Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 30 Records) |
Query Trace: Melgar M [original query] |
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Acute cardiac events in hospitalized older adults with respiratory syncytial virus infection
Woodruff RC , Melgar M , Pham H , Sperling LS , Loustalot F , Kirley PD , Austin E , Yousey-Hindes K , Openo KP , Ryan P , Brown C , Lynfield R , Davis SS , Barney G , Tesini B , Sutton M , Talbot HK , Zahid H , Kim L , Havers FP . JAMA Intern Med 2024 IMPORTANCE: Respiratory syncytial virus (RSV) infection can cause severe respiratory illness in older adults. Less is known about the cardiac complications of RSV disease compared with those of influenza and SARS-CoV-2 infection. OBJECTIVE: To describe the prevalence and severity of acute cardiac events during hospitalizations among adults aged 50 years or older with RSV infection. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed surveillance data from the RSV Hospitalization Surveillance Network, which conducts detailed medical record abstraction among hospitalized patients with RSV infection detected through clinician-directed laboratory testing. Cases of RSV infection in adults aged 50 years or older within 12 states over 5 RSV seasons (annually from 2014-2015 through 2017-2018 and 2022-2023) were examined to estimate the weighted period prevalence and 95% CIs of acute cardiac events. EXPOSURES: Acute cardiac events, identified by International Classification of Diseases, 9th Revision, Clinical Modification or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification discharge codes, and discharge summary review. MAIN OUTCOMES AND MEASURES: Severe disease outcomes, including intensive care unit (ICU) admission, receipt of invasive mechanical ventilation, or in-hospital death. Adjusted risk ratios (ARR) were calculated to compare severe outcomes among patients with and without acute cardiac events. RESULTS: The study included 6248 hospitalized adults (median [IQR] age, 72.7 [63.0-82.3] years; 59.6% female; 56.4% with underlying cardiovascular disease) with laboratory-confirmed RSV infection. The weighted estimated prevalence of experiencing a cardiac event was 22.4% (95% CI, 21.0%-23.7%). The weighted estimated prevalence was 15.8% (95% CI, 14.6%-17.0%) for acute heart failure, 7.5% (95% CI, 6.8%-8.3%) for acute ischemic heart disease, 1.3% (95% CI, 1.0%-1.7%) for hypertensive crisis, 1.1% (95% CI, 0.8%-1.4%) for ventricular tachycardia, and 0.6% (95% CI, 0.4%-0.8%) for cardiogenic shock. Adults with underlying cardiovascular disease had a greater risk of experiencing an acute cardiac event relative to those who did not (33.0% vs 8.5%; ARR, 3.51; 95% CI, 2.85-4.32). Among all hospitalized adults with RSV infection, 18.6% required ICU admission and 4.9% died during hospitalization. Compared with patients without an acute cardiac event, those who experienced an acute cardiac event had a greater risk of ICU admission (25.8% vs 16.5%; ARR, 1.54; 95% CI, 1.23-1.93) and in-hospital death (8.1% vs 4.0%; ARR, 1.77; 95% CI, 1.36-2.31). CONCLUSIONS AND RELEVANCE: In this cross-sectional study over 5 RSV seasons, nearly one-quarter of hospitalized adults aged 50 years or older with RSV infection experienced an acute cardiac event (most frequently acute heart failure), including 1 in 12 adults (8.5%) with no documented underlying cardiovascular disease. The risk of severe outcomes was nearly twice as high in patients with acute cardiac events compared with patients who did not experience an acute cardiac event. These findings clarify the baseline epidemiology of potential cardiac complications of RSV infection prior to RSV vaccine availability. |
Characteristics and outcomes among adults aged ≥60 years hospitalized with laboratory-confirmed respiratory syncytial virus - RSV-NET, 12 States, July 2022-June 2023
Havers FP , Whitaker M , Melgar M , Chatwani B , Chai SJ , Alden NB , Meek J , Openo KP , Ryan PA , Kim S , Lynfield R , Shaw YP , Barney G , Tesini BL , Sutton M , Talbot HK , Olsen KP , Patton ME . MMWR Morb Mortal Wkly Rep 2023 72 (40) 1075-1082 Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults. In May 2023, two RSV vaccines were approved for prevention of RSV lower respiratory tract disease in adults aged ≥60 years. In June 2023, CDC recommended RSV vaccination for adults aged ≥60 years, using shared clinical decision-making. Using data from the Respiratory Syncytial Virus-Associated Hospitalization Surveillance Network, a population-based hospitalization surveillance system operating in 12 states, this analysis examined characteristics (including age, underlying medical conditions, and clinical outcomes) of 3,218 adults aged ≥60 years who were hospitalized with