Schistosomes in the Lung: Immunobiology and Opportunity.

Schistosome infection is a major cause of global morbidity, particularly in sub-Saharan Africa. However, there is no effective vaccine for this major neglected tropical disease, and re-infection routinely occurs after chemotherapeutic treatment. Following invasion through the skin, larval schistosomula enter the circulatory system and migrate through the lung before maturing to adulthood in the mesenteric or urogenital vasculature. Eggs released from adult worms can become trapped in various tissues, with resultant inflammatory responses leading to hepato-splenic, intestinal, or urogenital disease - processes that have been extensively studied in recent years. In contrast, although lung pathology can occur in both the acute and chronic phases of schistosomiasis, the mechanisms underlying pulmonary disease are particularly poorly understood. In chronic infection, egg-mediated fibrosis and vascular destruction can lead to the formation of portosystemic shunts through which eggs can embolise to the lungs, where they can trigger granulomatous disease. Acute schistosomiasis, or Katayama syndrome, which is primarily evident in non-endemic individuals, occurs during pulmonary larval migration, maturation, and initial egg-production, often involving fever and a cough with an accompanying immune cell infiltrate into the lung. Importantly, lung migrating larvae are not just a cause of inflammation and pathology but are a key target for future vaccine design. However, vaccine efforts are hindered by a limited understanding of what constitutes a protective immune response to larvae. In this review, we explore the current understanding of pulmonary immune responses and inflammatory pathology in schistosomiasis, highlighting important unanswered questions and areas for future research.

The effect of pasture molluscicide on small lungworm infections and the productivity of grazing lambs.

The aim of this study was to assess the effect of pasture molluscicide treatment on the prevalence and severity of small lungworm infections, and the productivity of lambs grazing improved pastures in southeastern Australia. A randomised control field trial of 260 Merino-cross lambs was conducted on a commercially managed farm in South Australia with a history of high small lungworm prevalence. Separate groups of lambs rotationally grazed irrigated lucerne paddocks treated with iron chelate molluscicide or untreated control paddocks. Lambs were monitored every 2-6 weeks from weaning until slaughter with liveweight, lungworm and gastrointestinal nematode infection status measured. At slaughter indicators of small lungworm infection via inspection and carcass characteristics were assessed. The density of the intermediate host snail and lucerne pasture availability were also measured. There was a higher population of adult Prietocella barbara molluscs in the Control paddocks compared to the Treatment paddocks after molluscicide had been applied and prior to grazing commencing (206 vs. 14 snails/m2, respectively; P = 0.03; 95 % CI 8, 528). However, the overall mollusc density was similar between Control and Treatment. The prevalence of small lungworm infections was quite low during the trial (0-13 %), in both Control and Treatment lambs, except at day 94 when 48 % of 28 Control lambs were positive compared to none of 27 Treatment lambs (P < 0.001; 95 % CI 30, 66). A similar proportion of Treatment and Control lambs had evidence of small lungworm infection lesions at slaughter (both 67.8 %). Control lambs grew slightly faster than Treatment lambs, with an average daily gain of 202 (± 3 SEM) g/head/day for Control and 190 (± 4 SEM) for Treatment (P < 0.001) during the 112-day trial. Despite historic evidence of very high prevalence of lungworm infection in this region of southeastern Australia, iron chelate molluscicide treatment prior to lambs grazing the pasture had no demonstrable effect on the prevalence and severity of small lungworm infections, nor the productivity of lambs grazing these pastures. This study indicates that for a commercial sheep farm, additional molluscicide treatments of pastures after they are established, for the prevention of small lungworm infection, may not be warranted. Furthermore, requirements for more precisely monitoring snails are discussed.

[Travel-associated pneumonias]. / Pneumonien mit Reiseanamnese.

