Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 64 Records) |
Query Trace: Eberhard ME[original query] |
---|
Systematic review of microplastics and nanoplastics in indoor and outdoor air: identifying a framework and data needs for quantifying human inhalation exposures
Eberhard T , Casillas G , Zarus GM , Barr DB . J Expo Sci Environ Epidemiol 2024 BACKGROUND: Humans are likely exposed to microplastics (MPs) in a variety of places including indoor and outdoor air. Research to better understand how exposure to MPs correlates to health is growing. To fully understand the possible impacts of MPs on human health, it is necessary to quantify MP exposure and identify what critical data gaps exist. OBJECTIVES: The current paper provides a human exposure assessment of microplastics in the air using systematically reviewed literature that provided concentration of MPs in air as well as doses used in toxicology studies to calculate inhalation exposure dose. METHODS: All published peer-reviewed journal articles, non-published papers, and grey literature that focused on micro- or nano-plastics in indoor and outdoor air were systematically searched using PRISMA guidelines. Literature that defined specific concentrations and size of MPs in air or exposed to human lung cells, animals, or humans with measurable health impacts were included in data extraction. Inhalational exposures were calculated for different age groups using published MP concentrations from the included literature using exposure dose equations and values from U.S. ATSDR and EPA. RESULTS: Calculated mean indoor inhalational exposures from passive sampling methods were higher than those calculated from active sampling methods. When comparing indoor and outdoor sampling, calculated inhalation exposures from indoor samples were greater than those from outdoor samples. Inhalation exposures of MPs differed between age groups with infants having the highest calculated dose values for all locations followed by preschool age children, middle-school aged children, pregnant women, adolescents, and non-pregnant adults. MP doses used in toxicology studies produced higher calculated mean inhalational exposures than those from environmental samples. IMPACT: This study is the first known systematic review of inhalational MP exposure from indoor and outdoor air. It also provides inhalational exposures calculated from previously published environmental samples of MPs as well as from toxicology studies. |
Comparative genomics of the major parasitic worms (preprint)
International Helminth Genomes Consortium , Coghlan Avril , Tyagi Rahul , Cotton James A , Holroyd Nancy , Rosa Bruce A , Tsai Isheng Jason , Laetsch Dominik R , Beech Robin N , Day Tim A , Hallsworth-Pepin Kymberlie , Ke Huei-Mien , Kuo Tzu-Hao , Lee Tracy J , Martin John , Maizels Rick M , Mutowo Prudence , Ozersky Philip , Parkinson John , Reid Adam J , Rawlings Neil D , Ribeiro Diogo M , Seshadri Swapna Lakshmipuram , Stanley Eleanor , Taylor David W , Wheeler Nicolas J , Zamanian Mostafa , Zhang Xu , Allan Fiona , Allen Judith E , Asano Kazuhito , Babayan Simon A , Bah Germanus , Beasley Helen , Bennett Hayley M , Bisset Stewart A , Castillo Estela , Cook Joseph , Cooper Philip J , Cruz-Bustos Teresa , Cuéllar Carmen , Devaney Eileen , Doyle Stephen R , Eberhard Mark L , Emery Aidan , Eom Keeseon S , Gilleard John S , Gordon Daria , Harcus Yvonne , Harsha Bhavana , Hawdon John M , Hill Dolores E , Hodgkinson Jane , Horák Petr , Howe Kevin L , Huckvale Thomas , Kalbe Martin , Kaur Gaganjot , Kikuchi Taisei , Koutsovoulos Georgios , Kumar Sujai , Leach Andrew R , Lomax Jane , Makepeace Benjamin , Matthews Jacqueline B , Muro Antonio , O’Boyle Noel Michael , Olson Peter D , Osuna Antonio , Partono Felix , Pfarr Kenneth , Rinaldi Gabriel , Foronda Pilar , Rollinson David , Gomez Samblas Mercedes , Sato Hiroshi , Schnyder Manuela , Scholz Tomáš , Shafie Myriam , Tanya Vincent N , Toledo Rafael , Tracey Alan , Urban Joseph F , Wang Lian-Chen , Zarlenga Dante , Blaxter Mark L , Mitreva Makedonka , Berriman Matthew . bioRxiv 2017 236539 Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we compare the genomes of 81 nematode and platyhelminth species, including those of 76 parasites. From 1.4 million genes, we identify gene family births and hundreds of large expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We use a wide-ranging in silico screen to identify and prioritise new potential drug targets and compounds for testing. We also uncover lineage-specific differences in core metabolism and in protein families historically targeted for drug development. This is the broadest comparative study to date of the genomes of parasitic and non-parasitic worms. It provides a transformative new resource for the research community to understand and combat the diseases that parasitic worms cause. |