laboratory-confirmed RSV infection during July 2022-June 2023. Among a random sample of 1,634 older adult patients with RSV-associated hospitalization, 54.1% were aged ≥75 years, and the most common underlying medical conditions were obesity, chronic obstructive pulmonary disease, congestive heart failure, and diabetes. Severe outcomes occurred in 18.5% (95% CI = 15.9%-21.2%) of hospitalized patients aged ≥60 years. Overall, 17.0% (95% CI = 14.5%-19.7%) of patients with RSV infection were admitted to an intensive care unit, 4.8% (95% CI = 3.5%-6.3%) required mechanical ventilation, and 4.7% (95% CI = 3.6%-6.1%) died; 17.2% (95% CI = 14.9%-19.8%) of all cases occurred in long-term care facility residents. These data highlight the importance of prioritizing those at highest risk for severe RSV disease and suggest that clinicians and patients consider age (particularly age ≥75 years), long-term care facility residence, and underlying medical conditions, including chronic obstructive pulmonary disease and congestive heart failure, in shared clinical decision-making when offering RSV vaccine to adults aged ≥60 years. |
Multisystem inflammatory syndrome in children among persons who completed a two-dose COVID-19 vaccine primary series compared with those reporting no COVID-19 vaccination, US national MIS-C surveillance
Yousaf AR , Miller AD , Lindsey K , Shah AB , Wu MJ , Melgar M , Zambrano LD , Campbell AP . Pediatr Infect Dis J 2023 42 (12) e476-e478 We analyzed multisystem inflammatory syndrome in children cases by reported COVID-19 vaccination status (2-dose primary series vs. no vaccination). A total of 46% vaccinated versus 58% unvaccinated persons received intensive care unit-level care (P = 0.02); the risk of intensive care unit admission was 23% higher (adjusted relative risk: 1.23; 95% confidence interval: 1.03-1.48) among unvaccinated patients; 21 unvaccinated persons died. Multisystem inflammatory syndrome in children occurs after SARS-CoV-2 infection in vaccinated persons, but may be less severe. |
Time series modeling to estimate unrecorded burden of 12 symptomatic medical conditions among United States Medicare beneficiaries during the COVID-19 pandemic (preprint)
Melgar M , Leung J , Colombe J , Dooling K . medRxiv 2022 10 Objective: U.S. healthcare utilization declined during the COVID-19 pandemic, potentially leading to spurious drops in disease incidence recorded in administrative healthcare datasets used for public health surveillance. We used time series modeling to characterize the magnitude and duration of the COVID-19 pandemic's impact on claims-based monthly incidence of 12 symptomatic conditions among Medicare beneficiaries aged >=65 years. Method(s): Time series of observed monthly incidence of each condition were generated using Medicare claims data from January 2016-May 2021. Incidence time series were decomposed through seasonal and trend decomposition using Loess, resulting in seasonal, trend, and remainder components. We fit a non-linear mixed effects model to remainder time series components and used it to estimate underlying incidence and number of unrecorded cases of each condition during the pandemic period. Result(s): Observed incidence of all 12 conditions declined steeply in March 2020 with nadirs in April 2020, generally followed by return to pre-pandemic trends. The relative magnitude of the decrease varied by condition, but month of onset and duration did not. Estimated unrecorded cases during March 2020-May 2021 ranged from 9,543 (95% confidence interval [CI]: 854-15,703) for herpes zoster to 236,244 (95% CI: 188,583-292,369) for cataracts. Conclusion(s): Due to reduced healthcare utilization during the COVID-19 pandemic, claims-based data underestimate incidence of non-COVID-19 conditions. Time series modeling can be used to quantify this underestimation, facilitating longitudinal analyses of disease incidence pre- and post-pandemic. 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. |
Use of respiratory syncytial virus vaccines in older adults: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023
Melgar M , Britton A , Roper LE , Talbot HK , Long SS , Kotton CN , Havers FP . MMWR Morb Mortal Wkly Rep 2023 72 (29) 793-801 Respiratory syncytial virus (RSV) is a cause of severe respiratory illness in older adults. In May 2023, the Food and Drug Administration approved the first vaccines for prevention of RSV-associated lower respiratory tract disease in adults aged ≥60 years. Since May 2022, the Advisory Committee on Immunization Practices (ACIP) Respiratory Syncytial Virus Vaccines Adult Work Group met at least monthly to review available evidence regarding the safety, immunogenicity, and efficacy of these vaccines among adults aged ≥60 years. On June 21, 2023, ACIP voted to recommend that adults aged ≥60 years may receive a single dose of an RSV vaccine, using shared clinical decision-making. This report summarizes the body of evidence considered for this recommendation and provides clinical guidance for the use of RSV vaccines in adults aged ≥60 years. RSV vaccines have demonstrated moderate to high efficacy in preventing RSV-associated lower respiratory tract disease and have the potential to prevent substantial morbidity and mortality among older adults; postmarketing surveillance will direct future guidance. |
