Last data update: Nov 04, 2024. (Total: 48056 publications since 2009)
Records 1-30 (of 105 Records) |
Query Trace: Padilla M[original query] |
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Sentinel Surveillance reveals phylogenetic diversity and detection of linear plasmids harboring vanA and optrA among enterococci collected in the United States
Kent AG , Spicer LM , Campbell D , Breaker E , McAllister GA , Ewing TO , Longo C , Balbuena R , Burroughs M , Burgin A , Padilla J , Johnson JK , Halpin AL , McKay SL , Rasheed JK , Elkins CA , Karlsson M , Lutgring JD , Gargis AS . Antimicrob Agents Chemother 2024 e0059124 Enterococcus faecalis and Enterococcus faecium are frequent causes of healthcare-associated infections. Antimicrobial-resistant enterococci pose a serious public health threat, particularly vancomycin-resistant enterococci (VRE), for which treatment options are limited. The Centers for Disease Control and Prevention's Division of Healthcare Quality Promotion Sentinel Surveillance system conducted surveillance from 2018 to 2019 to evaluate antimicrobial susceptibility profiles and molecular epidemiology of 205 E. faecalis and 180 E. faecium clinical isolates collected from nine geographically diverse sites in the United States. Whole genome sequencing revealed diverse genetic lineages, with no single sequence type accounting for more than 15% of E. faecalis or E. faecium. Phylogenetic analysis distinguished E. faecium from 19 E. lactis (previously known as E. faecium clade B). Resistance to vancomycin was 78.3% among E. faecium, 7.8% among E. faecalis, and did not occur among E. lactis isolates. Resistance to daptomycin and linezolid was rare: E. faecium (5.6%, 0.6%, respectively), E. faecalis (2%, 2%), and E. lactis (5.3%, 0%). All VRE harbored the vanA gene. Three of the seven isolates that were not susceptible to linezolid harbored optrA, one chromosomally located and two on linear plasmids that shared a conserved backbone with other multidrug-resistant conjugative linear plasmids. One of these isolates contained optrA and vanA co-localized on the linear plasmid. By screening all enterococci, 20% of E. faecium were predicted to harbor linear plasmids, whereas none were predicted among E. faecalis or E. lactis. Continued surveillance is needed to assess the future emergence and spread of antimicrobial resistance by linear plasmids and other mechanisms.IMPORTANCEThis work confirms prior reports of E. faecium showing higher levels of resistance to more antibiotics than E. faecalis and identifies that diverse sequence types are contributing to enterococcal infections in the United States. All VRE harbored the vanA gene. We present the first report of the linezolid resistance gene optrA on linear plasmids in the United States, one of which co-carried a vanA cassette. Additional studies integrating epidemiological, antimicrobial susceptibility, and genomic methods to characterize mechanisms of resistance, including the role of linear plasmids, will be critical to understanding the changing landscape of enterococci in the United States. |
Notes from the field: Prevalence of previous dengue virus infection among children and adolescents aged 7-16 years - American Samoa, September-October 2023
Kiplagat S , Tavale N , Konrote A , Johansson AM , Papu A , Perez-Padilla J , Jones FK , Desale H , Ilimaleota AF , Tulafono JM , Delorey M , Jones E , Chutaro E , Camacho J , Medina F , Tosado-Acevedo R , Munoz-Jordan JL , Paz-Bailey G , Adams LE , Nua MT , Wong JM , Anesi S . MMWR Morb Mortal Wkly Rep 2024 73 (31) 686-688 |
Diagnostic accuracy of the Abbott BinaxNOW COVID-19 antigen card test, Puerto Rico
Madewell ZJ , Major CG , Graff N , Adams C , Rodriguez DM , Morales T , Medina Lopes NA , Tosado R , Sánchez-González L , Perez-Padilla J , Volkman HR , Bertrán-Pasarell J , Sainz de la Peña D , Munoz-Jordan J , Santiago GA , Lorenzi O , Rivera-Amill V , Rolfes MA , Paz-Bailey G , Adams LE , Wong JM . Influenza Other Respir Viruses 2024 18 (7) e13305 BACKGROUND: The COVID-19 pandemic underscored the need for rapid and accurate diagnostic tools. In August 2020, the Abbott BinaxNOW COVID-19 Antigen Card test became available as a timely and affordable alternative for SARS-CoV-2 molecular testing, but its performance may vary due to factors including timing and symptomatology. This study evaluates BinaxNOW diagnostic performance in diverse epidemiological contexts. METHODS: Using RT-PCR as reference, we assessed performance of the BinaxNOW COVID-19 test for SARS-CoV-2 detection in anterior nasal swabs from participants of two studies in Puerto Rico from December 2020 to May 2023. Test performance was assessed by days post symptom onset, collection strategy, vaccination status, symptomatology, repeated testing, and RT-PCR cycle threshold (Ct) values. RESULTS: BinaxNOW demonstrated an overall sensitivity of 84.1% and specificity of 98.8%. Sensitivity peaked within 1-6 days after symptom onset (93.2%) and was higher for symptomatic (86.3%) than asymptomatic (67.3%) participants. Sensitivity declined over the course of infection, dropping from 96.3% in the initial test to 48.4% in testing performed 7-14 days later. BinaxNOW showed 99.5% sensitivity in participants with low Ct values (≤ 25) but lower sensitivity (18.2%) for participants with higher Cts (36-40). CONCLUSIONS: BinaxNOW demonstrated high sensitivity and specificity, particularly in early-stage infections and symptomatic participants. In situations where test sensitivity is crucial for clinical decision-making, nucleic acid amplification tests are preferred. These findings highlight the importance of considering clinical and epidemiological context when interpreting test results and emphasize the need for ongoing research to adapt testing strategies to emerging SARS-CoV-2 variants. |
Sentinel enhanced dengue surveillance system - Puerto Rico, 2012-2022
Madewell ZJ , Hernandez-Romieu AC , Wong JM , Zambrano LD , Volkman HR , Perez-Padilla J , Rodriguez DM , Lorenzi O , Espinet C , Munoz-Jordan J , Frasqueri-Quintana VM , Rivera-Amill V , Alvarado-Domenech LI , Sainz D , Bertran J , Paz-Bailey G , Adams LE . MMWR Surveill Summ 2024 73 (3) 1-29 PROBLEM/CONDITION: Dengue is the most prevalent mosquitoborne viral illness worldwide and is endemic in Puerto Rico. Dengue's clinical spectrum can range from mild, undifferentiated febrile illness to hemorrhagic manifestations, shock, multiorgan failure, and death in severe cases. The disease presentation is nonspecific; therefore, various other illnesses (e.g., arboviral and respiratory pathogens) can cause similar clinical symptoms. Enhanced surveillance is necessary to determine disease prevalence, to characterize the epidemiology of severe disease, and to evaluate diagnostic and treatment practices to improve patient outcomes. The Sentinel Enhanced Dengue Surveillance System (SEDSS) was established to monitor trends of dengue and dengue-like acute febrile illnesses (AFIs), characterize the clinical course of disease, and serve as an early warning system for viral infections with epidemic potential. REPORTING PERIOD: May 2012-December 2022. DESCRIPTION OF SYSTEM: SEDSS conducts enhanced surveillance for dengue and other relevant AFIs in Puerto Rico. This report includes aggregated data collected from May 2012 through December 2022. SEDSS was launched in May 2012 with patients with AFIs from five health care facilities enrolled. The facilities included two emergency departments in tertiary acute care hospitals in the San Juan-Caguas-Guaynabo metropolitan area and Ponce, two secondary acute care hospitals in Carolina and Guayama, and one outpatient acute care clinic in Ponce. Patients arriving at any SEDSS site were eligible for enrollment if they reported having fever within the past 7 days. During the Zika epidemic (June 2016-June 2018), patients were eligible for enrollment if they had either rash and conjunctivitis, rash and