Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-7 (of 7 Records) |
Query Trace: Mrotz V [original query] |
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Author Correction: Ultra-long-acting in-situ forming implants with cabotegravir protect female macaques against rectal SHIV infection
Young IC , Massud I , Cottrell ML , Shrivastava R , Maturavongsadit P , Prasher A , Wong-Sam A , Dinh C , Edwards T , Mrotz V , Mitchell J , Seixas JN , Pallerla A , Thorson A , Schauer A , Sykes C , De la Cruz G , Montgomery SA , Kashuba ADM , Heneine W , Dobard CW , Kovarova M , Garcia JV , Garcίa-Lerma JG , Benhabbour SR . Nat Commun 2024 15 (1) 1054 |
Pharmacokinetic study of islatravir and etonogestrel implants in macaques
Daly MB , Wong-Sam A , Li L , Krovi A , Gatto GJ , Norton C , Luecke EH , Mrotz V , Forero C , Cottrell ML , Schauer AP , Gary J , Nascimento-Seixas J , Mitchell J , van der Straten A , Heneine W , Garcίa-Lerma JG , Dobard CW , Johnson LM . Pharmaceutics 2023 15 (12) The prevention of HIV and unintended pregnancies is a public health priority. Multi-purpose prevention technologies capable of long-acting HIV and pregnancy prevention are desirable for women. Here, we utilized a preclinical macaque model to evaluate the pharmacokinetics of biodegradable ε-polycaprolactone implants delivering the antiretroviral islatravir (ISL) and the contraceptive etonogestrel (ENG). Three implants were tested: ISL-62 mg, ISL-98 mg, and ENG-33 mg. Animals received one or two ISL-eluting implants, with doses of 42, 66, or 108 µg of ISL/day with or without an additional ENG-33 mg implant (31 µg/day). Drug release increased linearly with dose with median [range] plasma ISL levels of 1.3 [1.0-2.5], 1.9 [1.2-6.3] and 2.8 [2.3-11.6], respectively. The ISL-62 and 98 mg implants demonstrated stable drug release over three months with ISL-triphosphate (ISL-TP) concentr54ations in PBMCs above levels predicted to be efficacious for PrEP. Similarly, ENG implants demonstrated sustained drug release with median [range] plasma ENG levels of 495 [229-1110] pg/mL, which suppressed progesterone within two weeks and showed no evidence of altering ISL pharmacokinetics. Two of the six ISL-98 mg implants broke during the study and induced implant-site reactions, whereas no reactions were observed with intact implants. We show that ISL and ENG biodegradable implants are safe and yield sufficient drug levels to achieve prevention targets. The evaluation of optimized implants with increased mechanical robustness is underway for improved durability and vaginal efficacy in a SHIV challenge model. |
Ferrets as a mammalian model to study influenza virus-bacteria interactions
Basu Thakur P , Mrotz VJ , Maines TR , Belser JA . J Infect Dis 2023 Ferrets represent an invaluable model for the study of influenza virus pathogenicity and transmissibility due to the ability of this species to recapitulate clinical symptoms of influenza infection present in humans. Ferrets are also employed for the study of bacterial pathogens that naturally infect humans at different anatomical sites, including the respiratory and gastrointestinal tracts. While viral and bacterial infection studies in isolation using animal models are important for furthering our understanding of pathogen biology and for the development of improved therapeutics, it is also critical to extend our knowledge to pathogen coinfections in vivo, to more closely examine interkingdom dynamics that may contribute to overall disease outcomes. Despite the increasing use of ferrets for studies with influenza virus, few reports have investigated influenza and bacterial coinfection challenges in ferrets. In this review, we discuss how ferrets have been employed to study a diverse range of both influenza viruses and bacterial species and summarize key studies that have utilized the ferret model for primary influenza virus challenge followed by secondary bacterial infection. These co-pathogenesis studies have provided critical insight into the dynamic interplay between these pathogens, underscoring the utility of ferrets as a model system for investigating influenza virus-bacteria interactions. |
