Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 363 Records) |
Query Trace: Montgomery J [original query] |
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Determining herd immunity thresholds for hepatitis A virus transmission to inform vaccination strategies among people who inject drugs in 16 U.S. States
Yang J , Lo NC , Dankwa EA , Donnelly CA , Gupta R , Montgomery MP , Weng MK , Martin NK . Clin Infect Dis 2024 78 (4) 976-982 BACKGROUND: Widespread outbreaks of person-to-person transmitted hepatitis A virus (HAV), particularly among people who inject drugs (PWID), continue across the United States and globally. However, the herd immunity threshold and vaccination coverage required to prevent outbreaks are unknown. We used surveillance data and dynamic modeling to estimate herd immunity thresholds among PWID in 16 US states. METHODS: We used a previously published dynamic model of HAV transmission calibrated to surveillance data from outbreaks involving PWID in 16 states. Using state-level calibrated models, we estimated the basic reproduction number (R0) and herd immunity threshold for PWID in each state. We performed a meta-analysis of herd immunity thresholds to determine the critical vaccination coverage required to prevent most HAV outbreaks among PWID. RESULTS: Estimates of R0 for HAV infection ranged from 2.2 (95% confidence interval [CI], 1.9-2.5) for North Carolina to 5.0 (95% CI, 4.5-5.6) for West Virginia. Corresponding herd immunity thresholds ranged from 55% (95% CI, 47%-61%) for North Carolina to 80% (95% CI, 78%-82%) for West Virginia. Based on the meta-analysis, we estimated a pooled herd immunity threshold of 64% (95% CI, 61%-68%; 90% prediction interval, 52%-76%) among PWID. Using the prediction interval upper bound (76%) and assuming 95% vaccine efficacy, we estimated that vaccination coverage of 80% could prevent most HAV outbreaks. CONCLUSIONS: Hepatitis A vaccination programs in the United States may need to achieve vaccination coverage of at least 80% among PWID in order to prevent most HAV outbreaks among this population. |
Ten years of high-consequence pathogens-research gains, readiness gaps, and future goals
McQuiston JH , Montgomery JM , Hutson CL . Emerg Infect Dis 2024 30 (4) 800-802 |
Overview of U.S. COVID-19 vaccine safety surveillance systems
Gee J , Shimabukuro TT , Su JR , Shay D , Ryan M , Basavaraju SV , Broder KR , Clark M , Buddy Creech C , Cunningham F , Goddard K , Guy H , Edwards KM , Forshee R , Hamburger T , Hause AM , Klein NP , Kracalik I , Lamer C , Loran DA , McNeil MM , Montgomery J , Moro P , Myers TR , Olson C , Oster ME , Sharma AJ , Schupbach R , Weintraub E , Whitehead B , Anderson S . Vaccine 2024 The U.S. COVID-19 vaccination program, which commenced in December 2020, has been instrumental in preventing morbidity and mortality from COVID-19 disease. Safety monitoring has been an essential component of the program. The federal government undertook a comprehensive and coordinated approach to implement complementary safety monitoring systems and to communicate findings in a timely and transparent way to healthcare providers, policymakers, and the public. Monitoring involved both well-established and newly developed systems that relied on both spontaneous (passive) and active surveillance methods. Clinical consultation for individual cases of adverse events following vaccination was performed, and monitoring of special populations, such as pregnant persons, was conducted. This report describes the U.S. government's COVID-19 vaccine safety monitoring systems and programs used by the Centers for Disease Control and Prevention, the U.S. Food and Drug Administration, the Department of Defense, the Department of Veterans Affairs, and the Indian Health Service. Using the adverse event of myocarditis following mRNA COVID-19 vaccination as a model, we demonstrate how the multiple, complementary monitoring systems worked to rapidly detect, assess, and verify a vaccine safety signal. In addition, longer-term follow-up was conducted to evaluate the recovery status of myocarditis cases following vaccination. Finally, the process for timely and transparent communication and dissemination of COVID-19 vaccine safety data is described, highlighting the responsiveness and robustness of the U.S. vaccine safety monitoring infrastructure during the national COVID-19 vaccination program. |
Crimean-Congo hemorrhagic fever virus diversity and reassortment, Pakistan, 2017-2020
Umair M , Rehman Z , Whitmer S , Mobley M , Fahim A , Ikram A , Salman M , Montgomery JM , Klena JD . Emerg Infect Dis 2024 30 (4) 654-664 Sporadic cases and outbreaks of Crimean-Congo hemorrhagic fever (CCHF) have been documented across Pakistan since 1976; however, data regarding the diversity of CCHF virus (CCHFV) in Pakistan is sparse. We whole-genome sequenced 36 CCHFV samples collected from persons infected in Pakistan during 2017-2020. Most CCHF cases were from Rawalpindi (n = 10), followed by Peshawar (n = 7) and Islamabad (n = 4). Phylogenetic analysis revealed the Asia-1 genotype was dominant, but 4 reassorted strains were identified. Strains with reassorted medium gene segments clustered with Asia-2 (n = 2) and Africa-2 (n = 1) genotypes; small segment reassortments clustered with the Asia-2 genotype (n = 2). Reassorted viruses showed close identity with isolates from India, Iran, and Tajikistan, suggesting potential crossborder movement of CCHFV. Improved and continuous human, tick, and animal surveillance is needed to define the diversity of circulating CCHFV strains in Pakistan and prevent transmission. |
Novel Oliveros-like Clade C mammarenaviruses from rodents in Argentina, 1990-2020
Shedroff E , Martin ML , Whitmer SLM , Brignone J , Garcia JB , Sen C , Nazar Y , Fabbri C , Morales-Betoulle M , Mendez J , Montgomery J , Morales MA , Klena JD . Viruses 2024 16 (3) Following an Argentine Hemorrhagic Fever (AHF) outbreak in the early 1990s, a rodent survey for Junín virus, a New World Clade B arenavirus, in endemic areas of Argentina was conducted. Since 1990, INEVH has been developing eco-epidemiological surveillance of rodents, inside and outside the Argentine Hemorrhagic Fever endemic area. Samples from rodents captured between 1993 and 2019 that were positive for Arenavirus infection underwent Sanger and unbiased, Illumina-based high-throughput sequencing, which yielded 5 complete and 88 partial Mammarenaviruses genomes. Previously, 11 genomes representing four species of New World arenavirus Clade C existed in public records. This work has generated 13 novel genomes, expanding the New World arenavirus Clade C to 24 total genomes. Additionally, two genomes exhibit sufficient genetic diversity to be considered a new species, as per ICTV guidelines (proposed name Mammarenavirus vellosense). The 13 novel genomes exhibited reassortment between the small and large segments in New World Mammarenaviruses. This work demonstrates that Clade C Mammarenavirus infections circulate broadly among Necromys species in the Argentine Hemorrhagic Fever endemic area; however, the risk for Clade C Mammarenavirus human infection is currently unknown. |
