Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
Records 1-30 (of 61 Records) |
Query Trace: Ellison Z[original query] |
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The added value of serologic testing: a comparison of influenza incidence among pregnant persons based on molecular-based surveillance versus serologic testing
Kittikraisak W , Tinoco Y , Levine MZ , Mott JA , Kanjanapattanakul W , Munayco C , Rawangban B , Hunt DR , Mohanty S , Wesley M , Soto G , Florian R , Gonzales O , Cabrera S , Llajaruna E , Asavapiriyanont S , Ellison DW , Malek P , Azziz-Baumgartner E , Dawood FS . Int J Infect Dis 2024 107264 BACKGROUND: We examined the added value of serologic testing for estimating influenza virus infection incidence based on illness surveillance with molecular testing versus periodic serologic testing. METHODS: Pregnant persons unvaccinated against influenza at <28 weeks gestation were enrolled before the 2017 and 2018 influenza seasons in Peru and Thailand. Blood specimens were collected at enrollment and ≤14 days postpartum for testing by hemagglutination inhibition assay for antibodies against influenza reference viruses. Seroconversion was defined as a ≥4-fold rise in antibody titers from enrollment to postpartum with the second specimen's titer of ≥40. Throughout pregnancy, participants responded to twice weekly surveillance contacts asking about influenza vaccination and influenza-like symptoms (ILS). A mid-turbinate swab was collected with each ILS episode for influenza real-time reverse transcription PCR (rRT-PCR). RESULTS: Of 1,466 participants without evidence of influenza vaccination during pregnancy, 296 (20.2%) had evidence of influenza virus infections. Fifteen (5.1%) were detected by rRT-PCR only, 250 (84.4%) by serologic testing only, and 31 (10.5%) by both methods. CONCLUSIONS: Influenza virus infections during pregnancy occurred in 20% of cohort participants; >80% were not detected by a broad illness case definition coupled with rRT-PCR. |
Wastewater surveillance for influenza A virus and H5 subtype concurrent with the highly pathogenic avian influenza A(H5N1) virus outbreak in cattle and poultry and associated human cases - United States, May 12-July 13, 2024
Louis S , Mark-Carew M , Biggerstaff M , Yoder J , Boehm AB , Wolfe MK , Flood M , Peters S , Stobierski MG , Coyle J , Leslie MT , Sinner M , Nims D , Salinas V , Lustri L , Bojes H , Shetty V , Burnor E , Rabe A , Ellison-Giles G , Yu AT , Bell A , Meyer S , Lynfield R , Sutton M , Scholz R , Falender R , Matzinger S , Wheeler A , Ahmed FS , Anderson J , Harris K , Walkins A , Bohra S , O'Dell V , Guidry VT , Christensen A , Moore Z , Wilson E , Clayton JL , Parsons H , Kniss K , Budd A , Mercante JW , Reese HE , Welton M , Bias M , Webb J , Cornforth D , Santibañez S , Soelaeman RH , Kaur M , Kirby AE , Barnes JR , Fehrenbach N , Olsen SJ , Honein MA . MMWR Morb Mortal Wkly Rep 2024 73 (37) 804-809 As part of the response to the highly pathogenic avian influenza A(H5N1) virus outbreak in U.S. cattle and poultry and the associated human cases, CDC and partners are monitoring influenza A virus levels and detection of the H5 subtype in wastewater. Among 48 states and the District of Columbia that performed influenza A testing of wastewater during May 12-July 13, 2024, a weekly average of 309 sites in 38 states had sufficient data for analysis, and 11 sites in four states reported high levels of influenza A virus. H5 subtype testing was conducted at 203 sites in 41 states, with H5 detections at 24 sites in nine states. For each detection or high level, CDC and state and local health departments evaluated data from other influenza surveillance systems and partnered with wastewater utilities and agriculture departments to investigate potential sources. Among the four states with high influenza A virus levels detected in wastewater, three states had corresponding evidence of human influenza activity from other influenza surveillance systems. Among the 24 sites with H5 detections, 15 identified animal sources within the sewershed or adjacent county, including eight milk-processing inputs. Data from these early investigations can help health officials optimize the use of wastewater surveillance during the upcoming respiratory illness season. |
Salmonella Hadar linked to two distinct transmission vehicles highlights challenges to enteric disease outbreak investigations
Brandenburg JM , Stapleton GS , Kline KE , Khoury J , Mallory K , Machesky KD , Ladd-Wilson SG , Scholz R , Freiman J , Schwensohn C , Palacios A , Gieraltowski L , Ellison Z , Tolar B , Webb HE , Tagg KA , Salah Z , Nichols M . Epidemiol Infect 2024 1-27 |
Multistate outbreaks of salmonellosis linked to contact with backyard poultry-United States, 2015-2022
Stapleton GS , Habrun C , Nemechek K , Gollarza L , Ellison Z , Tolar B , Koski L , Brandenburg JM , Salah Z , Palacios A , Basler C , Varela K , Nichols M , Benedict K . Zoonoses Public Health 2024 AIMS: Contact with backyard poultry (i.e., privately-owned, non-commercial poultry) was first associated with a multistate outbreak of salmonellosis in 1955. In recent years, backyard poultry-associated salmonellosis outbreaks have caused more illnesses in the United States than salmonellosis outbreaks linked to any other type of animal. Here, we describe the epidemiology of outbreaks from 2015-2022 to inform prevention efforts. METHODS AND RESULTS: During 2015-2022, there were 88 multistate backyard poultry-associated salmonellosis outbreaks and 7866 outbreak-associated illnesses caused by 21 different Salmonella serotypes. Salmonella Enteritidis accounted for the most outbreaks (n = 21) and illnesses (n = 2400) of any serotype. Twenty-four percent (1840/7727) of patients with available information were <5 years of age. In total, 30% (1710/5644) of patients were hospitalized, and nine deaths were attributed to Salmonella infection. Throughout this period, patients reported behaviours that have a higher risk of Salmonella transmission, including kissing or snuggling poultry or allowing poultry inside their home. CONCLUSIONS: Despite ongoing efforts to reduce the burden of salmonellosis associated with backyard poultry, outbreak-associated illnesses have nearly tripled and hospitalizations more than quadrupled compared with those in 1990-2014. Because this public health problem is largely preventable, government officials, human and veterinary healthcare providers, hatcheries, and retailers might improve the prevention of illnesses by widely disseminating health and safety recommendations to the public and by continuing to develop and implement prevention measures to reduce zoonotic transmission of Salmonella by backyard poultry. |
