Last data update: Dec 09, 2024. (Total: 48320 publications since 2009)
Records 1-30 (of 37 Records) |
Query Trace: Mauldin M[original query] |
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Literature review of pathogen agnostic molecular testing of clinical specimens from difficult-to-diagnose patients: Implications for public health
Downie DL , Rao P , David-Ferdon C , Courtney S , Lee JS , Kugley S , MacDonald PDM , Barnes K , Fisher S , Andreadis JL , Chaitram J , Mauldin MR , Salerno RM , Schiffer J , Gundlapalli AV . Health Secur 2024 To better identify emerging or reemerging pathogens in patients with difficult-to-diagnose infections, it is important to improve access to advanced molecular testing methods. This is particularly relevant for cases where conventional microbiologic testing has been unable to detect the pathogen and the patient's specimens test negative. To assess the availability and utility of such testing for human clinical specimens, a literature review of published biomedical literature was conducted. From a corpus of more than 4,000 articles, a set of 34 reports was reviewed in detail for data on where the testing was being performed, types of clinical specimens tested, pathogen agnostic techniques and methods used, and results in terms of potential pathogens identified. This review assessed the frequency of advanced molecular testing, such as metagenomic next generation sequencing that has been applied to clinical specimens for supporting clinicians in caring for difficult-to-diagnose patients. Specimen types tested were from cerebrospinal fluid, respiratory secretions, and other body tissues and fluids. Publications included case reports and series, and there were several that involved clinical trials, surveillance studies, research programs, or outbreak situations. Testing identified both known human pathogens (sometimes in new sites) and previously unknown human pathogens. During this review, there were no apparent coordinated efforts identified to develop regional or national reports on emerging or reemerging pathogens. Therefore, development of a coordinated sentinel surveillance system that applies advanced molecular methods to clinical specimens which are negative by conventional microbiological diagnostic testing would provide a foundation for systematic characterization of emerging and underdiagnosed pathogens and contribute to national biodefense strategy goals. |
Surveillance for emerging and reemerging pathogens using pathogen agnostic metagenomic sequencing in the United States: A critical role for federal government agencies
Downie DL , Rao P , David-Ferdon C , Courtney S , Lee JS , Quiner C , MacDonald PDM , Barnes K , Fisher S , Andreadis JL , Chaitram J , Mauldin MR , Salerno RM , Schiffer J , Gundlapalli AV . Health Secur 2024 The surveillance and identification of emerging, reemerging, and unknown infectious disease pathogens is essential to national public health preparedness and relies on fluidity, coordination, and interconnectivity between public and private pathogen surveillance systems and networks. Developing a national sentinel surveillance network with existing resources and infrastructure could increase efficiency, accelerate the identification of emerging public health threats, and support coordinated intervention strategies that reduce morbidity and mortality. However, implementing and sustaining programs to detect emerging and reemerging pathogens in humans using advanced molecular methods, such as metagenomic sequencing, requires making large investments in testing equipment and developing networks of clinicians, laboratory scientists, and bioinformaticians. In this study, we sought to gain an understanding of how federal government agencies currently support such pathogen agnostic testing of human specimens in the United States. We conducted a landscape analysis of federal agency websites for publicly accessible information on the availability and type of pathogen agnostic testing and details on flow of clinical specimens and data. The website analysis was supplemented by an expert review of results with representatives from the federal agencies. Operating divisions within the US Department of Health and Human Services and the US Department of Veterans Affairs have developed and sustained extensive clinical and research networks to obtain patient specimens and perform metagenomic sequencing. Metagenomic facilities supported by US agencies were not equally geographically distributed across the United States. Although many entities have work dedicated to metagenomics and/or support emerging infectious disease surveillance specimen collection, there was minimal formal collaboration across agencies. |
Clinical manifestations of an outbreak of monkeypox virus in captive chimpanzees in Cameroon, 2016
Brien SC , LeBreton M , Doty JB , Mauldin MR , Morgan CN , Pieracci EG , Ritter JM , Matheny A , Tafon BG , Tamoufe U , Missoup AD , Nwobegahay J , Takuo JM , Nkom F , Mouiche MMM , Feussom JMK , Wilkins K , Wade A , McCollum AM . J Infect Dis 2024 Monkeypox virus (MPXV) is a re-emerging virus of global concern. An outbreak of Clade I MPXV affected 20 captive chimpanzees in Cameroon in 2016. We describe the epidemiology, virology, phylogenetics, and clinical progression of this outbreak. Clinical signs included exanthema, facial swelling, peri-laryngeal swelling, and eschar. Mpox can be lethal in captive chimpanzees with death likely resulting from respiratory complications. We advise avoiding anesthesia in animals with respiratory signs to reduce the likelihood of death. This outbreak presented a risk to animal care staff. There is a need for increased awareness and a One Health approach to preparation for outbreaks in wildlife rescue centers in primate range states where MPXV occurs. Control measures should include quarantining affected animals, limiting human contacts, surveillance of humans and animals, use of personal protective equipment, and regular decontamination of enclosures. |
From people to Panthera: Natural SARS-CoV-2 infection in tigers and lions at the Bronx Zoo (preprint)