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 |
2020 Ebola virus disease outbreak in Équateur Province, Democratic Republic of the Congo: a retrospective genomic characterisation
Kinganda-Lusamaki E , Whitmer S , Lokilo-Lofiko E , Amuri-Aziza A , Muyembe-Mawete F , Makangara-Cigolo JC , Makaya G , Mbuyi F , Whitesell A , Kallay R , Choi M , Pratt C , Mukadi-Bamuleka D , Kavunga-Membo H , Matondo-Kuamfumu M , Mambu-Mbika F , Ekila-Ifinji R , Shoemaker T , Stewart M , Eng J , Rajan A , Soke GN , Fonjungo PN , Otshudiema JO , Folefack GLT , Pukuta-Simbu E , Talundzic E , Shedroff E , Bokete JL , Legand A , Formenty P , Mores CN , Porzucek AJ , Tritsch SR , Kombe J , Tshapenda G , Mulangu F , Ayouba A , Delaporte E , Peeters M , Wiley MR , Montgomery JM , Klena JD , Muyembe-Tamfum JJ , Ahuka-Mundeke S , Mbala-Kingebeni P . Lancet Microbe 2024 BACKGROUND: The Democratic Republic of the Congo has had 15 Ebola virus disease (EVD) outbreaks, from 1976 to 2023. On June 1, 2020, the Democratic Republic of the Congo declared an outbreak of EVD in the western Équateur Province (11th outbreak), proximal to the 2018 Tumba and Bikoro outbreak and concurrent with an outbreak in the eastern Nord Kivu Province. In this Article, we assessed whether the 11th outbreak was genetically related to previous or concurrent EVD outbreaks and connected available epidemiological and genetic data to identify sources of possible zoonotic spillover, uncover additional unreported cases of nosocomial transmission, and provide a deeper investigation into the 11th outbreak. METHODS: We analysed epidemiological factors from the 11th EVD outbreak to identify patient characteristics, epidemiological links, and transmission modes to explore virus spread through space, time, and age groups in the Équateur Province, Democratic Republic of the Congo. Trained field investigators and health professionals recorded data on suspected, probable, and confirmed cases, including demographic characteristics, possible exposures, symptom onset and signs and symptoms, and potentially exposed contacts. We used blood samples from individuals who were live suspected cases and oral swabs from individuals who were deceased to diagnose EVD. We applied whole-genome sequencing of 87 available Ebola virus genomes (from 130 individuals with EVD between May 19 and Sept 16, 2020), phylogenetic divergence versus time, and Bayesian reconstruction of phylogenetic trees to calculate viral substitution rates and study viral evolution. We linked the available epidemiological and genetic datasets to conduct a genomic and epidemiological study of the 11th EVD outbreak. FINDINGS: Between May 19 and Sept 16, 2020, 130 EVD (119 confirmed and 11 probable) cases were reported across 13 Équateur Province health zones. The individual identified as the index case reported frequent consumption of bat meat, suggesting the outbreak started due to zoonotic spillover. Sequencing revealed two circulating Ebola virus variants associated with this outbreak-a Mbandaka variant associated with the majority (97%) of cases and a Tumba-like variant with similarity to the ninth EVD outbreak in 2018. The Tumba-like variant exhibited a reduced substitution rate, suggesting transmission from a previous survivor of EVD. INTERPRETATION: Integrating genetic and epidemiological data allowed for investigative fact-checking and verified patient-reported sources of possible zoonotic spillover. These results demonstrate that rapid genetic sequencing combined with epidemiological data can inform responders of the mechanisms of viral spread, uncover novel transmission modes, and provide a deeper understanding of the outbreak, which is ultimately needed for infection prevention and control during outbreaks. FUNDING: WHO and US Centers for Disease Control and Prevention. |
A qualitative assessment of cleaning and hand hygiene practices at shelters serving people experiencing homelessness during the COVID-19 pandemic, Atlanta, GA - May-June, 2020
Besrat BN , Mosites E , Montgomery MP , Garcia-Williams AG , Trautner E , Clarke KEN , Marshall B , Vassell C , Rutt C , Jones SL . BMC Public Health 2024 24 (1) 247 BACKGROUND: Cleaning practices and hand hygiene are important behaviors to prevent and control the spread of infectious disease, especially in congregate settings. This project explored hygiene- and cleaning-related experiences in shelters serving people experiencing homelessness (PEH) during May-June 2020 of the COVID-19 pandemic. METHODS: We conducted qualitative, in-depth interviews by phone with 22 staff from six shelters in Atlanta, Georgia. The interview guide included questions about cleaning routines, cleaning barriers and facilitators, cleaning promotion, hand hygiene promotion, and hand hygiene barriers and facilitators. We analyzed interview transcripts using thematic analysis. RESULTS: Multiple individuals, such as shelter individuals (clients), volunteers, and staff, played a role in shelter cleaning. Staff reported engaging in frequent hand hygiene and cleaning practices. Barriers to cleaning included staffing shortages and access to cleaning supplies. Staff reported barriers (e.g., differing perceptions of cleanliness) for clients who were often involved in cleaning activities. Barriers to hand hygiene included limited time to wash hands, forgetting, and inconvenient handwashing facilities. Specific guidance about when and how to clean, and what supplies to use, were requested. CONCLUSION: During the early months of the COVID-19 pandemic, shelters serving PEH in the Atlanta-metro area needed resources and support to ensure sufficient staffing and supplies for cleaning activities. As part of future pandemic planning and outbreak prevention efforts, shelters serving PEH could benefit from specific guidance and training materials on cleaning and hand hygiene practices. |