Deep dive into gaps and barriers to implementation of antimicrobial stewardship programs in hospitals in Latin America
Fabre V , Secaira C , Cosgrove SE , Lessa FC , Patel TS , Alvarez AA , Anchiraico LM , Del Carmen Bangher M , Barberis MF , Burokas MS , Castañeda X , Colque AM , De Ascencao G , Esquivel C , Ezcurra C , Falleroni LA , Frassone N , Garzón MI , Gomez C , Gonzalez JA , Hernandez D , Laplume D , Lemir CG , Maldonado Briones H , Melgar M , Mesplet F , Martinez G , Pertuz CM , Moreno C , Nemirovsky C , Nuccetelli Y , Palacio B , Sandoval N , Vergara H , Videla H , Villamandos S , Villareal O , Viteri A , Quiros R . Clin Infect Dis 2023 77 S53-s61 BACKGROUND: Antimicrobial resistance has worsened in Latin America. There is an urgent need to understand the development of antimicrobial stewardship programs (ASPs) and the barriers to implementing effective ASPs in light of limited national action plans or policies to promote ASPs in the region. METHODS: We performed a descriptive mixed-methods study of ASPs in 5 Latin American countries in March-July 2022. An electronic questionnaire with an associated scoring system (hospital ASP self-assessment) was used, and ASP development was classified based on the scores (inadequate, 0-25; basic, 26-50; intermediate, 51-75; or advanced, 76-100). Interviews among healthcare workers (HCWs) involved in antimicrobial stewardship (AS) inquired about behavioral and organizational factors that influence AS activities. Interview data were coded into themes. Results from the ASP self-assessment and interviews were integrated to create an explanatory framework. RESULTS: Twenty hospitals completed the self-assessment, and 46 AS stakeholders from these hospitals were interviewed. ASP development was inadequate/basic in 35% of hospitals, intermediate in 50%, and advanced in 15%. For-profit hospitals had higher scores than not-for-profit hospitals. Interview data validated the self-assessment findings and provided further insight into ASP implementation challenges, which included limited formal hospital leadership support, inadequate staffing and tools to perform AS work more efficiently, limited awareness of AS principles by HCWs, and limited training opportunities. CONCLUSIONS: We identified several barriers to ASP development in Latin America, suggesting the need to create accurate business cases for ASPs to obtain the necessary funding for their effective implementation and sustainability. |
A multicenter retrospective cohort study to characterize patients hospitalized with MIS-A and COVID-19 in the United States, 2020-2021
Melgar M , Abrams JY , Godfred-Cato S , Shah AB , Garg A , Strunk A , Narasimhan M , Koptyev J , Norden A , Musheyev D , Rashid F , Tannenbaum R , Estrada YMartin RM , Patel B , Karanth S , Achenbach CJ , Hall GT , Hockney SM , Caputo M , Abbo LM , Beauchamps L , Morris SB , Cifuentes RO , de St Maurice A , Bell DS , Prabaker KK , Sanz Vidorreta FJ , Bryant E , Cohen DK , Mohan R , Libby CP , SooHoo S , Domingo TJ , Campbell AP , Belay ED . Clin Infect Dis 2023 BACKGROUND: The diagnosis of SARS-CoV-2-associated multisystem inflammatory syndrome in adults (MIS-A) requires distinguishing it from acute COVID-19 and may impact clinical management. METHODS: In this retrospective cohort study, we applied the U.S. Centers for Disease Control and Prevention case definition to identify adults hospitalized with MIS-A at six academic medical centers during March 1, 2020-December 31, 2021. MIS-A patients were matched on age group, sex, site, and admission date at a 1:2 ratio to patients hospitalized with acute symptomatic COVID-19. Conditional logistic regression was used to compare demographics, presenting symptoms, laboratory and imaging results, treatments administered, and outcomes between cohorts. RESULTS: Through medical record review of 10,223 patients hospitalized with SARS-CoV-2-associated illness, we identified 53 MIS-A cases. Compared with 106 matched COVID-19 patients, MIS-A patients were more likely to be non-Hispanic Black and less likely to be non-Hispanic White. MIS-A patients more likely had laboratory-confirmed COVID-19 ≥ 14 days prior