Respiratory infections are responsible for up to 11% of febrile infections in travellers or immigrants from tropical and subtropical regions. The main pathogens are the same as in temperate climate zones: Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydophila pneumoniae, influenza viruses, Legionella pneumophila. However, some pulmonary diseases can be attributed to bacterial, parasitic, viral or fungal pathogens that are endemic in tropical and subtropical regions. The most commonly imported infections are malaria, dengue, and tuberculosis. Pulmonary symptoms and eosinophilia in returning travellers and migrants may be caused by several parasitic infections such as Katayama syndrome, Loeffler syndrome, tropical pulmonary eosinophilia, amebiasis, paragonimiasis, echinococcosis, and toxocariasis. In Asia, Tsutsugamushi fever is transmitted by chiggers, spotted fever rickettsiae are transmitted by ticks. Transmission of zoonotic diseases occurs mainly via contact with infected animals or their excretions, human-to-human transmission is generally rare: MERS-CoA (dromedary camels), pulmonary hantavirus infection (rodents), tularemia (rabbits and hares), leptospirosis (rats), Q-fever (sheep and goats), very rarely anthrax (hides of ruminants) and pest (infected rats and wildlife). Inhalation of contaminated dust can cause infections with dimorphic fungi: histoplasmosis (bat guano) and coccidioidomycosis in America and parts of Africa, blastomycosis in America. Some infections can cause symptoms years after a stay in tropical or subtropical regions (melioidosis, tuberculosis, histoplasmosis, schistosomiasis-associated pulmonary hypertension). Noninfectious respiratory diseases caused by inhalation of high amounts of air pollution or toxic dusts may also be considered.

[Pulmonary infections after lung transplantation]. / Tüdotranszplantált betegek pulmonalis infekciói.

Lung transplantation has become an accepted therapeutic modality for end-stage diseases of the lungs and the pulmonary circulation. In the past two decades more than 20,000 lung transplantations were performed all over the world. Due to improvements in immunosuppressive regimens the mortality rate of severe acute rejections has decreased up to 2% in the first post-transplant year. By contrast, infections became the most common cause of morbidity and mortality after lung transplantation. It was reported that 21.2 and 40% of annual deaths are due to infections in the first 30 days and one year, respectively. In the first month 35-70% of transplant recipients develop bacterial pneumonia caused often by Gram-negative organisms especially by Pseudomonas species. All patients should receive prophylactic antibiotics after the operation, which are to be modified according to the resistance patterns of pathogens isolated from the donor lungs. In the early post-operative period, the frequency of invasive fungal (Aspergillus and Candida) and cytomegalovirus (CMV) infections appears to be less then 10% due to prophylactic amphotericin inhalation and systemic valganciclovir administration for 100 days. After withdrawing these drugs, these infections became more common. In the late post-transplant period, the development of bronchiolitis obliterans syndrome (BOS) may predispose to infections. BOS may be manifested in approximately 50% of patients 5 years post-transplant. Routinely or urgently performed screening tests (laboratory and radiological investigations, lung function tests, sputum culture, bronchoscopy) and specific treatments are of central importance in the management of infections. In this review we discuss the clinical manifestation, the diagnosis and the treatment possibilities of the most common pulmonary infections in lung transplant recipients.

IL-31-IL-31R interactions negatively regulate type 2 inflammation in the lung.

Interleukin (IL) 31Ralpha (glycoprotein 130-like monocyte receptor and glycoprotein 130-like receptor) heterodimerizes with oncostatin M receptor beta to bind IL-31, a cytokine expressed preferentially by CD4(+) T helper type 2 (Th2) cells. However, the functions of IL-31-IL-31R signaling in immune regulation remain unknown. Here, we identify a novel role for IL-31R in limiting type 2 inflammation in the lung. After intravenous injection of Schistosoma mansoni eggs, IL-31Ralpha(-/-) mice developed severe pulmonary inflammation, characterized by an increase in the area of granulomatous inflammation, increased numbers of resistin-like molecule alpha(+) cells, and enhanced collagen deposition compared to WT counterparts. In vitro, macrophages generated from IL-31Ralpha(-/-) mice promoted enhanced ovalbumin-specific CD4(+) T cell proliferation and purified naive CD4(+) T cells from IL-31Ralpha(-/-) mice exhibited enhanced proliferation and expression of Th2 cytokines, identifying a T cell- and macrophage-intrinsic regulatory function for IL-31R signaling. In contrast, the generation of CD4(+) T cell-mediated Th1 responses were normal in IL-31Ralpha(-/-) mice, suggesting that the regulatory role of IL-31R signaling is limited to type 2 responses. Together, these data implicate IL-31R signaling as a novel negative regulatory pathway that specifically limits type 2 inflammation.

