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.

Workshop on research priorities for management and treatment of angiostrongyliasis(1).

In a concluding session of the workshop, the participants developed a list of 115 research and outreach needs, outlining the top 5-7 needs in each of 8 areas (Table). For complete information, including presenter details and abstracts, visit the workshop website at www.hawaii.edu/cowielab/Angio%20website%20home.htm.

Case Report: Management of Dead Intraocular Helminth Parasites in Asymptomatic Patients.

We report four asymptomatic patients from Nepal with an incidental finding of a dead intraocular helminth parasite on ophthalmological routine examination. Because the patients were asymptomatic and the intraocular helminth parasites dead without noted pathology present, it was decided to abstain from surgical removal and pursue a watch-and-wait strategy. The clinical follow-up of the four patients over two years was uneventful and showed no complications. We conclude that dead intraocular helminth parasites in asymptomatic patients without apparent pathology do not require surgical removal.

Causes of Fatal Cyathostomiasis in Brown Booby (Sula leucogaster) from Brazil: Identification of Pathogen and Implications for Management.

Fatal infection by Cyathostoma (Cyathostoma) phenisci (Nematoda: Syngamidae), was identified in 2 of 52 brown boobies (Sula leucogaster) collected on beaches in the state of Rio de Janeiro, Brazil, and admitted to the veterinary clinic for rehabilitation. Both infected birds were in poor physical condition, with atrophied pectoral muscles, and died soon after starting treatment. The parasitological and pathological examination of the carcasses revealed the presence of C. (C.) phenisci in the trachea, resulting in tracheitis, as well as severe parasitic granulomatous bronchopneumonia caused by eggs deposited in the lungs. In our opinion, these serious pathological changes were the primary cause of chronic respiratory illness. This is the first description of fatal cyathostomiasis in a fish-eating avian host caused by infection by a member of the subgenus Cyathostoma (Cyathostoma). Therefore, it is reasonable to consider C. (C.) phenisci to be a real threat to a wide range of their definitive hosts, and cyathostomiasis should be considered in the differential diagnosis for fish-eating marine birds, even in cases without respiratory signs. This is also the first record of the genus Cyathostoma in Brazil.

Gastrointestinal nematode infection interferes with experimental allergic airway inflammation but not atopic dermatitis.

BACKGROUND: Some helminth infections are negatively associated with the prevalence of allergic disorders, arguing for a modulation of allergic reactions by the parasites, depending on the worm species, intensity and phase of infection and the type of disease. OBJECTIVE: The aim of this study was to analyse the influence of a chronic infection with the gastrointestinal nematode Heligmosomoides polygyrus, in a murine model of allergic airway disease and of atopic dermatitis (AD), respectively. METHODS: Mice were infected with H. polygyrus and systemically sensitized with the model allergen ovalbumin. Subsequently, the animals were challenged with the allergen either via the airways for induction of airway disease, or via skin patches for induction of dermatitis. RESULTS: Mice concomitantly infected with H. polygyrus showed diminished eosinophil and lymphocyte recruitment into the lungs and decreased allergen-specific IgE levels when compared with sensitized and airway challenged controls. In addition, animals showed a trend towards reduced airway hyper-reactivity. In contrast, no significant differences in the severity of eczematous skin lesions were observed between infected and control animals in the AD model. Although H. polygyrus infection reduced CD8+ and CD4+ T-cell infiltration into the skin and production of allergen-specific IgE, mast cell recruitment was significantly increased in worm-infected mice in the dermatitis model. The worm infection was associated with significantly elevated numbers of Foxp3+ regulatory T cells (Treg) in peribronchial lymph nodes in H. polygyrus-infected sensitized and airway challenged mice. In contrast, Treg cells were basically absent in eczematous skin and their number was not increased in skin-draining lymph nodes of mice with experimental dermatitis. CONCLUSION: Infection with the gastrointestinal nematode used in our study leads to significant inhibition of mucosa-associated but not cutaneous allergic reactions, pointing to a site specificity of the immunomodulation exerted by helminths. This finding might be an important aspect for future considerations of helminths for treatment of allergic diseases.

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.

Removal of adult cyathostomins alters faecal microbiota and promotes an inflammatory phenotype in horses.

The interactions between parasitic helminths and gut microbiota are considered to be an important, although as yet incompletely understood, factor in the regulation of immunity, inflammation and a range of diseases. Infection with intestinal helminths is ubiquitous in grazing horses, with cyathostomins (about 50 species of which are recorded) predominating. Consequences of infection include both chronic effects, and an acute inflammatory syndrome, acute larval cyathostominosis, which sometimes follows removal of adult helminths by administration of anthelmintic drugs. The presence of cyathostomins as a resident helminth population of the equine gut (the "helminthome") provides an opportunity to investigate the effect helminth infection, and its perturbation, has on both the immune system and bacterial microbiome of the gut, as well as to determine the specific mechanisms of pathophysiology involved in equine acute larval cyathostominosis. We studied changes in the faecal microbiota of two groups of horses following treatment with anthelmintics (fenbendazole or moxidectin). We found decreases in both alpha diversity and beta diversity of the faecal microbiota at Day 7 post-treatment, which were reversed by Day 14. These changes were accompanied by increases in inflammatory biomarkers. The general pattern of faecal microbiota detected was similar to that seen in the relatively few equine gut microbiome studies reported to date. We conclude that interplay between resident cyathostomin populations and the bacterial microbiota of the equine large intestine is important in maintaining homeostasis and that disturbance of this ecology can lead to gut dysbiosis and play a role in the aetiology of inflammatory conditions in the horse, including acute larval cyathostominosis.