Comparative genomics of the major parasitic worms
International Helminth Genomes Consortium , Coghlan Avril , Tyagi Rahul , Cotton James A , Holroyd Nancy , Rosa Bruce A , Tsai Isheng Jason , Laetsch Dominik R , Beech Robin N , Day Tim A , Hallsworth-Pepin Kymberlie , Ke Huei-Mien , Kuo Tzu-Hao , Lee Tracy J , Martin John , Maizels Rick M , Mutowo Prudence , Ozersky Philip , Parkinson John , Reid Adam J , Rawlings Neil D , Ribeiro Diogo M , Seshadri Swapna Lakshmipuram , Stanley Eleanor , Taylor David W , Wheeler Nicolas J , Zamanian Mostafa , Zhang Xu , Allan Fiona , Allen Judith E , Asano Kazuhito , Babayan Simon A , Bah Germanus , Beasley Helen , Bennett Hayley M , Bisset Stewart A , Castillo Estela , Cook Joseph , Cooper Philip J , Cruz-Bustos Teresa , Cuéllar Carmen , Devaney Eileen , Doyle Stephen R , Eberhard Mark L , Emery Aidan , Eom Keeseon S , Gilleard John S , Gordon Daria , Harcus Yvonne , Harsha Bhavana , Hawdon John M , Hill Dolores E , Hodgkinson Jane , Horák Petr , Howe Kevin L , Huckvale Thomas , Kalbe Martin , Kaur Gaganjot , Kikuchi Taisei , Koutsovoulos Georgios , Kumar Sujai , Leach Andrew R , Lomax Jane , Makepeace Benjamin , Matthews Jacqueline B , Muro Antonio , O’Boyle Noel Michael , Olson Peter D , Osuna Antonio , Partono Felix , Pfarr Kenneth , Rinaldi Gabriel , Foronda Pilar , Rollinson David , Gomez Samblas Mercedes , Sato Hiroshi , Schnyder Manuela , Scholz Tomáš , Shafie Myriam , Tanya Vincent N , Toledo Rafael , Tracey Alan , Urban Joseph F , Wang Lian-Chen , Zarlenga Dante , Blaxter Mark L , Mitreva Makedonka , Berriman Matthew . Nat Genet 2019 51 (1) 163-174 Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we report a broad comparative study of 81 genomes of parasitic and non-parasitic worms. We have identified gene family births and hundreds of expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We reveal extensive lineage-specific differences in core metabolism and protein families historically targeted for drug development. From an in silico screen, we have identified and prioritized new potential drug targets and compounds for testing. This comparative genomics resource provides a much-needed boost for the research community to understand and combat parasitic worms. |
Certifying Guinea worm eradication: current challenges
Molyneux DH , Eberhard ML , Cleaveland S , Addey R , Guiguemdé RT , Kumar A , Magnussen P , Breman JG . Lancet 2020 396 (10265) 1857-1860 The Guinea Worm Eradication Programme (GWEP) is, along with polio, one of two active eradication programmes endorsed by the World Health Assembly. Currently, smallpox is the only human infection to have been eradicated. 1 Guinea worm disease, or dracunculiasis, is caused by infection with Dracunculus medinensis that is acquired by the ingestion of infected copepods (of the genera Cyclops and Mesocyclops) or by consuming viable infective larvae in fish or other paratenic hosts. 2 , 3 Polio and Guinea worm programmes have made great progress; however, both programmes face major challenges as they progress towards eradication because certifying the global absence of transmission of the pathogen requires meeting stringent criteria. The incidence of Guinea worm has declined from an estimated 3·6 million cases per year in the late 1980s to 53 human cases reported in 2019. 4 , 5 The overall epidemiological situation in 2019 has been summarised by WHO. 5 This Viewpoint describes the challenges facing the GWEP regarding the certification of zero global incidence following the findings of animal infections, particularly in dogs in Chad. 3 , 6 , 7 , 8 , 9 |
Population genomic evidence that human and animal infections in Africa come from the same populations of Dracunculus medinensis.
