Chronic neuroangiostrongyliasis: case study of chronic presentations in Hawaii.

This paper describes chronic features of neuroangiostrongyliasis (NAS), a long-term outcome of the disease that has not been adequately described. Current and past literature is predominantly limited to acute manifestations of NAS, and mention of chronic, ongoing clinical symptoms is usually limited to brief notes in a discussion of severe cases. This study investigated the long-term outcomes in ten individuals who were diagnosed with acute neuroangiostrongyliasis in Hawaii between 2009 and 2017. The study demonstrates a significant number of persons in Hawaii sustain residual symptoms for many years, including troublesome sensory paresthesia (abnormal spontaneous sensations of skin experienced as 'burning, pricking, pins and needles'; also described as allodynia or hyperesthesia) and extremity muscle pains. As a consequence, employment and economic hardships, domestic relocations, and psychological impairments affecting personal relationships occurred. The study summarizes common features of chronic disease, sensory paresthesia and hyperesthesia, diffuse muscular pain, insomnia, and accompanying emotional distress; highlights the frequently unsuccessful endeavours of individuals struggling to find effective treatment; proposes pathogenic mechanisms responsible for prolonged illness including possible reasons for differences in disease presentation in Hawaii compared to Southeast Asia.

Mitochondrial dynamics in Angiostrongylus cantonensis-infected mouse brain.

Angiostrongylus cantonensis is one of the most widespread parasites causing central nervous system (CNS) diseases in mammals. Since the mitochondrion is an essential cell organelle responsible for both physiological and pathological processes, its dysfunction might lead to inflammation and multiple disorders. In this study we aimed to investigate the changes in mitochondrial dynamics that occur in the mouse brain upon infection with A. cantonensis, using molecular biology techniques such as polymerase chain reaction (PCR), western blot analysis, transmission electron microscopy (TEM), and different staining methods. Here, we show that mouse brain infected with A. cantonensis exhibits altered mitochondrial dynamics, including fission, fusion, and biogenesis. Additionally, we demonstrate that caspases and B-cell lymphoma 2 (BCL-2) were significantly upregulated in A. cantonensis-infected brain. These results are indicative of the occurrence of apoptosis during A. cantonensis infection, which was further confirmed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. These findings suggest the change in mitochondrial dynamics in A. cantonensis-infected brain, providing another point of view on the pathogenesis of meningoencephalitis caused by A. cantonensis infection.

Case Report: Angiostrongylus cantonensis Meningoencephalitis in a 9-Month-Old Baby in Vietnam.

Meningoencephalitis is not a rare disease in small children. However, eosinophilic meningitis due to Angiostrongylus cantonensis is unusual in a baby. We describe the case of a 9-month-old baby from North Vietnam with eosinophilic meningoencephalitis. The baby lived in a rural area, where farming is widespread, and presented with fever and seizures. Laboratory results showed peripheral eosinophilia (16.1%), cerebrospinal fluid (CSF) white blood cell count 220/mm3 (26% eosinophils), CSF antibody test positive for Ascaris, CSF ELISA positive for Angiostrongylus cantonensis, and blood ELISA positive for A. cantonensis. A mobile worm was identified in the CSF. The presentation was consistent with a diagnosis of A. cantonensis eosinophilic meningitis. The baby recovered fully after administering albendazole (200 mg/day for 2 weeks), and intravenous dexamethasone (0.6 mg/kg/day every 8 hours) and mannitol (1.5 g/kg/day every 8 hours) for the first 3 days, followed by 5 days of oral prednisolone (2 mg/kg/day).

Gastrointestinal Helminth Infection Improves Insulin Sensitivity, Decreases Systemic Inflammation, and Alters the Composition of Gut Microbiota in Distinct Mouse Models of Type 2 Diabetes.

Type 2 diabetes (T2D) is a major health problem and is considered one of the top 10 diseases leading to death globally. T2D has been widely associated with systemic and local inflammatory responses and with alterations in the gut microbiota. Microorganisms, including parasitic worms and gut microbes have exquisitely co-evolved with their hosts to establish an immunological interaction that is essential for the formation and maintenance of a balanced immune system, including suppression of excessive inflammation. Herein we show that both prophylactic and therapeutic infection of mice with the parasitic hookworm-like nematode, Nippostrongylus brasiliensis, significantly reduced fasting blood glucose, oral glucose tolerance and body weight gain in two different diet-induced mouse models of T2D. Helminth infection was associated with elevated type 2 immune responses including increased eosinophil numbers in the mesenteric lymph nodes, liver and adipose tissues, as well as increased expression of IL-4 and alternatively activated macrophage marker genes in adipose tissue, liver and gut. N. brasiliensis infection was also associated with significant compositional changes in the gut microbiota at both the phylum and order levels. Our findings show that N. brasiliensis infection drives changes in local and systemic immune cell populations, and that these changes are associated with a reduction in systemic and local inflammation and compositional changes in the gut microbiota which cumulatively might be responsible for the improved insulin sensitivity observed in infected mice. Our findings indicate that carefully controlled therapeutic hookworm infection in humans could be a novel approach for treating metabolic syndrome and thereby preventing T2D.

