Methylprednisolone acetate induces, and Δ7-dafachronic acid suppresses, Strongyloides stercoralis hyperinfection in NSG mice.

Strongyloides stercoralis hyperinfection causes high mortality rates in humans, and, while hyperinfection can be induced by immunosuppressive glucocorticoids, the pathogenesis remains unknown. Since immunocompetent mice are resistant to infection with S. stercoralis, we hypothesized that NSG mice, which have a reduced innate immune response and lack adaptive immunity, would be susceptible to the infection and develop hyperinfection. Interestingly, despite the presence of large numbers of adult and first-stage larvae in S. stercoralis-infected NSG mice, no hyperinfection was observed even when the mice were treated with a monoclonal antibody to eliminate residual granulocyte activity. NSG mice were then infected with third-stage larvae and treated for 6 wk with methylprednisolone acetate (MPA), a synthetic glucocorticoid. MPA treatment of infected mice resulted in 50% mortality and caused a significant >10-fold increase in the number of parasitic female worms compared with infected untreated mice. In addition, autoinfective third-stage larvae, which initiate hyperinfection, were found in high numbers in MPA-treated, but not untreated, mice. Remarkably, treatment with Δ7-dafachronic acid, an agonist of the parasite nuclear receptor Ss-DAF-12, significantly reduced the worm burden in MPA-treated mice undergoing hyperinfection with S. stercoralis Overall, this study provides a useful mouse model for S. stercoralis autoinfection and suggests a therapeutic strategy for treating lethal hyperinfection.

Malignant Transformation of Hymenolepis nana in a Human Host.

Neoplasms occur naturally in invertebrates but are not known to develop in tapeworms. We observed nests of monomorphic, undifferentiated cells in samples from lymph-node and lung biopsies in a man infected with the human immunodeficiency virus (HIV). The morphologic features and invasive behavior of the cells were characteristic of cancer, but their small size suggested a nonhuman origin. A polymerase-chain-reaction (PCR) assay targeting eukaryotes identified Hymenolepis nana DNA. Although the cells were unrecognizable as tapeworm tissue, immunohistochemical staining and probe hybridization labeled the cells in situ. Comparative deep sequencing identified H. nana structural genomic variants that are compatible with mutations described in cancer. Invasion of human tissue by abnormal, proliferating, genetically altered tapeworm cells is a novel disease mechanism that links infection and cancer.

Possible Role of Fish as Transport Hosts for Dracunculus spp. Larvae.

To inform Dracunculus medinensis (Guinea worm) eradication efforts, we evaluated the role of fish as transport hosts for Dracunculus worms. Ferrets fed fish that had ingested infected copepods became infected, highlighting the importance of recommendations to cook fish, bury entrails, and prevent dogs from consuming raw fish and entrails.

Progress Toward Global Eradication of Dracunculiasis, January 2016-June 2017.

Dracunculiasis (Guinea worm disease) is caused by Dracunculus medinensis, a parasitic worm. Approximately 1 year after a person acquires infection from contaminated drinking water, the worm emerges through the skin, usually on a lower limb (1). Pain and secondary bacterial infection can cause temporary or permanent disability that disrupts work and schooling. The campaign to eradicate dracunculiasis worldwide began in 1980 at CDC. In 1986, the World Health Assembly called for dracunculiasis elimination,* and the global Guinea Worm Eradication Program, led by the Carter Center and supported by the World Health Organization (WHO), United Nations Children's Fund, CDC, and other partners, began assisting ministries of health in countries with endemic dracunculiasis. In 1986, an estimated 3.5 million cases occurred each year in 20 countries in Africa and Asia (2). Since then, although the goal of eradicating dracunculiasis has not been achieved, considerable progress has been made. Compared with the 1986 estimate, the annual number of reported cases in 2016 has declined by >99%, and cases are confined to three countries with endemic disease. This report updates published (3-4) and unpublished surveillance data reported by ministries of health and describes progress toward dracunculiasis eradication during January 2016-June 2017. In 2016, a total of 25 cases were reported from three countries (Chad [16], South Sudan [six], Ethiopia [three]), compared with 22 cases reported from the same three countries and Mali in 2015 (Table 1). The 14% increase in cases from 2015 to 2016 was offset by the 25% reduction in number of countries with indigenous cases. During the first 6 months of 2017, the overall number of cases declined to eight, all in Chad, from 10 cases in three countries (Chad [four], South Sudan [four] and Ethiopia [two]) during the same period of 2016. Continued active surveillance, aggressive detection, and appropriate management of cases are essential eradication program components; however, epidemiologic challenges, civil unrest, and insecurity pose potential barriers to eradication.