McAloose D , Laverack M , Wang L , Killian ML , Caserta LC , Yuan F , Mitchell PK , Queen K , Mauldin MR , Cronk BD , Bartlett SL , Sykes JM , Zec S , Stokol T , Ingerman K , Delaney MA , Fredrickson R , Ivančić M , Jenkins-Moore M , Mozingo K , Franzen K , Bergeson NH , Goodman L , Wang H , Fang Y , Olmstead C , McCann C , Thomas P , Goodrich E , Elvinger F , Smith DC , Tong S , Slavinski S , Calle PP , Terio K , Torchetti MK , Diel DG . bioRxiv 2020 2020.07.22.213959 We describe the first cases of natural SARS-CoV-2 infection detected in animals in the United States. In March 2020, four tigers and three lions at the Bronx Zoo developed mild respiratory signs. SARS-CoV-2 RNA was detected by rRT-PCR in respiratory secretions and/or feces from all seven affected animals; viral RNA and/or antibodies were detected in their keepers. SARS-CoV-2 was isolated from respiratory secretions or feces from three affected animals; in situ hybridization co-localized viral RNA with cellular damage. Whole genome sequence and haplotype network analyses showed tigers and lions were infected with two different SARS-CoV-2 strains, suggesting independent viral introductions. The source of SARS-CoV-2 infection in the lions is unknown. Epidemiological data and genetic similarities between keeper and tiger viruses indicate human to animal transmission.Competing Interest StatementThe authors have declared no competing interest. |
A Novel Restraint Device to Improve Safety and Efficacy of Blood Collection During Non-Terminal Sampling of Bats (preprint)
Morgan CN , Mauldin MR , Jones J , Collier B , Nakazawa Y . bioRxiv 2022 25 There are a variety of blood collection techniques described in the literature for unanesthetized bats, which typically require multiple sharps (e.g., needles, lancets, etc.), competent animal handling for prolonged periods, and usually involve two individuals. With the challenges inherent to non-terminal sampling of blood from bats, as well as the growing need for the use of this technique across multiple disciplines and industries, an improved blood collection method is needed. We report the creation of a bat restraint device specifically designed for a single individual to safely collect blood from anesthetized or non-anesthetized bats. The utility of this restraint device is multifaceted, serving as a safety measure for both animal and handler, as well as increasing the efficiency of blood collection. The restraint device was tested during two laboratory bat studies, Afterwards, the users of the restraint device were provided with a 10-question survey questionnaire to record their opinions on its usage. In total 80% of responses were considered positive, 15% considered neutral, and 5% considered negative. Survey questions that all participants responded to positively when in comparison to the traditional method of blood collection from bats include "easier to perform", "safer to bats", and "safer to the individual". While using the restraint devices during the laboratory studies, no needle sticks, bites, or scratches to laboratorians occurred, and no observable health issues or complication due to blood collection in the bats bled using the restraint devices. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. |
New nomenclature for mpox (monkeypox) and monkeypox virus clades.
Ulaeto D , Agafonov A , Burchfield J , Carter L , Happi C , Jakob R , Krpelanova E , Kuppalli K , Lefkowitz EJ , Mauldin MR , de Oliveira T , Onoja B , Otieno J , Rambaut A , Subissi L , Yinka-Ogunleye A , Lewis RF . Lancet Infect Dis 2023 23 (3) 273-275 In May, 2015, WHO recommended best practices for naming new infectious diseases to avoid offense or economic effect for any ethnic, regional, or other groups.1 Although mpox (formerly known as monkeypox) is not new, WHO has endorsed mpox as the new name for this re-emerging disease and backed the scientific community to agree on neutral nomenclature for variants of viruses. | | The first report of mpox that led to the discovery of the global outbreak was made to WHO on May 13, 2022. The outbreak spread to 110 countries2 and was declared a public health emergency of international concern. The Director-General of WHO called on member states to ensure respect for human rights and to address stigma and discrimination.3 As of Jan 31, 2023, there were 85 549 confirmed cases of mpox reported by 110 countries, including 89 deaths.2 |
Activity patterns and burrowing ecology of the giant pouched rat (Cricetomys emini) in Tshuapa Province, D. R. Congo
Kalemba LN , Morgan CN , Nakazawa YJ , Mauldin MR , Malekani JM , Doty JB . Mammalia 2022 86 (6) 562-569 Rodents of the genus Cricetomys have been reported to be nocturnal with a bimodal activity pattern and to frequently change burrows. However, no studies to date have examined these ecological aspects with the use of radio-telemetry. Five C. emini were captured and radio-collared to study their activity patterns and burrowing ecology from 9 March to 15 April 2016. Nocturnal activity ranged between the hours of 18:00 and 05:00 with a probable reduction of activities between 20:00-23:00 and around 04:00 with diurnal activity between 06:00 and 17:00 h with a reduction of activity between 11:00 and 14:00. While the present study does confirm nocturnal activity and a bimodal pattern, this study also suggests greater diurnal activity as compared to previous studies. Additionally, data presented here also suggest that C. emini may not change burrows as frequently as previously reported. 2022 Walter de Gruyter GmbH, Berlin/Boston 2022. |
Transmission of SARS-CoV-2 Delta variant (B.1.617.2) from a fully vaccinated human to a canine in Georgia, July 2021.
Wendling NM , Carpenter A , Liew A , Ghai RR , Gallardo-Romero N , Stoddard RA , Tao Y , Zhang J , Retchless AC , Ahmad A , Bunkley P , Godino C , Mauldin MR , Varela K , Ritter JM , Hennebelle J , Feldpausch A , Gabel J , Kainulainen MH , Herzegh O , Tong S , Spengler JR , Barton Behravesh C . Zoonoses Public Health 2022 69 (5) 587-592 SARS-CoV-2 infection has been described in a wide range of species, including domestic animals such as dogs and cats. Illness in dogs is usually self-limiting, and further diagnostics may not be pursued if clinical signs resolve or they respond to empirical treatment. As new variants emerge, the clinical presentation and role in transmission may vary in animals. This report highlights different clinical presentations and immunological responses in two SARS-CoV-2 Delta-variant-positive dogs with similar exposure to the same fully vaccinated human with a SARS-CoV-2 infection and emphasizes the need for active surveillance and additional One Health research on SARS-CoV-2 variant infections in companion animals and other species. |
A Cross Sectional Sampling Reveals Novel Coronaviruses in Bat Populations of Georgia.