Inflammasome-Independent Role for NLRP3 in Controlling Innate Antihelminth Immunity and Tissue Repair in the Lung.

Alternatively activated macrophages are essential effector cells during type 2 immunity and tissue repair following helminth infections. We previously showed that Ym1, an alternative activation marker, can drive innate IL-1R-dependent neutrophil recruitment during infection with the lung-migrating nematode, Nippostrongylus brasiliensis, suggesting a potential role for the inflammasome in the IL-1-mediated innate response to infection. Although inflammasome proteins such as NLRP3 have important proinflammatory functions in macrophages, their role during type 2 responses and repair are less defined. We therefore infected Nlrp3 -/- mice with N. brasiliensis Unexpectedly, compared with wild-type (WT) mice, infected Nlrp3 -/- mice had increased neutrophilia and eosinophilia, correlating with enhanced worm killing but at the expense of increased tissue damage and delayed lung repair. Transcriptional profiling showed that infected Nlrp3 -/- mice exhibited elevated type 2 gene expression compared with WT mice. Notably, inflammasome activation was not evident early postinfection with N. brasiliensis, and in contrast to Nlrp3 -/- mice, antihelminth responses were unaffected in caspase-1/11-deficient or WT mice treated with the NLRP3-specific inhibitor MCC950. Together these data suggest that NLRP3 has a role in constraining lung neutrophilia, helminth killing, and type 2 immune responses in an inflammasome-independent manner.

Magnetic resonance imaging findings and clinical manifestations in cerebral angiostrongyliasis from Dali, China.

PURPOSE: To analyze magnetic resonance imaging (MRI) findings and clinical diagnosis and treatment data relating to Angiostrongylus cantonensis infection to gain insight into the disease. MATERIALS AND METHODS: We retrospectively analyzed the epidemiology, clinical manifestations, diagnosis and treatment data, imaging manifestations, and outcomes of 27 patients who were clinically diagnosed with angiostrongyliasis and who underwent contrast-enhanced brain MRI. RESULTS: Patients with A. cantonensis infection had a history of eating raw mollusks in the endemic area, and they mainly presented with dizziness and headache of varying degrees and vomiting (n = 7). Laboratory examinations revealed increased peripheral blood and cerebrospinal fluid (CSF) eosinophils, as well as increased CSF protein levels. Brain MRI findings mainly included eosinophilic meningitis, whereas linear or nodular enhancement of the pia mater was observed in enhanced T1-weighted and fluid-attenuated inversion recovery images, accompanied by encephalitis or vasculitis. Meningitis manifested as multiple, thickened flow voids around the meninges, and contrast-enhanced scans showed substantial enhancement in intracranial dilated and hyperplastic blood vessels. CONCLUSION: The possibility of A. cantonensis infection should be considered in the effective use of albendazole or mebendazole as a treatment. Combining clinical history with laboratory examination is helpful in diagnosing A. cantonensis infection. A final definite diagnosis can be confirmed by detecting larvae in the CSF. The administration of corticosteroids during pathogen therapy can substantially reduce the therapeutic response.

Two cases of neuroangiostrongyliasis: A rare disease because rarely considered or rarely diagnosed?