The Emergence of Zoonotic Onchocerca lupi Infection in the United States--A Case-Series.

This case-series describes the 6 human infections with Onchocerca lupi, a parasite known to infect cats and dogs, that have been identified in the United States since 2013. Unlike cases reported outside the country, the American patients have not had subconjunctival nodules but have manifested more invasive disease (eg, spinal, orbital, and subdermal nodules). Diagnosis remains challenging in the absence of a serologic test. Treatment should be guided by what is done for Onchocerca volvulus as there are no data for O. lupi. Available evidence suggests that there may be transmission in southwestern United States, but the risk of transmission to humans is not known. Research is needed to better define the burden of disease in the United States and develop appropriately-targeted prevention strategies.

Guinea Worm (Dracunculus medinensis) Infection in a Wild-Caught Frog, Chad.

A third-stage (infective) larva of Dracunculus medinensis, the causative agent of Guinea worm disease, was recovered from a wild-caught Phrynobatrachus francisci frog in Chad. Although green frogs (Lithobates clamitans) have been experimentally infected with D. medinensis worms, our findings prove that frogs can serve as natural paratenic hosts.

Possible Role of Fish and Frogs as Paratenic Hosts of Dracunculus medinensis, Chad.

Copepods infected with Dracunculus medinensis larvae collected from infected dogs in Chad were fed to 2 species of fish and tadpoles. Although they readily ingested copepods, neither species of fish, Nile tilapia (Oreochromis niloticus) nor fathead minnow (Pimephalis promelas), were found to harbor Dracunculus larvae when examined 2-3 weeks later. Tadpoles ingested copepods much more slowly; however, upon examination at the same time interval, tadpoles of green frogs (Lithobates [Rana] clamitans) were found to harbor small numbers of Dracunculus larvae. Two ferrets (Mustela putorius furo) were fed fish or tadpoles that had been exposed to infected copepods. Only the ferret fed tadpoles harbored developing Dracunculus larvae at necropsy 70-80 days postexposure. These observations confirm that D. medinensis, like other species in the genus Dracunculus, can readily survive and remain infective in potential paratenic hosts, especially tadpoles.

Baylisascaris procyonis Roundworm Seroprevalence among Wildlife Rehabilitators, United States and Canada, 2012-2015.

Baylisascaris procyonis roundworms can cause potentially fatal neural larva migrans in many species, including humans. However, the clinical spectrum of baylisascariasis is not completely understood. We tested 347 asymptomatic adult wildlife rehabilitators for B. procyonis antibodies; 24 were positive, suggesting that subclinical baylisascariasis is occurring among this population.

Progress Toward Global Eradication of Dracunculiasis -January 2015-June 2016.