Durrant Caroline, Thiele Elizabeth A, Holroyd Nancy, Doyle Stephen R, Sallé Guillaume, Tracey Alan, Sankaranarayanan Geetha, Lotkowska Magda E, Bennett Hayley M, Huckvale Thomas, Abdellah Zahra, Tchindebet Ouakou, Wossen Mesfin, Logora Makoy Samuel Yibi, Coulibaly Cheick Oumar, Weiss Adam, Schulte-Hostedde Albrecht I, Foster Jeremy M, Cleveland Christopher A, Yabsley Michael J, Ruiz-Tiben Ernesto, Berriman Matthew, Eberhard Mark L, Cotton James A. PLoS neglected tropical diseases 2020 Nov 14(11) e0008623 . PLoS neglected tropical diseases 2020 Nov 14(11) e0008623 Durrant Caroline, Thiele Elizabeth A, Holroyd Nancy, Doyle Stephen R, Sallé Guillaume, Tracey Alan, Sankaranarayanan Geetha, Lotkowska Magda E, Bennett Hayley M, Huckvale Thomas, Abdellah Zahra, Tchindebet Ouakou, Wossen Mesfin, Logora Makoy Samuel Yibi, Coulibaly Cheick Oumar, Weiss Adam, Schulte-Hostedde Albrecht I, Foster Jeremy M, Cleveland Christopher A, Yabsley Michael J, Ruiz-Tiben Ernesto, Berriman Matthew, Eberhard Mark L, Cotton James A. PLoS neglected tropical diseases 2020 Nov 14(11) e0008623 |
Dracunculus Species in Meso-mammals from Georgia, United States, and Implications for the Guinea Worm Eradication Program in Chad, Africa.
Cleveland Christopher A, Eberhard Mark L, Garrett Kayla B, Thompson Alec T, Swanepoel Liandrie, Miller Elizabeth A, Stephens Odin L, Yabsley Michael J. The Journal of parasitology 2020 Oct 106(5) 616-622 . The Journal of parasitology 2020 Oct 106(5) 616-622 Cleveland Christopher A, Eberhard Mark L, Garrett Kayla B, Thompson Alec T, Swanepoel Liandrie, Miller Elizabeth A, Stephens Odin L, Yabsley Michael J. The Journal of parasitology 2020 Oct 106(5) 616-622 |
Elimination of onchocerciasis in Africa by 2025: the need for a broad perspective
Cupp E , Sauerbrey M , Cama V , Eberhard M , Lammie PJ , Unnasch TR . Infect Dis Poverty 2019 8 (1) 50 BACKGROUND: In response to the recent publication "Is onchocerciasis elimination in Africa feasible by 2025: a perspective based on lessons learnt from the African control programmes" by Dadzie et al., it is important to clarify and highlight the positive and unequivocal research and operational contributions from the American experience towards the worldwide elimination of human onchocerciasis (river blindness). MAIN TEXT: The strategies of twice or more rounds of mass drug administration (MDA) of ivermectin per year, as well as the use of OV-16 serology have allowed four American countries to be verified by World Health Organization to have eliminated transmission of Onchocerca volvulus, the etiological agent. These advances were also implemented in Sudan and Uganda; currently, both are the only African countries where ivermectin MDA was safely stopped in several transmission zones. CONCLUSIONS: Programmatic treatment and evaluation approaches, pioneered in the Americas, are the most efficient among the existing tools for elimination, and their broader use could catalyze the successful elimination of this disease in Africa. |
Economic impact of malaria-related hospitalizations in the United States, 2000-2014
Khuu D , Eberhard ML , Bristow BN , Javanbakht M , Ash LR , Shafir SC , Sorvillo FJ . J Infect Public Health 2019 12 (3) 424-433 BACKGROUND: Despite its elimination in the early 1950s, about 1700 cases of malaria are reported in the US every year. Few studies have quantified the direct and indirect costs of imported malaria in the US. METHODS: Disparities in the mean and total hospital days, hospital charges, and hospital costs for malaria-related hospitalizations in the US by demographic, clinical, species, financial, geographic, and institutional characteristics were examined using the 2000-2014 Nationwide Inpatient Sample (NIS). Trends and potential predictors for length of stay and hospital charges and costs were identified using negative binomial regression and linear regression, respectively. RESULTS: From 2000 to 2014, 22,029 malaria cases resulted in 95,948 hospital days for malaria-related hospitalizations, $176,391,466 in total hospital costs, and $555,435,849 in total charges. Mean charges increased significantly over the study period. Males, Blacks, and patients aged 25-44years accounted for the highest direct and indirect costs. Older age and having severe malaria was associated with a longer length of stay. Older age, severe malaria, HIV infection, and longer lengths of stay were associated with higher charges and costs. CONCLUSIONS: Malaria resulted in substantial direct and indirect costs in the US. Primary and secondary prevention measures should be prioritized among high-risk groups to reduce the economic burden. |
Development of Onchocerca volvulus in humanized NSG mice and detection of parasite biomarkers in urine and serum
Patton JB , Bennuru S , Eberhard ML , Hess JA , Torigian A , Lustigman S , Nutman TB , Abraham D . PLoS Negl Trop Dis 2018 12 (12) e0006977 BACKGROUND: The study of Onchocerca volvulus has been limited by its host range, with only humans and non-human primates shown to be susceptible to the full life cycle infection. Small animal models that support the development of adult parasites have not been identified. METHODOLOGY/PRINCIPAL FINDINGS: We hypothesized that highly immunodeficient NSG mice would support the survival and maturation of O. volvulus and alteration of the host microenvironment through the addition of various human cells and tissues would further enhance the level of parasite maturation. NSG mice were humanized with: (1) umbilical cord derived CD34+ stem cells, (2) fetal derived liver, thymus and CD34+ stem cells or (3) primary human skeletal muscle cells. NSG and humanized NSG mice were infected with 100 O. volvulus infective larvae (L3) for 4 to 12 weeks. When necropsies of infected animals were performed, it was observed that parasites survived and developed throughout the infection time course. In each of the different humanized mouse models, worms matured from L3 to advanced fourth stage larvae, with both male and female organ development. In addition, worms increased in length by up to 4-fold. Serum and urine, collected from humanized mice for identification of potential biomarkers of infection, allowed for the identification of 10 O. volvulus-derived proteins found specifically in either the urine or the serum of the humanized O. volvulus-infected NSG mice. CONCLUSIONS/SIGNIFICANCE: The newly identified mouse models for onchocerciasis will enable the development of O. volvulus specific biomarkers, screening for new therapeutic approaches and potentially studying the human immune response to infection with O. volvulus. |
Population genetic analysis of Chadian Guinea worms reveals that human and non-human hosts share common parasite populations.