to hospitalization, more likely had positive in-hospital SARS-CoV-2 serologic testing, and more often presented with gastrointestinal symptoms and chest pain. They were less likely to have underlying medical conditions and to present with cough and dyspnea. On admission, MIS-A patients had higher neutrophil-to-lymphocyte ratio, C-reactive protein, ferritin, procalcitonin and D-dimer, compared with COVID-19 patients. MIS-A patients had longer hospitalization and more likely required intensive care admission, invasive mechanical ventilation, and vasopressors. Mortality was 6% in both cohorts. CONCLUSIONS: Compared with patients with acute symptomatic COVID-19, adults with MIS-A more often manifest certain symptoms and laboratory findings early during hospitalization. These features may facilitate diagnosis and management. |
Spatiotemporal variation in risk of Shigella infection in childhood: a global risk mapping and prediction model using individual participant data
Badr HS , Colston JM , Nguyen NH , Chen YT , Burnett E , Ali SA , Rayamajhi A , Satter SM , Van Trang N , Eibach D , Krumkamp R , May J , Adegnika AA , Manouana GP , Kremsner PG , Chilengi R , Hatyoka L , Debes AK , Ateudjieu J , Faruque ASG , Hossain MJ , Kanungo S , Kotloff KL , Mandomando I , Nisar MI , Omore R , Sow SO , Zaidi AKM , Lambrecht N , Adu B , Page N , Platts-Mills JA , Mavacala Freitas C , Pelkonen T , Ashorn P , Maleta K , Ahmed T , Bessong P , Bhutta ZA , Mason C , Mduma E , Olortegui MP , Peñataro Yori P , Lima AAM , Kang G , Humphrey J , Ntozini R , Prendergast AJ , Okada K , Wongboot W , Langeland N , Moyo SJ , Gaensbauer J , Melgar M , Freeman M , Chard AN , Thongpaseuth V , Houpt E , Zaitchik BF , Kosek MN . Lancet Glob Health 2023 11 (3) e373-e384 BACKGROUND: Diarrhoeal disease is a leading cause of childhood illness and death globally, and Shigella is a major aetiological contributor for which a vaccine might soon be available. The primary objective of this study was to model the spatiotemporal variation in paediatric Shigella infection and map its predicted prevalence across low-income and middle-income countries (LMICs). METHODS: Individual participant data for Shigella positivity in stool samples were sourced from multiple LMIC-based studies of children aged 59 months or younger. Covariates included household-level and participant-level factors ascertained by study investigators and environmental and hydrometeorological variables extracted from various data products at georeferenced child locations. Multivariate models were fitted and prevalence predictions obtained by syndrome and age stratum. FINDINGS: 20 studies from 23 countries (including locations in Central America and South America, sub-Saharan Africa, and south and southeast Asia) contributed 66 563 sample results. Age, symptom status, and study design contributed most to model performance followed by temperature, wind speed, relative humidity, and soil moisture. Probability of Shigella infection exceeded 20% when both precipitation and soil moisture were above average and had a 43% peak in uncomplicated diarrhoea cases at 33°C temperatures, above which it decreased. Compared with unimproved sanitation, improved sanitation decreased the odds of Shigella infection by 19% (odds ratio [OR]=0·81 [95% CI 0·76-0·86]) and open defecation decreased them by 18% (OR=0·82 [0·76-0·88]). INTERPRETATION: The distribution of Shigella is more sensitive to climatological factors, such as temperature, than previously recognised. Conditions in much of sub-Saharan Africa are particularly propitious for Shigella transmission, although hotspots also occur in South America and Central America, the Ganges-Brahmaputra Delta, and the island of New Guinea. These findings can inform prioritisation of populations for future vaccine trials and campaigns. FUNDING: NASA, National Institutes of Health-The National Institute of Allergy and Infectious Diseases, and Bill & Melinda Gates Foundation. |
Longitudinal analysis of electronic health information to identify possible COVID-19 sequelae
Click ES , Malec D , Chevinsky J , Tao G , Melgar M , Giovanni J , Gundlapalli A , Datta D , Wong KK . Emerg Infect Dis 2023 29 (2) 389-392 Ongoing symptoms might follow acute COVID-19. Using electronic health information, we compared pre‒ and post‒COVID-19 diagnostic codes to identify symptoms that had higher encounter incidence in the post‒COVID-19 period as sequelae. This method can be used for hypothesis generation and ongoing monitoring of sequelae of COVID-19 and future emerging diseases. |
Council of State and Territorial Epidemiologists/CDC Surveillance Case Definition for Multisystem Inflammatory Syndrome in Children Associated with SARS-CoV-2 Infection - United States.