Considerations for defining homelessness in public health data collection
Meehan AA , Waddell CJ , Marx GE , Clarke KEN , Bratcher A , Montgomery MP , Marcus R , Ramirez V , Mosites E . Public Health Rep 2023 333549231215850 Public health problems cannot be addressed without timely and accurate data. However, data that provide insight into populations that may be at disproportionate risk for disease, including people experiencing homelessness, are insufficiently captured. Although the associations between homelessness and disease have been well documented,1-6 data on housing status are not universally or consistently collected in routine public health data.7 Improving collection of data on housing status in public health data collection efforts is necessary to address health disparities among people experiencing homelessness and advance health equity research and practice. | Collecting data related to homelessness and disease is complicated for several reasons, but one of the most salient reasons is that defining homelessness is challenging. Several federal agencies use their own definitions to identify people who might be eligible for assistance programs, creating confusion about which definition should be used for public health purposes. In addition, definitions of homelessness at federal agencies have changed over time, further complicating the collection of homelessness data. The US Department of Housing and Urban Development (HUD) defines homelessness as lacking a fixed, regular, and adequate nighttime residence8; this definition includes both people with a primary nighttime residence of a public or private place not meant for human habitation (eg, cars, parks, public spaces, abandoned buildings) and people residing in temporary shelters (eg, emergency homeless shelter, transitional housing). The US Department of Education (DOE) uses a broader lens, defining homelessness to include school-aged children whose housing situation meets the HUD criteria for homelessness while also including those who share housing with other people by doubling up or couch surfing; those who live in motels, hotels, or trailer parks; and those who are abandoned at hospitals.9 |
The role of asymptomatic infections in influenza transmission: what do we really know
Montgomery MP , Morris SE , Rolfes MA , Kittikraisak W , Samuels AM , Biggerstaff M , Davis WW , Reed C , Olsen SJ . Lancet Infect Dis 2023 Before the COVID-19 pandemic, the role of asymptomatic influenza virus infections in influenza transmission was uncertain. However, the importance of asymptomatic infection with SARS-CoV-2 for onward transmission of COVID-19 has led experts to question whether the role of asymptomatic influenza virus infections in transmission had been underappreciated. We discuss the existing evidence on the frequency of asymptomatic influenza virus infections, the extent to which they contribute to infection transmission, and remaining knowledge gaps. We propose priority areas for further evaluation, study designs, and case definitions to address existing knowledge gaps. |
Characterization of humoral responses to Nipah virus infection in the Syrian Hamster model of disease
Scholte FEM , Rodriguez SE , Welch SR , Davies KA , Genzer SC , Coleman-McCray JD , Harmon JR , Sorvillo TE , Lo MK , Karaaslan E , Bergeron E , Montgomery JM , Spengler JR , Spiropoulou CF . J Infect Dis 2023 Nipah virus (NiV) is a highly pathogenic paramyxovirus. The Syrian hamster model recapitulates key features of human NiV disease and is a critical tool for evaluating antivirals and vaccines. Here we describe longitudinal humoral immune responses in NiV-infected Syrian hamsters. Samples were obtained 1-28 days after infection and analyzed by ELISA, neutralization, and Fc-mediated effector function assays. NiV infection elicited robust antibody responses against the nucleoprotein and attachment glycoprotein. Levels of neutralizing antibodies were modest and only detectable in surviving animals. Fc-mediated effector functions were mostly observed in nucleoprotein-targeting antibodies. Antibody levels and activities positively correlated with challenge dose. |
HantaNet: A new microbetrace application for hantavirus classification, genomic surveillance, epidemiology and outbreak investigations
Cintron R , Whitmer SLM , Moscoso E , Campbell EM , Kelly R , Talundzic E , Mobley M , Chiu KW , Shedroff E , Shankar A , Montgomery JM , Klena JD , Switzer WM . Viruses 2023 15 (11) Hantaviruses zoonotically infect humans worldwide with pathogenic consequences and are mainly spread by rodents that shed aerosolized virus particles in urine and feces. Bioinformatics methods for hantavirus diagnostics, genomic surveillance and epidemiology are currently lacking a comprehensive approach for data sharing, integration, visualization, analytics and reporting. With the possibility of hantavirus cases going undetected and spreading over international borders, a significant reporting delay can miss linked transmission events and impedes timely, targeted public health interventions. To overcome these challenges, we built HantaNet, a standalone visualization engine for hantavirus genomes that facilitates viral surveillance and classification for early outbreak detection and response. HantaNet is powered by MicrobeTrace, a browser-based multitool originally developed at the Centers for Disease Control and Prevention (CDC) to visualize HIV clusters and transmission networks. HantaNet integrates coding gene sequences and standardized metadata from hantavirus reference genomes into three separate gene modules for dashboard visualization of phylogenetic trees, viral strain clusters for classification, epidemiological networks and spatiotemporal analysis. We used 85 hantavirus reference datasets from GenBank to validate HantaNet as a classification and enhanced visualization tool, and as a public repository to download standardized sequence data and metadata for building analytic datasets. HantaNet is a model on how to deploy MicrobeTrace-specific tools to advance pathogen surveillance, epidemiology and public health globally. |
Seroepidemiological investigation of Crimean Congo hemorrhagic fever virus in livestock in Uganda, 2017