Thiele EA , Eberhard ML , Cotton JA , Durrant C , Berg J , Hamm K , Ruiz-Tiben E . PLoS Negl Trop Dis 2018 12 (10) e0006747 Following almost 10 years of no reported cases, Guinea worm disease (GWD or dracunculiasis) reemerged in Chad in 2010 with peculiar epidemiological patterns and unprecedented prevalence of infection among non-human hosts, particularly domestic dogs. Since 2014, animal infections with Guinea worms have also been observed in the other three countries with endemic transmission (Ethiopia, Mali, and South Sudan), causing concern and generating interest in the parasites' true taxonomic identity and population genetics. We present the first extensive population genetic data for Guinea worm, investigating mitochondrial and microsatellite variation in adult female worms from both human and non-human hosts in the four endemic countries to elucidate the origins of Chad's current outbreak and possible host-specific differences between parasites. Genetic diversity of Chadian Guinea worms was considerably higher than that of the other three countries, even after controlling for sample size through rarefaction, and demographic analyses are consistent with a large, stable parasite population. Genealogical analyses eliminate the other three countries as possible sources of parasite reintroduction into Chad, and sequence divergence and distribution of genetic variation provide no evidence that parasites in human and non-human hosts are separate species or maintain isolated transmission cycles. Both among and within countries, geographic origin appears to have more influence on parasite population structure than host species. Guinea worm infection in non-human hosts has been occasionally reported throughout the history of the disease, particularly when elimination programs appear to be reaching their end goals. However, no previous reports have evaluated molecular support of the parasite species identity. Our data confirm that Guinea worms collected from non-human hosts in the remaining endemic countries of Africa are Dracunculus medinensis and that the same population of worms infects both humans and dogs in Chad. Our genetic data and the epidemiological evidence suggest that transmission in the Chadian context is currently being maintained by canine hosts. |
Evaluation of an OV-16 IgG4 enzyme-linked immunosorbent assay in humans and its application to determine the dynamics of antibody responses in a non-human primate model of Onchocerca volvulus infection
Cama VA , McDonald C , Arcury-Quandt A , Eberhard M , Jenks MH , Smith J , Feleke SM , Abanyie F , Thomson L , Wiegand RE , Cantey PT . Am J Trop Med Hyg 2018 99 (4) 1041-1048 Onchocerciasis is a neglected parasitic disease targeted for elimination. Current World Health Organization guidelines for elimination include monitoring antibody responses to the recombinant Onchocerca volvulus antigen OV-16 in children to demonstrate the absence of transmission. We report the performance characteristics of a modified OV-16 enzyme-linked immunosorbent assay (ELISA) and describe anti-OV-16 responses in serum samples from laboratory-inoculated nonhuman primates (NHPs) in relation to microfilariae (mf) in skin snip biopsies. This OV-16 IgG4 ELISA had sensitivity and specificity of 88.2% and 99.7%, respectively, as determined by receiver operator characteristic analysis using a serum panel of 110 positive and 287 negative samples from people infected with other filariae or other parasitic infections. Anti-OV-16 responses in inoculated NHP (N = 9) were evaluated at quarterly intervals for IgM and the four IgG subclasses. Enzyme-linked immunosorbent assay results showed a well-defined IgG4 reactivity pattern and moderate IgG1 antibody responses. Meanwhile, the reactivity by IgG2, IgG3, or IgM did not show a clear pattern. Temporal evolution of IgG4 reactivity was evaluated through monthly testing, showing that NHPs developed anti-OV-16 IgG4 on average at 15 months postinoculation (range: 10-18 months). The average time to detectable mf was also 15 months (range: 11-25). The OV-16 ELISA used in this study was robust and allowed the detection of IgG4 responses, which were observed only among animals with detectable mf (N = 5), four of which showed declines in antibody responses once mf cleared. These findings also confirmed that the most informative antibody subclass responses to OV-16 are IgG4. |
Dracunculiasis eradication: Are we there yet
Hopkins DR , Ruiz-Tiben E , Eberhard ML , Weiss A , Withers PC , Roy SL , Sienko DG . Am J Trop Med Hyg 2018 99 (2) 388-395 This report summarizes the status of the global Dracunculiasis Eradication Program as of the end of 2017. Dracunculiasis (guinea worm disease) has been eliminated from 19 of 21 countries where it was endemic in 1986, when an estimated 3.5 million cases occurred worldwide. Only Chad and Ethiopia reported cases in humans, 15 each, in 2017. Infections of animals, mostly domestic dogs, with Dracunculus medinensis were reported in those two countries and also in Mali. Insecurity and infections in animals are the two main obstacles remaining to interrupting dracunculiasis transmission completely. |