Rabies experts on demand: A cross-sectional study describing the use of a rabies telehealth service
Baker SE , Ross YB , Ellison JA , Monroe BP , Orciari LA , Petersen BW , Rao AK , Wallace RM . Public Health Chall 2023 2 (3) BACKGROUND: Rabies expert on demand (REOD) telehealth service is provided by the U.S. Centers for Disease Control and Prevention (CDC) to assist public health practitioners, health providers, and the public to interpret national and international rabies prevention guidelines. REOD is staffed by subject matter experts of the CDC Poxvirus and Rabies Branch to assess each unique situation and provide evidence-based guidance to stakeholders. This study aims to describe the utilization of a rabies telehealth system and provide insight into common consultations. METHODS: A cross-sectional study of the nature of inquiries to REOD was done using the data collected from September 1, 2017 to September 30, 2021. An inquiry tracking form and Microsoft Access database were developed to document all inquiries received. Inquired ones were summarized to determine the frequency of inquiries by month, category, and location. RESULTS: Over a 49-month period, REOD received 5228 inquiries. Peak inquiries (n = 108) occurred during August 2019. The most frequent inquiries received pertained to risk assessment and management of rabies exposures (n = 1109), requests for testing assistance (n = 912), consultation for suspected human rabies (n = 746), rabies exposures and post-bite treatment occurring internationally (n = 310), and consultation for deviations in the recommended pre- and postexposure prophylaxis regimen (n = 300). CONCLUSION: REOD is a global resource for consultation related to managing rabies exposures, diagnostic issues, and rabies control strategies. REOD is a regularly utilized CDC service, as the demand for up-to-date rabies guidance remains high. REOD fulfills a critical role for the interpretation and consultation on rabies prevention guidelines to stakeholder. |
Strain of multidrug-resistant salmonella newport remains linked to travel to Mexico and U.S. beef products - United States, 2021-2022
Ford L , Ellison Z , Schwensohn C , Griffin I , Birhane MG , Cote A , Fortenberry GZ , Tecle S , Higa J , Spencer S , Patton B , Patel J , Dow J , Maroufi A , Robbins A , Donovan D , Fitzgerald C , Burrell S , Tolar B , Folster JP , Cooley LA , Francois Watkins LK . MMWR Morb Mortal Wkly Rep 2023 72 (45) 1225-1229 In 2016, CDC identified a multidrug-resistant (MDR) strain of Salmonella enterica serotype Newport that is now monitored as a persisting strain (REPJJP01). Isolates have been obtained from U.S. residents in all 50 states and the District of Columbia, linked to travel to Mexico, consumption of beef products obtained in the United States, or cheese obtained in Mexico. In 2021, the number of isolates of this strain approximately doubled compared with the 2018-2020 baseline and remained high in 2022. During January 1, 2021- December 31, 2022, a total of 1,308 isolates were obtained from patients, cattle, and sheep; 86% were MDR, most with decreased susceptibility to azithromycin. Approximately one half of patients were Hispanic or Latino; nearly one half reported travel to Mexico during the month preceding illness, and one third were hospitalized. Two multistate outbreak investigations implicated beef products obtained in the United States. This highly resistant strain might spread through travelers, animals, imported foods, domestic foods, or other sources. Isolates from domestic and imported cattle slaughtered in the United States suggests a possible source of contamination. Safe food and drink consumption practices while traveling and interventions across the food production chain to ensure beef safety are necessary in preventing illness. |
Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission (preprint)
Karthikeyan S , Levy JI , De Hoff P , Humphrey G , Birmingham A , Jepsen K , Farmer S , Tubb HM , Valles T , Tribelhorn CE , Tsai R , Aigner S , Sathe S , Moshiri N , Henson B , Mark AM , Hakim A , Baer NA , Barber T , Belda-Ferre P , Chacón M , Cheung W , Cresini ES , Eisner ER , Lastrella AL , Lawrence ES , Marotz CA , Ngo TT , Ostrander T , Plascencia A , Salido RA , Seaver P , Smoot EW , McDonald D , Neuhard RM , Scioscia AL , Satterlund AM , Simmons EH , Abelman DB , Brenner D , Bruner JC , Buckley A , Ellison M , Gattas J , Gonias SL , Hale M , Hawkins F , Ikeda L , Jhaveri H , Johnson T , Kellen V , Kremer B , Matthews G , McLawhon RW , Ouillet P , Park D , Pradenas A , Reed S , Riggs L , Sanders A , Sollenberger B , Song A , White B , Winbush T , Aceves CM , Anderson C , Gangavarapu K , Hufbauer E , Kurzban E , Lee J , Matteson NL , Parker E , Perkins SA , Ramesh KS , Robles-Sikisaka R , Schwab MA , Spencer E , Wohl S , Nicholson L , McHardy IH , Dimmock DP , Hobbs CA , Bakhtar O , Harding A , Mendoza A , Bolze A , Becker D , Cirulli ET , Isaksson M , Barrett KMS , Washington NL , Malone JD , Schafer AM , Gurfield N , Stous S , Fielding-Miller R , Garfein RS , Gaines T , Anderson C , Martin NK , Schooley R , Austin B , MacCannell DR , Kingsmore SF , Lee W , Shah S , McDonald E , Yu AT , Zeller M , Fisch KM , Longhurst C , Maysent P , Pride D , Khosla PK , Laurent LC , Yeo GW , Andersen KG , Knight R . medRxiv 2022 As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission. |
Fatal Human Rabies Infection with Suspected Host-mediated Failure of Post-Exposure Prophylaxis Following a Recognized Zoonotic Exposure-Minnesota, 2021.