Nyakarahuka L , Kyondo J , Telford C , Whitesell A , Tumusiime A , Mulei S , Baluku J , Cossaboom CM , Cannon DL , Montgomery JM , Lutwama JJ , Nichol ST , Balinandi SK , Klena JD , Shoemaker TR . PLoS One 2023 18 (11) e0288587 Crimean-Congo Hemorrhagic fever (CCHF) is an important zoonotic disease transmitted to humans both by tick vectors and contact with fluids from an infected animal or human. Although animals are not symptomatic when infected, they are the main source of human infection. Uganda has reported sporadic human outbreaks of CCHF in various parts of the country since 2013. We designed a nationwide epidemiological study to investigate the burden of CCHF in livestock. A total of 3181 animals were sampled; 1732 cattle (54.4%), 1091 goats (34.3%), and 358 sheep (11.3%) resulting in overall livestock seropositivity of IgG antibodies against CCHF virus (CCHFV) of 31.4% (999/3181). Seropositivity in cattle was 16.9% and in sheep and goats was 48.8%. Adult and juvenile animals had higher seropositivity compared to recently born animals, and seropositivity was higher in female animals (33.5%) compared to male animals (24.1%). Local breeds had higher (36.8%) compared to exotic (2.8%) and cross breeds (19.3%). Animals that had a history of abortion or stillbirth had higher seropositivity compared to those without a history of abortion or stillbirth. CCHFV seropositivity appeared to be generally higher in northern districts of the country, though spatial trends among sampled districts were not examined. A multivariate regression analysis using a generalized linear mixed model showed that animal species, age, sex, region, and elevation were all significantly associated with CCHFV seropositivity after adjusting for the effects of other model predictors. This study shows that CCHFV is actively circulating in Uganda, posing a serious risk for human infection. The results from this study can be used to help target surveillance efforts for early case detection in animals and limit subsequent spillover into humans. |
Optimal reference genes for RNA tissue analysis in small animal models of hemorrhagic fever viruses
Davies KA , Welch SR , Sorvillo TE , Coleman-McCray JD , Martin ML , Brignone JM , Montgomery JM , Spiropoulou CF , Spengler JR . Sci Rep 2023 13 (1) 19384 Reverse-transcription quantitative polymerase chain reaction assays are frequently used to evaluate gene expression in animal model studies. Data analyses depend on normalization using a suitable reference gene (RG) to minimize effects of variation due to sample collection, sample processing, or experimental set-up. Here, we investigated the suitability of nine potential RGs in laboratory animals commonly used to study viral hemorrhagic fever infection. Using tissues (liver, spleen, gonad [ovary or testis], kidney, heart, lung, eye, brain, and blood) collected from naïve animals and those infected with Crimean-Congo hemorrhagic fever (mice), Nipah (hamsters), or Lassa (guinea pigs) viruses, optimal species-specific RGs were identified based on five web-based algorithms to assess RG stability. Notably, the Ppia RG demonstrated stability across all rodent tissues tested. Optimal RG pairs that include Ppia were determined for each rodent species (Ppia and Gusb for mice; Ppia and Hrpt for hamsters; and Ppia and Gapdh for guinea pigs). These RG pair assays were multiplexed with viral targets to improve assay turnaround time and economize sample usage. Finally, a pan-rodent Ppia assay capable of detecting Ppia across multiple rodent species was developed and successfully used in ecological investigations of field-caught rodents, further supporting its pan-species utility. |
In silico prediction of interaction between Nipah virus attachment glycoprotein and host cell receptors Ephrin-B2 and Ephrin-B3 in domestic and peridomestic mammals
Hoque AF , Rahman MDM , Lamia AS , Islam A , Klena JD , Satter SM , Epstein JH , Montgomery JM , Hossain ME , Shirin T , Jahid IK , Rahman MZ . Infect Genet Evol 2023 116 105516 Nipah virus (NiV) is a lethal bat-borne zoonotic virus that causes mild to acute respiratory distress and neurological manifestations in humans with a high mortality rate. NiV transmission to humans occurs via consumption of bat-contaminated fruit and date palm sap (DPS), or through direct contact with infected individuals and livestock. Since NiV outbreaks were first reported in pigs from Malaysia and Singapore, non-neutralizing antibodies against NiV attachment Glycoprotein (G) have also been detected in a few domestic mammals. NiV infection is initiated after NiV G binds to the host cell receptors Ephrin-B2 and Ephrin-B3. In this study, we assessed the degree of NiV host tropism in domestic and peridomestic mammals commonly found in Bangladesh that may be crucial in the transmission of NiV by serving as intermediate hosts. We carried out a protein-protein docking analysis of NiV G complexes (n = 52) with Ephrin-B2 and B3 of 13 domestic and peridomestic species using bioinformatics tools. Protein models were generated by homology modelling and the structures were validated for model quality. The different protein-protein complexes in this study were stable, and their binding affinity (ΔG) scores ranged between -8.0 to -19.1 kcal/mol. NiV Bangladesh (NiV-B) strain displayed stronger binding to Ephrin receptors, especially with Ephrin-B3 than the NiV Malaysia (NiV-M) strain, correlating with the observed higher pathogenicity of NiV-B strains. From the docking result, we found that Ephrin receptors of domestic rat (R. norvegicus) had a higher binding affinity for NiV G, suggesting greater susceptibility to NiV infections compared to other study species. Investigations for NiV exposure to domestic/peridomestic animals will help us knowing more the possible role of rats and other animals as intermediate hosts of NiV and would improve future NiV outbreak control and prevention in humans and domestic animals. |
Filoviruses: Scientific gaps and prototype pathogen recommendation
Dupuy LC , Spiropoulou CF , Towner JS , Spengler JR , Sullivan NJ , Montgomery JM . J Infect Dis 2023 228 S446-s459 Viruses in the family Filoviridae, including the commonly known Ebola (EBOV) and Marburg (MARV) viruses, can cause severe hemorrhagic fever in humans and nonhuman primates. Sporadic outbreaks of filovirus disease occur in sub-Saharan Africa with reported case fatality rates ranging from 25% to 90%. The high mortality and increasing frequency and magnitude of recent outbreaks along with the increased potential for spread from rural to urban areas highlight the importance of pandemic preparedness for these viruses. Despite their designation as high-priority pathogens, numerous scientific gaps exist in critical areas. In this review, these gaps and an assessment of potential prototype pathogen candidates are presented for this important virus family. |