arthralgia, or fever. Eligibility was expanded in April 2020 to include reported cough or shortness of breath within the past 14 days. Blood, urine, nasopharyngeal, and oropharyngeal specimens were collected at enrollment from all participants who consented. Diagnostic testing for dengue virus (DENV) serotypes 1-4, chikungunya virus, Zika virus, influenza A and B viruses, SARS-CoV-2, and five other respiratory viruses was performed by the CDC laboratory in San Juan. RESULTS: During May 2012-December 2022, a total of 43,608 participants with diagnosed AFI were enrolled in SEDSS; a majority of participants (45.0%) were from Ponce. During the surveillance period, there were 1,432 confirmed or probable cases of dengue, 2,293 confirmed or probable cases of chikungunya, and 1,918 confirmed or probable cases of Zika. The epidemic curves of the three arboviruses indicate dengue is endemic; outbreaks of chikungunya and Zika were sporadic, with case counts peaking in late 2014 and 2016, respectively. The majority of commonly identified respiratory pathogens were influenza A virus (3,756), SARS-CoV-2 (1,586), human adenovirus (1,550), respiratory syncytial virus (1,489), influenza B virus (1,430), and human parainfluenza virus type 1 or 3 (1,401). A total of 5,502 participants had confirmed or probable arbovirus infection, 11,922 had confirmed respiratory virus infection, and 26,503 had AFI without any of the arboviruses or respiratory viruses examined. INTERPRETATION: Dengue is endemic in Puerto Rico; however, incidence rates varied widely during the reporting period, with the last notable outbreak occurring during 2012-2013. DENV-1 was the predominant virus during the surveillance period; sporadic cases of DENV-4 also were reported. Puerto Rico experienced large outbreaks of chikungunya that peaked in 2014 and of Zika that peaked in 2016; few cases of both viruses have been reported since. Influenza A and respiratory syncytial virus seasonality patterns are distinct, with respiratory syncytial virus incidence typically reaching its annual peak a few weeks before influenza A. The emergence of SARS-CoV-2 led to a reduction in the circulation of other acute respiratory viruses. PUBLIC HEALTH ACTION: SEDSS is the only site-based enhanced surveillance system designed to gather information on AFI cases in Puerto Rico. This report illustrates that SEDSS can be adapted to detect dengue, Zika, chikungunya, COVID-19, and influenza outbreaks, along with other seasonal acute respiratory viruses, underscoring the importance of recognizing signs and symptoms of relevant diseases and understanding transmission dynamics among these viruses. This report also describes fluctuations in disease incidence, highlighting the value of active surveillance, testing for a panel of acute respiratory viruses, and the importance of flexible and responsive surveillance systems in addressing evolving public health challenges. Various vector control strategies and vaccines are being considered or implemented in Puerto Rico, and data from ongoing trials and SEDSS might be integrated to better understand epidemiologic factors underlying transmission and risk mitigation approaches. Data from SEDSS might guide sampling strategies and implementation of future trials to prevent arbovirus transmission, particularly during the expansion of SEDSS throughout the island to improve geographic representation. |
Outbreak of fusarium solani meningitis in immunocompetent persons associated with neuraxial blockade in Durango, Mexico, 2022-2023
García-Rodríguez G , Duque-Molina C , Kondo-Padilla I , Zaragoza-Jiménez CA , González-Cortés VB , Flores-Antonio R , Villa-Reyes T , Vargas-Rubalcava A , Ruano-Calderon LÁ , Tinoco-Favila JC , Sánchez-Salazar HC , Rivas-Ruiz R , Castro-Escamilla O , Martínez-Gamboa RA , González-Lara F , López-Martínez I , Chiller TM , Pelayo R , Bonifaz LC , Robledo-Aburto Z , Alcocer-Varela J . Open Forum Infect Dis 2024 11 (2) ofad690 BACKGROUND: Fungal meningitis can be associated with epidural anesthesia procedures. Fusariosis is a rare infection typically affecting immunocompromised patients and rarely causes meningitis. During 2022-2023, public health officials responded to a large outbreak of Fusarium solani meningitis associated with epidural anesthesia in Durango, Mexico. METHODS: The public health response and epidemiological and clinical features of patients affected by this outbreak were described. Coordinated actions were addressed to identify the etiological agent, determine its drug susceptibility, develop diagnostic tests, and implement clinical and epidemiological protocols. Retrospective analyses of clinical variables and outcomes were performed to determine association with better patient survival. RESULTS: A total of 1801 persons exposed to epidural anesthesia were identified, of whom 80 developed meningitis. Fusarium solani was found in 3 brain biopsies and showed susceptibility to voriconazole and amphotericin B. After F solani polymerase chain reaction (PCR) implementation, 57 patients with meningitis were PCR-screened, and 31 (38.8%) had a positive result. Most patients were female (95%), and cesarean section was the most common surgical procedure (76.3%). The case fatality rate was 51.3% (41 patients) and the median hospitalization duration was 39.5 days (interquartile range, 18-86 days). Seventy-one patients (88.8%) received voriconazole/amphotericin B and 64 subjects (80%) additionally received steroids. Cox regression analysis showed an increased lethality risk in patients who received antifungal treatment after 5 days (hazard ratio, 2.1 [95% confidence interval, 1.01-4.48], P < .05). CONCLUSIONS: The F solani meningitis outbreak in Durango was an unprecedented medical challenge. Timely treatment and effective healthcare management were associated with better survival outcomes. |
Notes from the field: Dengue outbreak - Peru, 2023
Munayco CV , Valderrama Rosales BY , Mateo Lizarbe SY , Yon Fabian CR , Peña Sánchez R , Vásquez Sánchez CH , García MP , Padilla-Rojas C , Suárez V , Sánchez-González L , Jones FK , Kohatsu L , Adams LE , Morgan J , Paz-Bailey G . MMWR Morb Mortal Wkly Rep 2024 73 (4) 86-88 |
Barriers and facilitators to HIV service access among Hispanic/Latino gay, bisexual, and other men who have sex with men in metropolitan Atlanta-a qualitative analysis
Hassan R , Saldana CS , Garlow EW , Gutierrez M , Hershow RB , Elimam D , Adame JF , Andía JF , Padilla M , Gonzalez Jimenez N , Freeman D , Johnson EN , Reed K , Holland DP , Orozco H , Pedraza G , Hayes C , Philpott DC , Curran KG , Wortley P , Agnew-Brune C , Gettings JR . J Urban Health 2023 100 (6) 1193-1201 Hispanic/Latino persons are disproportionately impacted by HIV in the US, and HIV diagnoses among Hispanic/Latino men in Georgia have increased over the past decade, particularly in metropolitan Atlanta. In 2022, the Georgia Department of Public Health detected five clusters of rapid HIV transmission centered among Hispanic/Latino gay, bisexual, and other men who have sex with men (HLMSM) in metropolitan Atlanta. We conducted in-depth interviews with 65 service providers and 29 HLMSM to identify barriers and facilitators to HIV service access for HLMSM. Interviews were audio recorded, transcribed, and translated, if needed. Initial data analyses were conducted rapidly in the field to inform public health actions. We then conducted additional analyses including line-by-line coding of the interview transcripts using a thematic analytic approach. We identified four main themes. First, inequity in language access was a predominant barrier. Second, multiple social and structural barriers existed. Third, HLMSM encountered intersectional stigma. Finally, the HLMSM community is characterized by its diversity, and there is not a one-size-fits-all approach to providing appropriate care to this population. The collection of qualitative data during an HIV cluster investigation allowed us to quickly identity barriers experienced by HLMSM when accessing HIV and other medical care, to optimize public health response and action. Well-designed program evaluation and implementation research may help elucidate specific strategies and tools to reduce health disparities, ensure equitable service access for HLMSM, and reduce HIV transmission in this population. |