Risk factors for severe malaria among hospitalized patients in the United States, 2000-2014
Khuu D , Eberhard ML , Bristow BN , Javanbakht M , Ash LR , Shafir SC , Sorvillo FJ . Infect Dis Health 2018 23 (2) 93-106 Background: Factors associated with the development of severe malaria have not been well described for cases occurring in the United States (US). Methods: Severe malaria hospitalizations data from the 2000-2014 Nationwide Inpatient Sample were analyzed. Frequencies were reported by demographic, clinical, species, financial, geographic, and institutional characteristics, and trends and disparities were identified. Logistic regression models were used to identify potential predictors for severe disease among those with malaria. Results: From 2000 to 2014, there were an estimated 4823 severe malaria cases, representing 21.9% of all malaria-related hospitalizations, including 182 severe malaria deaths. Severe malaria was most common among inpatients who were male, Black, aged 45-64 years, and hospitalized in the South Atlantic division of the US. Older age was associated with higher odds of severe malaria, cerebral malaria, ARDS, severe anemia, and renal failure. Males had higher odds of developing renal failure and jaundice, while females had higher odds of developing severe anemia. HIV infection was associated with increased odds of severe malaria, severe anemia, and renal failure. Conclusion: Primary and secondary prevention measures, such as pre-travel consultations, chemoprophylaxis, and early diagnosis and treatment, should be emphasized and improved among high-risk prospective travelers to malaria endemic countries. |
The role of national committees in eliminating onchocerciasis
Griswold E , Unnasch T , Eberhard M , Nwoke BEB , Morales Z , Muheki Tukahebwa E , Kebede B , Anagbogu I , Katabarwa M , Habomugisha P , Tadesse Z , Miri ES , Evans D , Cohn D , Elhassan E , Richards F . Int Health 2018 10 i60-i70 National onchocerciasis elimination committees (NOECs) serve to help ministries of health complete the pathway to successful verification of elimination of onchocerciasis (river blindness), as outlined in the 2016 World Health Organization guidelines. These guidelines, however, only take effect when the country believes it has reached a point that elimination can be demonstrated, and do not address the preceding milestones. Therefore, NOECs can be of great help with guiding and tailoring earlier planning, programming and assessments to empower national programs to aggressively move toward their countries' elimination goals. In this article, we provide suggestions for organizing NOECs and examples of four such committees that have successfully operated in Africa and the Americas. |
Progress toward global eradication of dracunculiasis, January 2016-June 2017
Hopkins DR , Ruiz-Tiben E , Eberhard ML , Roy SL , Weiss AJ . MMWR Morb Mortal Wkly Rep 2017 66 (48) 1327-1331 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. |
Methylprednisolone acetate induces, and Delta7-dafachronic acid suppresses, Strongyloides stercoralis hyperinfection in NSG mice
Patton JB , Bonne-Annee S , Deckman J , Hess JA , Torigian A , Nolan TJ , Wang Z , Kliewer SA , Durham AC , Lee JJ , Eberhard ML , Mangelsdorf DJ , Lok JB , Abraham D . Proc Natl Acad Sci U S A 2017 115 (1) 204-209 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 Delta7-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. |
Translating research into reality: Elimination of lymphatic filariasis from Haiti
Lammie PJ , Eberhard ML , Addiss DG , Won KY , Beau de Rochars M , Direny AN , Milord MD , Lafontant JG , Streit TG . Am J Trop Med Hyg 2017 97 71-75 Research provides the essential foundation of disease elimination programs, including the global program to eliminate lymphatic filariasis (GPELF). The development and validation of new diagnostic tools and intervention strategies, critical steps in the evolution of GPELF, required a global effort. Lymphatic filariasis research in Haiti involved many partners and was directly linked to the development of the national elimination program and to the success achieved to date. Ongoing research efforts involving many partners will continue to be important in resolving the challenges faced by the program today in its final efforts to achieve elimination. |
Possible role of fish as transport hosts for Dracunculus spp. larvae
Cleveland CA , Eberhard ML , Thompson AT , Smith SJ , Zirimwabagabo H , Bringolf R , Yabsley MJ . Emerg Infect Dis 2017 23 (9) 1590-1592 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. |
Malaria-related hospitalizations in the United States, 2000-2014
