Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-15 (of 15 Records) |
Query Trace: Matheny A[original query] |
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Tecovirimat resistance in Mpox patients, United States, 2022-2023
Smith TG , Gigante CM , Wynn NT , Matheny A , Davidson W , Yang Y , Condori RE , O'Connell K , Kovar L , Williams TL , Yu YC , Petersen BW , Baird N , Lowe D , Li Y , Satheshkumar PS , Hutson CL . Emerg Infect Dis 2023 29 (12) 2426-2432 During the 2022 multinational outbreak of monkeypox virus (MPXV) infection, the antiviral drug tecovirimat (TPOXX; SIGA Technologies, Inc., https://www.siga.com) was deployed in the United States on a large scale for the first time. The MPXV F13L gene homologue encodes the target of tecovirimat, and single amino acid changes in F13 are known to cause resistance to tecovirimat. Genomic sequencing identified 11 mutations previously reported to cause resistance, along with 13 novel mutations. Resistant phenotype was determined using a viral cytopathic effect assay. We tested 124 isolates from 68 patients; 96 isolates from 46 patients were found to have a resistant phenotype. Most resistant isolates were associated with severely immunocompromised mpox patients on multiple courses of tecovirimat treatment, whereas most isolates identified by routine surveillance of patients not treated with tecovirimat remained sensitive. The frequency of resistant viruses remains relatively low (<1%) compared with the total number of patients treated with tecovirimat. |
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. |
Resistance to anti-orthopoxviral drug tecovirimat (TPOXX) during the 2022 mpox outbreak in the US (preprint)
Smith TG , Gigante CM , Wynn NT , Matheny A , Davidson W , Yang Y , Condori RE , O'Connell K , Kovar L , Williams TL , Yu YC , Petersen BW , Baird N , Lowe D , Li Y , Satheshkumar PS , Hutson CL . medRxiv 2023 18 Background: During the 2022 multinational outbreak of monkeypox virus (MPXV) clade IIb, the antiviral drug tecovirimat (TPOXX) was deployed in the US on a large scale for the first time ever. The MPXV F13L gene homolog encodes the target of tecovirimat, and single amino acid changes in the F13 protein are known to cause resistance to tecovirimat in orthopoxviruses (OPXV). Method(s): Whole genome metagenomic sequencing and amplicon-based sequencing targeting the F13L gene was used to identify nine mutations previously reported to cause resistance in other OPXV along with ten novel mutations that have been identified from the 2022 mpox outbreak. A cytopathic effect assay, previously established at CDC as part of WHO smallpox research, was adapted to MPXV for tecovirimat phenotype testing of virus isolated from mpox patients. Result(s): As of March 2023, in total, 70 isolates from 40 patients were tested, and 50 of these isolates from 26 patients were found to have a resistant phenotype. Most resistant isolates were associated with severely immunocompromised mpox patients on multiple courses of TPOXX treatment; while isolates with F13 mutations identified by routine surveillance of patients not treated with TPOXX have remained sensitive. Conclusion(s): These data indicate that tecovirimat resistance is developing in immunocompromised patients treated with TPOXX and that for isolates that we have analyzed, the frequency of resistant viruses remain relatively low (< 1%) compared to the total number of patients treated with TPOXX. These findings inform our understanding of when tecovirimat resistance is likely to occur and highlight the need for additional OPXV therapeutics. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Genomic deletions and rearrangements in monkeypox virus from the 2022 outbreak, USA (preprint)
Gigante CM , Plumb M , Ruprecht A , Zhao H , Wicker V , Wilkins K , Matheny A , Khan T , Davidson W , Sheth M , Burgin A , Burroughs M , Padilla J , Lee JS , Batra D , Hetrick EE , Howard DT , Garfin J , Tate L , Hubsmith SJ , Mendoza RM , Stanek D , Gillani S , Lee M , Mangla A , Blythe D , SierraPatev S , Carpenter-Azevedo K , Huard RC , Gallagher G , Hall J , Ash S , Kovar L , Seabolt MH , Weigand MR , Damon I , Satheshkumar PS , McCollum AM , Hutson CL , Wang X , Li Y . bioRxiv 2022 17 Genomic surveillance of monkeypox virus (MPXV) during the 2022 outbreak has been mainly focused on single nucleotide polymorphism (SNP) changes. DNA viruses, including MPXV, have a lower SNP mutation rate than RNA viruses due to higher fidelity replication machinery. We identified a large genomic rearrangement in a MPXV sequence from a 2022 case in the state of Minnesota (MN), USA, from an abnormal, uneven MPXV read mapping coverage profile in whole-genome sequencing (WGS) data. We further screened WGS data of 206 U.S. MPXV samples and found seven (3.4 percent) sequenced genomes contained similar abnormal read coverage profiles that suggested putative large deletions or genomic rearrangements. Here, we present three MPXV genomes containing deletions ranging from 2.3 to 15 kb and four genomes containing more complex rearrangements. Five genomic changes were each only seen in one sample, but two sequences from linked cases shared an identical 2.3 kb deletion in the 3' terminal region. All samples were positive using VAC1 and Clade II (formerly West African)-specific MPXV diagnostic tests; however, large deletions and genomic rearrangements like the ones reported here have the potential to result in viruses in which the target of a PCR diagnostic test is deleted. The emergence of genomic rearrangements during the outbreak may have public health implications and highlight the importance of continued genomic surveillance. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
An Mpox-related death in the United States
Alarcón J , Kim M , Terashita D , Davar K , Garrigues JM , Guccione JP , Evans MG , Hemarajata P , Wald-Dickler N , Holtom P , Garcia Tome R , Anyanwu L , Shah NK , Miller M , Smith T , Matheny A , Davidson W , Hutson CL , Lucas J , Ukpo OC , Green NM , Balter SE . N Engl J Med 2023 388 (13) 1246-1247 Since May 2022, when the multinational mpox (formerly known as monkeypox) clade IIb virus outbreak was first reported, more than 30,000 cases have been identified in the United States.1 In one study involving more than 1900 patients with mpox, more than 35% of the patients also had human immunodeficiency virus (HIV) infection.2 | | We report a death due to mpox in a patient in the United States. A 33-year-old man with HIV infection (CD4+ T-cell count, <35 per cubic millimeter) and recently treated syphilis became infected with mpox virus (MPXV) (clade IIb). He received two courses of oral tecovirimat (from Aug. 6 through Aug. 20, 2022, and from Aug. 21 through Sept. 4, 2022) and died on hospital day 27. |
Orthopoxvirus infections in rodents, Nigeria, 2018-2019
Meseko C , Adedeji A , Shittu I , Obishakin E , Nanven M , Suleiman L , Okomah D , Tyakaray V , Kolade D , Yinka-Ogunleye A , Muhammad S , Morgan CN , Matheny A , Nakazawa Y , McCollum A , Doty JB . Emerg Infect Dis 2023 29 (2) 433-434 To investigate animal reservoirs of monkeypox virus in Nigeria, we sampled 240 rodents during 2018-2019. Molecular (real-time PCR) and serologic (IgM) evidence indicated orthopoxvirus infections, but presence of monkeypox virus was not confirmed. These results can be used to develop public health interventions to reduce human infection with orthopoxviruses. |
Environmental persistence of monkeypox virus on surfaces in household of person with travel-associated infection, Dallas, Texas, USA, 2021
Morgan CN , Whitehill F , Doty JB , Schulte J , Matheny A , Stringer J , Delaney LJ , Esparza R , Rao AK , McCollum AM . Emerg Infect Dis 2022 28 (10) 1982-1989 In July 2021, we conducted environmental sampling at the residence of a person in Dallas, Texas, USA, who had travel-associated human West African monkeypox virus (MPXV-WA). Targeted environmental swab sampling was conducted 15 days after the person who had monkeypox left the household. Results indicate extensive MPXV-WA DNA contamination, and viable virus from 7 samples was successfully isolated in cell culture. There was no statistical difference (p = 0.94) between MPXV-WA PCR positivity of porous (9/10, 90%) vs. nonporous (19/21, 90.5%) surfaces, but there was a significant difference (p<0.01) between viable virus detected in cultures of porous (6/10, 60%) vs. nonporous (1/21, 5%) surfaces. These findings indicate that porous surfaces (e.g., bedding, clothing) may pose more of a MPXV exposure risk than nonporous surfaces (e.g., metal, plastic). Viable MPXV was detected on household surfaces after at least 15 days. However, low titers (<10(2) PFU) indicate a limited potential for indirect transmission. |
High-contact object and surface contamination in a household of persons with Monkeypox Virus Infection - Utah, June 2022