Decolonization in nursing homes to prevent infection and hospitalization
Miller LG , McKinnell JA , Singh RD , Gussin GM , Kleinman K , Saavedra R , Mendez J , Catuna TD , Felix J , Chang J , Heim L , Franco R , Tjoa T , Stone ND , Steinberg K , Beecham N , Montgomery J , Walters D , Park S , Tam S , Gohil SK , Robinson PA , Estevez M , Lewis B , Shimabukuro JA , Tchakalian G , Miner A , Torres C , Evans KD , Bittencourt CE , He J , Lee E , Nedelcu C , Lu J , Agrawal S , Sturdevant SG , Peterson E , Huang SS . N Engl J Med 2023 389 (19) 1766-1777 BACKGROUND: Nursing home residents are at high risk for infection, hospitalization, and colonization with multidrug-resistant organisms. METHODS: We performed a cluster-randomized trial of universal decolonization as compared with routine-care bathing in nursing homes. The trial included an 18-month baseline period and an 18-month intervention period. Decolonization entailed the use of chlorhexidine for all routine bathing and showering and administration of nasal povidone-iodine twice daily for the first 5 days after admission and then twice daily for 5 days every other week. The primary outcome was transfer to a hospital due to infection. The secondary outcome was transfer to a hospital for any reason. An intention-to-treat (as-assigned) difference-in-differences analysis was performed for each outcome with the use of generalized linear mixed models to compare the intervention period with the baseline period across trial groups. RESULTS: Data were obtained from 28 nursing homes with a total of 28,956 residents. Among the transfers to a hospital in the routine-care group, 62.2% (the mean across facilities) were due to infection during the baseline period and 62.6% were due to infection during the intervention period (risk ratio, 1.00; 95% confidence interval [CI], 0.96 to 1.04). The corresponding values in the decolonization group were 62.9% and 52.2% (risk ratio, 0.83; 95% CI, 0.79 to 0.88), for a difference in risk ratio, as compared with routine care, of 16.6% (95% CI, 11.0 to 21.8; P<0.001). Among the discharges from the nursing home in the routine-care group, transfer to a hospital for any reason accounted for 36.6% during the baseline period and for 39.2% during the intervention period (risk ratio, 1.08; 95% CI, 1.04 to 1.12). The corresponding values in the decolonization group were 35.5% and 32.4% (risk ratio, 0.92; 95% CI, 0.88 to 0.96), for a difference in risk ratio, as compared with routine care, of 14.6% (95% CI, 9.7 to 19.2). The number needed to treat was 9.7 to prevent one infection-related hospitalization and 8.9 to prevent one hospitalization for any reason. CONCLUSIONS: In nursing homes, universal decolonization with chlorhexidine and nasal iodophor led to a significantly lower risk of transfer to a hospital due to infection than routine care. (Funded by the Agency for Healthcare Research and Quality; Protect ClinicalTrials.gov number, NCT03118232.). |
Recombinant Sudan virus and evaluation of humoral cross-reactivity between Ebola and Sudan virus glycoproteins after infection or rVSV-ΔG-ZEBOV-GP vaccination
Kainulainen MH , Harmon JR , Whitesell AN , Bergeron E , Karaaslan E , Cossaboom CM , Malenfant JH , Kofman A , Montgomery JM , Choi MJ , Albariño CG , Spiropoulou CF . Emerg Microbes Infect 2023 12 (2) 2265660 Ebola disease outbreaks are major public health events because of human-to-human transmission and high mortality. These outbreaks are most often caused by Ebola virus, but at least three related viruses can also cause the disease. In 2022, Sudan virus re-emerged causing more than 160 confirmed and probable cases. This report describes generation of a recombinant Sudan virus and demonstrates its utility by quantifying antibody cross-reactivity between Ebola and Sudan virus glycoproteins after human infection or vaccination with a licensed Ebola virus vaccine. |
Development of reverse genetic tools to study Chapare and Machupo viruses
Jain S , Shrivastava-Ranjan P , Flint M , Montgomery JM , Spiropoulou CF , Albariño CG . Virology 2023 588 109888 Arenaviruses are highly pathogenic viruses that pose a serious public health threat. Chapare virus (CHAV) and Machupo virus (MACV), two New World arenaviruses, cause hemorrhagic fevers with case fatality rates of up to 45%. Research on therapeutic drug targets and vaccines for these viruses is limited because biosafety level 4 containment is required for handling them. In this study, we developed reverse genetics systems, including minigenomes and recombinant viruses, that will facilitate the study of these pathogens. The minigenome system is based on the S segment of CHAV or MACV genomes expressing the fluorescent reporter gene ZsGreen (ZsG). We also generated recombinant CHAV and MACV with and without the ZsG reporter gene. As a proof-of-concept study, we used both minigenomes and recombinant viruses to test the inhibitory effects of previously reported antiviral compounds. The new reverse genetics system described here will facilitate future therapeutic studies for these two life-threatening arenaviruses. |
Tackling a global epidemic threat: Nipah surveillance in Bangladesh, 2006-2021
Satter SM , Aquib WR , Sultana S , Sharif AR , Nazneen A , Alam MR , Siddika A , Akther Ema F , Chowdhury KIA , Alam AN , Rahman M , Klena JD , Rahman MZ , Banu S , Shirin T , Montgomery JM . PLoS Negl Trop Dis 2023 17 (9) e0011617 Human Nipah virus (NiV) infection is an epidemic-prone disease and since the first recognized outbreak in Bangladesh in 2001, human infections have been detected almost every year. Due to its high case fatality rate and public health importance, a hospital-based Nipah sentinel surveillance was established in Bangladesh to promptly detect Nipah cases and respond to outbreaks at the earliest. The surveillance has been ongoing till present. The hospital-based sentinel surveillance was conducted at ten strategically chosen tertiary care hospitals distributed throughout Bangladesh. The surveillance staff ensured that routine screening, enrollment, data, and specimen collection from suspected Nipah cases were conducted daily. The specimens were then processed and transported to the reference laboratory of Institute of Epidemiology, Disease Control and Research (IEDCR) and icddr,b for confirmation of diagnosis through serology and molecular detection. From 2006 to 2021, through this hospital-based surveillance platform, 