Holzbauer SM , Schrodt CA , Prabhu RM , Asch-Kendrick RJ , Ireland M , Klumb C , Firestone MJ , Liu G , Harry K , Ritter JM , Levine MZ , Orciari LA , Wilkins K , Yager P , Gigante CM , Ellison JA , Zhao H , Niezgoda M , Li Y , Levis R , Scott D , Satheshkumar PS , Petersen BW , Rao AK , Bell WR , Bjerk SM , Forrest S , Gao W , Dasheiff R , Russell K , Pappas M , Kiefer J , Bickler W , Wiseman A , Jurantee J , Reichard RR , Smith KE , Lynfield R , Scheftel J , Wallace RM , Bonwitt J . Clin Infect Dis 2023 77 (8) 1201-1208 BACKGROUND: No rabies post-exposure prophylaxis (PEP) failure has been documented in humans in the United States using modern cell-culture vaccines. In January 2021, an 84-year-old male died from rabies six months after being bitten by a rabid bat despite receiving timely rabies post-exposure prophylaxis (PEP). We investigated the cause of breakthrough infection. METHODS: We reviewed medical records, laboratory results, and autopsy findings, and performed whole genome sequencing (WGS) to compare patient and bat virus sequences. Storage, administration, and integrity of PEP biologics administered to the patient were assessed; samples from leftover rabies immunoglobulin were evaluated for potency. We conducted risk assessments for persons potentially exposed to the bat and for close contacts of the patient. RESULTS: Rabies virus antibodies present in serum and cerebrospinal fluid were non-neutralizing. Antemortem blood testing revealed the patient had unrecognized monoclonal gammopathy of unknown significance. Autopsy findings showed rabies meningoencephalitis and metastatic prostatic adenocarcinoma. Rabies virus sequences from the patient and the offending bat were identical by WGS. No deviations were identified in potency, quality control, administration, or storage of administered PEP. Of 332 persons assessed for potential rabies exposure to the case patient, three (0.9%) warranted PEP. CONCLUSION: This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is any suspicion for immunocompromise. |
Genome Sequences of 18 Salmonella enterica Serotype Hadar Strains Collected from Patients in the United States.
Webb HE , Kim JY , Tagg KA , de la Cruz F , Peñil-Celis A , Tolar B , Ellison Z , Schwensohn C , Brandenburg J , Nichols M , Folster JP . Microbiol Resour Announc 2022 11 (10) e0052222 Despite being linked to a number of recent poultry-associated outbreaks in the United States, few reference genomes are available for Salmonella enterica serotype Hadar. Here, we address this need by reporting 18 Salmonella Hadar genomes from samples collected from patients in the United States between 2014 and 2020. |
A recombinant rabies vaccine that prevents viral shedding in rabid common vampire bats (Desmodus rotundus).
Cárdenas-Canales EM , Velasco-Villa A , Ellison JA , Satheshkumar PS , Osorio JE , Rocke TE . PLoS Negl Trop Dis 2022 16 (8) e0010699 Vampire bat transmitted rabies (VBR) is a continuing burden to public health and agricultural sectors in Latin America, despite decades-long efforts to control the disease by culling bat populations. Culling has been shown to disperse bats, leading to an increased spread of rabies. Thus, non-lethal strategies to control VBR, such as vaccination, are desired. Here, we evaluated the safety and efficacy of a viral-vectored recombinant mosaic glycoprotein rabies vaccine candidate (RCN-MoG) in vampire bats (Desmodus rotundus) of unknown history of rabies exposure captured in México and transported to the United States. Vaccination with RCN-MoG was demonstrated to be safe, even in pregnant females, as no evidence of lesions or adverse effects were observed. We detected rabies neutralizing antibodies in 28% (8/29) of seronegative bats post-vaccination. Survival proportions of adult bats after rabies virus (RABV) challenge ranged from 55-100% and were not significantly different among treatments, pre- or post-vaccination serostatus, and route of vaccination, while eight pups (1-2.5 months of age) used as naïve controls all succumbed to challenge (P<0.0001). Importantly, we found that vaccination with RCN-MoG appeared to block viral shedding, even when infection proved lethal. Using real-time PCR, we did not detect RABV nucleic acid in the saliva samples of 9/10 vaccinated bats that succumbed to rabies after challenge (one was inconclusive). In contrast, RABV nucleic acid was detected in saliva samples from 71% of unvaccinated bats (10/14 sampled, plus one inconclusive) that died of the disease, including pups. Low seroconversion rates post-vaccination and high survival of non-vaccinated bats, perhaps due to earlier natural exposure, limited our conclusions regarding vaccine efficacy. However, our findings suggest a potential transmission-blocking effect of vaccination with RCN-MoG that could provide a promising strategy for controlling VBR in Latin America beyond longstanding culling programs. |
Wastewater sequencing reveals early cryptic SARS-CoV-2 variant transmission.