Melgar M , Lee EH , Miller AD , Lim S , Brown CM , Yousaf AR , Zambrano LD , Belay ED , Godfred-Cato S , Abrams JY , Oster ME , Campbell AP . MMWR Recomm Rep 2022 71 (4) 1-14 THIS REPORT SUMMARIZES THE EVIDENCE AND RATIONALE SUPPORTING THE COMPONENTS OF THE CSTE/CDC MIS-C SURVEILLANCE CASE DEFINITION AND DESCRIBES THE METHODS USED TO DEVELOP THE DEFINITION. THESE METHODS INCLUDED CONVENING MIS-C CLINICAL EXPERTS (I.E., CONSULTANTS): regarding identification of MIS-C and its distinction from other pediatric conditions, a review of available literature comparing MIS-C phenotype with that of pediatric COVID-19 and other hyperinflammatory syndromes, and retrospective application of different criteria to data from MIS-C cases previously reported to CDC. |
Decline in severe varicella disease during the United States varicella vaccination program: Hospitalizations and deaths, 1990-2019
Marin M , Lopez AS , Melgar M , Dooling K , Curns AT , Leung J . J Infect Dis 2022 226 S407-s415 To describe the impact of the US varicella vaccination program on severe varicella outcomes, we analyzed varicella hospitalizations using the National Inpatient Sample 1993-2019 and varicella deaths using the National Center for Health Statistics data 1990-2019. Over 25 years of vaccination program (1995-2019), varicella hospitalizations, and deaths declined 94% and 97%, respectively, among persons aged <50 years. Most of the decline (90%) occurred during the 1-dose period (through 2006/2007) by attaining and maintaining high vaccination coverage; additional declines occurred during the 2-dose period, especially in the age groups covered by the 2-dose recommendation. The greatest decline for both hospitalizations and deaths (97% and >99%, respectively) was among persons aged <20 years, born during the varicella vaccination program. In the <20 age group, varicella hospitalization has become a rare event, and varicella deaths have been practically eliminated in the United States. A total of >10 500 varicella hospitalizations and 100 varicella deaths are now prevented annually in the United States as a direct result of vaccination and reduction in varicella-zoster virus circulation. |
A forty-year review of Rocky Mountain spotted fever cases in California shows clinical and epidemiologic changes
Kjemtrup AM , Padgett K , Paddock CD , Messenger S , Hacker JK , Feiszli T , Melgar M , Metzger ME , Hu R , Kramer VL . PLoS Negl Trop Dis 2022 16 (9) e0010738 Rocky Mountain spotted fever (RMSF) is a life-threatening tick-borne disease documented in North, Central, and South America. In California, RMSF is rare; nonetheless, recent fatal cases highlight ecological cycles of the two genera of ticks, Dermacentor and Rhipicephalus, known to transmit the disease. These ticks occur in completely different habitats (sylvatic and peridomestic, respectively) resulting in different exposure risks for humans. This study summarizes the demographic, exposure, and clinical aspects associated with the last 40 years of reported RMSF cases to the California Department of Public Health (CDPH). Seventy-eight RMSF cases with onsets from 1980 to 2019 were reviewed. The incidence of RMSF has risen in the last 20 years from 0.04 cases per million to 0.07 cases per million (a two-fold increase in reports), though the percentage of cases that were confirmed dropped significantly from 72% to 25% of all reported cases. Notably, Hispanic/Latino populations saw the greatest rise in incidence. Cases of RMSF in California result from autochthonous and out-of-state exposures. During the last 20 years, more cases reported exposure in Southern California or Mexico than in the previous 20 years. The driver of these epidemiologic changes is likely the establishment and expansion of Rhipicephalus sanguineus sensu lato ticks in Southern California and on-going outbreaks of RMSF in northern Mexico. Analysis of available electronically reported clinical data from 2011 to 2019 showed that 57% of reported cases presented with serious illness requiring hospitalization with a 7% mortality. The difficulty in recognizing RMSF is due to a non-specific clinical presentation; however, querying patients on the potential of tick exposure in both sylvatic and peridomestic environments may facilitate appropriate testing and treatment. |
Treatment of Multisystem Inflammatory Syndrome in Children: Understanding Differences in Results of Comparative Effectiveness Studies.