7,150 individuals were enrolled and tested for Nipah virus. Since 2001, 322 Nipah infections were identified in Bangladesh, 75% of whom were laboratory confirmed cases. Half of the reported cases were primary cases (162/322) having an established history of consuming raw date palm sap (DPS) or tari (fermented date palm sap) and 29% were infected through person-to-person transmission. Since the initiation of surveillance, 68% (218/322) of Nipah cases from Bangladesh have been identified from various parts of the country. Fever, vomiting, headache, fatigue, and increased salivation were the most common symptoms among enrolled Nipah patients. Till 2021, the overall case fatality rate of NiV infection in Bangladesh was 71%. This article emphasizes that the overall epidemiology of Nipah virus infection in Bangladesh has remained consistent throughout the years. This is the only systematic surveillance to detect human NiV infection globally. The findings from this surveillance have contributed to early detection of NiV cases in hospital settings, understanding of Nipah disease epidemiology, and have enabled timely public health interventions for prevention and containment of NiV infection. Although we still have much to learn regarding the transmission dynamics and risk factors of human NiV infection, surveillance has played a significant role in advancing our knowledge in this regard. |
Enhanced broad spectrum in vitro antiviral efficacy of 3-F-4-MeO-Bn, 3-CN, and 4-CN derivatives of lipid remdesivir nucleoside monophosphate prodrugs
McMillan RE , Lo MK , Zhang XQ , Beadle JR , Valiaeva N , Garretson AF , Clark AE , Freshman J , Murphy J , Montgomery JM , Spiropoulou CF , Schooley RT , Hostetler KY , Carlin AF . Antiviral Res 2023 219 105718 Broad spectrum oral antivirals are urgently needed for the early treatment of many RNA viruses of clinical concern. We previously described the synthesis of 1-O-octadecyl-2-O-benzyl-glycero-3-phospho-RVn (V2043), an orally bioavailable lipid prodrug of remdesivir nucleoside (RVn, GS-441524) with broad spectrum antiviral activity against viruses with pandemic potential. Here we compared the relative activity of V2043 with new RVn lipid prodrugs containing sn-1 alkyl ether or sn-2 glycerol modifications. We found that 3-F-4-MeO-Bn, 3-CN-Bn, and 4-CN-Bn sn-2 glycerol modifications improved antiviral activity compared to V2043 when tested in vitro against clinically important RNA viruses from 5 virus families. These results support the continued development of V2043 and sn-2 glycerol modified RVn lipid prodrugs for the treatment of a broad range of RNA viruses for which there are limited therapies. |
Molecular characterization of the 2022 Sudan virus disease outbreak in Uganda
Balinandi S , Whitmer S , Mulei S , Nassuna C , Pimundu G , Muyigi T , Kainulainen M , Shedroff E , Krapiunaya I , Scholte F , Nyakarahuka L , Tumusiime A , Kyondo J , Baluku J , Kiconco J , Harris JR , Ario AR , Kagirita A , Bosa HK , Ssewanyana I , Nabadda S , Mwebesa HG , Aceng JR , Atwine D , Lutwama JJ , Shoemaker TR , Montgomery JM , Kaleebu P , Klena JD . J Virol 2023 97 (10) e0059023 Uganda experienced five Ebola disease outbreaks caused by Bundibugyo virus (n = 1) and Sudan virus (SUDV) (n = 4) from 2000 to 2021. On 20 September 2022, Uganda declared a fifth Sudan virus disease outbreak in the Mubende district, resulting in 142 confirmed and 22 probable cases by the end of the outbreak declaration on 11 January 2023. The earliest identified cases, through retrospective case investigations, had onset in early August 2022. From the 142 confirmed cases, we performed unbiased (Illumina) and SUDV-amplicon-specific (Minion) high-throughput sequencing to obtain 120 SUDV genome-and coding-complete sequences, representing 95.4% (104/109) of SVD-confirmed individuals within a sequence-able range (Ct ≤30) and 10 genome sequences outside of this range and 6 duplicate genome sequences. A comparison of the nucleotide genetic relatedness for the newly emerged Mubende variant indicated that it was most closely related to the Nakisamata SUDV sequence from 2011, represented a likely new zoonotic spillover event, and exhibited an inter- and intra-outbreak substitution rate consistent with previous outbreaks. The most recent common ancestor for the Mubende variant was estimated to have occurred in October and November 2021. The Mubende variant glycoprotein amino acid sequences exhibited 99.7% similarity altogether and a maximum of 96.1% glycoprotein similarity compared to historical SUDV strains from 1976. Integrating the genetic sequence and epidemiological data into the response activities generated a broad overview of the outbreak, allowing for quick fact-checking of epidemiological connections between the identified patients. IMPORTANCE Ebola disease (EBOD) is a public health threat with a high case fatality rate. Most EBOD outbreaks have occurred in remote locations, but the 2013-2016 Western Africa outbreak demonstrated how devastating EBOD can be when it reaches an urban population. Here, the 2022 Sudan virus disease (SVD) outbreak in Mubende District, Uganda, is summarized, and the genetic relatedness of the new variant is evaluated. The Mubende variant exhibited 96% amino acid similarity with historic SUDV sequences from the 1970s and a high degree of conservation throughout the outbreak, which was important for ongoing diagnostics and highly promising for future therapy development. Genetic differences between viruses identified during the Mubende SVD outbreak were linked with epidemiological data to better interpret viral spread and contact tracing chains. This methodology should be used to better integrate discrete epidemiological and sequence data for future viral outbreaks. |
Hepatitis C cascades: Data to inform hepatitis C elimination in the United States
