Comparative Characterization of Dengue Virus Serotype 2 Isolates from a South Pacific Epidemic Sweep.

Ph.D. Thesis. University of Hawaiʻi at Mānoa 2017

In vivo efficacy of pyrantel pamoate as a post-exposure prophylactic for rat lungworm (\u3ci\u3eAngiostrongylus cantonensis\u3c/i\u3e)

Rat lungworm (Angiostrongylus cantonensis) is a neurotropic nematode, and the leading cause of eosinophilic meningitis worldwide. The parasite is usually contracted through ingestion of infected gastropods, often hidden in raw or partially cooked produce. Pharmaceutical grade pyrantel pamoate was evaluated as a post-exposure prophylactic against A. cantonensis. Pyrantel pamoate is readily available over-the-counter in most pharmacies in the USA and possesses anthelmintic activity exclusive to the gastrointestinal tract (GIT). Administering pyrantel pamoate immediately after exposure should theoretically paralyze the larvae in the GIT, causing the larvae to be expelled via peristalsis without entering the systemic circulation. In this study, pyrantel pamoate (11 mg/kg) was orally administered to experimentally infected rats at 0, 2-, 4-, 6-, or 8-h post-infection. The rats were euthanized six weeks post-infection, and worm burden was evaluated from the heart-lung complex. This is the first in vivo study to evaluate its efficacy against A. cantonensis. This study demonstrates that pyrantel pamoate can significantly reduce worm burden by 53–72% (P = 0.004), and thus likely reduce the severity of infection that is known to be associated with worm burden. This paralyzing effect of pyrantel pamoate on the parasite may also be beneficial for delaying the establishment of infection until a more suitable anthelmintic such as albendazole is made available to the patient

Comparison of Antibody Isotype Response to <i>Angiostrongylus cantonensis</i> in Experimentally Infected Rats (<i>Rattus norvegicus</i>) Using Hawai’i 31 kDa Antigen in an Indirect ELISA

Neuroangiostrongyliasis (NAS) is an emerging tropical disease in humans and some animals which is caused by infection with the parasitic nematode Angiostrongylus cantonensis. It is the leading cause of eosinophilic meningitis worldwide. Diagnoses in humans and susceptible animals are generally presumptive and easily confused with other central nervous system disorders. The 31 kDa antigen is currently the only NAS immunodiagnostic assay that has achieved 100% sensitivity. However, little is known about the humoral immune response against the 31 kDa antigen in NAS infections, which would be critical for widespread adoption of this assay. We used the Hawai’i 31 kDa isolate in an indirect ELISA assay to confirm the presence of immunoglobulin IgG, IgM, IgA, and IgE isotypes in six-week post-infection plasma from lab-reared rats infected with 50 live, third-stage, A. cantonensis larvae isolated from a wild Parmarion martensi semi-slug. Our results confirmed the presence of all four isotypes against the Hawaii 31 kDa isolate, with sensitivity ranging from 22–100%. The IgG isotype showed 100% sensitivity in detecting A. cantonensis infection, which validates the use of IgG indirect ELISA with 31 kDa antigen as an effective immunodiagnostic assay for rats six weeks post-infection. Given each isotype may be present at different times during NAS infections, our data provides preliminary information on the humoral immune response to A. cantonensis infection in lab-reared rats and serves as a baseline for future studies

Management of Rat Lungworm Disease (Neuroangiostrongyliasis) Using Anthelmintics: Recent Updates and Recommendations

While there have been legitimate concerns in the past regarding the use of anthelmintics for the management of neuroangiostrongyliasis (rat lungworm disease), recent studies demonstrate that they can be considered safe and efficacious, particularly albendazole, which is regarded as the choice anthelmintic for its management. However, physician hesitancy to prescribe, as well as problems of availability persist, at least in Hawaii, which is considered the epicenter of this disease in the US. As a result, many patients suffer a diminished quality of life or even death. Here, we discuss recent studies that provide insights into new treatments and preventative interventions, which can be more rigorously used for the management of neuroangiostrongyliasis. In summary, results from recent studies suggest that albendazole and avermectins are beneficial for post-exposure management, pyrantel pamoate is beneficial as a post-exposure prophylactic, and levamisole is deserving of further study for the treatment of neuroangiostrongyliasis

Larvicidal Efficacy of Ozone and Ultrasound on Angiostrongylus cantonensis (Rat Lungworm) Third-Stage Larvae

The parasitic nematode Angiostrongylus cantonensis (rat lungworm) is the leading cause of human eosinophilic meningitis worldwide. Most human infections occur through the accidental consumption of A. cantonensis hidden within produce as infectious third-stage larvae (L3), yet little research has been published addressing possible methods to mitigate this means of transmission. Here, we describe our tests of ozone gas&mdash;an oxidizing agent&mdash;and ultrasound, both used for disinfection of food and municipal water supplies and in industrial cleaning. We found that exposure to ozone, produced using two different commercially available ozone generators over varying durations of time and concentrations, was capable of achieving 100% larval mortality. In addition, we evaluated the impact of different sound frequencies on A. cantonensis L3 survival using two different commercially available ultrasonic cleaners, and found that 60 s of 40 kHz produced 46% mortality within 2 h. The combined use of ultrasound and ozone gas simultaneously resulted in a minimum of 89% normalized mean percent mortality within 2 h of treatment. Our study suggests that both ozone and ultrasound show high larvicidal efficacy, both independently and together, and thus show promise as methods for reducing the risk of rat lungworm infection via accidental consumption

Protein folding includes oligomerization - examples from the endoplasmic reticulum and cytosol

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