Evaluation of the durability of long-lasting insecticidal nets in Guatemala (preprint)
Castellanos ME , Rodas S , Juárez JG , Lol JC , Chanquin S , Morales Z , Vizcaino L , Smith SC , Vanden Eng J , Woldu HG , Lenhart A , Padilla N . medRxiv 2020 2020.07.30.20165316 Background Insecticide-treated bednets (ITNs) are widely used for the prevention and control of malaria. In Guatemala, since 2006, ITNs have been distributed free of charge in the highest risk malaria-endemic areas and constitute one of the primary vector control measures in the country. Despite relying on ITNs for almost 15 years, there is a lack of data to inform the timely replacement of ITNs whose effectiveness becomes diminished by routine use.Methods We assessed the survivorship, physical integrity, insecticide content and bio-efficacy of ITNs through cross-sectional surveys conducted at 18, 24 and 32 months after a 2012 distribution of PermaNet® 2.0 in a malaria focus in Guatemala. A total of 988 ITNs were analyzed (290 at 18 months, 349 at 24 months and 349 at 32 months).Results The functional survivorship of bednets decreased over time, from 92% at 18 months, to 81% at 24 months and 69% at 32 months. Independent of the time of the survey, less than 80% of the bednets that were still present in the household were reported to have been used the night before. Most of the bednets had been washed at least once (88% at 18 months, 92% at 24 months and 96% at 32 months). The proportion of bednets categorized as “in good condition” per WHO guidelines of the total hole surface area, diminished from 77% at 18 months to 58% at 32 months. The portion of ITNs with deltamethrin concentration less than 10mg/m2 increased over time (14% at 18 months, 23% at 24 months, and 35% at 32 months). Among the bednets for which bioassays were conducted, the percentage that met WHO criteria for efficacy dropped from 90% at 18 months to 52% at 32 months.Conclusion While our assessment demonstrated that nets were in relatively good physical condition over time, the combination of declining bio-efficacy over time and low use rates limited the overall effectiveness of the LLINs. Efforts to encourage the community to retain, use, and properly care for the LLINs may improve their impact. Durability assessments should be included in future campaigns.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThe funding for this study was provided by the United States Agency for International Development (USAID) via the Amazon Malaria Initiative (AMI), Centers for Disease Control and Prevention (CDC) of the United States of America, Guatemalan Ministry of Public Health and Social Welfare and Center for Health Studies and Universidad del Valle de Guatemala. The funding bodies had no role in the design of the study and collection, analysis, and interpretation of the data and in writing the manuscript.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Oral informed consent was obtained from all participants prior to study inclusion. This study was approved by the Ethics Committee of the Center for Health Studies at Universidad del Valle de Guatemala (Approval Number: 081-06-2013); CDC investigators were not considered to be engaged in human subjects research.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe data that support the findings of this study are availa le on request from the senior author, NP. The data are not publicly available due to containing information that could compromise the privacy of participants.GISgeographic information systemGISgeographic information systemGPSGlobal positioning systemIQRinterquartile rangeITNInsecticide-treated bednetLLINlong-lasting insecticide-treated bednetLOESSLocally Weighted Scatterplot SmoothingMoHMinistry of HealthPDApersonal digital assistantTHSAtotal hole surface areatmmedian survival timeWHOWorld Health OrganizationXRFx-ray fluorescence |
Geographic heterogeneity in Anopheles albimanus microbiota is lost within one generation of laboratory colonization (preprint)
Dada N , Benedict AC , López F , Lol JC , Sheth M , Dzuris N , Padilla N , Lenhart A . bioRxiv 2020 2020.06.02.129619 Research on mosquito-microbe interactions may lead to new tools for mosquito and mosquito-borne disease control. To date, such research has largely utilized laboratory-reared mosquitoes that may lack the microbial diversity of wild populations. To better understand how mosquito microbiota may vary across different geographic locations and upon laboratory colonization, we characterized the microbiota of F1 progeny of wild-caught adult Anopheles albimanus from four locations in Guatemala using high throughput 16S rRNA amplicon sequencing. A total of 132 late instar larvae and 135 2-5day old, non-blood-fed virgin adult females were reared under identical laboratory conditions, pooled (3 individuals/pool) and analyzed. Larvae from mothers collected at different sites showed different microbial compositions (p=0.001; F = 9.5), but these differences were no longer present at the adult stage (p=0.12; F = 1.6). This indicates that mosquitoes retain a significant portion of their field-derived microbiota throughout immature development but shed them before or during adult eclosion. This is the first time the microbiota of F1 progeny of wild-caught mosquitoes has been characterized in relation to parental collection site, and our findings provide evidence that geographically associated heterogeneity in microbiota composition persists for a single generation, but only until the end of the larval stage. These findings advance our understanding of how the mosquito microbiota is altered upon first laboratory colonization, and raises considerations for how mosquito microbiome research may be extended beyond the laboratory to field settings.Competing Interest StatementThe authors have declared no competing interest. |
Pyrethroid exposure alters Anopheles albimanus microbiota and resistant mosquitoes harbor more insecticide-metabolizing bacteria (preprint)
Dada N , Lol JC , Benedict AC , Lopez F , Sheth M , Dzuris N , Padilla N , Lenhart A . bioRxiv 2019 537480 A deeper understanding of the mechanisms underlying insecticide resistance is needed to mitigate its threat to malaria vector control. Building upon our earlier identified associations between mosquito microbiota and insecticide resistance, we demonstrate for the first time, type-specific effects of pyrethroid exposure on internal and cuticle surface bacteria in adult progeny of field-collected Anopheles albimanus. In contrast, larval cuticle surface—but not internal—bacteria were affected by pyrethroid exposure. Being over five-folds more abundant in pyrethroid resistant adults, as compared to susceptible or non-insecticide-exposed mosquitoes, Klebsiella (alphacypermethrin), Pantoea and Asaia (permethrin) were identified as potential markers of pyrethroid resistance in An. albimanus. We also show for the first time that An. albimanus larvae and adult cuticles harbor more diverse bacterial communities than their internal microbial niches. Our findings indicate insecticide selection pressures on mosquito microbiota, and support the hypothesis of an undescribed microbe-mediated mechanism of insecticide metabolism in mosquitoes. |
Effectiveness of 2 and 3 mRNA COVID-19 Vaccines Doses against Omicron and Delta-Related Outpatient Illness among Adults, October 2021 - February 2022 (preprint)