Pfeiffer JA , Collingwood A , Rider LE , Minhaj FS , Matheny AM , Kling C , McCollum AM , Nolen LD , Morgan CN . MMWR Morb Mortal Wkly Rep 2022 71 (34) 1092-1094 In May 2022, the Salt Lake County Health Department reported two real-time polymerase chain reaction (PCR)-confirmed travel-associated cases of monkeypox to the Utah Department of Health and Human Services (UDHHS). The two persons with monkeypox (patients A and B) lived together without other housemates. Both persons experienced prodromal symptoms (e.g., fatigue and body aches). Eight days after symptom onset, patient A experienced penile lesions; lesions spread to the lips, hands, legs, chest, and scalp by day 10. Patient B experienced prodromal symptoms 8 days after illness onset of patient A; patient B experienced a lesion on the foot which spread to the leg and finger by day 11. Although both patients had lesions in multiple anatomic areas, the overall number of lesions was small, and lesions varied in presentation from "pimple-like" or ulcerated, to characteristically well-circumscribed and centrally umbilicated. Both patients had mild illness. The time from symptom onset to resolution was approximately 30 days for patient A and approximately 22 days for patient B. |
Rapid diagnostic testing for response to the monkeypox outbreak - Laboratory Response Network, United States, May 17-June 30, 2022
Aden TA , Blevins P , York SW , Rager S , Balachandran D , Hutson CL , Lowe D , Mangal CN , Wolford T , Matheny A , Davidson W , Wilkins K , Cook R , Roulo RM , White MK , Berman L , Murray J , Laurance J , Francis D , Green NM , Berumen RA3rd , Gonzalez A , Evans S , Hudziec M , Noel D , Adjei M , Hovan G , Lee P , Tate L , Gose RB , Voermans R , Crew J , Adam PR , Haydel D , Lukula S , Matluk N , Shah S , Featherston J , Ware D , Pettit D , McCutchen E , Acheampong E , Buttery E , Gorzalski A , Perry M , Fowler R , Lee RB , Nickla R , Huard R , Moore A , Jones K , Johnson R , Swaney E , Jaramillo J , Reinoso Webb C , Guin B , Yost J , Atkinson A , Griffin-Thomas L , Chenette J , Gant J , Sterkel A , Ghuman HK , Lute J , Smole SC , Arora V , Demontigny CK , Bielby M , Geeter E , Newman KAM , Glazier M , Lutkemeier W , Nelson M , Martinez R , Chaitram J , Honein MA , Villanueva JM . MMWR Morb Mortal Wkly Rep 2022 71 (28) 904-907 As part of public health preparedness for infectious disease threats, CDC collaborates with other U.S. public health officials to ensure that the Laboratory Response Network (LRN) has diagnostic tools to detect Orthopoxviruses, the genus that includes Variola virus, the causative agent of smallpox. LRN is a network of state and local public health, federal, U.S. Department of Defense (DOD), veterinary, food, and environmental testing laboratories. CDC developed, and the Food and Drug Administration (FDA) granted 510(k) clearance* for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set (non-variola Orthopoxvirus [NVO] assay), a polymerase chain reaction (PCR) diagnostic test to detect NVO. On May 17, 2022, CDC was contacted by the Massachusetts Department of Public Health (DPH) regarding a suspected case of monkeypox, a disease caused by the Orthopoxvirus Monkeypox virus. Specimens were collected and tested by the Massachusetts DPH public health laboratory with LRN testing capability using the NVO assay. Nationwide, 68 LRN laboratories had capacity to test approximately 8,000 NVO tests per week during June. During May 17-June 30, LRN laboratories tested 2,009 specimens from suspected monkeypox cases. Among those, 730 (36.3%) specimens from 395 patients were positive for NVO. NVO-positive specimens from 159 persons were confirmed by CDC to be monkeypox; final characterization is pending for 236. Prompt identification of persons with infection allowed rapid response to the outbreak, including isolation and treatment of patients, administration of vaccines, and other public health action. To further facilitate access to testing and increase convenience for providers and patients by using existing provider-laboratory relationships, CDC and LRN are supporting five large commercial laboratories with a national footprint (Aegis Science, LabCorp, Mayo Clinic Laboratories, Quest Diagnostics, and Sonic Healthcare) to establish NVO testing capacity of 10,000 specimens per week per laboratory. On July 6, 2022, the first commercial laboratory began accepting specimens for NVO testing based on clinician orders. |
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. |
Laboratory infection of novel Akhmeta virus in CAST/EiJ mice