AIM: The rat lungworm, Angiostrongylus cantonensis, is well established in eastern Australia, where it is the almost exclusive cause of human eosinophilic meningoencephalitis (EME). While neuroangiostrongyliasis can result in severe morbidity or death, its diagnosis requires a high index of clinical suspicion among medical practitioners. Prevention requires a high level of public awareness. METHODS: We report two cases of EME in children from Queensland and summarise all reported Australian cases from the literature. We discuss the pathogenesis of neuroangiostrongyliasis, with particular reference to the timing of prophylaxis and treatment. RESULTS: A 5-year-old girl developed severe headache, eosinophilic meningitis and abnormal neuroimaging following a holiday to Bali. A 10-year-old boy with Rubinstein-Taybi syndrome, marked developmental delay and pica developed EME following ingestion of a snail, resulting in long-term morbidity. From 1971 to 2018, 28 Australian cases have been reported, with acquisition restricted to Southeast Queensland and New South Wales. Ages ranged from 10 months to 45 years; most were male and most likely acquired infection from consuming unwashed lettuce or vegetables. The mortality rate was 18%; most fatalities occurred in children <1 year old. Long-term neurological deficit was reported in 14% of cases and a full recovery in 57% of cases. CONCLUSIONS: Heightened medical and public awareness of the parasite is required to prevent infection and subsequent disease. A better understanding of the efficacy of prophylactic anthelmintic following ingestion or handling of molluscs and further studies of epidemiology of this parasite will inform and facilitate public health recommendations.

Evaluation of the mucosal inflammatory responses to equine cyathostomins in response to anthelmintic treatment.

Members of Cyathostominae are pervasive parasites of equids that can cause larval cyathostominosis, a potentially life-threatening disease that occurs when a multitude of encysted larvae synchronously excyst from the wall of the large intestine. Moxidectin and fenbendazole are the two current labeled drugs that target the encysted larval stages; however, there is limited knowledge of the local inflammatory response to the larvae and to the two treatments in clinically healthy horses. This study is the first to evaluate the local inflammatory response to cyathostomin larvae and to larvicidal treatment at 2 and 5 weeks post treatment. Thirty-six ponies with naturally acquired cyathostomin infections were randomly allocated into 3 groups: Group 1, fenbendazole at 10 mg/kg for 5 days, Group 2, a single dose of moxidectin at 0.4 mg/kg, and Group 3, untreated controls. Tissue samples from the cecum and dorsal and ventral colons were used for histopathological and immunohistochemical evaluation. Tissues were stained with routine hematoxylin and eosin (H&E) for light microscopy and immunohistochemically for MAC387, CD20, and CD3 for differentiation of activated macrophages, B cells, and T cells, respectively. Semiquantitative scores were assigned for all inflammatory cell types and fibrous connective tissue. Larvae observed by light microscopy were enumerated and classified by stage. Mucosal ulcerations and submucosal granulomas were also enumerated. Mean macrophage scores were higher in the moxidectin group than the fenbendazole group (p = 0.0185) and the control group had a higher activated macrophage score than both treatment groups (p = 0.0104, p = 0.0004). T lymphocyte scores were higher in the moxidectin group when compared to the control group (p = 0.0069). Goblet cell hyperplasia scores were elevated at 5 weeks post treatment compared to 2 weeks post treatment (p = 0.0047) and were elevated in the ventral colon compared to the dorsal colon (p = 0.0301). Eosinophil scores were elevated surrounding degenerative larvae when compared to intact larvae (p = 0.0001). Mucosal ulcerations were found only in the control group at 2 weeks post treatment. This study found subtle inflammatory differences between treatment groups but provided new information about goblet cells and eosinophils in relation to encysted cyathostomin larvae.

Nippostrongylus brasiliensis infection leads to impaired reference memory and myeloid cell interference.

Hookworm infection is endemic in developing countries, leading to poor cognitive function-among other disruptions. In this study, the effects of Nippostrongylus brasiliensis infection (a murine model of Necator Americanus) on cognitive function were investigated. Though impaired cognition has been extensively reported, the exact domain of cognition affected is still unknown, hence requiring investigation. The objective of this study was to identify possible cognitive changes during Nippostrongylus brasiliensis infection in mice, using the Morris water maze. Here, we show for the first time that mice infected with Nippostrongylus brasiliensis were able to learn the Morris water maze task, but demonstrated impaired reference memory. Anxiety measured by thigmotaxis in the maze, did not play a role for the observed cognitive impairment. Of further interest, an increase in the number of hippocampal macrophages and microglia with training and/or infection suggested a significant role of these cell types during spatial learning. Together, these experimental mouse studies suggest that helminth infections do have an impact on cognition. Further experimental animal studies on cognition and infection might open new approaches for a better understanding and impact of pathogen infections.

Plasmatic coagulation and fibrinolysis in healthy and Otostrongylus-affected Northern elephant seals (Mirounga angustirostris).