Urushadze L , Babuadze G , Shi M , Escobar LE , Mauldin MR , Natradeze I , Machablishvili A , Kutateladze T , Imnadze P , Nakazawa Y , Velasco-Villa A . Viruses 2021 14 (1) Mammal-associated coronaviruses have a long evolutionary history across global bat populations, which makes them prone to be the most likely ancestral origins of coronavirus-associated epidemics and pandemics globally. Limited coronavirus research has occurred at the junction of Europe and Asia, thereby investigations in Georgia are critical to complete the coronavirus diversity map in the region. We conducted a cross-sectional coronavirus survey in bat populations at eight locations of Georgia, from July to October of 2014. We tested 188 anal swab samples, remains of previous pathogen discovery studies, for the presence of coronaviruses using end-point pan-coronavirus RT-PCR assays. Samples positive for a 440 bp amplicon were Sanger sequenced to infer coronavirus subgenus or species through phylogenetic reconstructions. Overall, we found a 24.5% positive rate, with 10.1% for Alphacoronavirus and 14.4% for Betacoronavirus. Albeit R. euryale, R. ferrumequinum, M. blythii and M. emarginatus were found infected with both CoV genera, we could not rule out CoV co-infection due to limitation of the sequencing method used and sample availability. Based on phylogenetic inferences and genetic distances at nucleotide and amino acid levels, we found one putative new subgenus and three new species of Alphacoronavirus, and two new species of Betacoronavirus. |
Teaching a new mouse old tricks: Humanized mice as an infection model for Variola virus
Hutson CL , Kondas AV , Ritter JM , Reed Z , Ostergaard SD , Morgan CN , Gallardo-Romero N , Tansey C , Mauldin MR , Salzer JS , Hughes CM , Goldsmith CS , Carroll D , Olson VA . PLoS Pathog 2021 17 (9) e1009633 Smallpox, caused by the solely human pathogen Variola virus (VARV), was declared eradicated in 1980. While known VARV stocks are secure, smallpox remains a bioterrorist threat agent. Recent U.S. Food and Drug Administration approval of the first smallpox anti-viral (tecovirimat) therapeutic was a successful step forward in smallpox preparedness; however, orthopoxviruses can become resistant to treatment, suggesting a multi-therapeutic approach is necessary. Animal models are required for testing medical countermeasures (MCMs) and ideally MCMs are tested directly against the pathogen of interest. Since VARV only infects humans, a representative animal model for testing therapeutics directly against VARV remains a challenge. Here we show that three different humanized mice strains are highly susceptible to VARV infection, establishing the first small animal model using VARV. In comparison, the non-humanized, immunosuppressed background mouse was not susceptible to systemic VARV infection. Following an intranasal VARV challenge that mimics the natural route for human smallpox transmission, the virus spread systemically within the humanized mouse before mortality (~ 13 days post infection), similar to the time from exposure to symptom onset for ordinary human smallpox. Our identification of a permissive/representative VARV animal model can facilitate testing of MCMs in a manner consistent with their intended use. |
Use of partial N-gene sequences as a tool to monitor progress on rabies control and elimination efforts in Ethiopia.
Binkley L , Deressa A , Shi M , Jara M , Escobar LE , Mauldin MR , Matheny A , O'Quin J , Pieracci EG , Kling C , Hartloge C , Yimer G , Abate E , Gebreyes W , Reynolds M , Belay E , Shiferaw M , Nakazawa Y , Velasco-Villa A . Acta Trop 2021 221 106022 Ethiopia is one of the African countries most affected by rabies. A coarse catalog of rabies viruses (RABV) was created as a benchmark to assess the impact of control and elimination activities. We evaluated a 726 bp amplicon at the end of the N-gene to infer viral lineages in circulation using maximum likelihood and Bayesian methods for phylogenetic reconstruction. We sequenced 228 brain samples from wild and domestic animals collected in five Ethiopian regions during 2010-2017. Results identified co-circulating RABV lineages that are causing recurrent spillover infections into wildlife and domestic animals. We found no evidence of importation of RABVs from other African countries or vaccine-induced cases in the area studied. A divergent RABV lineage might be involved in an independent rabies cycle in jackals. This investigation provides a feasible approach to assess rabies control and elimination efforts in resource-limited countries. |
Demographic, clinical, and epidemiologic characteristics of persons under investigation for Coronavirus Disease 2019-United States, January 17-February 29, 2020.
McGovern OL , Stenger M , Oliver SE , Anderson TC , Isenhour C , Mauldin MR , Williams N , Griggs E , Bogere T , Edens C , Curns AT , Lively JY , Zhou Y , Xu S , Diaz MH , Waller JL , Clarke KR , Evans ME , Hesse EM , Morris SB , McClung RP , Cooley LA , Logan N , Boyd AT , Taylor AW , Bajema KL , Lindstrom S , Elkins CA , Jones C , Hall AJ , Graitcer S , Oster AM , Fry AM , Fischer M , Conklin L , Gokhale RH . PLoS One 2021 16 (4) e0249901 BACKGROUND: The Coronavirus Disease 2019 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), evolved rapidly in the United States. This report describes the demographic, clinical, and epidemiologic characteristics of 544 U.S. persons under investigation (PUI) for COVID-19 with complete SARS-CoV-2 testing in the beginning stages of the pandemic from January 17 through February 29, 2020. METHODS: In this surveillance cohort, the U.S. Centers for Disease Control and Prevention (CDC) provided consultation to public health and healthcare professionals to identify PUI for SARS-CoV-2 testing by quantitative real-time reverse-transcription PCR. Demographic, clinical, and epidemiologic characteristics of PUI were reported by public health and healthcare professionals during consultation with on-call CDC clinicians and subsequent submission of a CDC PUI Report Form. Characteristics of laboratory-negative and laboratory-positive persons were summarized as proportions for the period of January 17-February 29, and characteristics of all PUI were compared before and after February 12 using prevalence ratios. RESULTS: A total of 36 PUI tested positive for SARS-CoV-2 and were classified as confirmed cases. Confirmed cases and PUI testing negative for SARS-CoV-2 had similar demographic, clinical, and epidemiologic characteristics. Consistent with changes in PUI evaluation criteria, 88% (13/15) of confirmed cases detected before February 12, 2020, reported travel from China. After February 12, 57% (12/21) of confirmed cases reported no known travel- or contact-related exposures. CONCLUSIONS: These findings can inform preparedness for future pandemics, including capacity for rapid expansion of novel diagnostic tests to accommodate broad surveillance strategies to assess community transmission, including potential contributions from asymptomatic and presymptomatic infections. |
Geographic distribution and genetic characterization of poxviruses from human infections in Georgia, 2009-2014.