Kim SS , Chung JR , Talbot HK , Grijalva CG , Wernli KJ , Martin ET , Monto AS , Belongia EA , McLean HQ , Gaglani M , Mamawala M , Nowalk MP , Geffel KM , Tartof SY , Florea A , Lee JS , Tenforde MW , Patel MM , Flannery B , Bentz ML , Burgin A , Burroughs M , Davis ML , Howard D , Lacek K , Madden JC , Nobles S , Padilla J , Sheth M , Arroliga A , Beeram M , Dunnigan K , Ettlinger J , Graves A , Hoffman E , Jatla M , McKillop A , Murthy K , Mutnal M , Priest E , Raiyani C , Rao A , Requenez L , Settele N , Smith M , Stone K , Thomas J , Volz M , Walker K , Zayed M , Annan E , Daley P , Kniss K , Merced-Morales A , Ayala E , Amundsen B , Aragones M , Calderon R , Hong V , Jimenez G , Kim J , Ku J , Lewin B , McDaniel A , Reyes A , Shaw S , Takhar H , Torres A , Burganowski R , Kiniry E , Moser KA , Nguyen M , Park S , Wellwood S , Wickersham B , Alvarado-Batres J , Benz S , Berger H , Bissonnette A , Blake J , Boese K , Botten E , Boyer J , Braun M , Breu B , Burbey G , Cravillion C , Delgadillo C , Donnerbauer A , Dziedzic T , Eddy J , Edgren H , Ermeling A , Ewert K , Fehrenbach C , Fernandez R , Frome W , Guzinski S , Heeren L , Herda D , Hertel M , Heuer G , Higdon E , Ivacic L , Jepsen L , Kaiser S , Karl J , Keffer B , King J , Koepel TK , Kohl S , Kohn S , Kohnhorst D , Kronholm E , Le T , Lemieux A , Marcis C , Maronde M , McCready I , McGreevey K , Meece J , Mehta N , Miesbauer D , Moon V , Moran J , Nikolai C , Olson B , Olstadt J , Ott L , Pan N , Pike C , Polacek D , Presson M , Price N , Rayburn C , Reardon C , Rotar M , Rottscheit C , Salzwedel J , Saucedo J , Scheffen K , Schug C , Seyfert K , Shrestha R , Slenczka A , Stefanski E , Strupp M , Tichenor M , Watkins L , Zachow A , Zimmerman B , Bauer S , Beney K , Cheng CK , Faraj N , Getz A , Grissom M , Groesbeck M , Harrison S , Henson K , Jermanus K , Johnson E , Kaniclides A , Kimberly A , Lamerato LE , Lauring A , Lehmann-Wandell R , McSpadden EJ , Nabors L , Truscon R , Balasubramani GK , Bear T , Bobeck J , Bowser E , Clarke K , Clarke LG , Dauer K , Deluca C , Dierks B , Haynes L , Hickey R , Johnson M , Jonsson A , Luosang N , McKown L , Peterson A , Phaturos D , Rectenwald A , Sax TM , Stiegler M , Susick M , Suyama J , Taylor L , Walters S , Weissman A , Williams JV , Blair M , Carter J , Chappell J , Copen E , Denney M , Graes K , Halasa N , Lindsell C , Liu Z , Longmire S , McHenry R , Short L , Tan HN , Vargas D , Wrenn J , Wyatt D , Zhu Y . medRxiv 2022 10 Background: We estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Method(s): Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) x 100%. Result(s): Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients. Conclusion(s): In this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rd mRNA COVID-19 vaccine dose. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Genomic deletions and rearrangements in monkeypox virus from the 2022 outbreak, USA (preprint)
Gigante CM , Plumb M , Ruprecht A , Zhao H , Wicker V , Wilkins K , Matheny A , Khan T , Davidson W , Sheth M , Burgin A , Burroughs M , Padilla J , Lee JS , Batra D , Hetrick EE , Howard DT , Garfin J , Tate L , Hubsmith SJ , Mendoza RM , Stanek D , Gillani S , Lee M , Mangla A , Blythe D , SierraPatev S , Carpenter-Azevedo K , Huard RC , Gallagher G , Hall J , Ash S , Kovar L , Seabolt MH , Weigand MR , Damon I , Satheshkumar PS , McCollum AM , Hutson CL , Wang X , Li Y . bioRxiv 2022 17 Genomic surveillance of monkeypox virus (MPXV) during the 2022 outbreak has been mainly focused on single nucleotide polymorphism (SNP) changes. DNA viruses, including MPXV, have a lower SNP mutation rate than RNA viruses due to higher fidelity replication machinery. We identified a large genomic rearrangement in a MPXV sequence from a 2022 case in the state of Minnesota (MN), USA, from an abnormal, uneven MPXV read mapping coverage profile in whole-genome sequencing (WGS) data. We further screened WGS data of 206 U.S. MPXV samples and found seven (3.4 percent) sequenced genomes contained similar abnormal read coverage profiles that suggested putative large deletions or genomic rearrangements. Here, we present three MPXV genomes containing deletions ranging from 2.3 to 15 kb and four genomes containing more complex rearrangements. Five genomic changes were each only seen in one sample, but two sequences from linked cases shared an identical 2.3 kb deletion in the 3' terminal region. All samples were positive using VAC1 and Clade II (formerly West African)-specific MPXV diagnostic tests; however, large deletions and genomic rearrangements like the ones reported here have the potential to result in viruses in which the target of a PCR diagnostic test is deleted. The emergence of genomic rearrangements during the outbreak may have public health implications and highlight the importance of continued genomic surveillance. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing.
Allix-Béguec C , Arandjelovic I , Bi L , Beckert P , Bonnet M , Bradley P , Cabibbe AM , Cancino-Muñoz I , Caulfield MJ , Chaiprasert A , Cirillo DM , Clifton DA , Comas I , Crook DW , De Filippo MR , de Neeling H , Diel R , Drobniewski FA , Faksri K , Farhat MR , Fleming J , Fowler P , Fowler TA , Gao Q , Gardy J , Gascoyne-Binzi D , Gibertoni-Cruz AL , Gil-Brusola A , Golubchik T , Gonzalo X , Grandjean L , He G , Guthrie JL , Hoosdally S , Hunt M , Iqbal Z , Ismail N , Johnston J , Khanzada FM , Khor CC , Kohl TA , Kong C , Lipworth S , Liu Q , Maphalala G , Martinez E , Mathys V , Merker M , Miotto P , Mistry N , Moore DAJ , Murray M , Niemann S , Omar SV , Ong RT , Peto TEA , Posey JE , Prammananan T , Pym A , Rodrigues C , Rodrigues M , Rodwell T , Rossolini GM , Sánchez Padilla E , Schito M , Shen X , Shendure J , Sintchenko V , Sloutsky A , Smith EG , Snyder M , Soetaert K , Starks AM , Supply P , Suriyapol P , Tahseen S , Tang P , Teo YY , Thuong TNT , Thwaites G , Tortoli E , van Soolingen D , Walker AS , Walker TM , Wilcox M , Wilson DJ , Wyllie D , Yang Y , Zhang H , Zhao Y , Zhu B . N Engl J Med 2018 379 (15) 1403-1415 BACKGROUND: The World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear. METHODS: We obtained whole-genome sequences and associated phenotypes of resistance or susceptibility to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and pyrazinamide for isolates from 16 countries across six continents. For each isolate, mutations associated with drug resistance and drug susceptibility were identified across nine genes, and individual phenotypes were predicted unless mutations of unknown association were also present. To identify how whole-genome sequencing might direct first-line drug therapy, complete susceptibility profiles were predicted. These profiles were predicted to be susceptible to all four drugs (i.e., pansusceptible) if they were predicted to be susceptible to isoniazid and to the other drugs or if they contained mutations of unknown association in genes that affect susceptibility to the other drugs. We simulated the way in which the negative predictive value changed with the prevalence of drug resistance. RESULTS: A total of 10,209 isolates were analyzed. The largest proportion of phenotypes was predicted for rifampin (9660 [95.4%] of 10,130) and the smallest was predicted for ethambutol (8794 [89.8%] of 9794). Resistance to isoniazid, rifampin, ethambutol, and pyrazinamide was correctly predicted with 97.1%, 97.5%, 94.6%, and 91.3% sensitivity, respectively, and susceptibility to these drugs was correctly predicted with 99.0%, 98.8%, 93.6%, and 96.8% specificity. Of the 7516 isolates with complete phenotypic drug-susceptibility profiles, 5865 (78.0%) had complete genotypic predictions, among which 5250 profiles (89.5%) were correctly predicted. Among the 4037 phenotypic profiles that were predicted to be pansusceptible, 3952 (97.9%) were correctly predicted. CONCLUSIONS: Genotypic predictions of the susceptibility of M. tuberculosis to first-line drugs were found to be correlated with phenotypic susceptibility to these drugs. (Funded by the Bill and Melinda Gates Foundation and others.). |
Erratum: Vol. 71, No. 6.