Morgan CN , Matheny AM , Nakazawa YJ , Kling C , Gallardo-Romero N , Seigler L , Barbosa Costa G , Hutson C , Maghlakelidze G , Olson V , Doty JB . Viruses 2020 12 (12) Akhmeta virus is a zoonotic Orthopoxvirus first identified in 2013 in the country of Georgia. Subsequent ecological investigations in Georgia have found evidence that this virus is widespread in its geographic distribution within the country and in its host-range, with rodents likely involved in its circulation in the wild. Yet, little is known about the pathogenicity of this virus in rodents. We conducted the first laboratory infection of Akhmeta virus in CAST/EiJ Mus musculus to further characterize this novel virus. We found a dose-dependent effect on mortality and weight loss (p < 0.05). Anti-orthopoxvirus antibodies were detected in the second- and third-highest dose groups (5 × 10(4) pfu and 3 × 10(2) pfu) at euthanasia by day 10, and day 14 post-infection, respectively. Anti-orthopoxvirus antibodies were not detected in the highest dose group (3 × 10(6) pfu), which were euthanized at day 7 post-infection and had high viral load in tissues, suggesting they succumbed to disease prior to mounting an effective immune response. In order of highest burden, viable virus was detected in the nostril, lung, tail, liver and spleen. All individuals tested in the highest dose groups were DNAemic. Akhmeta virus was highly pathogenic in CAST/EiJ Mus musculus, causing 100% mortality when ≥3 × 10(2) pfu was administered. |
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. |
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. |
Epidemiologic and ecologic investigations of monkeypox, Likouala Department, Republic of the Congo, 2017
Doshi RH , Guagliardo SAJ , Doty JB , Babeaux AD , Matheny A , Burgado J , Townsend MB , Morgan CN , Satheshkumar PS , Ndakala N , Kanjingankolo T , Kitembo L , Malekani J , Kalemba L , Pukuta E , N'Kaya T , Kangoula F , Moses C , McCollum AM , Reynolds MG , Mombouli JV , Nakazawa Y , Petersen BW . Emerg Infect Dis 2019 25 (2) 281-289 Monkeypox, caused by a zoonotic orthopoxvirus, is endemic in Central and West Africa. Monkeypox has been sporadically reported in the Republic of the Congo. During March 22-April 5, 2017, we investigated 43 suspected human monkeypox cases. We interviewed suspected case-patients and collected dried blood strips and vesicular and crust specimens (active lesions), which we tested for orthopoxvirus antibodies by ELISA and monkeypox virus and varicella zoster virus DNA by PCR. An ecologic investigation was conducted around Manfouete, and specimens from 105 small mammals were tested for anti-orthopoxvirus antibodies or DNA. Among the suspected human cases, 22 met the confirmed, probable, and possible case definitions. Only 18 patients had available dried blood strips; 100% were IgG positive, and 88.9% (16/18) were IgM positive. Among animals, only specimens from Cricetomys giant pouched rats showed presence of orthopoxvirus antibodies, adding evidence to this species' involvement in the transmission and maintenance of monkeypox virus in nature. |
Recommendations for returning genomic incidental findings? We need to talk!
Burke W , Antommaria AH , Bennett R , Botkin J , Clayton EW , Henderson GE , Holm IA , Jarvik GP , Khoury MJ , Knoppers BM , Press NA , Ross LF , Rothstein MA , Saal H , Uhlmann WR , Wilfond B , Wolf SM , Zimmern R . Genet Med 2013 15 (11) 854-9 The American College of Medical Genetics and Genomics recently issued recommendations for reporting incidental findings from clinical whole-genome sequencing and whole-exome sequencing. The recommendations call for evaluating a specific set of genes as part of all whole-genome sequencing/whole-exome sequencing and reporting all pathogenic variants irrespective of patient age. The genes are associated with highly penetrant disorders for which treatment or prevention is available. The effort to generate a list of genes with actionable findings is commendable, but the recommendations raise several concerns. They constitute a call for opportunistic screening, through intentional effort to identify pathogenic variants in specified genes unrelated to the clinical concern that prompted testing. Yet for most of the genes, we lack evidence about the predictive value of testing, genotype penetrance, spectrum of phenotypes, and efficacy of interventions in unselected populations. Furthermore, the recommendations do not allow patients to decline the additional findings, a position inconsistent with established norms. Finally, the recommendation to return adult-onset disease findings when children are tested is inconsistent with current professional consensus, including other policy statements of the American College of Medical Genetics and Genomics. Instead of premature practice recommendations, we call for robust dialogue among stakeholders to define a pathway to normatively sound, evidence-based guidelines. |
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