Human angiostrongyliasis.

Human angiostrongyliasis caused by Angiostrongylus cantonensis, a rat lungworm, has been reported globally. Human infections are acquired by ingestion of raw or undercooked snails or slugs, paratenic hosts such as prawns, or contaminated vegetables that contain the infective larvae of the worm. So far, at least 2827 cases of the disease have been documented worldwide. During the past few years, several outbreaks of human angiostrongyliasis have been reported in mainland China, Taiwan, and the USA. Additionally, sporadic cases in travellers who have returned from endemic areas have been reported. We review the clinical features, diagnosis, and treatment of human angiostrongyliasis, and describe the geographical distribution and prevalence of A cantonensis. Educating the public about the dangers of eating raw or undercooked intermediate and paratenic hosts in endemic areas is essential for the prevention and control of this foodborne zoonotic disease.

Pediatric angiostrongyliasis.

Angiostrongyliasis, the leading cause worldwide of eosinophilic meningitis, is an emergent disease due to Angiostrongylus cantonensis larvae, transmitted accidentally to humans. Contamination of children usually occurs by direct contact with an infected mollusk. Eosinophilic meningoencephalitis is the major clinical feature of this parasitic infection in humans. It is usually benign for adults, but more severe for children. Clinical symptoms usually combine fever, meningitis, and neurological signs (somnolence, moaning, hypotonia, convulsions, and increased intracranial pressure). Presumptive diagnosis of human angiostrongyliasis is based on epidemiologic characteristics, clinical symptoms, medical history, and laboratory findings, in particular, hypereosinophilia in blood and cerebrospinal fluid. Treatment is based on corticosteroids associated with anthelmintics. This work reviews the diagnosis and treatment of this life-threatening (especially in children) parasitic disease and the need for preventive action.

Differences between IL-4R alpha-deficient and IL-4-deficient mice reveal a role for IL-13 in the regulation of Th2 responses.

Allergens and infections with parasitic helminths preferentially induced Th2 immune responses associated with elevated levels of serum immunoglobulin E (IgE) and expansion of eosinophils and mast cells. Interleukin-4 (IL-4) is a key cytokine in the differentiation of naive CD4+ T cells into Th2 cells, which produce a panel of cytokines including IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13 [1] and have been shown to trigger recovery from gastrointestinal nematodes [2]. Nonetheless, mice deficient for IL-4 have been shown to develop residual Th2 responses [3-5] and can expel the nematode Nippostrongylus brasiliensis [6], suggesting that there is a functional equivalent of IL-4 in these processes. IL-13 is a cytokine that shares some, but not all, biological activities with IL-4 [7,8]. There is now compelling evidence that IL-4 and IL-13 share receptor components, including IL-4R alpha and IL-13R alpha 1 [9]. In order to dissect the roles of IL-4 and IL-13 in the regulation of Th2 cells and in the response to nematode infections, we looked for differences between mice deficient for either the IL-4 gene or the IL-4R alpha gene. Unlike IL-4, IL-4R alpha was required for control of N. brasiliensis, and Th2 development during infection--as characterized by cytokine production, GATA-3 and surface CD30 expression--was more severely affected in IL-4R alpha-/- mice than in IL-4-/- mice. Injection of recombinant IL-13 induced worm expulsion in otherwise incompetent RAG2-/- mice. Our results suggest that IL-13 regulates Th2 responses to nematode infection and requires IL-4R alpha.

Eosinophilic meningitis caused by Angiostrongylus cantonensis after ingestion of raw frogs.

Angiostrongylus cantonensis is the most common cause of eosinophilic meningitis in humans after ingestion of raw or inadequately cooked intermediate hosts or food contaminated with infective third-stage larvae. Frogs are known to be a paratenic host of A. cantonensis, but have never been reported as the infectious source of human angiostrongyliasis in Taiwan. We report the first case of eosinophilic meningitis caused by A. cantonensis after ingestion of raw frogs (Rana plancyi).

Intraocular angiostrongyliasis: clinical findings, treatments and outcomes.