Dracunculiasis (Guinea worm disease) is caused by Dracunculus medinensis, a parasitic worm. Approximately 1 year after a person acquires infection from drinking contaminated water, the worm emerges through the skin, usually on the leg. Pain and secondary bacterial infection can cause temporary or permanent disability that disrupts work and schooling. The campaign to eradicate dracunculiasis worldwide began in 1980 at CDC. In 1986, the World Health Assembly called for dracunculiasis elimination (1), and the global Guinea Worm Eradication Program, led by the Carter Center and supported by the World Health Organization (WHO), United Nations Children's Fund (UNICEF), CDC, and other partners, began assisting ministries of health in countries where dracunculiasis was endemic. In 1986, an estimated 3.5 million cases were occurring each year in 20 countries in Africa and Asia (1,2). Since then, although the goal of eradicating dracunculiasis has not been achieved, substantial progress has been made. Compared with the 1986 estimate, the annual number of reported cases in 2015 has been reduced by >99%, and cases are confined to four countries with endemic disease. This report updates published (3-5) and unpublished surveillance data reported by ministries of health and describes progress toward dracunculiasis eradication during January 2015-June 2016. In 2015, a total of 22 cases were reported from four countries (Chad [nine cases], Mali [five], South Sudan [five], and Ethiopia [three]), compared with 126 cases reported in 2014 from the same four countries (Table 1). The overall 83% reduction in cases from 2014 to 2015 is the largest such annual overall reduction ever achieved during this global campaign. During the first 6 months of 2016, however, cases increased 25% compared with the same period in 2015. Continued active surveillance and aggressive detection and appropriate management of cases are essential eradication program components; however, epidemiologic challenges and civil unrest and insecurity pose potential barriers to eradication.

Canine Infections with Onchocerca lupi Nematodes, United States, 2011-2014.

Infections with Onchocerca lupi nematodes are diagnosed sporadically in the United States. We report 8 cases of canine onchocercosis in Minnesota, New Mexico, Colorado, and Florida. Identification of 1 cytochrome c oxidase subunit 1 gene haplotype identical to 1 of 5 from Europe suggests recent introduction of this nematode into the United States.

Isolation of Onchocerca lupi in Dogs and Black Flies, California, USA.

In southern California, ocular infections caused by Onchocerca lupi were diagnosed in 3 dogs (1 in 2006, 2 in 2012). The infectious agent was confirmed through morphologic analysis of fixed parasites in tissues and by PCR and sequencing of amplicons derived from 2 mitochondrially encoded genes and 1 nuclear-encoded gene. A nested PCR based on the sequence of the cytochrome oxidase subunit 1 gene of the parasite was developed and used to screen Simulium black flies collected from southern California for O. lupi DNA. Six (2.8%; 95% CI 0.6%-5.0%) of 213 black flies contained O. lupi DNA. Partial mitochondrial16S rRNA gene sequences from the infected flies matched sequences derived from black fly larvae cytotaxonomically identified as Simulium tribulatum. These data implicate S. tribulatum flies as a putative vector for O. lupi in southern California.

Progress Toward Global Eradication of Dracunculiasis, January 2014-June 2015.

Dracunculiasis (Guinea worm disease) is caused by Dracunculus medinensis, a parasitic worm. Approximately 1 year after a person acquires infection from contaminated drinking water, the worm emerges through the skin, usually on the lower limb. Pain and secondary bacterial infection can cause temporary or permanent disability that disrupts work and schooling. The campaign to eradicate dracunculiasis worldwide began in 1980 at CDC. In 1986, the World Health Assembly called for dracunculiasis elimination, and the global Guinea Worm Eradication Program, led by the Carter Center and supported by the World Health Organization (WHO), United Nations Children's Fund (UNICEF), CDC, and other partners, began assisting ministries of health in countries where dracunculiasis was endemic. In 1986, an estimated 3.5 million cases occurred each year in 20 countries in Africa and Asia. Since then, although the goal of eradicating dracunculiasis has not been achieved, considerable progress has been made. Compared with the 1986 estimate, the annual number of reported cases in 2015 has been reduced by 99% and cases are confined to four endemic countries. This report updates published and unpublished surveillance data reported by ministries of health and describes progress toward dracunculiasis eradication from January 2014 through June 2015. During 2014, a total of 126 cases were reported from four countries (Chad [13 cases], Ethiopia [three], Mali [40], and South Sudan [70]), compared with 148 cases reported in 2013, from the same four countries. The overall 15% reduction in cases during 2013­2014 was less than that experienced in recent years, but the rate of decline increased again to 70% in the first 6 months of 2015 compared with the same period during 2014. Continued active surveillance with aggressive detection and appropriate management of cases are essential program components; however, epidemiologic challenges and civil unrest and insecurity pose potential barriers to eradication.