Lambrou AS , Shirk P , Steele MK , Paul P , Paden CR , Cadwell B , Reese HE , Aoki Y , Hassell N , Caravas J , Kovacs NA , Gerhart JG , Ng HJ , Zheng XY , Beck A , Chau R , Cintron R , Cook PW , Gulvik CA , Howard D , Jang Y , Knipe K , Lacek KA , Moser KA , Paskey AC , Rambo-Martin BL , Nagilla RR , Rethchless AC , Schmerer MW , Seby S , Shephard SS , Stanton RA , Stark TJ , Uehara A , Unoarumhi Y , Bentz ML , Burhgin A , Burroughs M , Davis ML , Keller MW , Keong LM , Le SS , Lee JS , Madden Jr JC , Nobles S , Owouor DC , Padilla J , Sheth M , Wilson MM , Talarico S , Chen JC , Oberste MS , Batra D , McMullan LK , Halpin AL , Galloway SE , MacCannell DR , Kondor R , Barnes J , MacNeil A , Silk BJ , Dugan VG , Scobie HM , Wentworth DE . MMWR Morb Mortal Wkly Rep 2022 71 (14) 528 The report “Genomic Surveillance for SARS-CoV-2 Variants: Predominance of the Delta (B.1.617.2) and Omicron (B.1.1.529) Variants — United States, June 2021–January 2022” contained several errors. |
Notes from the field: Prevalence of previous dengue virus infection among children and adolescents - U.S. Virgin Islands, 2022
Mac VV , Wong JM , Volkman HR , Perez-Padilla J , Wakeman B , Delorey M , Biggerstaff BJ , Fagre A , Gumbs A , Drummond A , Zimmerman B , Lettsome B , Medina FA , Paz-Bailey G , Lawrence M , Ellis B , Rosenblum HG , Carroll J , Roth J , Rossington J , Meeker JR , Joseph J , Janssen J , Ekpo LL , Carrillo M , Hernandez N , Charles P , Tosado R , Soto R , Battle S , Bart SM , Wanga V , Valentin W , Powell W , Battiste Z , Ellis EM , Adams LE . MMWR Morb Mortal Wkly Rep 2023 72 (11) 288-289 In May 2019, the Food and Drug Administration issued approval for Dengvaxia (Sanofi Pasteur), a live-attenuated, chimeric tetravalent dengue vaccine (1). In June 2021, the Advisory Committee on Immunization Practices (ACIP) recommended vaccination with Dengvaxia for children and adolescents aged 9–16 years with laboratory confirmation of previous dengue virus infection and who live in areas with endemic dengue transmission, such as the U.S. Virgin Islands (USVI)† (2). Confirming previous dengue virus infection before vaccine administration (prevaccination screening) is important because 1) although Dengvaxia decreases hospitalization and severe disease from dengue among persons with a previous infection, it increases the risk for these outcomes among persons without a previous infection; 2) many dengue virus infections are asymptomatic; and 3) many patients with symptomatic infections do not seek medical attention or receive appropriate testing (3). Sufficient laboratory evidence of previous dengue virus infection includes a history of laboratory-confirmed dengue§ or a positive serologic test result that meets ACIP-recommended performance standards for prevaccination screening, defined as high specificity (≥98%) and sensitivity (≥75%). A seroprevalence of 20% in the vaccine-eligible population (corresponding to a positive predictive value of ≥90% for a test with minimum sensitivity of 75% and minimum specificity of 98%) is recommended to maximize vaccine safety and minimize the risk for vaccinating persons without a previous dengue virus infection (2). |
Public Health Response to Clusters of Rapid HIV Transmission Among Hispanic or Latino Gay, Bisexual, and Other Men Who Have Sex with Men - Metropolitan Atlanta, Georgia, 2021-2022.
Saldana C , Philpott DC , Mauck DE , Hershow RB , Garlow E , Gettings J , Freeman D , France AM , Johnson EN , Ajmal A , Elimam D , Reed K , Sulka A , Adame JF , Andía JF , Gutierrez M , Padilla M , Jimenez NG , Hayes C , McClung RP , Cantos VD , Holland DP , Scott JY , Oster AM , Curran KG , Hassan R , Wortley P . MMWR Morb Mortal Wkly Rep 2023 72 (10) 261-264 During February 2021-June 2022, the Georgia Department of Public Health (GDPH) detected five clusters of rapid HIV transmission concentrated among Hispanic or Latino (Hispanic) gay, bisexual, and other men who have sex with men (MSM) in metropolitan Atlanta. The clusters were detected through routine analysis of HIV-1 nucleotide sequence data obtained through public health surveillance (1,2). Beginning in spring 2021, GDPH partnered with health districts with jurisdiction in four metropolitan Atlanta counties (Cobb, DeKalb, Fulton, and Gwinnett) and CDC to investigate factors contributing to HIV spread, epidemiologic characteristics, and transmission patterns. Activities included review of surveillance and partner services interview data,(†) medical chart reviews, and qualitative interviews with service providers and Hispanic MSM community members. By June 2022, these clusters included 75 persons, including 56% who identified as Hispanic, 96% who reported male sex at birth, 81% who reported male-to-male sexual contact, and 84% of whom resided in the four metropolitan Atlanta counties. Qualitative interviews identified barriers to accessing HIV prevention and care services, including language barriers, immigration- and deportation-related concerns, and cultural norms regarding sexuality-related stigma. GDPH and the health districts expanded coordination, initiated culturally concordant HIV prevention marketing and educational activities, developed partnerships with organizations serving Hispanic communities to enhance outreach and services, and obtained funding for a bilingual patient navigation program with academic partners to provide staff members to help persons overcome barriers and understand the health care system. HIV molecular cluster detection can identify rapid HIV transmission among sexual networks involving ethnic and sexual minority groups, draw attention to the needs of affected populations, and advance health equity through tailored responses that address those needs. |
Attitudes and beliefs about HIV treatment as prevention among people who are not engaged in HIV care, 2018-2019
Padilla M , Gutierrez M , Basu M , Fagan J . AIDS Behav 2023 27 (9) 3122-3132 Treatment as prevention (TasP) is an effective HIV prevention strategy. Our objectives were to explore TasP attitudes and beliefs among people with HIV (PWH) who are not engaged in care and to examine attitudes and beliefs by selected characteristics. We sampled PWH who had participated in the Medical Monitoring Project (MMP), a structured interview survey, from June 2018-May 2019 to participate in 60-minute semi-structured telephone interviews. We obtained sociodemographic and behavioral quantitative data from the MMP structured interview. We used applied thematic analysis to analyze the qualitative data and integrated the qualitative and quantitative data during analysis. Negative attitudes and beliefs, especially skepticism and mistrust, about TasP were pervasive. Only one participant who identified as female, was not sexually active, and had not heard of TasP held positive attitudes and beliefs about TasP. TasP messages should use clear and unambiguous language, address mistrust, and reach people who are not engaged in medical care. |
Racial differences in social determinants of health and outcomes among Hispanic/Latino persons with HIV-United States, 2015-2020