Registro de um caso de Aelurostrongylus abstrusus (Railliet, 1898) em um gato doméstico no Rio de Janeiro, RJ / A case of feline Aelurostrongylus abstrusus (Railliet, 1898) infection in Rio de Janeiro, RJ

Aelurostrongylus abstrusus é uma espécie de parasito pulmonar que infecta preferencialmente gatos domésticos. Seu ciclo biológico é indireto, utilizando moluscos como hospedeiros intermediários, e diversos hospedeiros paratênicos que auxiliam na sua dispersão. A infecção pode ser assintomática ou cursar com sinais clínicos pulmonares inespecíficos. O diagnóstico pode ser realizado pela demonstração de larvas nas fezes dos pacientes, lavado bronqueal ou por necrópsia. O tratamento ainda não está definido, entretanto, a droga mais recomendada é a ivermectina. O presente trabalho descreve as lesões anatomopatológicas encontradas nos pulmões de um felino doméstico, submetido à necropsia de rotina no Serviço de Anatomia Patológica da Universidade Federal Fluminense.

Aelurostrongylus abstrusus is a lungworm that affects mainly domestic cats. It has an indirect life cicle, with molluscans as intermediate hosts and a large variety of auxiliary hosts that play an important role on its dispersion on the environment. Infection can be asymptomatic or unspecific pulmonary signs can be detected. Diagnosis can be made by recovering larvae from faeces, bronchoalveolar lavage or necropsy. Treatment still has to be defined, but ivermectin is the most recommended drug. This present work describes histopathologic lesions found in lungs of a domestic cat, observed in a routine necropsy at the Pathology Department of Universidade Federal Fluminense.

Vaccination with recombinant Ascaris suum 24-kilodalton antigen induces a Th1/Th2-mixed type immune response and confers high levels of protection against challenged Ascaris suum lung-stage infection in BALB/c mice.

Previous studies have shown that antigens from various life-cycle stages of Ascaris suum can induce host-protective immunity against challenge infections with infective eggs of A. suum. This study evaluated whether Escherichia coli-expressed recombinant 24-kDa antigen from A. suum (rAs24) was a suitable vaccine candidate for the control of Ascaris infections by examining its performance in a mouse model. Immunization of BALB/c mice in three consecutive doses with rAs24 in Freund's Complete Adjuvant (FCA) results in protection against challenge infections as manifested by a 58% reduction (P<0.001) in recovery and stunted development of A. suum lung-stage larvae at day 7 post-challenge. Sera obtained from immune protected mice had a significantly increased level of immunoglobulin G (IgG) (P<0.0001) but had no IgE response. Analysis of IgG-subclass profiles revealed that IgG1 (P<0.0001) showed the greatest increase followed by IgG2b (P<0.005), IgG2a (P<0.006) and IgG3 (P<0.04). Splenic T cells from rAs24-FCA immunized mice secreted significantly high levels of both Th1 cytokine gamma-interferon (P<0.005) and Th2 cytokine interleukin-10 (P<0.001) after stimulation with rAs24 in vitro. Interestingly, affinity purified anti-rAs24 IgG was shown to inhibit moulting of A. suum lung-stage L3 to L4 in vitro by 26%, indicating an in vivo function of the endogenous As24 in the moulting processes. An intense expression of endogenous As24 in the hypodermis and gut epithelium of A. suum lung-stage L3 by immunofluorescence supports a function for endogenous As24. These findings may contribute to the understanding of rAs24-induced Th1/Th2-mediated effector mechanisms required for the protection of A. suum lung-stage larval infection.