Zoonotic anatrichosomiasis in a mother and daughter.

Zoonotic anatrichosomiasis in a mother and daughter is reported. Both presented with a 10-week history of multiple painful oral ulcers. Biopsy specimens revealed the presence of small, coiled trichuroid nematodes with distinctive morphological features, including stichocytes and paired bacillary bands. This represents an unusual infection by a zoonotic Anatrichosoma species.

Progress toward global eradication of dracunculiasis--January 2013-June 2014.

Dracunculiasis (Guinea worm disease) is caused by Dracunculus medinensis, a parasitic worm. Approximately 1 year after a person acquires infection from contaminated drinking water, the worm will emerge through the skin, usually on the lower limb. Pain and secondary bacterial infection can cause temporary or permanent disability that disrupts work and schooling. In 1986, the World Health Assembly called for dracunculiasis elimination. The global Guinea Worm Eradication Program, supported by The Carter Center, World Health Organization (WHO), UNICEF, CDC, and other partners, began assisting ministries of health of countries in which dracunculiasis is endemic in meeting this goal. At that time, an estimated 3.5 million cases occurred each year in 20 countries in Africa and Asia. This report updates published (3-5) and unpublished surveillance data reported by ministries of health and describes progress toward dracunculiasis eradication. A total of 148 cases were reported in 2013 from five countries (in order of prevalence: South Sudan, Chad, Mali, Ethiopia, and Sudan) compared with 542 cases in 2012 from four countries (South Sudan, Chad, Mali, and Ethiopia). The disease remains endemic in four countries in 2014 (South Sudan, Chad, Mali, and Ethiopia), but the overall incidence is falling faster in 2013 compared with 2012 (by 73%) and continues to fall faster in the first 6 months of 2014 (by 71%) compared with the same period in 2013. Failures in surveillance and containment, lack of clean drinking water, insecurity in Mali and parts of South Sudan, and an unusual epidemiologic pattern in Chad are the main remaining challenges to dracunculiasis eradication.

The etiology of severe acute gastroenteritis among adults visiting emergency departments in the United States.

BACKGROUND: Acute gastroenteritis (AGE) remains a common cause of clinic visits and hospitalizations in the United States, but the etiology is rarely determined. METHODS: We performed a prospective, multicenter emergency department-based study of adults with AGE. Subjects were interviewed on presentation and 3-4 weeks later. Serum samples, rectal swab specimens, and/or whole stool specimens were collected at presentation, and serum was collected 3-4 weeks later. Fecal specimens were tested for a comprehensive panel of viral, bacterial, and parasitic pathogens; serum was tested for calicivirus antibodies. RESULTS: Pathogens were detected in 25% of 364 subjects, including 49% who provided a whole stool specimen. The most commonly detected pathogens were norovirus (26%), rotavirus (18%), and Salmonella species (5.3%). Pathogens were detected significantly more often from whole stool samples versus a rectal swab specimen alone. Nine percent of subjects who provided whole stool samples had >1 pathogen identified. CONCLUSIONS: Viruses, especially noroviruses, play a major role as agents of severe diarrhea in adults. Further studies to confirm the unexpectedly high prevalence of rotaviruses and to explore the causes of illness among patients from whom a pathogen cannot be determined are needed. Studies of enteric pathogens should require the collection of whole stool samples.

A rodent model for Dirofilaria immitis, canine heartworm: parasite growth, development, and drug sensitivity in NSG mice.