Padilla M , Luna-Gierke RE , Carree T , Gutierrez M , Yuan X , Dasgupta S . J Racial Ethn Health Disparities 2023 BACKGROUND: Hispanic/Latino people with HIV (PWH) experience disparities in health outcomes compared with other racial and ethnic groups. Disaggregated data based on race for Hispanic/Latino PWH in the United States are rarely reported, potentially masking inequities. METHODS: The Medical Monitoring Project (MMP) is a complex sample survey of adults with diagnosed HIV. We used weighted interview and medical record data collected from June 2015-May 2021 to examine differences in social determinants of health (SDH) and health outcomes by self-reported race among Hispanic/Latino adults with diagnosed HIV. RESULTS: Compared with White Hispanic/Latino PWH, Black Hispanic/Latino PWH were more likely to be unemployed (PR, 1.4; CI, 1.2-1.8), have a disability (PR, 1.3; CI, 1.2-1.5), have experienced homelessness (PR, 1.8; CI, 1.2-2.6), and have been incarcerated (PR, 2.6; CI, 1.5-4.5). American Indian/Alaska Native (AI/AN) (PR, 1.8; CI, 1.1-2.7) and multiracial (PR, 2.0; CI, 1.4-2.9) Hispanic/Latino PWH were more likely to have experienced homelessness than White Hispanic/Latino PWH. Black (PR, 1.3; CI, 1.2-1.5) and multiracial (PR, 1.2; CI, 1.1-1.5) Hispanic/Latino PWH were more likely to be virally unsuppressed than White Hispanic/Latino PWH. CONCLUSION: Black, multiracial, and AI/AN Hispanic/Latino PWH experience disparities in SDH and HIV outcomes. Lumping Hispanic/Latino people into one racial and ethnic category obscures health disparities, which might limit our progress towards reaching national HIV goals. Future studies should consider disaggregating by other factors such as Hispanic origin, place of birth, immigration status, and primary language. Doing so recognizes the diversity of the Hispanic/Latino population. |
Using semistructured telephone interviews to collect qualitative data from people with HIV who are not in medical care: Implementation study
Padilla M , Gutierrez M , Fagan J . JMIR Res Protoc 2022 11 (11) e40041 BACKGROUND: The Medical Monitoring Qualitative (MMP-Qual) Project was designed to collect qualitative data from people with HIV not engaged in medical care that would complement quantitative data collected by the Medical Monitoring Project (MMP)-a national surveillance system-and inform the MMP's recruitment and data collection methods. OBJECTIVE: Our objectives were to describe the methodology of this project, reflect on the challenges and lessons learned from conducting qualitative telephone interviews at a national level, and describe how we used and plan to use the qualitative data to evaluate our recruitment procedures and quantitative data collection instrument as well as knowledge of HIV care engagement. METHODS: We used stratified purposive sampling to identify and recruit participants who had participated in the structured MMP interview into the MMP-Qual Project. To be eligible, participants must have had an HIV diagnosis, be aged ≥18 years, have lived in an MMP jurisdiction, and have not been engaged in HIV medical care. From August 1, 2018, to May 31, 2019, we conducted semistructured telephone interviews with 36 people with HIV across the United States about several topics (eg, facilitators and barriers to care and experience with surveys). Four trained interviewers conducted semistructured 60-minute telephone interviews with 36 participants. Data collection lasted from August 1, 2018, to May 31, 2019. RESULTS: From 2018 to 2019, 113 people were eligible to participate in the MMP-Qual Project. Of the people recruited, 28% (22/79) refused to participate. Of those who agreed to participate, 63% (36/57) were interviewed, and 37% (21/57) were no-shows. Of the 34 participants for whom we had complete data, 15 (44%) were aged ≥50 years, 26 (76%) identified as male, 22 (65%) were Black or African American, and 12 (35%) lived in the Southern United States. CONCLUSIONS: We learned that it is possible to obtain rich qualitative data from people with HIV who are not in care via telephone interviews and that this mode might be conducive to talking about sensitive topics. We also learned the importance of flexibility, communication, and coordination because we relied on health department staff to perform recruitment and had difficulty implementing our original sampling strategy. We hope that other projects will learn from our experience conducting qualitative telephone interviews with people with HIV on a national level. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/40041. |
Clinical Features of COVID-19, Dengue, and Influenza among Adults Presenting to Emergency Departments and Urgent Care Clinics-Puerto Rico, 2012-2021.
Wong JM , Volkman HR , Adams LE , OliverasGarca C , Martinez-Quiones A , Perez-Padilla J , Bertrn-Pasarell J , SainzdelaPea D , Tosado-Acevedo R , Santiago GA , Muoz-Jordn JL , Torres-Velsquez BC , Lorenzi O , Snchez-Gonzlez L , Rivera-Amill V , Paz-Bailey G . Am J Trop Med Hyg 2022 108 (1) 107-114 Dengue and influenza are pathogens of global concern and cause febrile illness similar to COVID-19. We analyzed data from an enhanced surveillance system operating from three emergency departments and an urgent care clinic in Puerto Rico to identify clinical features predictive of influenza or dengue compared with COVID-19. Participants with fever or respiratory symptoms and aged 18 years enrolled May 2012-January 2021 with dengue, influenza, or SARS-CoV-2 confirmed by reverse transcriptase polymerase chain reaction were included. We calculated adjusted odds ratios (aORs) and 95% CIs using logistic regression to assess clinical characteristics of participants with COVID-19 compared to those with dengue or influenza, adjusting for age, subregion, and days from illness onset to presentation for clinical care. Among 13,431 participants, we identified 2,643 with dengue (N = 303), influenza (N = 2,064), or COVID-19 (N = 276). We found differences in days from onset to presentation among influenza (2 days [interquartile range: 1-3]), dengue (3 days [2-4]), and COVID-19 cases (4 days [2-7]; P < 0.001). Cough (aOR: 0.12 [95% CI: 0.07-0.19]) and shortness of breath (0.18 [0.08-0.44]) were less common in dengue compared with COVID-19. Facial flushing (20.6 [9.8-43.5]) and thrombocytopenia (24.4 [13.3-45.0]) were more common in dengue. Runny nose was more common in influenza compared with COVID-19 (8.3 [5.8-12.1]). In summary, cough, shortness of breath, facial flushing, and thrombocytopenia helped distinguish between dengue and COVID-19. Although few features distinguished influenza from COVID-19, presentation > 4 days after symptom onset suggests COVID-19. These findings may assist clinicians making time-sensitive decisions regarding triage, isolation, and management while awaiting pathogen-specific testing. |
HIV stigma and health care discrimination experienced by Hispanic or Latino persons with HIV - United States, 2018-2020