Khmaladze E , Mauldin MR , Tsaguria D , Gavashelidze M , Sidamonidze K , Tevdoradze T , Li Y , Reynolds MG , Imnadze P , Nakazawa Y . Arch Virol 2021 166 (6) 1729-1733 Anthrax is endemic in Georgia, as are multiple zoonotic poxviruses. Poxvirus-associated infections share some clinical manifestations and exposure risks with anthrax, and so it is important to distinguish between the two. With this in mind, an archived collection of anthrax-negative DNA samples was retrospectively screened for poxviruses, and of the 148 human samples tested, 64 were positive. Sequence analysis confirmed the presence of orf virus, bovine papular stomatitis virus, and pseudocowpox virus. This study provides evidence of previously unrecognized poxvirus infections in Georgia and highlights the benefit of the timely identification of such infections by improving laboratory capacity. |
Pharmacokinetics and efficacy of a potential smallpox therapeutic, brincidofovir, in a lethal monkeypox virus animal model
Hutson CL , Kondas AV , Mauldin MR , Doty JB , Grossi IM , Morgan CN , Ostergaard SD , Hughes CM , Nakazawa Y , Kling C , Martin BE , Ellison JA , Carroll DD , Gallardo-Romero NF , Olson VA . mSphere 2021 6 (1) Smallpox, caused by Variola virus (VARV), was eradicated in 1980; however, VARV bioterrorist threats still exist, necessitating readily available therapeutics. Current preparedness activities recognize the importance of oral antivirals and recommend therapeutics with different mechanisms of action. Monkeypox virus (MPXV) is closely related to VARV, causing a highly similar clinical human disease, and can be used as a surrogate for smallpox antiviral testing. The prairie dog MPXV model has been characterized and used to study the efficacy of antipoxvirus therapeutics, including recently approved TPOXX (tecovirimat). Brincidofovir (BCV; CMX001) has shown antiviral activity against double-stranded DNA viruses, including poxviruses. To determine the exposure of BCV following oral administration to prairie dogs, a pharmacokinetics (PK) study was performed. Analysis of BCV plasma concentrations indicated variability, conceivably due to the outbred nature of the animals. To determine BCV efficacy in the MPXV prairie dog model, groups of animals were intranasally challenged with 9 × 10(5) plaque-forming units (PFU; 90% lethal dose [LD(90)]) of MPXV on inoculation day 0 (ID0). Animals were divided into groups based on the first day of BCV treatment relative to inoculation day (ID-1, ID0, or ID1). A trend in efficacy was noted dependent upon treatment initiation (57% on ID-1, 43% on ID0, and 29% on ID1) but was lower than demonstrated in other animal models. Analysis of the PK data indicated that BCV plasma exposure (maximum concentration [C (max)]) and the time of the last quantifiable concentration (AUC(last)) were lower than in other animal models administered the same doses, indicating that suboptimal BCV exposure may explain the lower protective effect on survival.IMPORTANCE Preparedness activities against highly transmissible viruses with high mortality rates have been highlighted during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Smallpox, caused by variola virus (VARV) infection, is highly transmissible, with an estimated 30% mortality. Through an intensive vaccination campaign, smallpox was declared eradicated in 1980, and routine smallpox vaccination of individuals ceased. Today's current population has little/no immunity against VARV. If smallpox were to reemerge, the worldwide results would be devastating. Recent FDA approval of one smallpox antiviral (tecovirimat) was a successful step in biothreat preparedness; however, orthopoxviruses can become resistant to treatment, suggesting the need for multiple therapeutics. Our paper details the efficacy of the investigational smallpox drug brincidofovir in a monkeypox virus (MPXV) animal model. Since brincidofovir has not been tested in vivo against smallpox, studies with the related virus MPXV are critical in understanding whether it would be protective in the event of a smallpox outbreak. |
From People to Panthera : Natural SARS-CoV-2 Infection in Tigers and Lions at the Bronx Zoo.