One Health Investigation of SARS-CoV-2 Infection and Seropositivity among Pets in Households with Confirmed Human COVID-19 Cases — Utah and Wisconsin, 2020 (preprint)
Goryoka GW , Cossaboom CM , Gharpure R , Dawson P , Tansey C , Rossow J , Mrotz V , Rooney J , Torchetti M , Loiacono CM , Killian ML , Jenkins-Moore M , Lim A , Poulsen K , Christensen D , Sweet E , Peterson D , Sangster AL , Young EL , Oakeson KF , Taylor D , Price A , Kiphibane T , Klos R , Konkle D , Bhattacharyya S , Dasu T , Chu VT , Lewis NM , Queen K , Zhang J , Uehara A , Dietrich EA , Tong S , Kirking HL , Doty JB , Murrell LS , Spengler JR , Straily A , Wallace R , Barton Behravesh C . bioRxiv 2021 2021.04.11.439379 Background Approximately 67% of U.S. households have pets. Limited data are available on SARS-CoV-2 in pets. We assessed SARS-CoV-2 infection in pet cohabitants as a sub-study of an ongoing COVID-19 household transmission investigation.Methods Mammalian pets from households with ≥1 person with laboratory-confirmed COVID-19 were eligible for inclusion from April–May 2020. Demographic/exposure information, oropharyngeal, nasal, rectal, and fur swabs, feces, and blood were collected from enrolled pets and tested by rRT-PCR and virus neutralization assays.Findings We enrolled 37 dogs and 19 cats from 34 of 41 eligible households. All oropharyngeal, nasal, and rectal swabs tested negative by rRT-PCR; one dog’s fur swabs (2%) tested positive by rRT-PCR at the first animal sampling. Among 47 pets with serological results from 30 households, eight (17%) pets (4 dogs, 4 cats) from 6 (20%) households had detectable SARS-CoV-2 neutralizing antibodies. In households with a seropositive pet, the proportion of people with laboratory-confirmed COVID-19 was greater (median 79%; range: 40–100%) compared to households with no seropositive pet (median 37%; range: 13–100%) (p=0.01). Thirty-three pets with serologic results had frequent daily contact (≥1 hour) with the human index patient before the person’s COVID-19 diagnosis. Of these 33 pets, 14 (42%) had decreased contact with the human index patient after diagnosis and none (0%) were seropositive; of the 19 (58%) pets with continued contact, 4 (21%) were seropositive.Interpretations Seropositive pets likely acquired infection from humans, which may occur more frequently than previously recognized. People with COVID-19 should restrict contact with animals.Funding Centers for Disease Control and Prevention, U.S. Department of AgricultureCompeting Interest StatementThe authors have declared no competing interest. |
Ultra-long-acting in-situ forming implants with cabotegravir protect female macaques against rectal SHIV infection
Young IC , Massud I , Cottrell ML , Shrivastava R , Maturavongsadit P , Prasher A , Wong-Sam A , Dinh C , Edwards T , Mrotz V , Mitchell J , Seixas JN , Pallerla A , Thorson A , Schauer A , Sykes C , De la Cruz G , Montgomery SA , Kashuba ADM , Heneine W , Dobard CW , Kovarova M , Garcia JV , García-Lerma JG , Benhabbour SR . Nat Commun 2023 14 (1) 708 Ultra-long-acting delivery platforms for HIV pre-exposure prophylaxis (PrEP) may increase adherence and maximize public health benefit. We report on an injectable, biodegradable, and removable in-situ forming implant (ISFI) that is administered subcutaneously and can release the integrase inhibitor cabotegravir (CAB) above protective benchmarks for more than 6 months. CAB ISFIs are well-tolerated in female mice and female macaques showing no signs of toxicity or chronic inflammation. In macaques, median plasma CAB concentrations exceed established PrEP protection benchmarks within 3 weeks and confer complete protection against repeated rectal SHIV challenges. Implant removal via a small incision in 2 macaques at week 12 results in a 7- to 48-fold decrease in plasma CAB levels within 72 hours. Modeling to translate CAB ISFI dosing suggests that a 3 mL injection would exceed protective benchmarks in humans for over 5 months post administration. Our results support the clinical advancement of CAB ISFIs for ultra-long-acting PrEP in humans. |