Montgomery MP , Randall LM , Morrison M , Gupta N , Doshani M , Teshale E . Public Health Rep 2023 333549231193508 The United States has a goal to eliminate hepatitis C as a public health threat by 2030. To accomplish this goal, hepatitis C virus (HCV) care cascades (hereinafter, HCV cascades) can be used to measure progress toward HCV elimination and identify disparities in HCV testing and care. In this topical review of HCV cascades, we describe common definitions of cascade steps, review the application of HCV cascades in health care and public health settings, and discuss the strengths and limitations of data sources used. We use examples from the Massachusetts Department of Public Health as a case study to illustrate how multiple data sources can be leveraged to produce HCV cascades for public health purposes. HCV cascades in health care settings provide actionable data to improve health care quality and delivery of services in a single health system. In public health settings at jurisdictional and national levels, HCV cascades describe HCV diagnosis and treatment for populations, which can be challenging in the absence of a single data source containing complete, comprehensive, and timely data representing all steps of a cascade. Use of multiple data sources and strategies to improve interoperability of health care and public health data systems can advance the use of HCV cascades and speed progress toward HCV elimination. |
Vaccination with the Crimean-Congo hemorrhagic fever virus viral replicon vaccine induces NP-based T-cell activation and antibodies possessing Fc-mediated effector functions
Scholte FEM , Karaaslan E , O'Neal TJ , Sorvillo TE , Genzer SC , Welch SR , Coleman-McCray JD , Spengler JR , Kainulainen MH , Montgomery JM , Pegan SD , Bergeron E , Spiropoulou CF . Front Cell Infect Microbiol 2023 13 1233148 Crimean-Congo hemorrhagic fever virus (CCHFV; family Nairoviridae) is a tick-borne pathogen that frequently causes lethal disease in humans. CCHFV has a wide geographic distribution, and cases have been reported in Africa, Asia, the Middle East, and Europe. Availability of a safe and efficacious vaccine is critical for restricting outbreaks and preventing disease in endemic countries. We previously developed a virus-like replicon particle (VRP) vaccine that provides complete protection against homologous and heterologous lethal CCHFV challenge in mice after a single dose. However, the immune responses induced by this vaccine are not well characterized, and correlates of protection remain unknown. Here we comprehensively characterized the kinetics of cell-mediated and humoral immune responses in VRP-vaccinated mice, and demonstrate that they predominantly target the nucleoprotein (NP). NP antibodies are not associated with protection through neutralizing activity, but VRP vaccination results in NP antibodies possessing Fc-mediated antibody effector functions, such as complement activation (ADCD) and antibody-mediated cellular phagocytosis (ADCP). This suggests that Fc-mediated effector functions may contribute to this vaccine's efficacy. |
Rio Negro virus infection, Bolivia, 2021
Loayza Mafayle R , Morales-Betoulle ME , Whitmer S , Cossaboom C , Revollo J , Loayza NM , Méndez HA , Chuquimia Valdez JA , Subieta FA , Espinoza Morales MX , Canedo Sánchez MV , Romero MER , Brault AC , Hugues HR , Mendez-Rico J , Malenfant JH , Shoemaker T , Klena JD , Montgomery JM , Marquina Salas JD . Emerg Infect Dis 2023 29 (8) 1705-1708 In May 2021, an agricultural worker originally from Trementinal, Argentina, sought treatment for febrile illness in Tarija, Bolivia, where he resided at the time of illness onset. The patient tested negative for hantavirus RNA, but next-generation sequencing of a serum sample yielded a complete genome for Rio Negro virus. |
Revisiting the minimum incubation period of Zaire ebolavirus
Kofman AD , Haberling DL , Mbuyi G , Martel LD , Whitesell AN , Van Herp M , Makaya G , Corvil S , Abedi AA , Ngoma PM , Mbuyi F , Mossoko M , Koivogui E , Soke N , Gbamou N , Fonjungo PN , Keita L , Keita S , Shoemaker TR , Richards GA , Montgomery JM , Breman JG , Geisbert TW , Choi MJ , Rollin PE . Lancet Infect Dis 2023 23 (10) 1111-1112 Ebola virus disease (EVD) caused by Ebola virus species Zaire ebolavirus (EBOV) is a major global health challenge causing sporadic outbreaks with high mortality. The minimum incubation period of EBOV, or the time from infection with the virus to the development of first symptoms, is thought to be 2 days and was initially established during the first EVD investigation in 1976.1 A published observation from the investigation noted that, “in one case of the disease, the only possible source of infection was contact with a probable case 48 hours before the latter developed symptoms”, and this observation was restated in another publication.2, 3 However, concluding that the minimum incubation period for EBOV is 2 days based on these reports is flawed for several reasons. First, the presumed source of the infection was a probable case of EVD and was not laboratory-confirmed; it is therefore uncertain whether the source truly had EVD. Second, since the report describes the contact between the source and the case occurring before the source developed symptoms, this implies asymptomatic transmission, which has been established to not occur with EBOV.4, 5, 6 Finally, the report's description of 48 h refers to the time between the case's contact with the alleged source and the source's onset of symptoms, which is itself not an incubation period. |
Perspectives on advancing countermeasures for filovirus disease: Report from a multi-sector meeting
Sprecher A , Cross R , Marzi A , Martins KA , Wolfe D , Montgomery JM , Spiropoulou CF , Cihlar T , Ahuka-Mundeke S , Nyhuis T , Teicher C , Crozier I , Strong J , Kobinger G , Woolsey C , Geisbert TW , Feldmann H , Muyembe JJ . J Infect Dis 2023 228 S474-S478 Although there are now approved treatments and vaccines for Ebola virus disease (EVD), the case fatality of EVD remains unacceptably high even when treated with the newly approved therapeutics; furthermore, these countermeasures are not expected to be effective against disease caused by other filoviruses. A meeting of subject matter experts from public health, research, and countermeasure development agencies and manufacturers was held during the 10th International Filovirus Symposium to discuss strategies to address these gaps, including how newer countermeasures could be advanced for field readiness. Several investigational therapeutics, vaccine candidates, and combination strategies were presented. In all, a common theme emerged: the greatest challenge to completing development was the implementation of well-designed clinical trials of safety and efficacy during filovirus disease outbreaks. These outbreaks are usually of short duration, providing but a brief opportunity for trials to be launched, and have too few cases to allow for full enrollment during a single outbreak, so clinical trials will necessarily need to span multiple outbreaks which may occur in a number of at-risk countries. Preparing for this will require agreed-upon common protocols for trials intended to bridge multiple outbreaks across all at-risk countries. A multi-national research consortium including, and led by, at-risk countries would be an ideal mechanism to negotiate agreement on protocol design and coordinate preparation. Discussion participants recommended a follow-up meeting be held in Africa with national public health and research agencies from at-risk countries to establish such a consortium. |