Karthikeyan S , Levy JI , De Hoff P , Humphrey G , Birmingham A , Jepsen K , Farmer S , Tubb HM , Valles T , Tribelhorn CE , Tsai R , Aigner S , Sathe S , Moshiri N , Henson B , Mark AM , Hakim A , Baer NA , Barber T , Belda-Ferre P , Chacón M , Cheung W , Cresini ES , Eisner ER , Lastrella AL , Lawrence ES , Marotz CA , Ngo TT , Ostrander T , Plascencia A , Salido RA , Seaver P , Smoot EW , McDonald D , Neuhard RM , Scioscia AL , Satterlund AM , Simmons EH , Abelman DB , Brenner D , Bruner JC , Buckley A , Ellison M , Gattas J , Gonias SL , Hale M , Hawkins F , Ikeda L , Jhaveri H , Johnson T , Kellen V , Kremer B , Matthews G , McLawhon RW , Ouillet P , Park D , Pradenas A , Reed S , Riggs L , Sanders A , Sollenberger B , Song A , White B , Winbush T , Aceves CM , Anderson C , Gangavarapu K , Hufbauer E , Kurzban E , Lee J , Matteson NL , Parker E , Perkins SA , Ramesh KS , Robles-Sikisaka R , Schwab MA , Spencer E , Wohl S , Nicholson L , McHardy IH , Dimmock DP , Hobbs CA , Bakhtar O , Harding A , Mendoza A , Bolze A , Becker D , Cirulli ET , Isaksson M , Schiabor Barrett KM , Washington NL , Malone JD , Schafer AM , Gurfield N , Stous S , Fielding-Miller R , Garfein RS , Gaines T , Anderson C , Martin NK , Schooley R , Austin B , MacCannell DR , Kingsmore SF , Lee W , Shah S , McDonald E , Yu AT , Zeller M , Fisch KM , Longhurst C , Maysent P , Pride D , Khosla PK , Laurent LC , Yeo GW , Andersen KG , Knight R . Nature 2022 609 (7925) 101-108 As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases(1-3). SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing(4,5). Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission. |
A cocktail of human monoclonal antibodies broadly neutralizes North American rabies virus variants as a promising candidate for rabies post-exposure prophylaxis.
Ejemel M , Smith TG , Greenberg L , Carson WC , Lowe D , Yang Y , Jackson FR , Morgan CN , Martin BE , Kling C , Hutson CL , Gallardo-Romero N , Ellison JA , Moore S , Buzby A , Sullivan-Bolyai J , Klempner M , Wang Y . Sci Rep 2022 12 (1) 9403 Human rabies remains a globally significant public health problem. Replacement of polyclonal anti-rabies immunoglobulin (RIG), a passive component of rabies post-exposure prophylaxis (PEP), with a monoclonal antibody (MAb), would eliminate the cost and availability constraints associated with RIG. Our team has developed and licensed a human monoclonal antibody RAB1 (Rabishield()), as the replacement for RIG where canine rabies is enzootic. However, for the highly diverse rabies viruses of North America, a cocktail containing two or more MAbs targeting different antigenic sites of the rabies glycoprotein should be included to ensure neutralization of all variants of the virus. In this study, two MAb cocktails, R172 (RAB1-RAB2) and R173 (RAB1-CR57), were identified and evaluated against a broad range of rabies variants from North America. R173 was found to be the most potent cocktail, as it neutralized all the tested North American RABV isolates and demonstrated broad coverage of isolates from both terrestrial and bat species. R173 could be a promising candidate as an alternative or replacement for RIG PEP in North America. |
A field placement approach to enhance state and local capacity for opioid-related issues affecting pregnant and postpartum people and infants prenatally exposed to opioids and other substances
Weber MK , Tran EL , Kroelinger CD , Ellison C , Mueller T , Romero L , Ellick KL , Rice ME , Garcia G , Pliska E , Akbarali S , Dronamraju R , Patterson K , Fehrenbach SN , Barfield WD . J Womens Health (Larchmt) 2022 31 (2) 145-153 Opioid use disorder (OUD) poses a significant public health concern impacting maternal and infant outcomes. In 2018, the Centers for Disease Control and Prevention (CDC) partnered with the Association of State and Territorial Health Officials (ASTHO) to develop the Opioid use disorder, Maternal outcomes, and Neonatal abstinence syndrome Initiative Learning Community (OMNI LC) to identify and disseminate best practices and strategies for implementing systems-level changes in state health departments to address OUD affecting pregnant and postpartum persons and infants prenatally exposed to opioids. In 2019, the OMNI LC incorporated a field placement approach that assigned temporary field placement staff in five select OMNI LC states to provide important linkages, facilitate information sharing, and strengthen capacity among state and local health departments and other partners supporting maternal and child health communities affected by the opioid crisis. Using an implementation science framework, the field placement approach was assessed using five implementation outcome measures: appropriateness, acceptability, implementation cost, sustainability, and feasibility. Written responses from the participating OMNI LC states on these implementation outcome measures were analyzed to (1) highlight key strategies used by field placement staff, (2) assess the implementation of the OMNI LC field placement approach within the context of implementation science, and (3) identify implementation barriers. This report describes the implementation of a temporary field placement approach and suggests that this approach could be replicated to enhance state and local capacity to respond to the opioid crisis or other high-consequence events. |
Outbreak of Multidrug-Resistant Salmonella Heidelberg Infections Linked to Dairy Calf Exposure, United States, 2015-2018.