Pulmonary hydatid and other lung parasitic infections.

The lung may be infested by a great number of parasites. Hydatidosis is the most frequent parasitic lung disease. Diagnosis of lung hydatidosis is usually easy on chest radiography, ultrasonography, and CT scan, and immunodiagnosis may help in dubious cases. Surgery is necessary in most cases, but it must be conservative. Complex forms, such as disseminated disease and secondary lung hydatidosis (metastatic or bronchogenic) are difficult to treat and may be considered malignant. Medical treatment may be helpful in complex forms, in poor surgical risk patients, and in cases of preoperative spillage of hydatic fluid. Prevention programs are necessary in endemic areas, and research must be directed toward vaccination against the parasite. Other parasitic diseases are reported less frequently in the literature, and the majority of published articles are either case reports or only report a small number of cases. Clinical presentation is variable according to the great variety of parasites that may involve the lungs.

Cross-sectional serological survey on gastrointestinal and lung nematode infections in first and second-year replacement stock in the netherlands: relation with management practices and use of anthelmintics.

A cross-sectional survey was carried out on 86 farms randomly distributed in The Netherlands. After housing following the first and the second grazing season (FGS and SGS) serum samples were collected to determine IgG levels against Cooperia oncophora and Dictyocaulus viviparus, and the pepsinogen content. A questionnaire was used to inquire on grazing management practices and the use of anthelmintic drugs. On 80.7 and 60.2% of the farms FGS and SGS animals, respectively, were treated at least once with an anthelmintic drug. The percentage for the SGS animals indicates that the use of anthelmintic drugs in those animals has increased enormously over the last 10-15 years. Generally, parasitic nematode control in the FGS is good on most farms, but it can be characterised as being overprotective. There is a tendency that if anthelmintic drugs are used in the FGS they also are used more often in the SGS. On 12 farms (14%), no anthelmintic drugs were given in the FGS and the SGS. These farms did not differ from the others with respect to management practices in any obvious way. The serological results were in general very low, indicating low levels of exposure to gastrointestinal nematode infection in both FGS and SGS animals. This was not surprising in view of the good to high level of nematode control practices reported by the farmers. Although not statistically significant, a consistent result was that serological results for the SGS animals were more often positive or on average higher on those farms where FGS parasite control tended to be excessive. For D. viviparus, a prevalence rate of 41% positive farms was found. Following comparison with previous data, it is speculated that lungworm (sero-)prevalence in replacement stock may be declining as a result of continuing high levels of parasite control in replacement stock. It is concluded that the results confirm previous surveys, lending support to the conclusion that parasitic nematode control on Dutch dairy farms, certainly in FGS calves, is good but tends to be overprotective.

IL-13 is a key regulatory cytokine for Th2 cell-mediated pulmonary granuloma formation and IgE responses induced by Schistosoma mansoni eggs.

Schistosoma mansoni egg-induced pulmonary granuloma formation is a cell-mediated inflammatory response associated with dominant Th2-type cytokine expression, tissue eosinophilia, and high levels of serum IgE. In the present study, we show that in vivo blockade of the Th2 cytokine IL-13, using soluble IL-13R alpha2-Fc fusion protein, significantly reduced the size of pulmonary granulomas in unsensitized as well as egg-sensitized mice. Blocking IL-13 also significantly reduced total serum IgE levels. Interestingly, however, IL-13 blockade did not affect the evolving egg-induced Th2-type cytokine response. IL-4, IL-5, as well as IL-13 responses were indistinguishable in control-Fc- and soluble IL-13R alpha2-Fc fusion protein-treated animals. The smaller granulomas were also phenotypically like the control Fc-treated mice, displaying a similar eosinophil content. Additional studies in IL-4-deficient mice demonstrated that IL-13 was produced, but at much lower levels than in wild-type mice, while IL-4 expression was completely independent of IL-13. Moreover, while granuloma formation was partially reduced in IL-4-deficient mice, blocking IL-13 in these animals almost completely abrogated granuloma development and the pulmonary eosinophilia, while it simultaneously increased IFN-gamma production. Together, these data demonstrate that IL-13 serves as an important mediator of Th2-mediated inflammation and plays a role in eliciting IgE responses triggered by schistosome eggs.