Infants admitted to US intensive care units for RSV infection during the 2022 seasonal peak
Halasa N , Zambrano LD , Amarin JZ , Stewart LS , Newhams MM , Levy ER , Shein SL , Carroll CL , Fitzgerald JC , Michaels MG , Bline K , Cullimore ML , Loftis L , Montgomery VL , Jeyapalan AS , Pannaraj PS , Schwarz AJ , Cvijanovich NZ , Zinter MS , Maddux AB , Bembea MM , Irby K , Zerr DM , Kuebler JD , Babbitt CJ , Gaspers MG , Nofziger RA , Kong M , Coates BM , Schuster JE , Gertz SJ , Mack EH , White BR , Harvey H , Hobbs CV , Dapul H , Butler AD , Bradford TT , Rowan CM , Wellnitz K , Staat MA , Aguiar CL , Hymes SR , Randolph AG , Campbell AP . JAMA Netw Open 2023 6 (8) e2328950 IMPORTANCE: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide. OBJECTIVE: To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection. EXPOSURE: Respiratory syncytial virus. MAIN OUTCOMES AND MEASURES: Data were captured on demographics, clinical characteristics, signs and symptoms, laboratory values, severity measures, and clinical outcomes, including receipt of noninvasive respiratory support, invasive mechanical ventilation, vasopressors or extracorporeal membrane oxygenation, and death. Mixed-effects multivariable log-binomial regression models were used to assess associations between intubation status and demographic factors, gestational age, and underlying conditions, including hospital as a random effect to account for between-site heterogeneity. RESULTS: The first 15 to 20 consecutive eligible infants from each site were included for a target sample size of 600. Among the 600 infants, the median (IQR) age was 2.6 (1.4-6.0) months; 361 (60.2%) were male, 169 (28.9%) were born prematurely, and 487 (81.2%) had no underlying medical conditions. Primary reasons for admission included LRTI (594 infants [99.0%]) and apnea or bradycardia (77 infants [12.8%]). Overall, 143 infants (23.8%) received invasive mechanical ventilation (median [IQR], 6.0 [4.0-10.0] days). The highest level of respiratory support for nonintubated infants was high-flow nasal cannula (243 infants [40.5%]), followed by bilevel positive airway pressure (150 infants [25.0%]) and continuous positive airway pressure (52 infants [8.7%]). Infants younger than 3 months, those born prematurely (gestational age <37 weeks), or those publicly insured were at higher risk for intubation. Four infants (0.7%) received extracorporeal membrane oxygenation, and 2 died. The median (IQR) length of hospitalization for survivors was 5 (4-10) days. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, most US infants who required intensive care for RSV LRTIs were young, healthy, and born at term. These findings highlight the need for RSV preventive interventions targeting all infants to reduce the burden of severe RSV illness. |
Retrospective evaluation of an integrated molecular-epidemiological approach to cyclosporiasis outbreak investigations - United States, 2021
Ahart L , Jacobson D , Rice M , Richins T , Peterson A , Zheng Y , Barratt J , Cama V , Qvarnstrom Y , Montgomery S , Straily A . Epidemiol Infect 2023 151 e131 Cyclosporiasis results from an infection of the small intestine by Cyclospora parasites after ingestion of contaminated food or water, often leading to gastrointestinal distress. Recent developments in temporally linking genetically related Cyclospora isolates demonstrated effectiveness in supporting epidemiological investigations. We used 'temporal-genetic clusters' (TGCs) to investigate reported cyclosporiasis cases in the United States during the 2021 peak-period (1 May - 31 August 2021). Our approach split 655 genotyped isolates into 55 genetic clusters and 31 TGCs. We linked two large multi-state epidemiological clusters (Epidemiologic Cluster 1 [n = 136 cases, 54 genotyped] and Epidemiologic Cluster 2 [n = 42 cases, 15 genotyped]) to consumption of lettuce varieties; however, product traceback did not identify a specific product for either cluster due to the lack of detailed product information. To evaluate the utility of TGCs, we performed a retrospective case study comparing investigation outcomes of outbreaks first detected using epidemiological methods with those of the same outbreaks had TGCs been used to first detect them. Our study results indicate that adjustments to routine epidemiological approaches could link additional cases to epidemiological clusters of cyclosporiasis. Overall, we show that CDC's integrated genotyping and epidemiological investigations provide valuable insights into cyclosporiasis outbreaks in the United States. |
Single-dose mucosal replicon-particle vaccine protects against lethal Nipah virus infection up to 3 days after vaccination
Welch SR , Spengler JR , Genzer SC , Coleman-McCray JD , Harmon JR , Sorvillo TE , Scholte FEM , Rodriguez SE , O'Neal TJ , Ritter JM , Ficarra G , Davies KA , Kainulainen MH , Karaaslan E , Bergeron É , Goldsmith CS , Lo MK , Nichol ST , Montgomery JM , Spiropoulou CF . Sci Adv 2023 9 (31) eadh4057 Nipah virus (NiV) causes a highly lethal disease in humans who present with acute respiratory or neurological signs. No vaccines against NiV have been approved to date. Here, we report on the clinical impact of a novel NiV-derived nonspreading replicon particle lacking the fusion (F) protein gene (NiVΔF) as a vaccine in three small animal models of disease. A broad antibody response was detected that included immunoglobulin G (IgG) and IgA subtypes with demonstrable Fc-mediated effector function targeting multiple viral antigens. Single-dose intranasal vaccination up to 3 days before challenge prevented clinical signs and reduced virus levels in hamsters and immunocompromised mice; decreases were seen in tissues and mucosal secretions, critically decreasing potential for virus transmission. This virus replicon particle system provides a vital tool to the field and demonstrates utility as a highly efficacious and safe vaccine candidate that can be administered parenterally or mucosally to protect against lethal Nipah disease. |
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