Nichols M , Gollarza L , Sockett D , Aulik N , Patton E , Francois Watkins LK , Gambino-Shirley KJ , Folster JP , Chen JC , Tagg KA , Stapleton GS , Trees E , Ellison Z , Lombard J , Morningstar-Shaw B , Schlater L , Elbadawi L , Klos R . Foodborne Pathog Dis 2022 19 (3) 199-208 In August 2016, the Wisconsin Department of Health Services notified the U.S. Centers for Disease Control and Prevention of multidrug-resistant (MDR) Salmonella enterica serovar Heidelberg infections in people who reported contact with dairy calves. Federal and state partners investigated this to identify the source and scope of the outbreak and to prevent further illnesses. Cases were defined as human Salmonella Heidelberg infection caused by a strain that had one of seven pulsed-field gel electrophoresis (PFGE) patterns or was related by whole genome sequencing (WGS), with illness onset from January 1, 2015, through July 2, 2018. Patient exposure and calf purchase information was collected and analyzed; calves were traced back from the point of purchase. Isolates obtained from animal and environmental samples collected on-farm were supplied by veterinary diagnostic laboratories and compared with patient isolates using PFGE and WGS. Antimicrobial susceptibility testing by standardized broth microdilution was performed. Sixty-eight patients from 17 states were identified. Forty (63%) of 64 patients noted cattle contact before illness. Thirteen (33%) of 40 patients with exposure to calves reported that calves were sick or had died. Seven individuals purchased calves from a single Wisconsin livestock market. One hundred forty cattle from 14 states were infected with the outbreak strain. WGS indicated that human, cattle, and environmental isolates from the livestock market were genetically closely related. Most isolates (88%) had resistance or reduced susceptibility to antibiotics of ≥5 antibiotic classes. This resistance profile included first-line antibiotic treatments for patients with severe salmonellosis, including ampicillin, ceftriaxone, and ciprofloxacin. In this outbreak, MDR Salmonella Heidelberg likely spread from sick calves to humans, emphasizing the importance of illness surveillance in animal populations to prevent future spillover of this zoonotic disease. |
Determination of freedom-from-rabies for small Indian mongoose populations in the United States Virgin Islands, 2019-2020
Browne AS , Cranford HM , Morgan CN , Ellison JA , Berentsen A , Wiese N , Medley A , Rossow J , Jankelunas L , McKinley AS , Lombard CD , Angeli NF , Kelley T , Valiulus J , Bradford B , Burke-France VJ , Harrison CJ , Guendel I , Taylor M , Blanchard GL , Doty JB , Worthington DJ , Horner D , Garcia KR , Roth J , Ellis BR , Bisgard KM , Wallace R , Ellis EM . PLoS Negl Trop Dis 2021 15 (7) e0009536 Mongooses, a nonnative species, are a known reservoir of rabies virus in the Caribbean region. A cross-sectional study of mongooses at 41 field sites on the US Virgin Islands of St. Croix, St. John, and St. Thomas captured 312 mongooses (32% capture rate). We determined the absence of rabies virus by antigen testing and rabies virus exposure by antibody testing in mongoose populations on all three islands. USVI is the first Caribbean state to determine freedom-from-rabies for its mongoose populations with a scientifically-led robust cross-sectional study. Ongoing surveillance activities will determine if other domestic and wildlife populations in USVI are rabies-free. |
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. |
Incidence of influenza during pregnancy and association with pregnancy and perinatal outcomes in three middle-income countries: a multisite prospective longitudinal cohort study
Dawood FS , Kittikraisak W , Patel A , Rentz Hunt D , Suntarattiwong P , Wesley MG , Thompson MG , Soto G , Mundhada S , Arriola CS , Azziz-Baumgartner E , Brummer T , Cabrera S , Chang HH , Deshmukh M , Ellison D , Florian R , Gonzales O , Kurhe K , Kaoiean S , Rawangban B , Lindstrom S , Llajaruna E , Mott JA , Saha S , Prakash A , Mohanty S , Sinthuwattanawibool C , Tinoco Y . Lancet Infect Dis 2020 21 (1) 97-106 BACKGROUND: Influenza vaccination during pregnancy prevents influenza among women and their infants but remains underused among pregnant women. We aimed to quantify the risk of antenatal influenza and examine its association with perinatal outcomes. METHODS: We did a prospective cohort study in pregnant women in India, Peru, and Thailand. Before the 2017 and 2018 influenza seasons, we enrolled pregnant women aged 18 years or older with expected delivery dates 8 weeks or more after the season started. We contacted women twice weekly until the end of pregnancy to identify illnesses with symptoms of myalgia, cough, runny nose or nasal congestion, sore throat, or difficulty breathing and collected mid-turbinate nasal swabs from symptomatic women for influenza real-time RT-PCR testing. We assessed the association of antenatal influenza with preterm birth, late pregnancy loss (≥13 weeks gestation), small for gestational age (SGA), and birthweight of term singleton infants using Cox proportional hazards models or generalised linear models to adjust for potential confounders. FINDINGS: Between March 13, 2017, and Aug 3, 2018, we enrolled 11 277 women with a median age of 26 years (IQR 23-31) and gestational age of 19 weeks (14-24). 1474 (13%) received influenza vaccines. 310 participants (3%) had influenza (270 [87%] influenza A and 40 [13%] influenza B). Influenza incidences weighted by the population of women of childbearing age in each study country were 88·7 per 10 000 pregnant woman-months (95% CI 68·6 to 114·8) during the 2017 season and 69·6 per 10 000 pregnant woman-months (53·8 to 90·2) during the 2018 season. Antenatal influenza was not associated with preterm birth (adjusted hazard ratio [aHR] 1·4, 95% CI 0·9 to 2·0; p=0·096) or having an SGA infant (adjusted relative risk 1·0, 95% CI 0·8 to 1·3, p=0·97), but was associated with late pregnancy loss (aHR 10·7, 95% CI 4·3 to 27·0; p<0·0001) and reduction in mean birthweight of term, singleton infants (-55·3 g, 95% CI -109·3 to -1·4; p=0·0445). INTERPRETATION: Women had a 0·7-0·9% risk of influenza per month of pregnancy during the influenza season, and antenatal influenza was associated with increased risk for some adverse pregnancy outcomes. These findings support the added value of antenatal influenza vaccination to improve perinatal outcomes. FUNDING: US Centers for Disease Control and Prevention. TRANSLATIONS: For the Thai, Hindi, Marathi and Spanish translations of the abstract see Supplementary Materials section. |
Bat and Lyssavirus exposure among humans in area that celebrates bat festival, Nigeria, 2010 and 2013
Vora NM , Osinubi MOV , Davis L , Abdurrahman M , Adedire EB , Akpan H , Aman-Oloniyo AF , Audu SW , Blau D , Dankoli RS , Ehimiyein AM , Ellison JA , Gbadegesin YH , Greenberg L , Haberling D , Hutson C , Idris JM , Kia GSN , Lawal M , Matthias SY , Mshelbwala PP , Niezgoda M , Ogunkoya AB , Ogunniyi AO , Okara GC , Olugasa BO , Ossai OP , Oyemakinde A , Person MK , Rupprecht CE , Saliman OA , Sani M , Sanni-Adeniyi OA , Satheshkumar PS , Smith TG , Soleye MO , Wallace RM , Yennan SK , Recuenco S . Emerg Infect Dis 2020 26 (7) 1399-1408 Using questionnaires and serologic testing, we evaluated bat and lyssavirus exposure among persons in an area of Nigeria that celebrates a bat festival. Bats from festival caves underwent serologic testing for phylogroup II lyssaviruses (Lagos bat virus, Shimoni bat virus, Mokola virus). The enrolled households consisted of 2,112 persons, among whom 213 (10%) were reported to have ever had bat contact (having touched a bat, having been bitten by a bat, or having been scratched by a bat) and 52 (2%) to have ever been bitten by a bat. Of 203 participants with bat contact, 3 (1%) had received rabies vaccination. No participant had neutralizing antibodies to phylogroup II lyssaviruses, but >50% of bats had neutralizing antibodies to these lyssaviruses. Even though we found no evidence of phylogroup II lyssavirus exposure among humans, persons interacting with bats in the area could benefit from practicing bat-related health precautions. |
Influenza-associated medical visits prevented by influenza vaccination in young children in Thailand, 2012-2014
Rolfes MA , Olsen SJ , Kittikraisak W , Suntarattiwong P , Klungthong C , Ellison D , Mott JA , Chotpitayasunondh T . J Pediatric Infect Dis Soc 2020 10 (3) 349-351 Despite recommendations, few children aged 6-35 months in Thailand receive seasonal influenza vaccination. Using previously estimated incidence and vaccine effectiveness data from the period 2012-2014, we estimate that up to 121 000 medical visits could be prevented each year with 50% coverage and expanded recommendations to children aged <5 years. |
Candida auris outbreak involving liver transplant recipients in a Surgical Intensive Care Unit.
Theodoropoulos NM , Bolstorff B , Bozorgzadeh A , Brandeburg C , Cumming M , Daly JS , Ellison RT3rd , Forsberg K , Gade L , Gibson L , Greenough T , Litvintseva AP , Mack DA , Madoff L , Martins PN , McHale E , Melvin Z , Movahedi B , Stiles T , Vallabhaneni S , Levitz SM . Am J Transplant 2020 20 (12) 3673-3679 Candida auris is a difficult to eradicate yeast that has caused outbreaks in healthcare facilities. We report a cluster of five patients in one intensive care unit who were colonized or infected in 2017. The initial two patients were recipients of liver transplants who had cultures that grew C. auris within three days of each other in June 2017 (days 43 and 30 post-transplant). Subsequent screening cultures identified two additional patients with C. auris colonization. Respiratory and urine cultures from a fifth patient yielded C. auris. All isolates were fluconazole-resistant but susceptible to echinocandins. Whole genome sequencing showed the strains were clonal, suggesting in-hospital transmission, and related but distinct from NY/NJ strains, consistent with a separate introduction. However, no source or contact was found. Two of the five patients died. C. auris infection likely contributed to one patient death by infecting a vascular aneurysm at the graft anastomosis. Strict infection control precautions were initiated to control the outbreak. Our experience reveals that while severe disease from C. auris can occur in transplant recipients, outbreaks can be controlled using recommended infection control practices. We have had no further patients infected with C. auris to date. |
Projected estimates of cancer in Canada in 2020
Brenner DR , Weir HK , Demers AA , Ellison LF , Louzado C , Shaw A , Turner D , Woods RR , Smith LM . CMAJ 2020 192 (9) E199-e205 BACKGROUND: Cancer projections to the current year help in policy development, planning of programs and allocation of resources. We sought to provide an overview of the expected incidence and mortality of cancer in Canada in 2020 in follow-up to the Canadian Cancer Statistics 2019 report. METHODS: We obtained incidence data from the National Cancer Incidence Reporting System (1984-1991) and Canadian Cancer Registry (1992-2015). Mortality data (1984-2015) were obtained from the Canadian Vital Statistics - Death Database. All databases are maintained by Statistics Canada. Cancer incidence and mortality counts and age-standardized rates were projected to 2020 for 23 cancer types by sex and geographic region (provinces and territories) for all ages combined. RESULTS: An estimated 225 800 new cancer cases and 83 300 cancer deaths are expected in Canada in 2020. The most commonly diagnosed cancers are expected to be lung overall (29 800), breast in females (27 400) and prostate in males (23 300). Lung cancer is also expected to be the leading cause of cancer death, accounting for 25.5% of all cancer deaths, followed by colorectal (11.6%), pancreatic (6.4%) and breast (6.1%) cancers. Incidence and mortality rates will be generally higher in the eastern provinces than in the western provinces. INTERPRETATION: The number of cancer cases and deaths remains high in Canada and, owing to the growing and aging population, is expected to continue to increase. Although progress has been made in reducing deaths for most major cancers (breast, prostate and lung), there has been limited progress for pancreatic cancer, which is expected to be the third leading cause of cancer death in Canada in 2020. Additional efforts to improve uptake of existing programs, as well as to advance research, prevention, screening and treatment, are needed to address the cancer burden in Canada. |
Clinical presentation and serologic response during a rabies epizootic in captive common vampire bats (Desmodus rotundus)
Cardenas-Canales EM , Gigante CM , Greenberg L , Velasco-Villa A , Ellison JA , Satheshkumar PS , Medina-Magues LG , Griesser R , Falendysz E , Amezcua I , Osorio JE , Rocke TE . Trop Med Infect Dis 2020 5 (1) We report mortality events in a group of 123 common vampire bats (Desmodus rotundus) captured in Mexico and housed for a rabies vaccine efficacy study in Madison, Wisconsin. Bat mortalities occurred in Mexico and Wisconsin, but rabies cases reported herein are only those that occurred after arrival in Madison (n = 15). Bats were confirmed positive for rabies virus (RABV) by the direct fluorescent antibody test. In accordance with previous reports, we observed long incubation periods (more than 100 days), variability in clinical signs prior to death, excretion of virus in saliva, and changes in rabies neutralizing antibody (rVNA) titers post-infection. We observed that the furious form of rabies (aggression, hyper-salivation, and hyper-excitability) manifested in three bats, which has not been reported in vampire bat studies since 1936. RABV was detected in saliva of 5/9 bats, 2-5 days prior to death, but was not detected in four of those bats that had been vaccinated shortly after exposure. Bats from different capture sites were involved in two separate outbreaks, and phylogenetic analysis revealed differences in the glycoprotein gene sequences of RABV isolated from each event, indicating that two different lineages were circulating separately during capture at each site. |
Human rabies - Utah, 2018
Peterson D , Barbeau B , McCaffrey K , Gruninger R , Eason J , Burnett C , Dunn A , Dimond M , Harbour J , Rossi A , Lopansri B , Dascomb K , Scribellito T , Moosman T , Saw L , Jones C , Belenky M , Marsden L , Niezgoda M , Gigante CM , Condori RE , Ellison JA , Orciari LA , Yager P , Bonwitt J , Whitehouse ER , Wallace RM . MMWR Morb Mortal Wkly Rep 2020 69 (5) 121-124 On November 3, 2018, the Utah Department of Health (UDOH) was notified of a suspected human rabies case in a man aged 55 years. The patient's symptoms had begun 18 days earlier, and he was hospitalized for 15 days before rabies was suspected. As his symptoms worsened, he received supportive care, but he died on November 4. On November 7, a diagnosis of rabies was confirmed by CDC. This was the first documented rabies death in a Utah resident since 1944. This report summarizes the patient's clinical course and the subsequent public health investigation, which determined that the patient had handled several bats in the weeks preceding symptom onset. Public health agencies, in partnership with affected health care facilities, identified and assessed the risk to potentially exposed persons, facilitated receipt of postexposure prophylaxis (PEP), and provided education to health care providers and the community about the risk for rabies associated with bats. Human rabies is rare and almost always fatal. The findings from this investigation highlight the importance of early recognition of rabies, improved public awareness of rabies in bats, and the use of innovative tools after mass rabies exposure events to ensure rapid and recommended risk assessment and provision of PEP. |
Antiviral ranpirnase TMR-001 inhibits rabies virus release and cell-to-cell infection in vitro
Smith TG , Jackson FR , Morgan CN , Carson WC , Martin BE , Gallardo-Romero N , Ellison JA , Greenberg L , Hodge T , Squiquera L , Sulley J , Olson VA , Hutson CL . Viruses 2020 12 (2) Currently, no rabies virus-specific antiviral drugs are available. Ranpirnase has strong antitumor and antiviral properties associated with its ribonuclease activity. TMR-001, a proprietary bulk drug substance solution of ranpirnase, was evaluated against rabies virus in three cell types: mouse neuroblastoma, BSR (baby hamster kidney cells), and bat primary fibroblast cells. When TMR-001 was added to cell monolayers 24 h preinfection, rabies virus release was inhibited for all cell types at three time points postinfection. TMR-001 treatment simultaneous with infection and 24 h postinfection effectively inhibited rabies virus release in the supernatant and cell-to-cell spread with 50% inhibitory concentrations of 0.2-2 nM and 20-600 nM, respectively. TMR-001 was administered at 0.1 mg/kg via intraperitoneal, intramuscular, or intravenous routes to Syrian hamsters beginning 24 h before a lethal rabies virus challenge and continuing once per day for up to 10 days. TMR-001 at this dose, formulation, and route of delivery did not prevent rabies virus transit from the periphery to the central nervous system in this model (n = 32). Further aspects of local controlled delivery of other active formulations or dose concentrations of TMR-001 or ribonuclease analogues should be investigated for this class of drugs as a rabies antiviral therapeutic. |
Characterization of Monkeypox virus dissemination in the black-tailed prairie dog (Cynomys ludovicianus) through in vivo bioluminescent imaging
Weiner ZP , Salzer JS , LeMasters E , Ellison JA , Kondas AV , Morgan CN , Doty JB , Martin BE , Satheshkumar PS , Olson VA , Hutson CL . PLoS One 2019 14 (9) e0222612 Monkeypox virus (MPXV) is a member of the genus Orthopoxvirus, endemic in Central and West Africa. This viral zoonosis was introduced into the United States in 2003 via African rodents imported for the pet trade and caused 37 human cases, all linked to exposure to MPXV-infected black-tailed prairie dogs (Cynomys ludovicianus). Prairie dogs have since become a useful model of MPXV disease, utilized for testing of potential medical countermeasures. In this study, we used recombinant MPXV containing the firefly luciferase gene (luc) and in vivo imaging technology to characterize MPXV pathogenesis in the black-tailed prairie dog in real time. West African (WA) MPXV could be visualized using in vivo imaging in the nose, lymph nodes, intestines, heart, lung, kidneys, and liver as early as day 6 post infection (p.i.). By day 9 p.i., lesions became visible on the skin and in some cases in the spleen. After day 9 p.i., luminescent signal representing MPXV replication either increased, indicating a progression to what would be a fatal infection, or decreased as infection was resolved. Use of recombinant luc+ MPXV allowed for a greater understanding of how MPXV disseminates throughout the body in prairie dogs during the course of infection. This technology will be used to reduce the number of animals required in future pathogenesis studies as well as aid in determining the effectiveness of potential medical countermeasures. |
Notes from the Field: Rabies outbreak investigation - Pedernales, Dominican Republic, 2019
Mandra A , Moran D , Santana PV , Marrero MC , Diaz E , Gil M , Nolasco RR , Capellan R , Acosta X , Perez R , Cespedes C , Baez B , Condori RE , Smith T , Ellison J , Greenberg L , Monroe B , Gibson A , Wallace RM , Petersen B . MMWR Morb Mortal Wkly Rep 2019 68 (32) 704-706 On July 13, 2018, a child from Pedernales, Dominican Republic, died after developing clinical signs and symptoms consistent with rabies. Because of the child’s signs and symptoms, history of having been bitten by a dog 4 months earlier, and not having a received postexposure prophylaxis (PEP) (1), the patient was reported as having a probable case of rabies to the Ministerio de Salud Pública (MSP; i.e., Ministry of Public Health) (1). This case was the first reported from Pedernales Province in >30 years. During November 29–December 20, 2018, two additional probable rabies cases (based on clinical signs and history of dog bites) in children were reported from this province. The second patient did not receive any PEP. The third patient began PEP 10 days after being bitten and received 4 doses of vaccine before symptom onset; no rabies immunoglobulin was available in the province. All three children died from rabies encephalitis. |
Human rabies - Virginia, 2017
Murphy J , Sifri CD , Pruitt R , Hornberger M , Bonds D , Blanton J , Ellison J , Cagnina RE , Enfield KB , Shiferaw M , Gigante C , Condori E , Gruszynski K , Wallace RM . MMWR Morb Mortal Wkly Rep 2019 67 (5152) 1410-1414 On May 9, 2017, the Virginia Department of Health was notified regarding a patient with suspected rabies. The patient had sustained a dog bite 6 weeks before symptom onset while traveling in India. On May 11, CDC confirmed that the patient was infected with a rabies virus that circulates in dogs in India. Despite aggressive treatment, the patient died, becoming the ninth person exposed to rabies abroad who has died from rabies in the United States since 2008. A total of 250 health care workers were assessed for exposure to the patient, 72 (29%) of whom were advised to initiate postexposure prophylaxis (PEP). The total pharmaceutical cost for PEP (rabies immunoglobulin and rabies vaccine) was approximately $235,000. International travelers should consider a pretravel consultation with travel health specialists; rabies preexposure prophylaxis is warranted for travelers who will be in rabies endemic countries for long durations, in remote areas, or who plan activities that might put them at risk for a rabies exposures. |
Potential confounding of diagnosis of rabies in patients with recent receipt of intravenous immune globulin
Vora NM , Orciari LA , Bertumen JB , Damon I , Ellison JA , Fowler VG Jr , Franka R , Petersen BW , Satheshkumar PS , Schexnayder SM , Smith TG , Wallace RM , Weinstein S , Williams C , Yager P , Niezgoda M . MMWR Morb Mortal Wkly Rep 2018 67 (5) 161-165 Rabies is an acute encephalitis that is nearly always fatal. It is caused by infection with viruses of the genus Lyssavirus, the most common of which is Rabies lyssavirus. The Council of State and Territorial Epidemiologists (CSTE) defines a confirmed human rabies case as an illness compatible with rabies that meets at least one of five different laboratory criteria.* Four of these criteria do not depend on the patient's rabies vaccination status; however, the remaining criterion, "identification of Lyssavirus-specific antibody (i.e. by indirect fluorescent antibody...test or complete [Rabies lyssavirus] neutralization at 1:5 dilution) in the serum," is only considered diagnostic in unvaccinated patients. Lyssavirus-specific antibodies include Rabies lyssavirus-specific binding immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies and Rabies lyssavirus neutralizing antibodies (RLNAs). This report describes six patients who were tested for rabies by CDC and who met CSTE criteria for confirmed human rabies because they had illnesses compatible with rabies, had not been vaccinated for rabies, and were found to have serum RLNAs (with complete Rabies lyssavirus neutralization at a serum dilution of 1:5). An additional four patients are described who were tested for rabies by CDC who were found to have serum RLNAs (with incomplete Rabies lyssavirus neutralization at a serum dilution of 1:5) despite having not been vaccinated for rabies. None of these 10 patients received a rabies diagnosis; rather, they were considered to have been passively immunized against rabies through recent receipt of intravenous immune globulin (IVIG). Serum RLNA test results should be interpreted with caution in patients who have not been vaccinated against rabies but who have recently received IVIG. |
In Vivo Efficacy of a Cocktail of Human Monoclonal Antibodies (CL184) Against Diverse North American Bat Rabies Virus Variants
Franka R , Carson WC , Ellison JA , Taylor ST , Smith TG , Kuzmina NA , Kuzmin IV , Marissen WE , Rupprecht CE . Trop Med Infect Dis 2017 2 (3) Following rabies virus (RABV) exposure, a combination of thorough wound washing, multiple-dose vaccine administration and the local infiltration of rabies immune globulin (RIG) are essential components of modern post-exposure prophylaxis (PEP). Although modern cell-culture-based rabies vaccines are increasingly used in many countries, RIG is much less available. The prohibitive cost of polyclonal serum RIG products has prompted a search for alternatives and design of anti-RABV monoclonal antibodies (MAbs) that can be manufactured on a large scale with a consistent potency and lower production costs. Robust in vitro neutralization activity has been demonstrated for the CL184 MAb cocktail, a 1:1 protein mixture of two human anti-RABV MAbs (CR57/CR4098), against a large panel of RABV isolates. In this study, we used a hamster model to evaluate the efficacy of experimental PEP against a lethal challenge. Various doses of CL184 and commercial rabies vaccine were assessed for the ability to protect against lethal infection with representatives of four distinct bat RABV lineages of public health relevance: silver-haired bat (Ln RABV); western canyon bat (Ph RABV); big brown bat (Ef-w1 RABV) and Mexican free-tailed bat RABV (Tb RABV). 42⁻100% of animals survived bat RABV infection when CL184 (in combination with the vaccine) was administered. A dose-response relationship was observed with decreasing doses of CL184 resulting in increasing mortality. Importantly, CL184 was highly effective in neutralizing and clearing Ph RABV in vivo, even though CR4098 does not neutralize this virus in vitro. By comparison, 19⁻95% survivorship was observed if human RIG (20 IU/kg) and vaccine were used following challenge with different bat viruses. Based on our results, CL184 represents an efficacious alternative for RIG. Both large-scale and lower cost production could ensure better availability and affordability of this critical life-saving biologic in rabies enzootic countries and as such, significantly contribute to the reduction of human rabies deaths globally. |
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). |
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