The efficacy of Michel's dose and move system on gastrointestinal nematode infections in diary calves.

The efficacy of a move to aftermath in July combined with moxidectin or fenbendazole treatment for the control of parasitic gastroenteritis (PGE) in calves was evaluated in three field experiments in the Netherlands. In all five treated groups high gastrointestinal nematode infections and PGE were prevented by a dose and move in July. Cooperia infections increased to moderate levels in two groups treated with moxidectin and one group treated with fenbendazole. In both other groups and also for Ostertagia in these three groups, low to extremely low infections were acquired. In the first experiment high primary infections, resulting in high faecal egg counts and a moderate increase of blood pepsinogen values occurred before the dose and move. Nevertheless, these primary infections were not high enough to result in PGE. In both other experiments primary infection levels were low and faecal egg counts increased to 100-650 eggs/g faeces at the end of the grazing season. The blood pepsinogen values of non-treated control groups demonstrated that it took more than a month after their move to aftermath before substantial reinfection occurred on the new pasture. In the first and the last experiment only, high Ostertagia and Cooperia infections developed in the control group at the end of the grazing season, though it did not result in clinical PGE. The experiments demonstrate all theoretical risks of the dose and move system: (1) PGE early in the grazing season as a result of high overwintered pasture infectivity. (2) PGE just before the move as a result of an early midsummer increase in pasture infectivity. (3) PGE around housing as a result of insufficient suppression of pasture infectivity late in the grazing season. (4) Underexposure to nematode infections due to a high suppression of nematode infections. Nevertheless, it can be concluded that under normal conditions the dose and move system remains to be a valuable and easily applicable system for the control of PGE.

Field evaluation of a topical doramectin formulation for the chemoprophylaxis of parasitic bronchitis in calves.

A study was conducted to evaluate the efficacy of two topical treatments with doramectin on the season-long control of lungworm and gastrointestinal infections in first grazing season (FGS) calves. At the start of the study, 20 FGS calves were randomly allocated into two treatment groups of 10 animals each. Calves in the D-group were treated with doramectin pour-on on days 0 and 56, at a dosage of 500 microg kg(-1) BW: calves in the C-group were designated as controls. A permanent pasture was divided in two blocks and these were randomly allocated to the treatment groups. Throughout the study, tracers (n = 32) were grazed on each paddock at 3-week intervals. Clinical signs of parasitic bronchitis (PB) were observed in the C-group in July and this necessitated two salvage treatments with levamisole. From day 28, post-turnout lungworm larvae were recovered from faeces of the C-calves until housing. No signs of PB were observed in the D-group during the entire grazing season. Shedding of lungworm larvae in the principals of the D-group did not occur until 112 days post-turnout. From the data obtained from the tracer calves. it appeared that larvae had overwintered on both pastures. On the C-pasture, the number of lungworms recovered from the tracer calves gradually increased to a peak in September, whereas on the D-pasture, the increase was observed only at the end of the pasture season. Both strongyle faecal egg counts and pepsinogen levels were relatively low in both groups throughout the present study. At the end of the grazing period (day 161). the principals were housed and treated with oxfendazole. During the housing period, all principal animals (D- and C-groups) and a third group of four helminth free animals (N-group) received a challenge infection with Dictyocaulus viviparus. It appeared that the different exposure to the parasite during the grazing season resulted in different establishment rates, i.e.. group C < group D < group N. The present results show that overwintering of lungworm larvae occurs in Belgium and that in such conditions, doramectin pour-on given at turnout and at 8 weeks controls PB in calves during the first grazing season.

Induction of protective immunity and modulation of granulomatous hypersensitivity in mice using PIII, an anionic fraction of Schistosoma mansoni adult worm.