BACKGROUND: Prepatent Otostrongylus arteritis results in hemorrhagic diathesis in free-ranging Northern elephant seals (Mirounga angustirostris) attributed to aberrant larval migration of the lungworm, Otostrongylus circumlitus. Clinical signs are often nonspecific, including lethargy, anorexia, and blepharospasm, but can progress to spontaneous frank hemorrhage and death within 72 hours of onset. Previously published case reports describe coagulopathy with prolonged PT and APTT, normal to elevated platelet counts, normal antithrombin concentrations, and low concentrations of fibrinogen degradation products. Disseminated intravascular coagulation was proposed as the cause of hemorrhage, but is inconsistent with some of the reported clinicopathologic changes. OBJECTIVE: The purpose of this study was to compare plasmatic coagulation and fibrinolysis in healthy and Otostrongylus-affected elephant seals, in order to identify potential therapy. We hypothesized that hyperfibrinolysis contributed to hemorrhage in these cases. METHODS: Citrated plasma samples were collected from 3- to 4-month-old Northern elephant seals in a wildlife rehabilitation hospital. The sampled population included 25 healthy, prerelease seals and 32 clinically ill seals diagnosed with presumptive Otostrongylus arteritis. Twenty-one of the included seals had Otostrongylus infestation confirmed at necropsy. Standard coagulation tests and plasma thromboelastography were performed for a complete assessment of coagulation and fibrinolysis. RESULTS: Northern elephant seals with definitive Otostrongylus infestation were hypocoagulable and hypofibrinolytic compared to healthy controls. CONCLUSIONS: Results were most consistent with disseminated intravascular coagulation. Treatment with antifibrinolytic drugs to control hemorrhage may be unrewarding; alternative therapies such as plasma transfusions or coagulation factor concentrates should be investigated.

Effects of experimental Angiostrongylus cantonensis infection on the reproductive biology of Biomphalaria straminea and Biomphalaria tenagophila.

Eosinophilic meningoencephalitis is an endemic zoonosis in Southeast Asia and the Pacific Islands, but in recent years, new cases have been reported in various countries outside these regions, including Brazil, where it is considered an emerging disease. In this study, the effect of infection by the nematode Angiostrongylus cantonensis, one of the main etiologic agent of this disease, on the reproductive biology of the planorbid snails Biomphalaria straminea and B. tenagophila was investigated during the pre-patent period. Alterations in the reproductive biology of B. straminea and B. tenagophila were analyzed in laboratory-reared specimens infected by A. cantonensis during 21days; the number of eggs, number of egg masses, number of eggs/mass, number of eggs/snail, viable eggs/snail, survival and galactogen content in the albumen gland were measured. The results indicated the occurrence of initial compensation in reproductive effort in both snail species, but at different moments in the pre-patent period. More specifically, a reduction of 46.53% in the eggs/egg mass ratio in infected B. straminea was observed, a reflection of a 50% decline in the concentration of galactogen contained in the albumen gland. Changes in this parameter were also noted in B. tenagophila, but only at the end of the study period, with a reduction of 15.49%. Histological analyses indicate that changes observed can be explained by the tissue damages caused by the migration and development of the larvae. These results shed more light on the host-parasite relationship and indicate the importance of studying reproductive aspects for efforts to control infected snails. Considering that terrestrial snails can also transmit eosinophilic meningitis (in addition to aquatic mollusks), the data obtained expand knowledge of this host-parasite relationship and provide support for programs to control this zoonosis.

Angiostrongylus vasorum in wolves in Italy: prevalence and pathological findings.

BACKGROUND: Angiostrongylus vasorum is a nematode residing in the heart and pulmonary vessels of dogs and wild carnivores. In Europe the red fox is its reservoir, while only three records from wolves have been published. Angiostrongylus vasorum has a worldwide distribution, and many pieces of evidence demonstrate that it is spreading from endemic areas to new ones. In Italy, A. vasorum was reported with increasing frequency in dogs and foxes in the last decades, and now it is considered endemic throughout the country. Angiostrongylus vasorum can be asymptomatic or cause respiratory and circulatory disorders, at times causing severe disseminated infections. METHODS: Between February 2012 and December 2016, 25 wolves found dead in central Italy were submitted to the Istituto Zooprofilattico del Lazio e della Toscana for post-mortem examination. Samples of lungs, heart, liver, spleen, kidneys, mediastinic lymph nodes and brain were collected from each animal for histological examination. When adult and larval nematodes were microscopically seen in lungs, the other organs were processed, and five histological sections for each organ were examined. To confirm parasite identification, lung samples were submitted to a PCR-sequencing protocol targeting the ITS2 region of A. vasorum. RESULTS: Seven wolves (28.0%) harboured nematode larvae in lung sections. In two of the positive wolves, adult nematodes were visible in pulmonary arteries, in four animals larvae were also detected in other organs. DNA sequencing reactions confirmed parasite identification as A. vasorum in all the cases. CONCLUSIONS: As a result of the high prevalence of A. vasorum reported in wolves in the present study, a focus of high circulation could be hypothesised in central Italy. Nevertheless, the similarly high prevalence in foxes originating from the same areas were reported in previous papers. Histopathological evidence highlights the pathogenic potential of A. vasorum in the wolf, especially in juvenile animals.