Khuu D , Eberhard ML , Bristow BN , Javanbakht M , Ash LR , Shafir SC , Sorvillo FJ . Am J Trop Med Hyg 2017 97 (1) 213-221 Few data are available on the burden of malaria hospitalization in the United States. Study of malaria using hospital-based data can better define the impact of malaria and help inform prevention efforts. U.S. malaria cases identified from hospitalization discharge records in the 2000-2014 Nationwide Inpatient Sample were examined. Frequencies and population rates were reported by demographics, infecting species, clinical, financial, institutional, geographic, and seasonal characteristics, and disparities were identified. Time trends in malaria cases were assessed using negative binomial regression. From 2000 to 2014, there were an estimated 22,029 malaria-related hospitalizations (4.88 per 1 million population) in the United States, including 182 in-hospital deaths and 4,823 severe malaria cases. The rate of malaria-related hospitalizations did not change significantly over the study period. The largest number of malaria-related hospitalizations occurred in August. Malaria-related hospitalizations occurred disproportionately among patients who were male, black, or 25-44 years of age. Plasmodium falciparum accounted for the majority of malaria-related hospitalizations. On average, malaria patients were hospitalized for 4.36 days with charges of $25,789. Patients with a malaria diagnosis were more often hospitalized in the Middle Atlantic and South Atlantic census divisions, urban teaching, private not-for-profit, and large-bed-size hospitals. Malaria imposes a substantial disease burden in the United States. Enhanced primary and secondary prevention measures, including strategies to increase the use of pretravel consultations and prompt diagnosis and treatment are needed. |
Recurrence of Guinea worm disease in Chad after a 10-year absence: Risk factors for human cases identified in 2010-2011
Sreenivasan N , Weiss A , Djiatsa JP , Toe F , Djimadoumaji N , Ayers T , Eberhard M , Ruiz-Tiben E , Roy S . Am J Trop Med Hyg 2017 97 (2) 575-582 A decade after reporting its last case of Guinea worm disease (GWD), a waterborne parasitic disease targeted for eradication, Chad reported 20 confirmed human cases from 17 villages-10 cases in 2010 and 10 cases in 2011. In 2012, the first GWD dog infections were diagnosed. We conducted a case-control study during April-May 2012 to identify human transmission risk factors and epidemiologic links. We recruited 19 cases and 45 controls matched by age, sex, time, and location of exposure based on the case patients' periods of infection 10-14 months earlier. Data were analyzed with simple conditional logistic regression models using Firth penalized likelihood methods. Unusually, GWD did not appear to be associated with household primary water sources. Instead, secondary water sources, used outside the village or other nonprimary sources used at home, were risk factors (matched odds ratio = 38.1, 95% confidence interval = 1.6-728.2). This study highlights the changing epidemiology of GWD in Chad-household primary water sources were not identified as risk factors and few epidemiologic links were identified between the handfuls of sporadic cases per year, a trend that continues. Since this investigation, annual dog infections have increased, far surpassing human cases. An aquatic paratenic host is a postulated mode of transmission for both dogs and humans, although fish could not be assessed in this case-control study due to their near-universal consumption. GWD's evolving nature in Chad underscores the continued need for interventions to prevent both waterborne and potential foodborne transmission until the true mechanism is established. |
Skin snips have no role in programmatic evaluations for onchocerciasis elimination: a reply to Bottomley et al
Eberhard ML , Cupp EW , Katholi CR , Richards FO , Unnasch TR . Parasit Vectors 2017 10 (1) 154 A critique of the recommendation that skin snips be used for post-MDA surveillance of formerly endemic onchocerciasis areas is provided. After considering several fundamental aspects of the use of this methodology within the context of prolonged mass distribution of ivermectin, we argue that skin-snipping has no value for monitoring onchocerciasis elimination programs. |
Baylisascaris procyonis roundworm seroprevalence among wildlife rehabilitators, United States and Canada, 2012-2015
Sapp SG , Rascoe LN , Wilkins PP , Handali S , Gray EB , Eberhard M , Woodhall DM , Montgomery SP , Bailey KL , Lankau EW , Yabsley MJ . Emerg Infect Dis 2016 22 (12) 2128-2131 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. |
Letter to the Editor: Onchocerca lupi infection