This study was performed in order to define Schistosoma mansoni antigens that are able to function as modulator agents in the granulomatous hypersensitivity to parasite eggs in BALB/c and C57BL/6 mice. A fraction of S. mansoni, designated PIII, derived from adult worm antigen preparation (SWAP) was obtained using anion-exchange chromatography on an FPLC system. Immunization of mice with PIII in the presence of Corynebacterium parvum and Al(OH)3 as adjuvant induced an immune response in this animals as determined by ELISA and spleen cell proliferation assays against S. mansoni antigens SEA, SWAP and PIII. In addition, PIII caused a significant degree of protection against a challenge infection in immunized mice as observed by the decrease on worm burden recovered from the portal system. We also showed that PIII profoundly inhibited the vigorous anamnestic granulomatous response to eggs in the liver and lungs. This suppression correlated with a significant decrease in granuloma size. From these results we conclude that the PIII preparation contains antigens that can mediate protective anti-parasite immunity and downregulate granulomatous hypersensitivity to S. mansoni eggs.

Use of fenbendazole for long-term control of protostrongylid lungworms in free-ranging Rocky Mountain bighorn sheep.

In an effort to control Protostrongylus spp. in a Rocky Mountain bighorn sheep herd (Ovis canadensis canadensis) of approximately 30 animals, fenbendazole-medicated salt was placed on the Stillwater bighorn winter range in southcentral Montana (USA) for four consecutive winters, 1990 to 1993. Sheep of all age and sex classes were observed using the medicated salt throughout the study period. Prevalence and average number of lungworm larvae per gram of bighorn feces declined significantly (P < 0.05) from pretreatment levels (1987 to 1989), and remained low throughout the study period. Free-choice availability of fenbendazole-medicated salt is a potentially effective management tool for long-term control of protostrongylid lungworm.

Recombinant IL-10 and IL-10/Fc treatment down-regulate egg antigen-specific delayed hypersensitivity reactions and egg granuloma formation in schistosomiasis.

In infection with the helminth Schistosoma mansoni, parasite eggs elicit a Th cell-mediated hepatic granulomatous inflammation that leads to scarring, portal hypertension, hemorrhage, and death. On the other hand, the cytokine IL-10 has been shown to decrease egg Ag-specific Th cell responses by down-regulating MHC class II as well as B7 costimulatory molecule expression on accessory cells. We now test the effect of IL-10 in vivo on models of egg Ag-specific hypersensitivity as well as on the natural disease. Systemic administration of IL-10 significantly inhibited delayed-type hypersensitivity reactions to egg Ag as well as primary and secondary granuloma formation to eggs embolized in the lung. However, significant inhibition of hepatic granuloma formation associated with the natural infection required the use of an IL-10/Fc fusion protein with a prolonged in vivo half-life. Lymph node cells from IL-10/Fc-treated mice produced less IL-2 and IFN-gamma, and more IL-4 and IL-10 than control cells, suggesting that reduced egg granuloma formation resulted primarily from down-regulation of Th1 responses. These results indicate that suitable administration of exogenous IL-10 can be effective in ameliorating immunopathologic damage associated with schistosomiasis.

Residual effect of injectable moxidectin against lungworm and gastrointestinal nematodes in calves exposed to high pasture infectivity levels in the Netherlands.