McAloose D , Laverack M , Wang L , Killian ML , Caserta LC , Yuan F , Mitchell PK , Queen K , Mauldin MR , Cronk BD , Bartlett SL , Sykes JM , Zec S , Stokol T , Ingerman K , Delaney MA , Fredrickson R , Ivančić M , Jenkins-Moore M , Mozingo K , Franzen K , Bergeson NH , Goodman L , Wang H , Fang Y , Olmstead C , McCann C , Thomas P , Goodrich E , Elvinger F , Smith DC , Tong S , Slavinski S , Calle PP , Terio K , Torchetti MK , Diel DG . mBio 2020 11 (5) Despite numerous barriers to transmission, zoonoses are the major cause of emerging infectious diseases in humans. Among these, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and ebolaviruses have killed thousands; the human immunodeficiency virus (HIV) has killed millions. Zoonoses and human-to-animal cross-species transmission are driven by human actions and have important management, conservation, and public health implications. The current SARS-CoV-2 pandemic, which presumably originated from an animal reservoir, has killed more than half a million people around the world and cases continue to rise. In March 2020, New York City was a global epicenter for SARS-CoV-2 infections. During this time, four tigers and three lions at the Bronx Zoo, NY, developed mild, abnormal respiratory signs. We detected SARS-CoV-2 RNA in respiratory secretions and/or feces from all seven animals, live virus in three, and colocalized viral RNA with cellular damage in one. We produced nine whole SARS-CoV-2 genomes from the animals and keepers and identified different SARS-CoV-2 genotypes in the tigers and lions. Epidemiologic and genomic data indicated human-to-tiger transmission. These were the first confirmed cases of natural SARS-CoV-2 animal infections in the United States and the first in nondomestic species in the world. We highlight disease transmission at a nontraditional interface and provide information that contributes to understanding SARS-CoV-2 transmission across species.IMPORTANCE The human-animal-environment interface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important aspect of the coronavirus disease 2019 (COVID-19) pandemic that requires robust One Health-based investigations. Despite this, few reports describe natural infections in animals or directly link them to human infections using genomic data. In the present study, we describe the first cases of natural SARS-CoV-2 infection in tigers and lions in the United States and provide epidemiological and genetic evidence for human-to-animal transmission of the virus. Our data show that tigers and lions were infected with different genotypes of SARS-CoV-2, indicating two independent transmission events to the animals. Importantly, infected animals shed infectious virus in respiratory secretions and feces. A better understanding of the susceptibility of animal species to SARS-CoV-2 may help to elucidate transmission mechanisms and identify potential reservoirs and sources of infection that are important in both animal and human health. |
Exportation of Monkeypox virus from the African continent.
Mauldin MR , McCollum AM , Nakazawa YJ , Mandra A , Whitehouse ER , Davidson W , Zhao H , Gao J , Li Y , Doty J , Yinka-Ogunleye A , Akinpelu A , Aruna O , Naidoo D , Lewandowski K , Afrough B , Graham V , Aarons E , Hewson R , Vipond R , Dunning J , Chand M , Brown C , Cohen-Gihon I , Erez N , Shifman O , Israeli O , Sharon M , Schwartz E , Beth-Din A , Zvi A , Mak TM , Ng YK , Cui L , Lin RTP , Olson VA , Brooks T , Paran N , Ihekweazu C , Reynolds MG . J Infect Dis 2020 225 (8) 1367-1376 BACKGROUND: The largest West African monkeypox outbreak began September 2017, in Nigeria. Four individuals traveling from Nigeria to the UK (2), Israel, and Singapore became the first human monkeypox cases exported from Africa, and a related nosocomial transmission event in the UK became the first confirmed human-to-human monkeypox transmission event outside of Africa. METHODS: Epidemiological and molecular data for exported and Nigerian cases were analyzed jointly to better understand the exportations in the temporal and geographic context of the outbreak. RESULTS: Isolates from all travelers and a Bayelsa case shared a most recent common ancestor and traveled to Bayelsa, Delta, or Rivers states. Genetic variation for this cluster was lower than would be expected from a random sampling of genomes from this outbreak, but data did not support direct links between travelers. CONCLUSIONS: Monophyly of exportation cases and the Bayelsa sample, along with the intermediate levels of genetic variation suggest a small pool of related isolates is the likely source for the exported infections. This may be the result of the level of genetic variation present in monkeypox isolates circulating within the contiguous region of Bayelsa, Delta, and Rivers states, or another more restricted, yet unidentified source pool. |
COVID-19 in Americans aboard the Diamond Princess cruise ship.
Plucinski MM , Wallace M , Uehara A , Kurbatova EV , Tobolowsky FA , Schneider ZD , Ishizumi A , Bozio CH , Kobayashi M , Toda M , Stewart A , Wagner RL , Moriarty LF , Murray R , Queen K , Tao Y , Paden C , Mauldin MR , Zhang J , Li Y , Elkins CA , Lu X , Herzig CTA , Novak R , Bower W , Medley AM , Acosta AM , Knust B , Cantey PT , Pesik NT , Halsey ES , Cetron MS , Tong S , Marston BJ , Friedman CR . Clin Infect Dis 2020 72 (10) e448-e457 BACKGROUND: The Diamond Princess cruise ship was the site of a large outbreak of coronavirus disease 2019 (COVID-19). Of 437 Americans and their travel companions on the ship, 114 (26%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We interviewed 229 American passengers and crew after disembarkation following a ship-based quarantine to identify risk factors for infection and characterize transmission onboard the ship. RESULTS: The attack rate for passengers in single-person cabins or without