Cantey PT , Eberhard M , Weeks J , Swoboda S , Ostovar GA . J Neurosurg Pediatr 2016 17 (1) 118-9 It was with great interest that we | read the paper by Chen and colleagues2 | (Chen T, Moon K, | deMello DE, et al: Case report of an epidural cervical Onchocerca lupi infection in a 13-year-old boy. J Neurosurg | Pediatr 16:217–221, August 2015). Our understanding of | this complex emerging pathogen is evolving, and this case | report adds to that understanding. However, we are concerned by several points made by the authors that could be | misleading or wrong. The first statement of concern is that | O. lupi is the only species other than O. volvulus, the parasite that causes river blindness, that has been reported to | infect humans. This is incorrect, as several other zoonotic | species have been reported to infect humans.5 | It is, however, the only zoonotic onchocercal infection reported to | have involved the spine. This report increases the number | of patients with spinal involvement to three.4,5 | Later in the paper the authors discuss options for medical | therapy for the parasite. They state that doxycycline therapy was not effective in their patient because re-exploration | and debulking of the original mass was required when it | became inflamed 10 weeks after the initial surgery. They | mention the case of the 22-month-old girl who was treated | with doxycycline followed by ivermectin. First, to the best | of our knowledge the girl was not treated with doxycycline.5 | Second, recommendations for medical therapy for | O. lupi are based primarily on what is known about the | treatment of O. volvulus. Based on what is known, it would | be premature to make any statement on the efficacy of either therapy. Ivermectin kills the microfilariae (juvenile | form) of O. volvulus, preventing the symptomatic manifestations of river blindness and reducing the probability that | black flies will become infected and maintain the cycle of | transmission.1 | There are limited data that treating an individual with ivermectin 4 times a year will accelerate the | sterilization and death of the adult female parasites; however, this effect takes up to 5 years or more.3 | Doxycycline | is known to kill the adult form of O. volvulus because of | its effects on the Wolbachia endosymbiont, which is required for reproduction and the long-term survival of the | parasite.6 | However, this effect takes 21–27 months.6,7 The | patient discussed by Chen and colleagues has not been on | ivermectin therapy long enough for it to have resulted in | the death of adult parasites, nor has enough time elapsed | to determine the efficacy of doxycycline. Because we do | not currently have a noninvasive test, medical therapy is | primarily directed at the prevention of symptoms due to | parasites not found in the resected biopsy. | Although Chen and colleagues state that they believe | their patient may have been reinfected, there are other potential explanations. One possible explanation for what occurred could be that the biopsy killed the adult parasite(s) | in the nodule but did not result in complete resection of it | (them). The expected inflammatory response to the dead | parasite(s) may have been delayed by the use of dexamethasone, so the inflammation surrounding the dead | parasite(s) did not become symptomatic until 10 weeks | after the initial surgery. Importantly, the case report illustrates that there may be a role for corticosteroids in patients with spinal nodules due to O. lupi, although more | information will be needed to determine if their use can | reduce the need for additional surgical interventions |
Guinea worm (Dracunculus medinensis) infection in a wild-caught frog, Chad
Eberhard ML , Cleveland CA , Zirimwabagabo H , Yabsley MJ , Ouakou PT , Ruiz-Tiben E . Emerg Infect Dis 2016 22 (11) 1961-1962 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. |
Dogs and Guinea worm eradication
Eberhard ML , Ruiz-Tiben E , Hopkins DR . Lancet Infect Dis 2016 16 (11) 1225-1226 Teresa Galán-Puchades, in her Correspondence on dogs and Guinea worm eradication,1 noted several critical points about the Guinea Worm Eradication Program (GWEP) in Chad. We would like to clarify several of the issues. | Dog infections have been addressed programmatically in Chad for the past 4 and a half years. The situation in Chad is different from previous reports of sporadic Guinea worm infections in dogs. What is not made clear by Galán-Puchade is that human Guinea worm has infected dogs occasionally, but when eliminated from the human population, dog infections disappear.2, 3 By contrast, in Chad, dog infections are probably responsible for the small number of cases in human beings.4 We expect human infections in Chad to stop once transmission of Guinea worms among dogs is interrupted. Lastly, all evidence suggests transmission is not occurring via common drinking water sources, but via a paratenic aquatic host that people and dogs are eating raw or only partly cooked.4 | Previous laboratory studies have shown that dogs (and cats and monkeys) are good experimental hosts for Dracunculus medinensis.5, 6 Hence, the ease with which this infection was established in dogs is not surprising. |
Progress toward global eradication of dracunculiasis - January 2015-June 2016
Hopkins DR , Ruiz-Tiben E , Eberhard ML , Roy SL , Weiss AJ . MMWR Morb Mortal Wkly Rep 2016 65 (40) 1112-1116 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. |
Quantifying the removal of red blood cells in Macaca mulatta during a Plasmodium coatneyi infection.