Padilla M , Patel D , Beer L , Tie Y , Nair P , Salabarría-Peña Y , Henny KD , Thomas D , Dasgupta S . MMWR Morb Mortal Wkly Rep 2022 71 (41) 1293-1300 Hispanic or Latino (Hispanic) persons with HIV experience disparities in HIV health outcomes compared with some other racial and ethnic groups. A previous report found that the percentages of Hispanic persons who received HIV care, were retained in care, and were virally suppressed were lower than those among non-Hispanic White persons with HIV (1). HIV stigma and discrimination are human rights issues associated with adverse HIV outcomes; eliminating stigma and discrimination among persons with HIV is a national priority*(,)(†)(,)(§) (2,3). CDC analyzed data from the Medical Monitoring Project (MMP), an annual, cross-sectional study designed to report nationally representative estimates of experiences and outcomes among adults with diagnosed HIV. Data from the 2018-2020 cycles were analyzed to assess self-reported stigma and health care discrimination using adapted versions of validated multi-component scales among 2,690 adult Hispanic persons with HIV in the United States overall and by six characteristics.(¶) The median HIV stigma score on a scale of 0-100 was 31.7, with women (35.6) and American Indian or Alaska Native (AI/AN) persons (38.9) reporting the highest scores among Hispanic persons with HIV. HIV stigma was primarily attributed to disclosure concerns (e.g., fearing others will disclose one's HIV status and being careful about who one tells about one's HIV status). Nearly one in four (23%) Hispanic persons with HIV experienced health care discrimination. Health care discrimination was experienced more frequently by Hispanic men (23%) than by Hispanic women (18%) and by Black or African American (Black) Hispanic persons (28%) than by White Hispanic persons (21%). Understanding disparities in experiences of stigma and discrimination is important when designing culturally appropriate interventions to reduce stigma and discrimination. |
Design and evaluation of neutralizing and fusion inhibitory peptides to Crimean-Congo hemorrhagic fever virus
Mears MC , Rodriguez SE , Schmitz KS , Padilla A , Biswas S , Cajimat MNB , Mire CE , Welch SR , Bergeron , Alabi CA , Porotto M , Bente DA . Antiviral Res 2022 207 105401 Crimean-Congo hemorrhagic fever (CCHF) is a medically relevant tick-borne viral disease caused by the Bunyavirus, Crimean-Congo hemorrhagic fever virus (CCHFV). CCHFV is endemic to Asia, the Middle East, South-eastern Europe, and Africa and is transmitted in enzootic cycles among ticks, mammals, and birds. Human infections are mostly subclinical or limited to mild febrile illness. Severe disease may develop, resulting in multi-organ failure, hemorrhagic manifestations, and case-fatality rates up to 30%. Despite the widespread distribution and life-threatening potential, no treatments have been approved for CCHF. Antiviral inhibitory peptides, which antagonize viral entry, are licensed for clinical use in certain viral infections and have been experimentally designed against human pathogenic bunyaviruses, with in vitro and in vivo efficacies. We designed inhibitory peptides against CCHFV with and without conjugation to various polyethylene glycol and sterol groups. These additions have been shown to enhance both cellular uptake and antiviral activity. Peptides were evaluated against pseudotyped and wild-type CCHFV via neutralization tests, Nairovirus fusion assays, and cytotoxicity profiling. Four peptides neutralized CCHFV with two of these peptides shown to inhibit viral fusion. This work represents the development of experimental countermeasures for CCHF, describes a nairovirus immunofluorescence fusion assay, and illustrates the utility of pseudotyped CCHFV for the screening of entry antagonists at low containment settings for CCHF. |
Knowledge, attitudes, and practices on Rocky Mountain Spotted Fever among physicians in a highly endemic region-Mexicali, Mexico
Bestul N , Padilla R , Montaño T , Márquez A , Fierro M , Zazueta OE , Armstrong PA . Am J Trop Med Hyg 2022 107 (4) 773-779 Rocky Mountain spotted fever (RMSF) is a potentially fatal tickborne disease caused by the bacterium, Rickettsia rickettsii and transmitted primarily by the brown dog tick (Rhipicephalus sanguineus) in the southwestern United States and Mexico. RMSF can be rapidly fatal if not treated early with doxycycline, making healthcare worker awareness and education critical to reduce morbidity and mortality. During 2008-2019, Mexicali experienced a RMSF epidemic with 779 confirmed cases, and an 11-year case-fatality rate of 18% (N = 140). A cross-sectional study was conducted with 290 physicians and physicians-in-training across 12 medical facilities in Mexicali. They were asked to complete a 23-item questionnaire to assess knowledge, attitudes, and practices for clinical, epidemiologic, and preventive aspects of RMSF. Half of participants were female, the largest age group was aged 25 to 44 (47%), and median time in practice was 6 years (interquartile rate: 1-21.5). Less than half (48%) surveyed were confident where diagnostic testing could be performed, and two-thirds did not regularly order serology (67%) or molecular diagnostic (66%) tests for RMSF when a patient presented with fever. Sixty-four percent knew doxycycline as first-line treatment of children < 8 years with suspected RMSF. When comparing healthcare workers with < 6 years of experience to those with ≥ 6 years, more experience was associated with greater confidence in where to have diagnostic testing performed (prevalence odds ratio [prevalence odds ratios [pOR]] = 2.3; P = 0.004), and frequency of ordering laboratory tests (serology, pOR = 3.3; P = 0.002; polymerase chain reaction, pOR = 3.9; P = 0.001). Continued education, including information on diagnostic testing is key to reducing morbidity and mortality from RMSF. |
The boundary of HIV care: Barriers and facilitators to care engagement among people with HIV in the United States
Padilla M , Carter B , Gutierrez M , Fagan J . AIDS Patient Care STDS 2022 36 (8) 321-331 Treating people with HIV (PWH) quickly and effectively to achieve viral suppression is a key strategy for Ending the HIV Epidemic. Understanding barriers and facilitators to HIV care engagement could improve outcomes among PWH and reduce HIV infections. We sampled PWH who participated in the Medical Monitoring Project from June 2018 to May 2019 and were not engaged in HIV care to participate in 60-min semistructured telephone interviews on barriers and facilitators to HIV care engagement. We used applied thematic analysis and placed codes into themes based on their frequency and salience. Participants reported various intrapersonal, health system, and structural barriers to care. We conceptualize the boundary of care as the space between the stages of the HIV care continuum, where PWH may find themselves when they lack intrapersonal, health system, and structural support. Research and interventions tackling these barriers are needed to improve outcomes among PWH and reduce HIV infections. |
Effectiveness of two and three mRNA COVID-19 vaccine doses against Omicron- and Delta-Related outpatient illness among adults, October 2021-February 2022.