Ocular angiostrongyliasis, diagnosed by identification of Angiostrongylus cantonensis in any part of the eye, is a very rare manifestation. We report seven cases of intraocular angiostrongyliasis in Srinagarind Hospital, Khon Kaen University, Thailand. From a total of 654 cases of angiostrongyliasis diagnosed between January 1995 and April 2005, 7 cases (1.1%) with ocular manifestations were found. Four men and three women were diagnosed, with a mean age of 32.1 years (range 21-46 years). All of the patients lived in the northeast of Thailand and acquired the infection by eating raw Pila spp. snails, the intermediate host of A. cantonensis. The incubation period lasted from 2 weeks to 2 months. The most common symptom, blurred vision without eosinophilic meningitis, occurred as a presenting symptom in five cases. The other two cases presented with eosinophilic meningitis prior to development of poor visual acuity. Both cases had papilloedema, neck stiffness and eosinophilia without fever. The visual acuity of the patient was mostly lower than 2/60 and, evidently, visual impairment in all patients was caused by retinal pigment epithelial defects. All cases had only one immature A. cantonensis worm in the eye, with the most common site being the intravitreous area. Several treatments, including oral prednisolone, topical prednisolone, argon laser, diode laser, Nd:YAG laser, surgical removal of the parasite and combination therapy, were used. There is no evidence that surgical and laser interventions improve the course of the disease, and both have associated risks. Visual outcome depends on the initial visual defects.

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.

Angiostrongyliasis (Rat Lungworm Disease): Viewpoints from Hawai'i Island.

Hawai'i, particularly east Hawai'i Island, is the epicenter for angiostrongyliasis in the United States. Case numbers have been increasing and appear to parallel the introduction and spread of the semislug (Parmarion martensi) to east Hawai'i. The infective larvae in rainwater catchment as a source for household and agricultural water may also play a role. The spread of Angiostrongylus cantonensis as well as the potential introduction of the semislug P. martensi should be a concern to the mainland United States. The State of Hawai'i should recognize the seriousness of this growing problem and thus collaborate to fund studies to address the growing challenges surrounding angiostrongyliasis.

[The carnivorous fungi hyphomycetes are natural regulators of the size of animal parasitic nematodes].

The carnivorous fungi hyphomycetes are natural enemies of soil nematodes. Laboratory tests examining the effect of the effective strain Duddingtonia flagrans T-89 on equine strongyle larvae have indicated that their size can be reduced 5-48-fold under the action of the fungus. Using helminth-infected mice as an example has ascertained that when the animals are fed a biopreparation, the chlamydial spores of the carnivorous fungus D. flagrans remain viable and continue their development in the excrements. The dead nematodes show cell structural impairments in all tissues and organs, which may be associated with the action of the substances contained in the cell envelope of the fungus.

Angiostrongylus vasorum Causing Severe Granulomatous Hepatitis with Concurrent Multiple Acquired PSS.

A 14 mo old female Jack Russell terrier presented with a 12 hr history of vomiting and inappetence. She was subsequently diagnosed with multiple acquired portosystemic shunts during an exploratory celiotomy. Gross and histopathological hepatic abnormalities were consistent with chronic disease, including features suggestive of portal hypertension that was potentially caused by migrating and resident Angiostrongylus vasorum larvae. Fecal analysis and polymerase chain reaction of hepatic tissue confirmed the presence of Angiostrongylus vasorum . The dog recovered clinically following empirical treatment and supportive care. A lack of parasite burden was confirmed 9 wk postdiagnosis; however, serum biochemical analysis at that time was suggestive of ongoing hepatic dysfunction.

Central nervous system manifestations of Angiostrongylus cantonensis infection.

Over 20 species of Angiostrongylus have been described from around the world, but only Angiostrongylus cantonensis has been confirmed to cause central nervous system disease in humans. A neurotropic parasite that matures in the pulmonary arteries of rats, A. cantonensis is the most common cause of eosinophilic meningitis in southern Asia and the Pacific and Caribbean islands. The parasite can also cause encephalitis/encephalomyelitis and rarely ocular angiostrongyliasis. The present paper reviews the life cycle, epidemiology, pathogenesis, clinical features, diagnosis, treatment, prevention and prognosis of A. cantonesis infection. Emphasis is given on the spectrum of central nervous system manifestations and disease pathogenesis.

Historical perspective of cyathostomes: prevalence, treatment and control programs.

Small strongyles are highly prevalent in horses and can be found worldwide. Even though over 50 species of these parasites have been described, about 10 species comprise the bulk of the total number present in horses. Efforts to control small strongyles and other equine internal parasites have been undertaken for many years. Some of the early medications and control measures provided questionable activity against endoparasites; whether effective or not, they could be detrimental to the horse. Beginning in the early 1900s, scientific effort was used to evaluate activity of antiparasitic compounds. Only a relatively low number of classes of compounds has been used for parasite control. Progressively, in time, newer drugs have become broad-spectrum, safer, and available in lower dose rates than previously. With extensive use of parasiticides, small strongyles have been found to be resistant to all commercially-available classes of compounds except the macrocyclic lactones. Innovative parasite-control programs, relying less on drugs, need to be developed.