independent of parasite-induced changes in gastric pH. Alterations in protein metabolism have been well documented in ruminants harbouring monospecific infections with either abomasal or intestinal nematodes. More recently, however, the effects of dual abomasal and intestinal infections have been investigated and demonstrated that the host is able to compensate for impaired abomasal digestion provided that the intestinal parasite burden does not occupy the main site of digestion and absorption in the latter organ. An alternative method of improving the host's protein balance, dietary supplementation, has been shown not only to improve productivity, but also to enhance the innate resistance of susceptible breeds of sheep to Haemonchus and to accelerate the development of immunity to Ostertagia in lambs.

Animals↗