infected cabinmates was 18% (58/329), compared with 63% (27/43) for those sharing a cabin with an asymptomatic infected cabinmate, and 81% (25/31) for those with a symptomatic infected cabinmate. Whole genome sequences from specimens from passengers who shared cabins clustered together. Of 66 SARS-CoV-2-positive American travelers with complete symptom information, 14 (21%) were asymptomatic while on the ship. Among SARS-CoV-2-positive Americans, 10 (9%) required intensive care, of whom 7 were ≥70 years. CONCLUSION: Our findings highlight the high risk of SARS-CoV-2 transmission on cruise ships. High rates of SARS-CoV-2 positivity in cabinmates of individuals with asymptomatic infections suggest that triage by symptom status in shared quarters is insufficient to halt transmission. A high rate of intensive care unit admission among older individuals complicates the prospect of future cruise travel during the pandemic, given typical cruise passenger demographics. The magnitude and severe outcomes of this outbreak were major factors contributing to the Centers for Disease Control and Prevention's decision to halt cruise ship travel in U.S. waters in March 2020. |
Pharmacokinetic profiles of gabapentin after oral and subcutaneous administration in black-tailed prairie dogs (Cynomys ludovicianus)
Mills PO , Tansey CO , Genzer SC , Mauldin MR , Howard RA , Kling CA , Jackson FR , Matheny AM , Boothe DM , Lathrop GW , Powell N , Gallardo-Romero N . J Am Assoc Lab Anim Sci 2020 59 (3) 305-309 In veterinary and human medicine, gabapentin (a chemical analog of gamma-aminobutyric acid) is commonly prescribed to treat postoperative and chronic neuropathic pain. This study explored the pharmacokinetics of oral and subcutaneous administration of gabapentin at high (80 mg/kg) and low (30 mg/kg) doses as a potential analgesic in black-tailed prairie dogs (Cynomys ludovicianus; n = 24). The doses (30 and 80 mg/kg) and half maximal effective concentration (1.4 to 16.7 ng/mL) for this study were extrapolated from pharmacokinetic efficacy studies in rats, rabbits, and cats. Gabapentin in plasma was measured by using an immunoassay, and data were evaluated using noncompartmental analysis. The peak plasma concentrations (mean +/-1 SD) were 42.6 +/-14.8 and 115.5 +/-15.2 ng/mL, respectively, after 30 and 80 mg/kg SC and 14.5 +/-3.5 and 20.7 +/-6.1 ng/mL after the low and high oral dosages, respectively. All peak plasma concentrations of gabapentin occurred within 5 h of administration. Disappearance half-lives for the low and high oral doses were 7.4 +/- 6.0 h and 5.0 +/- 0.8 h, respectively. The results of this study demonstrate that oral administration of gabapentin at low (30 mg/kg) doses likely would achieve and maintain plasma concentrations at half maximum effective concentration for 12 h, making it a viable option for an every 12-h treatment. |
Progressive vaccinia acquired through zoonotic transmission in a patient with HIV/AIDS, Colombia
Laiton-Donato K , Avila-Robayo P , Paez-Martinez A , Benjumea-Nieto P , Usme-Ciro JA , Pinzon-Narino N , Giraldo I , Torres-Castellanos D , Nakazawa Y , Patel N , Wilkins K , Li Y , Davidson W , Burgado J , Satheshkumar PS , Styczynski A , Mauldin MR , Gracia-Romero M , Petersen BW . Emerg Infect Dis 2020 26 (3) 601-605 In March 2015, a patient in Colombia with HIV/AIDS was hospitalized for disseminated ulcers after milking cows that had vesicular lesions on their udders. Vaccinia virus was detected, and the case met criteria for progressive vaccinia acquired by zoonotic transmission. Adherence to an optimized antiretroviral regimen resulted in recovery. |
Isolation and phylogenomic analysis of Buffalopox virus from Human and Buffaloes in India.
Yadav PD , Mauldin MR , Nyayanit DA , Albarino CG , Sarkale P , Shete A , Guerrero LW , Nakazawa Y , Nichol ST , Mourya DT . Virus Res 2019 277 197836 Three genome sequences of Buffalopox virus (BPVX) were retrieved from a human and two buffaloes scab samples. Phylogenomic analysis of the BPXV indicates that it shares a most recent common ancestor with Lister and closely related vaccine strains when compared to potential wild-type VACV strains (like Horsepox virus). |
Seroprevalence and risk factors possibly associated with emerging zoonotic vaccinia virus in a farming community, Colombia
Styczynski A , Burgado J , Walteros D , Usme-Ciro J , Laiton K , Farias AP , Nakazawa Y , Chapman C , Davidson W , Mauldin M , Morgan C , Martinez-Ceron J , Patina E , Lopez Sepulveda LL , Torres CP , Cruz Suarez AE , Olaya GP , Riveros CE , Cepeda DY , Lopez LA , Espinosa DG , Gutierrez Lozada FA , Li Y , Satheshkumar PS , Reynolds M , Gracia-Romero M , Petersen B . Emerg Infect Dis 2019 25 (12) 2169-76 In 2014, vaccinia virus (VACV) infections were identified among farmworkers in Caqueta Department, Colombia; additional cases were identified in Cundinamarca Department in 2015. VACV, an orthopoxvirus (OPXV) used in the smallpox vaccine, has caused sporadic bovine and human outbreaks in countries such as Brazil and India. In response to the emergence of this disease in Colombia, we surveyed and collected blood from 134 farmworkers and household members from 56 farms in Cundinamarca Department. We tested serum samples for OPXV antibodies and correlated risk factors with seropositivity by using multivariate analyses. Fifty-two percent of farmworkers had OPXV antibodies; this percentage decreased to 31% when we excluded persons who would have been eligible for smallpox vaccination. The major risk factors for seropositivity were municipality, age, smallpox vaccination scar, duration of time working on a farm, and animals having vaccinia-like lesions. This investigation provides evidence for possible emergence of VACV as a zoonosis in South America. |
Isolation and characterization of Akhmeta virus from wild caught rodents ( Apodemus spp.) in Georgia.