Heartworm disease, caused by Dirofilaria immitis, remains a significant threat to canines and felines. The development of parasites resistant to macrocyclic lactones (ML) has created a significant challenge to the control of the infection. The goal of this study was to determine if mice lacking a functional immune response would be susceptible to D. immitis. Immunodeficient NSG mice were susceptible to the infection, sustaining parasites for at least 15 weeks, with infective third-stage larvae molting and developing into the late fourth-stage larvae. Proteomic analysis of host responses to the infection revealed a complex pattern of changes after infection, with at least some of the responses directed at reducing immune control mechanisms that remain in NSG mice. NSG mice were infected with isolates of D. immitis that were either susceptible or resistant to MLs, as a population. The susceptible isolate was killed by ivermectin whereas the resistant isolate had improved survivability, while both isolates were affected by moxidectin. It was concluded that D. immitis survives in NSG mice for at least 15 weeks. NSG mice provide an ideal model for monitoring host responses to the infection and for testing parasites in vivo for susceptibility to direct chemotherapeutic activity of new agents.

Structural and immunologic cross-reactivity among filarial and mite tropomyosin: implications for the hygiene hypothesis.

BACKGROUND: The hygiene hypothesis suggests that parasitic infection modulates host immune responses and decreases atopy. Other data suggest parasitic infections may induce allergic responsiveness. OBJECTIVE: To assess the structural and immunologic relationships between the known Dermatophagoides pteronyssinus (Der p 10) tropomyosin allergen and filarial tropomyosin of Onchocerca volvulus (OvTrop). METHODS: The molecular, structural, and immunologic relationships between OvTrop and Der p 10 were compared. Levels of OvTrop-specific and Der p 10-specific IgE, IgG, and IgG4 in sera of filaria-infected and filarial-uninfected D pteronyssinus-atopic individuals were compared, as were the responses in nonhuman primates infected with the filarial parasite Loa loa. Cross-reactivity was compared by antigen-mediated depletion assays and functionality by passive basophil sensitization. RESULTS: Filarial and mite tropomyosins were very similar, with 72% identity at the amino acid level, and overlapping predicted 3-dimensional structures. The prevalence of IgE and IgG to Der p 10 was increased in filaria-infected individuals compared with uninfected subjects. There was a strong correlation between serum levels of Ov- and Der p 10-tropomyosin-specific IgE, IgG, and IgG4 (P < .0001; r > 0.79). Preincubation of sera from anti-Der p 10-positive subjects with OvTrop completely depleted IgE, IgG, and IgG4 anti-Der p 10. Basophils sensitized with sera from individuals allergic to Der p 10 released histamine similarly when triggered with OvTrop or Der p 10. Primates experimentally infected with L loa developed IgE that cross-reacted with Der p 10. CONCLUSION: Filarial infection induces strong cross-reactive antitropomyosin antibody responses that may affect sensitization and regulation of allergic reactivity.

Public health implications of cysticercosis acquired in the United States.

Cysticercosis has emerged as a cause of severe neurologic disease in the United States that primarily affects immigrants from Latin America. Moreover, the relevance of cysticercosis as a public health problem has been highlighted by local transmission. We searched the biomedical literature for reports documenting cases of cysticercosis acquired in the United States. A total of 78 cases, principally neurocysticercosis, were reported from 12 states during 1954-2005. A confirmed or presumptive source of infection was identified among household members or close personal contacts of 16 (21%) case-patients. Several factors, including the severe, potentially fatal, nature of cysticercosis; its fecal-oral route of transmission; the considerable economic effect; the availability of a sensitive and specific serologic test for infection by adult Taenia solium tapeworms; and the demonstrated ability to find a probable source of infection among contacts, all provide a compelling rationale for implementation of public health control efforts.

Viability of Baylisascaris procyonis Eggs.

Infection with Baylisascaris procyonis roundworms is rare but often fatal and typically affects children. We attempted to determine parameters of viability and methods of inactivating the eggs of these roundworms. Loss of viability resulted when eggs were heated to 62°C or desiccated for 7 months but not when frozen at -15°C for 6 months.