Effects of buprenorphine treatment on influenza pathogenesis in the ferret (Mustela putorius furo)
Mrotz VJ , Nestor KM , Maines TR , Powell N , Belser JA . Comp Med 2022 72 (1) 22-29 Ferrets are the gold-standard model for influenza A virus (IAV) research due to their natural susceptibility to human and zoonotic IAV, comparable respiratory anatomy and physiology to humans, and development of clinical signs similar to those seen in infected people. Because the presence and progression of clinical signs can be useful in infectious disease research, uncertainty in how analgesics alter research outcomes or compromise characteristics of disease progression have outweighed the concern regarding animal discomfort from these symptoms. Nonetheless, the principles of animal research require consideration of refinements for this important model for IAV research. Opioids offer a possible refinement option that would not directly affect the inflammatory cascade involved in IAV infection. Mirroring pathogenicity studies that use ferrets, 12 ferrets were inoculated intranasally with the A(H3N2) IAV A/Panama/2007/1999 and divided into 3 treatment groups ( n = 4 each), of which 2 groups received buprenorphine treatments on different schedules and the third received a saline control. The duration and location of viral replication, lymphohematopoietic changes, and clinical signs were comparable across all groups at all time points. High quantities of infectious virus in nasal wash specimens were detected in ferrets from all groups through day 5 after inoculation, and peak viral titers from the upper respiratory tract did not differ between ferrets receiving buprenorphine treatments on either schedule. Compared with the saline group, ferrets receiving buprenorphine exhibited transient weight loss and pyrexia, but all groups ultimately achieved similar peaks in both of these measurements. Collectively, these findings support the continued evaluation of buprenorphine as a refinement for IAV-challenged ferrets. |
One Health Investigation of SARS-CoV-2 Infection and Seropositivity among Pets in Households with Confirmed Human COVID-19 Cases-Utah and Wisconsin, 2020.
Goryoka GW , Cossaboom CM , Gharpure R , Dawson P , Tansey C , Rossow J , Mrotz V , Rooney J , Torchetti M , Loiacono CM , Killian ML , Jenkins-Moore M , Lim A , Poulsen K , Christensen D , Sweet E , Peterson D , Sangster AL , Young EL , Oakeson KF , Taylor D , Price A , Kiphibane T , Klos R , Konkle D , Bhattacharyya S , Dasu T , Chu VT , Lewis NM , Queen K , Zhang J , Uehara A , Dietrich EA , Tong S , Kirking HL , Doty JB , Murrell LS , Spengler JR , Straily A , Wallace R , Barton Behravesh C . Viruses 2021 13 (9) Approximately 67% of U.S. households have pets. Limited data are available on SARS-CoV-2 in pets. We assessed SARS-CoV-2 infection in pets during a COVID-19 household transmission investigation. Pets from households with ≥1 person with laboratory-confirmed COVID-19 were eligible for inclusion from April-May 2020. We enrolled 37 dogs and 19 cats from 34 households. All oropharyngeal, nasal, and rectal swabs tested negative by rRT-PCR; one dog's fur swabs (2%) tested positive by rRT-PCR at the first sampling. Among 47 pets with serological results, eight (17%) pets (four dogs, four cats) from 6/30 (20%) households had detectable SARS-CoV-2 neutralizing antibodies. In households with a seropositive pet, the proportion of people with laboratory-confirmed COVID-19 was greater (median 79%; range: 40-100%) compared to households with no seropositive pet (median 37%; range: 13-100%) (p = 0.01). Thirty-three pets with serologic results had frequent daily contact (≥1 h) with the index patient before the person's COVID-19 diagnosis. Of these 33 pets, 14 (42%) had decreased contact with the index patient after diagnosis and none were seropositive; of the 19 (58%) pets with continued contact, four (21%) were seropositive. Seropositive pets likely acquired infection after contact with people with COVID-19. People with COVID-19 should restrict contact with pets and other animals. |
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