Kim SS , Chung JR , Talbot HK , Grijalva CG , Wernli KJ , Kiniry E , Martin ET , Monto AS , Belongia EA , McLean HQ , Gaglani M , Mamawala M , Nowalk MP , Moehling Geffel K , Tartof SY , Florea A , Lee JS , Tenforde MW , Patel MM , Flannery B , Bentz ML , Burgin A , Burroughs M , Davis ML , Howard D , Lacek K , Madden JC , Nobles S , Padilla J , Sheth M . Influenza Other Respir Viruses 2022 16 (6) 975-985 Background: We estimated SARS-CoV-2 Delta- and Omicron-specific effectiveness of two and three mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Methods: Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving two or three mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 − adjusted odds ratio) × 100%. Results: Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA two-dose recipients and 96% (95% CI: 93% to 98%) for three-dose recipients. When Omicron predominated, VE was 21% (95% CI: −6% to 41%) among two-dose recipients and 62% (95% CI: 48% to 72%) among three-dose recipients. Conclusions: In this adult population, three mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the United States. These findings support the recommendation for a third mRNA COVID-19 vaccine dose. Published 2022. This article is a U.S. Government work and is in the public domain in the USA. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd. |
Emergence of dengue virus serotype 2 cosmopolitan genotype, Brazil
Giovanetti M , Pereira LA , Santiago GA , Fonseca V , Mendoza MPG , de Oliveira C , de Moraes L , Xavier J , Tosta S , Fristch H , de Castro Barbosa E , Rodrigues ES , Figueroa-Romero D , Padilla-Rojas C , Cáceres-Rey O , Mendonça AF , de Bruycker Nogueira F , Venancio da Cunha R , de Filippis AMB , Freitas C , Peterka CRL , de Albuquerque CFC , Franco L , Méndez Rico JA , Muñoz-Jordán JL , Lemes da Silva V , Alcantara LCJ . Emerg Infect Dis 2022 28 (8) 1725-1727 We used nanopore sequencing and phylogenetic analyses to identify a cosmopolitan genotype of dengue virus serotype 2 that was isolated from a 56-year-old male patient from the state of Goiás in Brazil. The emergence of a cosmopolitan genotype in Brazil will require risk assessment and surveillance to reduce epidemic potential. |
Early childhood neurodevelopmental outcomes in children with prenatal Zika virus exposure: a cohort study in Puerto Rico
Pérez-Padilla J , Paz-Bayley G . J Pediatr 2022 247 38-45 e5 OBJECTIVE: To describe anthropometric, sensory, and neurodevelopmental outcomes of Zika virus exposed children from birth to 36 months. STUDY DESIGN: The cohort includes 114 children born to mothers with confirmed and probable ZIKV pregnancy infection, from 2016-2017. Children attending study visits from May 2017 through February 2020 underwent physical/neurologic, sensory examinations, and neurodevelopmental assessments with Bayley Scales of Infant and Toddler Development (BSID-III) and Ages and Stages Questionnaires (ASQ-3). RESULTS: Three of 114 (2.6%) children had microcephaly (z score < -2) at birth, 19 of 35 (54.3%) had posterior eye abnormalities in retinal image, and 11 of 109 (10.1%) had nonspecific findings on brain ultrasound. Three of 107 (2.8%) failed hearing screening at birth. Of those with follow up, 17 of 97 (17.5%) failed age-appropriate vision screening; BSID-III identified developmental delay in at least one domain in at least one-third of children, with higher prevalence in the language domain. ASQ-3 screen positive delay peaked around 24 or 36 months, some domains showing decrease at older ages. Correlations were observed among BSID-III and ASQ-3 scores, representing professional and parental perspectives at 24 and 36 months (r = 0.32 to 0.78 p<.05). CONCLUSION: The presence of neurodevelopmental sequelae in early childhood suggests that identification of long-term impairment remains critical to attaining optimal child development. Long-term follow up highlights vulnerability in the language domain, which likely could be influenced by early intervention, promoting cognitive development and school readiness among exposed children. |
Predominance of severe plasma leakage in pediatric patients with severe dengue in Puerto Rico
Paz-Bailey G , Sánchez-González L , Torres-Velasquez B , Jones E , Perez-Padilla J , Sharp TM , Lorenzi O , Delorey M , Munoz-Jordan J , Tomashek KM , Waterman SH , Alvarado LI , Rivera-Amil V . J Infect Dis 2022 226 (11) 1949-1958 BACKGROUND: We evaluated clinical and laboratory findings among patients with non-severe or severe dengue in Puerto Rico to examine whether clinical manifestations vary by age. METHODS: During 2012-2014, we enrolled patients who arrived at the emergency department with fever or history of fever within 7 days of presentation. Serum samples were tested for dengue virus (DENV) by RT-PCR and IgM ELISA. Severe dengue was defined as severe plasma leakage or shock, severe bleeding, or organ involvement at presentation, during hospitalization, or follow-up. RESULTS: Of 1089 dengue patients identified, 281 (26%) were severe. Compared to those with non-severe dengue, patients with severe dengue were more often aged 10-19 years (55% vs. 40%, p < 0.001) and hospitalized (87% vs. 30%, p < 0.001). Severe plasma leakage or shock was more common among children aged 0-9 (59%) or 10-19 years (86%) than adults (49%) (p < 0.01). Severe bleeding was less common among 10-19 year-olds (24%) compared to 0-9 year-olds (45%) and adults (52%; p < 0.01). CONCLUSIONS: Severe plasma leakage was the most common presentation among children, highlighting important differences with adults. Vaccination against dengue could help prevent severe dengue among children in Puerto Rico. |
Association between violence and mental distress, self-harm and suicidal ideation and attempts among young people in Malawi
Villaveces A , Shankar V , Palomeque F , Padilla M , Kress H . Inj Prev 2022 BACKGROUND: Mental health problems ranging from depression to more severe acts such as self-harm or suicidal behaviours are a serious problem among adolescents and young adults. Exposure to violence during the life of young people can increase mental health issues for youth. This study examines the relationship between exposure to violence and mental health issues among youth using a nationally representative study in Malawi. METHODS: We analysed data from the nationally representative Violence Against Children Survey from Malawi (2013) to quantify the association between exposures to violence (physical, sexual and emotional) and their relationship with mental distress, self-harm behaviours and suicidal ideation and attempts among youth aged 13-24 years. We evaluated the association of exposures to violence against children with reported mental health conditions among women and men. We used ordinal logistic regression models with appropriate survey weights to assess exposures to violence and the three outcomes of interest. RESULTS: Children and youth aged 13-24 years exposed to violence in childhood reported higher levels of adverse mental health effects, including mental distress, self-harm behaviours and suicidal ideation and attempts. The odds of reporting these outcomes increased as the number of violence types increased. CONCLUSIONS: Understanding the risks based on different combinations of exposures to violence in Malawi can help identify populations at higher risk and optimise violence prevention strategies. |
Sentinel Surveillance Reveals Emerging Daptomycin-Resistant ST736 Enterococcus faecium and Multiple Mechanisms of Linezolid Resistance in Enterococci in the United States.
Gargis AS , Spicer LM , Kent AG , Zhu W , Campbell D , McAllister G , Ewing TO , Albrecht V , Stevens VA , Sheth M , Padilla J , Batra D , Johnson JK , Halpin AL , Rasheed JK , Elkins CA , Karlsson M , Lutgring JD . Front Microbiol 2021 12 807398 Enterococcus faecalis and faecium with resistance to daptomycin and/or linezolid are emerging globally. We present the genomic characterization of daptomycin- and linezolid-resistant E. faecalis and E. faecium surveillance isolates from the United States, 2013-2016. Daptomycin resistance was low among E. faecalis (2/364, 0.5%) and E. faecium (17/344, 5%). The majority (71%, 12/17) of daptomycin-resistant E. faecium isolates belonged to the emerging ST736 clone and contained mutations in liaFSR and cls previously associated with resistance. However, 1/2 E. faecalis and 3/17 E. faecium did not contain these mutations previously associated with daptomycin resistance. Linezolid resistance was rare among E. faecalis (1/364, 0.3%) and E. faecium (2/344, 0.6%). These two E. faecium isolates, one of which was also resistant to daptomycin and vancomycin, contained the 23S rRNA nucleotide mutation (G2576T) associated with linezolid resistance. Long-read sequencing revealed the linezolid-resistant E. faecalis isolate contained chromosomal- and plasmid-encoded copies of optrA. The chromosomal optrA was located on the recently described Tn6674 multiresistance transposon. The second copy of optrA was encoded on an ∼65 kb mosaic plasmid, with component regions sharing high sequence identity to optrA-encoding multiresistance plasmids of animal origin. The optrA-encoding plasmid contained open reading frames predicted to encode proteins associated with a pheromone-responsive plasmid transfer system, and filter mating experiments confirmed the plasmid was conjugative. Continued surveillance of enterococci is necessary to assess the prevalence and trends of daptomycin and linezolid resistance in the United States, characterize resistance mechanisms and how they transfer, and monitor for emerging sequence types associated with resistance. |
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