Eosinophilic Meningitis Caused by Angiostrongylus cantonensis.

Rat lungworm, Angiostrongylus cantonensis, is one major cause of human eosinophilic meningitis. This helminth is endemic in Southeast Asia, Pacific Islands, and the Caribbean and has recently expanded to South America. The infection is characterized by an elevated eosinophil count in cerebrospinal fluid. Common symptoms and signs include headache, neck stiffness, paresthesia and nausea/vomiting. The unique history of eating freshwater and land snails or slugs within 2 weeks before onset is helpful for diagnosis. Antihelminthic agents have not shown efficacy in human infection; treatment involves supportive care with management of inflammation and intracranial pressure.

Characterizing longitudinal changes in rabbit brains infected with Angiostrongylus Cantonensis based on diffusion anisotropy.

Angiostrongylus cantonensis has become a global source of infection in recent years, and the differential diagnosis and timely follow-up are crucial in the management of the infection. Magnetic resonance imaging (MRI) has been suggested as a non-invasive technique in characterizing and localizing lesions during the parasitic infections in the brain. Non-invasive diffusion tensor imaging (DTI) can be used to distinguish microscopic cerebral structures but cannot resolve the more complicated neural structure. Several methods have been proposed to overcome this limitation. One such method, generalized q-sampling imaging (GQI), can be applied to a variety of datasets, including the single shell, multi-shell or grid sampling schemes, which are believed to resolve complicated crossing fibers. This study aimed to characterize angiostrongyliasis in the rabbit brain over a 6-week period using anatomical and diffusion MRI, including DTI and GQI. Our anatomical T2WI and R2 mapping results showed that the ventricle size of the rabbit brain increased after A. cantonensis larvae infection, and the DTI and GQI indices both showed pathological changes in the corpus callosum, hippocampus and cortex over a 6-week infection period. These results were consistent with our histopathological findings. Our results demonstrated that the diagnosis of larvae infection using anatomical and diffusion MRI is possible and that follow-up characterization is informative in revealing the effects of angiostrongyliasis in various brain areas. These support the use of anatomical and diffusion MRI was helpful for diagnosis of eosinophilic meningitis caused by A. cantonensis infection. This non-invasive MRI platform could be used to improve the management of eosinophilic meningitis or eosinophilic meningoencephalitis in humans.

Hematological and histopathological changes in Rattus norvegicus (Wistar) experimentally infected by Angiostrongylus cantonensis (Chen, 1935).

Eosinophilic meningitis caused by Angiostrongylus cantonensis is a zoonosis endemic to Southeast Asia and the Pacific islands. It is considered an emerging disease because it has been expanding both geographically and in terms of the range of hosts. In South America, the first cases were reported in Brazil and were attributed to eating infected snails. In this study, 70 adult females of Rattus norvegicus (Wistar) were used to evaluate hematology, blood gases, cardiac markers and lung histopathology changes caused by this parasite. Of them, 60 were individually infected by orogastric gavage with 100 L(3) larvae and 10 uninfected animals formed the control group. The results obtained demonstrate that infection caused by A. cantonensis in R. norvegicus promotes significant hematological changes induced in the vertebrate host, manifested mainly in the form of regenerative anemia, thrombocytopenia and eosinophilia. Additionally, histopathological changes in the lung parenchyma demonstrated in rodents reveal the occurrence of areas of necrosis and extensive fibrosis, being directly related to the development of cellular hypoxia and enzyme cardiac changes. This study can contribute to a better understanding of the relationship between A. cantonensis and R. norvegicus.

Enzootic angiostrongyliasis in Guangzhou, China, 2008-2010.