Doty JB , Maghlakelidze G , Sikharulidze I , Tu SL , Morgan CN , Mauldin MR , Parkadze O , Kartskhia N , Turmanidze M , Matheny A , Davidson W , Tang S , Gao J , Li Y , Upton C , Carroll DS , Emerson GL , Nakazawa Y . J Virol 2019 93 (24) In 2013, a novel orthopoxvirus was detected in skin lesions of two cattle herders from the Kakheti region of Georgia (country), this virus was named Akhmeta virus. Subsequent investigation of these cases revealed that small mammals in the area had serological evidence of orthopoxvirus infections, suggesting their involvement in the maintenance of these viruses in nature. In October 2015, we began a longitudinal study assessing the natural history of orthopoxviruses in Georgia. As part of this effort, we trapped small mammals near Akhmeta (n=176) and Gudauri (n=110). Here, we describe the isolation and molecular characterization of Akhmeta virus from lesion material and pooled heart and lung samples collected from five wood mice (Apodemus uralensis and A. flavicollis) in these two locations. The genomes of Akhmeta virus obtained from rodents group into 2 clades; one clade represented by viruses isolated from A. uralensis samples, and one clade represented by viruses isolated from A. flavicollis samples. These genomes also display several presumptive recombination events for which gene truncation and identity has been examined.Importance Akhmeta virus is a unique Orthopoxvirus that was described in 2013 from the country of Georgia. This paper presents the first isolation of this virus from small mammal (Rodentia; Apodemus spp.) samples and the molecular characterization of those isolates. The identification of the virus in small mammals is an essential component to understanding of the natural history of this virus and its transmission to human populations; and could guide public health interventions in Georgia. Akhmeta virus genomes harbor evidence suggestive of recombination with a variety of other orthopoxviruses; this has implications for the evolution of orthopoxviruses, their ability to infect mammalian hosts, and their ability to adapt to novel host species. |
Outbreak of human monkeypox in Nigeria in 2017-18: a clinical and epidemiological report.
Yinka-Ogunleye A , Aruna O , Dalhat M , Ogoina D , McCollum A , Disu Y , Mamadu I , Akinpelu A , Ahmad A , Burga J , Ndoreraho A , Nkunzimana E , Manneh L , Mohammed A , Adeoye O , Tom-Aba D , Silenou B , Ipadeola O , Saleh M , Adeyemo A , Nwadiutor I , Aworabhi N , Uke P , John D , Wakama P , Reynolds M , Mauldin MR , Doty J , Wilkins K , Musa J , Khalakdina A , Adedeji A , Mba N , Ojo O , Krause G , Ihekweazu C . Lancet Infect Dis 2019 19 (8) 872-879 BACKGROUND: In September, 2017, human monkeypox re-emerged in Nigeria, 39 years after the last reported case. We aimed to describe the clinical and epidemiological features of the 2017-18 human monkeypox outbreak in Nigeria. METHODS: We reviewed the epidemiological and clinical characteristics of cases of human monkeypox that occurred between Sept 22, 2017, and Sept 16, 2018. Data were collected with a standardised case investigation form, with a case definition of human monkeypox that was based on previously established guidelines. Diagnosis was confirmed by viral identification with real-time PCR and by detection of positive anti-orthopoxvirus IgM antibodies. Whole-genome sequencing was done for seven cases. Haplotype analysis results, genetic distance data, and epidemiological data were used to infer a likely series of events for potential human-to-human transmission of the west African clade of monkeypox virus. FINDINGS: 122 confirmed or probable cases of human monkeypox were recorded in 17 states, including seven deaths (case fatality rate 6%). People infected with monkeypox virus were aged between 2 days and 50 years (median 29 years [IQR 14]), and 84 (69%) were male. All 122 patients had vesiculopustular rash, and fever, pruritus, headache, and lymphadenopathy were also common. The rash affected all parts of the body, with the face being most affected. The distribution of cases and contacts suggested both primary zoonotic and secondary human-to-human transmission. Two cases of health-care-associated infection were recorded. Genomic analysis suggested multiple introductions of the virus and a single introduction along with human-to-human transmission in a prison facility. INTERPRETATION: This study describes the largest documented human outbreak of the west African clade of the monkeypox virus. Our results suggest endemicity of monkeypox virus in Nigeria, with some evidence of human-to-human transmission. Further studies are necessary to explore animal reservoirs and risk factors for transmission of the virus in Nigeria. FUNDING: None. |
Field identification key and guide for bats of the United States of America
Morgan CN , Ammerman LK , Demere KD , Doty JB , Nakazawa YJ , Mauldin MR . Occas Pap Tex Tech Univ Mus 2019 360 Bats are the second most speciose lineage of mammals with more than 1,300 recognized species. Overall, bats are extremely ecologically and morphologically diverse, making them of interest to a wide variety of biologists. Bats are also known reservoirs for an assortment of zoonotic diseases, including rabies, for which they are commonly tested if identified as sick, behaving abnormally, or in instances where there has been a significant human exposure. In these cases, proper identification of bat species is important to public health experts as it will inform future testing procedures and management practices, as well as broaden our understanding of rabies virus bat variant distributions and disease ecology. Despite the multiple disciplines interested in bats, no key has been developed which includes all species found within the United States. For this reason, a dichotomous key and bat identification guide, designed to differentiate bats to species level, has been developed. This document can be used by people with a variety of backgrounds to morphologically identify bats quickly and accurately using only a scale, a ruler, and attention to detail. |
Morphometric and genetic variation in eight breeds of Ethiopian camels (Camelus dromedarius).
Legesse YW , Dunn CD , Mauldin MR , Garza NO , Rowden GR , Mekasha Y , Kurtu MY , Mohammed SA , Whibesilassie WD , Ballou M , Tefera M , Perry G , Bradley RD . J Anim Sci 2018 96 (12) 4925-4934 Dromedary camels (Camelus dromedarius) are a domesticated and closely guarded economic staple of indigenous people located throughout Ethiopian territorial states. Seventeen morphometric variables were examined to determine intraspecific variation among 8 pastoralist-designated breeds of camels. Additionally, DNA sequences from mitochondrial cytochrome-b gene and genotyping of 6 nuclear microsatellite loci were examined to assess genetic diversity and phylogenetic relationship of Ethiopian camels. Examination of 525 individuals revealed significant morphometric differentiation in Afar as compared with the remaining 7 breeds. Analysis of cytochrome-b sequences failed to recover monophyletic groups associated with pastoralist-recognized breeds. Analysis of 6 microsatellite loci from 104 individuals depicted no resolution of distinct genetic lineages in accordance to geographical or designated breeds. Overall, separation of 2 ecotypes based on the morphometric data was supported; however, genetic analysis of cytochrome-b and microsatellite data failed to support any unique genetic lineage or statistically significant population structure. |
Novel poxvirus in proliferative lesions of wild rodents in East Central Texas, USA
Hodo CL , Mauldin MR , Light JE , Wilkins K , Tang S , Nakazawa Y , Emerson GL , Ritter JM , Mansell JL , Hamer SA . Emerg Infect Dis 2018 24 (6) 1069-1072 Northern pygmy mice from 2 localities in East Central Texas, USA, had proliferative epidermal lesions on the tail and feet. Electron microscopy of lesion tissue revealed poxvirus. Phylogenetic analyses indicated the virus differed 35% from its closest relatives, the Chordopoxvirinae. Future research is needed to determine whether this virus could affect human health. |
Understanding orthopoxvirus host range and evolution: from the enigmatic to the usual suspects.