Fonseca LL , Alezi HS , Moreno A , Barnwell JW , Galinski MR , Voit EO . Malar J 2016 15 (1) 410 BACKGROUND: Malaria is the most deadly parasitic disease in humans globally, and the long-time coexistence with malaria has left indelible marks in the human genome that are the causes of a variety of genetic disorders. Although anaemia is a common clinical complication of malaria, the root causes and mechanisms involved in the pathogenesis of malarial anaemia are unclear and difficult to study in humans. Non-human primate (NHP) model systems enable the mechanistic study and quantification of underlying causative factors of malarial anaemia, and particularly the onset of severe anaemia. METHODS: Data were obtained in the course of Plasmodium coatneyi infections of malaria-naive and semi-immune rhesus macaques (Macaca mulatta), whose red blood cells (RBCs) were labelled in situ with biotin at the time the infections were initiated. The data were used for a survival analysis that permitted, for the first time, an accurate estimation of the lifespan of erythrocytes in macaques. The data furthermore formed the basis for the development and parameterization of a recursive dynamic model of erythrocyte turnover, which was used for the quantification of RBC production and removal in each macaque. RESULTS: The computational analysis demonstrated that the lifespan of erythrocytes in macaques is 98 +/- 21 days. The model also unambiguously showed that death due to senescence and parasitaemia is not sufficient to account for the extent of infection-induced anaemia. Specifically, the model permits, for the first time, the quantification of the different causes of RBC death, namely, normal senescence, age-independent random loss, parasitization, and bystander effects in uninfected cells. Such a dissection of the overall RBC removal process is hardly possible with experimental means alone. In the infected malaria-naive macaques, death of erythrocytes by normal physiological senescence processes accounts for 20 % and parasitization for only 4 %, whereas bystander effects are associated with an astonishing 76 % of total RBC losses. Model-based comparisons of alternative mechanisms involved in the bystander effect revealed that most of the losses are likely due to a process of removing uninfected RBCs of all age classes and only minimally due to an increased rate of senescence of the uninfected RBCs. CONCLUSIONS: A new malaria blood-stage model was developed for the analysis of data characterizing P. coatneyi infections of M. mulatta. The model used a discrete and recursive framework with age-structure that allowed the quantification of the most significant pathophysiological processes of RBC removal. The computational results revealed that the malarial anaemia caused by this parasite is mostly due to a loss of uninfected RBCs by an age-independent process. The biological identity and complete mechanism of this process is not fully understood and requires further investigation. |
Possible role of fish and frogs as paratenic hosts of Dracunculus medinensis, Chad
Eberhard ML , Yabsley MJ , Zirimwabagabo H , Bishop H , Cleveland CA , Maerz JC , Bringolf R , Ruiz-Tiben E . Emerg Infect Dis 2016 22 (8) 1428-30 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. |
The emergence of zoonotic Onchocerca lupi infection in the United States - a case-series
Cantey PT , Weeks J , Edwards M , Rao S , Ostovar GA , Dehority W , Alzona M , Swoboda S , Christiaens B , Ballan W , Hartley J , Terranella A , Weatherhead J , Dunn JJ , Marx DP , Hicks MJ , Rauch RA , Smith C , Dishop MK , Handler MH , Dudley RW , Chundu K , Hobohm D , Feiz-Erfan I , Hakes J , Berry RS , Stepensaski S , Greenfield B , Shroeder L , Bishop H , de Aleida M , Mathison B , Eberhard M . Clin Infect Dis 2015 62 (6) 778-83 This case-series describes the six 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 (e.g. 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. |
Malignant Transformation of Hymenolepis nana in a Human Host.
Muehlenbachs A , Bhatnagar J , Agudelo CA , Hidron A , Eberhard ML , Mathison BA , Frace MA , Ito A , Metcalfe MG , Rollin DC , Visvesvara GS , Pham CD , Jones TL , Greer PW , Velez Hoyos A , Olson PD , Diazgranados LR , Zaki SR . N Engl J Med 2015 373 (19) 1845-52 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. |
- Page last reviewed:Feb 1, 2024
- Page last updated:May 06, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure