Papers by Lauren Greenberg
Morbidity and Mortality Weekly Report, May 20, 2022
The CDC Poxvirus and Rabies Branch and the Quarantine and Border Health Services Branch led a mul... more The CDC Poxvirus and Rabies Branch and the Quarantine and Border Health Services Branch led a multistate investigation to implement prevention and control measures and to determine the source of importation control failures. The Chicago Department of Public Health and the Pennsylvania Department of Agriculture investigated potential human exposures to dog A. During June 10-13, dog A traveled by private vehicle to the adopting family's home, two pet stores, and one veterinary clinic. Thirty-seven persons in the United States had potential exposures to dog A during its infectious period from June 2 (10 days before symptom onset) to June 13. After risk assessments, 15 persons, including one airport worker, seven household contacts, three pet store workers, and four veterinary staff members reported exposures that could have resulted in rabies virus infection and were recommended to receive rabies postexposure prophylaxis. § Three additional persons pursued postexposure prophylaxis out of an abundance of caution. Through the network of national focal points maintained by the World Health Organization under the International Health Regulations, CDC informed the Azerbaijani government and recommended contact tracing. Antemortem serum specimens from dog A collected on June 13 were tested for rabies virus-neutralizing antibody titer by the rapid fluorescent focus inhibition test at CDC's Rabies
Journal of Global Health Reports, 2021
Background In 2015, Ethiopia designated rabies as a priority zoonotic disease. Challenges in rabi... more Background In 2015, Ethiopia designated rabies as a priority zoonotic disease. Challenges in rabies diagnostic capacity, including laboratory safety, were identified in 2016. As a pilot evaluation, the national rabies laboratory in Ethiopia (EPHI) was chosen to participate in an evaluation of necropsy laboratory facilities and procedures which was conducted over two years. This evaluation identified areas for improvement that strengthening would enhance safety in the laboratory environment. Process changes, specifically in cleaning procedures, will decrease the likelihood of cross contamination and improve precision of testing. Methods This evaluation consisted of two sections: a 38-question verbal interview and an observational evaluation of necropsy laboratory practice. In March 2018, we evaluated EPHI's laboratory biosafety procedures, and the laboratory technicians' knowledge, practices, and attitudes in the animal necropsy laboratory before CDC-led laboratory trainings (September and December 2018). A post-training evaluation was conducted in March 2019.
Emerging Infectious Diseases, 2020
B ats are vital to many ecosystems and provide benefits to humans (1). However, under certain cir... more B ats are vital to many ecosystems and provide benefits to humans (1). However, under certain circumstances, bats may pose a risk to human health, as they host several zoonotic pathogens (2). Humans should therefore avoid bat contact unless appropriate precautions are taken. Among the most concerning batborne pathogens are viruses within the genus Lyssavirus. Previously unimmunized humans exposed to any of the >16 currently recognized and putative lyssaviruses (typically through a bite from an infected animal) will have 1 of 3 outcomes. First is a complete lack of any lyssavirus infection, characterized by the absence of both illness and lyssavirus-neutralizing antibody production. Second is a productive lyssavirus infection, characterized by a fatal encephalitis known as rabies (3). A human with rabies may produce lyssavirus-neutralizing antibodies in the end stages of illness as the disease progresses, although this response is typically inadequate for viral clearance (4). Third is an abortive lyssavirus infection (sometimes termed an exposure) characterized by the absence of frank encephalitis but with production of lyssavirus-neutralizing antibodies. Although
Viruses, 2020
Currently, no rabies virus-specific antiviral drugs are available. Ranpirnase has strong antitumo... more 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,...
MMWR. Morbidity and Mortality Weekly Report, 2019
PloS one, 2017
Current post-exposure prophylaxis for rabies virus infection has several limitations in terms of ... more Current post-exposure prophylaxis for rabies virus infection has several limitations in terms of supply, cost, safety, and efficacy. Attempts to replace human or equine rabies immune globulins (HRIG or ERIG) have been made by several companies and institutes. We developed potent monoclonal antibodies to neutralize a broad spectrum of rabies viruses by screening hybridomas received from the U.S. Centers for Disease Control and Prevention (CDC). Two kinds of chimeric human antibodies (chimeric #7 and #17) were constructed by cloning the variable regions from selected hybridomas and the constant region of a human antibody. Two antibodies were bound to antigenic site III and I/IV, respectively, and were able to neutralize 51 field isolates of rabies virus that were isolated at different times and places such as Asia, Africa, North America, South America, and Australia. These two antibodies neutralize rabies viruses with high efficacy in an in vivo test using Syrian hamster and mouse mod...
PLoS neglected tropical diseases, Jan 3, 2017
The direct fluorescent antibody test (DFA), is performed in all rabies reference laboratories acr... more The direct fluorescent antibody test (DFA), is performed in all rabies reference laboratories across Latin America and the Caribbean (LAC). Despite DFA being a critical capacity in the control of rabies, there is not a standardized protocol in the region. We describe the results of the first inter-laboratory proficiency exercise of national rabies laboratories in LAC countries as part of the regional efforts towards dog-maintained rabies elimination in the American region. Twenty three laboratories affiliated to the Ministries of Health and Ministries of Agriculture participated in this exercise. In addition, the laboratories completed an online questionnaire to assess laboratory practices. Answers to the online questionnaire indicated large variability in the laboratories throughput, equipment used, protocols availability, quality control standards and biosafety requirements. Our results will inform actions to improve and harmonize laboratory rabies capacities across LAC in support...
PLOS Neglected Tropical Diseases, 2017
Rabies, resulting from infection by Rabies virus (RABV) and related lyssaviruses, is one of the m... more Rabies, resulting from infection by Rabies virus (RABV) and related lyssaviruses, is one of the most deadly zoonotic diseases and is responsible for up to 70,000 estimated human deaths worldwide each year. Rapid and accurate laboratory diagnosis of rabies is essential for timely administration of post-exposure prophylaxis in humans and control of the disease in animals. Currently, only the direct fluorescent antibody (DFA) test is recommended for routine rabies diagnosis. Reverse-transcription polymerase chain reaction (RT-PCR) based diagnostic methods have been widely adapted for the diagnosis of other viral pathogens, but there is currently no widely accepted rapid real-time RT-PCR assay for the detection of all lyssaviruses. In this study, we demonstrate the validation of a newly developed multiplex real-time RT-PCR assay named LN34, which uses a combination of degenerate primers and probes along with probe modifications to achieve superior coverage of the Lyssavirus genus while maintaining sensitivity and specificity. The primers and probes of the LN34 assay target the highly conserved non-coding leader region and part of the nucleoprotein (N) coding sequence of the Lyssavirus genome to maintain assay robustness. The probes were further modified by locked nucleotides to increase their melting temperature to meet the requirements for an optimal real-time RT-PCR assay. The LN34 assay was able to detect all RABV variants and other lyssaviruses in a validation panel that included representative RABV isolates from most regions of the world as well as representatives of 13 additional Lyssavirus species. The LN34 assay was successfully used for both ante-mortem and post-mortem diagnosis of over 200 clinical samples as well as field derived surveillance samples. This assay represents a major improvement over previously published rabies specific RT-PCR and real-time RT-PCR assays because of its ability to universally detect RABV and other lyssaviruses, its high throughput capability and its simplicity of use, which can be quickly adapted in a laboratory to enhance the capacity of rabies molecular diagnostics. The LN34 assay provides an alternative approach for rabies diagnostics, especially in rural areas and rabies endemic regions that lack the conditions and broad experience required to run the standard DFA assay.
Vaccine, 2009
Despite progress in vaccine development in the past century the mechanisms behind immune response... more Despite progress in vaccine development in the past century the mechanisms behind immune responses elicited by rabies biologics or via natural infection remain largely unknown. In this study, we compared protection elicited by standard, early, or delayed prophylaxis with a reduced number of vaccine doses using inactivated and live-attenuated vaccines. Two-month-old Syrian hamsters, 4-week-old ICR mice or adult rhesus macaques were inoculated with canine rabies virus variants. Thereafter, prophylaxis was initiated 6 h, 1, 2, 3, 4, 5, 6 or 7 days post-exposure (p.e.). One or several doses of inactivated (HDCV), or reverse genetically attenuated (live), or gamma-irradiated (inactivated)-ERAG333 vaccines were administered intramuscularly. The dynamics of virus spread were measured over time in the rodent models. Rabies virus reached the spinal cord at day 4 and brain at day 6 p.e. All hamsters succumbed in groups in which live ERAG333 was delayed until days 5 and 6 p.e. However, 78%, 44%, 56% and 22% of hamsters survived when one dose of live ERAG333 was administered 6 h, 1, 2, 3, and 4 days p.e., respectively. Similarly, 67% survived when inactivated ERAG333 was administered at 24 h p.e. All hamsters succumbed when standard prophylaxis (the Essen regimen) was delayed until days 3-6, but 67% and 33% of hamsters survived when PEP began 1 or 2 days p.e., respectively. Macaques were protected by one dose of attenuated ERAG333 at 24 h p.e. The highly attenuated (live) and inactivated ERAG333 vaccines elicited potent protective immune responses, even when prophylaxis initiation was delayed. When 2-5 doses of commercial vaccine and HRIG were administered according to the Essen scheme, 89-100% of the animals survived. Reduced vaccine schedules provided efficacious intervention, regardless of the total number of vaccine doses administered.
Journal of the American Veterinary Medical Association, 2005
During 2004, 49 states and Puerto Rico reported 6,836 cases of rabies in nonhuman animals and 8 c... more During 2004, 49 states and Puerto Rico reported 6,836 cases of rabies in nonhuman animals and 8 cases in human beings to the CDC, representing a 4.6% decrease from the 7,170 cases in nonhuman animals and 3 cases in human beings reported in 2003. Approximately 92% of the cases were in wildlife, and 8% were in domestic animals (compared with 91% and 9%, respectively, in 2003). Relative contributions by the major animal groups were as follows: 2,564 raccoons (37.5%), 1,856 skunks (27.1%), 1,361 bats (19.9%), 389 foxes (5.7%), 281 cats (4.1%), 115 cattle (1.7%), and 94 dogs (1.4%). Compared with the numbers of reported cases in 2003, cases in 2004 decreased among all groups, except bats, cattle, human beings, and "other domestics" (1 llama). Decreases in numbers of rabid raccoons during 2004 were reported by 12 of the 20 eastern states in which raccoon rabies was enzootic. In the East, Massachusetts reported the first cases of raccoon rabies detected beyond the Cape Cod oral r...
Viruses, 2020
Rabies virus (RABV) is the only lyssavirus known to be present within the Caribbean. The island o... more Rabies virus (RABV) is the only lyssavirus known to be present within the Caribbean. The island of Trinidad, is richly diverse in chiropteran fauna and endemic for bat-transmitted rabies with low RABV isolation rates observed in this population. We aimed to determine the seroprevalence of rabies virus neutralizing antibodies (RVNA) in light of spatio-temporal and bat demographic factors to infer the extent of natural exposure to RABV in the Trinidadian bat population. RVNA titers were determined by the RABV micro-neutralization test on 383 bat samples representing 21 species, comprising 30.9% of local bat diversity, from 31 locations across the island over 5 years. RVNA was positively detected in 33 samples (8.6%) representing 6 bat species (mainly frugivorous) with titers ranging from 0.1 to 19 IU/mL (mean 1.66 IU/mL). The analyses based on a multivariable binomial generalised linear mixed-effects model showed that bat age and year of capture were significant predictors of seroposi...
Javma Journal of the American Veterinary Medical Association, 2014
Preventive Veterinary Medicine, 2015
Please cite this article in press as: Gilbert, A., et al., Antibody response of cattle to vaccina... more Please cite this article in press as: Gilbert, A., et al., Antibody response of cattle to vaccination with commercial modified live rabies vaccines in Guatemala. PREVET (2014), http://dx.
Preventive Veterinary Medicine, 2015
Please cite this article in press as: Gilbert, A., et al., Antibody response of cattle to vaccina... more Please cite this article in press as: Gilbert, A., et al., Antibody response of cattle to vaccination with commercial modified live rabies vaccines in Guatemala. PREVET (2014), http://dx.
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Papers by Lauren Greenberg