Reynolds MG , Guagliardo SAJ , Nakazawa YJ , Doty JB , Mauldin MR . Curr Opin Virol 2017 28 108-115 In general, orthopoxviruses can be considered as falling into one of three host-utilization categories: highly specialized, single-host; broad host range; or 'cryptic', the last encompassing those viruses about which very little is known. Single-host viruses tend to exploit abundant hosts that have consistent patterns of interaction. For these viruses, observed genome reduction and loss of presumptive host-range genes is thought to be a consequence of relaxed selection. In contrast, the large genome size retained among broad host range orthopoxviruses suggests these viruses may depend on multiple host species for persistence in nature. Our understanding of the ecologic requirements of orthopoxviruses is strongly influenced by geographic biases in data collection. This hinders our ability to predict potential sources for emergence of orthopoxvirus-associated infections. |
Notes from the field: Postexposure prophylaxis for rabies after consumption of a prepackaged salad containing a bat carcass - Florida, 2017
Krishnasamy V , Mauldin MR , Wise ME , Wallace R , Whitlock L , Basler C , Morgan C , Grissom D , Worley S , Stanek D , DeMent J , Yager P , Carson W , Condori RE , Nakazawa Y , Walker C , Li Y , Wynens C , Wellman A , Ellison J , Pieracci E . MMWR Morb Mortal Wkly Rep 2017 66 (42) 1154-1155 On April 3, 2017, two Florida residents consumed part of the same prepackaged salad before reportedly discovering the partial remains of a bat carcass in the salad. Bats are known reservoirs for rabies virus, which causes rabies disease in both animals and humans (1). The persons who ate the salad contacted the Florida Department of Health (FLDOH), which notified CDC’s Poxvirus and Rabies Branch. CDC and FLDOH determined that the immediate concern was for potential rabies virus exposure, because approximately 6% of bats submitted to U.S. public health departments annually test positive for rabies virus (2,3). | Although percutaneous exposures are more likely to result in successful transmission of rabies virus to humans (1), transmission can occur when infectious material, such as saliva or nervous tissue from an infected animal, comes into direct contact with human mucosa (2). Infection with rabies virus causes an acute, progressive encephalitis that is nearly always fatal once clinical signs have begun. The disease is preventable if exposed persons receive timely postexposure prophylaxis (PEP), which includes human rabies immunoglobulin and 4 doses of inactivated rabies vaccine administered over 14 days (4). |
Assessing monkeypox virus prevalence in small mammals at the human-animal interface in the Democratic Republic of the Congo
Doty JB , Malekani JM , Kalemba LN , Stanley WT , Monroe BP , Nakazawa YU , Mauldin MR , Bakambana TL , Liyandja Dja Liyandja T , Braden ZH , Wallace RM , Malekani DV , McCollum AM , Gallardo-Romero N , Kondas A , Peterson AT , Osorio JE , Rocke TE , Karem KL , Emerson GL , Carroll DS . Viruses 2017 9 (10) During 2012, 2013 and 2015, we collected small mammals within 25 km of the town of Boende in Tshuapa Province, the Democratic Republic of the Congo. The prevalence of monkeypox virus (MPXV) in this area is unknown; however, cases of human infection were previously confirmed near these collection sites. Samples were collected from 353 mammals (rodents, shrews, pangolins, elephant shrews, a potamogale, and a hyrax). Some rodents and shrews were captured from houses where human monkeypox cases have recently been identified, but most were trapped in forests and agricultural areas near villages. Real-time PCR and ELISA were used to assess evidence of MPXV infection and other Orthopoxvirus (OPXV) infections in these small mammals. Seven (2.0%) of these animal samples were found to be anti-orthopoxvirus immunoglobulin G (IgG) antibody positive (six rodents: two Funisciurus spp.; one Graphiurus lorraineus; one Cricetomys emini; one Heliosciurus sp.; one Oenomys hypoxanthus, and one elephant shrew Petrodromus tetradactylus); no individuals were found positive in PCR-based assays. These results suggest that a variety of animals can be infected with OPXVs, and that epidemiology studies and educational campaigns should focus on animals that people are regularly contacting, including larger rodents used as protein sources. |
Cowpox virus: What's in a Name?
Mauldin MR , Antwerpen M , Emerson GL , Li Y , Zoeller G , Carroll DS , Meyer H . Viruses 2017 9 (5) Traditionally, virus taxonomy relied on phenotypic properties; however, a sequence-based virus taxonomy has become essential since the recent requirement of a species to exhibit monophyly. The species Cowpox virus has failed to meet this requirement, necessitating a reexamination of this species. Here, we report the genomic sequences of nine Cowpox viruses and, by combining them with the available data of 37 additional genomes, confirm polyphyly of Cowpox viruses and find statistical support based on genetic data for more than a dozen species. These results are discussed in light of the current International Committee on Taxonomy of Viruses species definition, as well as immediate and future implications for poxvirus taxonomic classification schemes. Data support the recognition of five monophyletic clades of Cowpox viruses as valid species. |
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