This study was conducted to gain an understanding of the Angiostrongylus cantonensis infection status of rodent definitive host, snail intermediate host, and local residents in Guangzhou, China. A total of 430 rats were captured and 23 rats, from two species, were infected, with an average infection rate of 5.35%. A total of 795 Achatina fulica snails and 734 Pomacea canaliculata snails were collected. The average infection rates of these two species were 13.96% (111 of 795) and 1.50% (11 of 734), respectively. As for the seroprevalence of different occupations, the rate among the "general group" was significantly lower than the "occupational group." From this survey, Guangzhou is implicated to be the natural focus of Angiostrongylus cantonensis. Rattus norvegicus and Achatina fulica play important roles in spreading this nematode in Guangzhou. Residents who live in Guangzhou, especially those working in certain industries such as agriculture, food-making, and aquaculture, face a higher risk of infection.

Changes in the reproductive biology of Biomphalaria glabrata experimentally infected with the nematode Angiostrongylus cantonensis.

This study showed for the first time changes in the reproductive biology of Biomphalaria glabrata experimentally infected with Angiostrongylus cantonensis. The values of all the parameters analyzed (total number of eggs, number of egg masses, number of eggs/mass, number of eggs/snail, percentage of viable eggs and galactogen content in albumen gland) changed with progressive infection. The results indicate the occurrence of partial parasitic castration of B. glabrata by A. cantonensis larvae, probably in response to the depletion of energy reserves, with no injuries to the gonadal tissues.

Dietary protein and energy supplies differentially affect resistance to parasites in lactating mammals.

Periparturient relaxation of immunity (PPRI) to parasites in mammals results in higher worm burden and worm egg excretion and may have a nutritional basis. Nippostrongylus brasiliensis re-infected lactating rats fed low-crude protein (CP) diets show an augmented degree of PPRI compared with their high CP-fed counterparts. However, such effects of CP scarcity have been confounded by metabolisable energy (ME) scarcity due to increased intake of the high-CP foods. Here, we independently assessed the effects of dietary CP and ME scarcity on the degree of PPRI. Second, parity rats were infected with N. brasiliensis larvae before mating. Upon parturition, dams were allocated to one of six feeding treatments (1-6), consisting of two levels of dietary ME supply, each with three levels of CP supply. On day 2 of lactation, dams were either re-infected with 1600 N. brasiliensis larvae or sham-infected with PBS, while litter size was standardised at ten pups. Dams and litters were weighed daily until either day 8 or 11 of lactation, when worm burdens were assessed as a proxy for PPRI. Increased CP and ME supply independently improved lactational performance. While ME supply did not affect parasitism, increasing CP supply reduced worm burden and the percentage of female worms in the small intestine; the latter was especially pronounced at the lower level of ME supply. The present results support the view that PPRI to parasites may be sensitive to CP scarcity, but not to moderate ME scarcity.

Genome-wide transcriptomic analysis of intestinal tissue to assess the impact of nutrition and a secondary nematode challenge in lactating rats.

BACKGROUND: Gastrointestinal nematode infection is a major challenge to the health and welfare of mammals. Although mammals eventually acquire immunity to nematodes, this breaks down around parturition, which renders periparturient mammals susceptible to re-infection and an infection source for their offspring. Nutrient supplementation reduces the extent of periparturient parasitism, but the underlying mechanisms remain unclear. Here, we use a genome wide approach to assess the effects of protein supplementation on gene expression in the small intestine of periparturient rats following nematode re-infection. METHODOLOGY/PRINCIPAL FINDINGS: The use of a rat whole genome expression microarray (Affymetrix Gene 1.0ST) showed significant differential regulation of 91 genes in the small intestine of lactating rats, re-infected with Nippostrongylus brasiliensis compared to controls; affected functions included immune cell trafficking, cell-mediated responses and antigen presentation. Genes with a previously described role in immune response to nematodes, such as mast cell proteases, and intelectin, and others newly associated with nematode expulsion, such as anterior gradient homolog 2 were identified. Protein supplementation resulted in significant differential regulation of 64 genes; affected functions included protein synthesis, cellular function and maintenance. It increased cell metabolism, evident from the high number of non-coding RNA and the increased synthesis of ribosomal proteins. It regulated immune responses, through T-cell activation and proliferation. The up-regulation of transcription factor forkhead box P1 in unsupplemented, parasitised hosts may be indicative of a delayed immune response in these animals. CONCLUSIONS/SIGNIFICANCE: This study provides the first evidence for nutritional regulation of genes related to immunity to nematodes at the site of parasitism, during expulsion. Additionally it reveals genes induced following secondary parasite challenge in lactating mammals, not previously associated with parasite expulsion. This work is a first step towards defining disease predisposition, identifying markers for nutritional imbalance and developing sustainable measures for parasite control in domestic mammals.