The residual effect of a 0.2 mg kg-1 injectable formulation of moxidectin against lungworm and gastrointestinal nematodes in cattle was studied in a grazing experiment in the Netherlands. Five groups of four calves were grazed between May and October 1991 and one similar group was used as permanently housed control group for the evaluation of the development of immunity against lungworm by challenge infections with 5000 larvae of all six groups. The main parameter used to determine the residual effect for lungworm was faecal larval counts. Additional information was derived from pasture larval counts, enzyme-linked immunosorbent assay (ELISA), respiration frequency, coughing score and, particularly for evaluating development of immunity, worm counts. For gastrointestinal nematode infections faecal egg counts and larval differentiation of faecal cultures were the main parameters used. Pasture larval counts and an ELISA for Ostertagia and Cooperia were used as additional parameters. In three treated groups lungworm larvae (re)appeared in the faeces after 67, 95 and 119 days, respectively. This implies that a 100% residual effect did not last longer than 67-21 = 46 days. The treated group with patency starting on Day 95 was exposed to extremely high infection pressure and the ELISA indicated some host-parasite interactions from 2-4 weeks after treatment. Thus some interaction between moxidectin treatment and high infection pressure delayed the onset of patency in comparison to another treated group under much lower infection pressure. In all treated groups, including the one under high infection pressure, lungworm disease was prevented and the worm counts demonstrated development of immunity. In contrast, severe lungworm disease occurred in two control groups grazing together with the 'high infection pressure' treated group. The faecal egg counts and differentiation of larvae from faecal cultures demonstrated a 100% residual effect of at least 3 weeks and indicated a high residual effect of approximately 5 weeks against Ostertagia. Moxidectin suppressed Cooperia faecal egg counts for over 98% and the results indicated a more than 95% residual effect on faecal egg output during 2-3 weeks. The ELISA results were indicative for a delay of 2 weeks in the acquisition of gastrointestinal nematode infections following moxidectin treatment.

Immunoregulatory potential of exogenous Schistosoma mansoni soluble egg antigen in a model of experimental schistosomiasis--I. Regulation of granuloma formation in vivo.

This study was undertaken to assess the optimum conditions required to reduce the vigorous host granulomatous reaction around Schistosoma mansoni eggs. Soluble schistosomal egg antigen (SEA) at a concentration of 10 or 100 micrograms protein was administered i.p. or i.v. into unprimed C57BL/6 mice. SEA was injected either alone or in combination with cyclophosphamide (CY) 100 or 50 mg/kg via i.p. route. Seven or 14 days later viable eggs of S. mansoni were injected via the tail vein into treated groups and untreated normal controls. Mice were sacrificed 8, 16 and 24 days after the injection of eggs. The lungs were removed for histopathological study, measurement of granuloma diameter and phenotypic analysis of granuloma intralesional T-cell subsets. Compared to untreated controls, the lower concentration of SEA (10 micrograms) administered by the i.v. route 7 days before egg injection, induced a significant reduction in granuloma diameter 16 days after egg injection than that by the i.p. route or at a higher SEA concentration (100 micrograms). Compared to untreated controls, the higher dose of CY (100 mg/kg), given i.p. alone or in combination with 10 micrograms SEA by the i.v. or i.p. route, induced a significant reduction in granuloma diameter, while 50 mg/kg CY did not cause any reduction. The reduction in granuloma diameter by i.v. administration of low SEA concentration alone or in combination with CY IP, was associated with a decrease in the granuloma intralesional L3T4+/Lyt2+ ratio. The decrease in the ratio was due to an increase in Lyt2+ cells. The results suggest that the use of low dose SEA by the i.v. route alone or combined with an immunosuppressive drug ameliorates pathological changes concurrent with S. mansoni infection.

The distribution of nematode egg counts and larval counts in grazing sheep and their implications for parasite control.

The frequency distribution of gastrointestinal nematode egg and lungworm larval counts was examined in 101 and 87 naturally infected ewes on two farms. The egg and larval outputs of the two flocks followed the negative binomial pattern of distribution (with k values below unity) at each time of sampling, which suggests highly overdispersed worm burdens. The results of the statistical analysis indicated that a relatively small part of the two flocks was responsible for the excretion of the majority of both gastrointestinal nematode eggs and Dictyocaulus filaria larvae. It is concluded that by eliminating "wormy" individuals of flocks either by selective breeding or by their selective anthelmintic treatment, effective control of parasite transmission can be achieved. Because of the phenomenon of nematode "clumping" it seems necessary to expand new methods for estimation of flock productivity caused by nematodes in livestock and to incorporate negative binomial parameter (k) in mathematical models of nematode population dynamics.