Melgar M , Seaby EG , McArdle AJ , Young CC , Campbell AP , Murray NL , Patel MM , Levin M , Randolph AG , Son MBF . ACR Open Rheumatol 2022 4 (9) 804-810 OBJECTIVE: Two cohort studies in patients with multisystem inflammatory syndrome in children (MIS-C) demonstrated contrasting results regarding the benefit of initial immunomodulatory treatment with intravenous immunoglobulin (IVIG) alone versus IVIG and glucocorticoids. We sought to determine whether application of different MIS-C definitions and differing disease severity between cohorts underlay discrepant results. METHODS: The Overcoming COVID-19 Public Health Surveillance Registry (OC-19) included patients meeting the US Centers for Disease Control and Prevention (CDC) MIS-C definition, whereas the Best Available Treatment Study (BATS) applied the World Health Organization (WHO) definition. We applied the WHO definition to the OC-19 cohort and the CDC definition to the BATS cohort and determined the proportion that did not meet the alternate definition. We compared illness severity indicators between cohorts. RESULTS: Of 349 OC-19 patients, 9.5% did not meet the WHO definition. Of 350 BATS patients, 10.3% did not meet the CDC definition. Most organ system involvement was similar between the cohorts, but more OC-19 patients had WHO-defined cardiac involvement (87.1% vs 79.4%, P = 0.008). OC-19 patients were more often admitted to intensive care (61.0% vs 44.8%, P < 0.001) and more often received vasopressors or inotropes (39.5% vs 22.9%, P < 0.001) before immunomodulatory treatment. CONCLUSION: Greater illness severity and cardiovascular involvement in the OC-19 cohort compared with the BATS cohort, and not use of different MIS-C case definitions, may have contributed to differing study conclusions about optimal initial treatment for MIS-C. Disease severity should be considered in future MIS-C study designs and treatment recommendations to identify patients who would benefit from aggressive immunomodulatory treatment. |
Impact of vaccine effectiveness and coverage on preventing large mumps outbreaks on college campuses: Implications for vaccination strategy
Melgar M , Yockey B , Marlow MA . Epidemics 2022 40 100594 Recent mumps outbreaks among highly vaccinated populations, including college students, have called into question the vaccine effectiveness (VE) of routine two-dose measles, mumps, and rubella (MMR2) immunization. We aimed to estimate the VE required for a novel vaccination strategy (e.g., MMR booster dose, novel vaccine) to prevent large mumps outbreaks on college campuses. Using mumps college outbreak data reported to the U.S. Centers for Disease Control and Prevention during 2016-2017, we estimated current MMR2 VE using the screening method and implemented a compartmental model of mumps transmission. We performed 2000 outbreak simulations, following introduction of an infectious person to a population of 10,000, over ranges of MMR2 vaccine coverage (VC) and VE (30.0-99.0%). We compared the impact of varying VC and VE on mumps and mumps orchitis case counts and determined VE thresholds that ensured < 5.0% and < 2.0% of the outbreak simulations exceeded 20 and 100 mumps cases. Median estimated MMR2 VE in reported mumps outbreaks was 60.5% and median reported MMR2 VC was 97.5%. Simulated mumps case count was more sensitive to changes in VE than in VC. The opposite was true for simulated mumps orchitis case count, though orchitis case count was small (mean <10 cases across simulations for VE near 60.5% and VC near 97.5%). At 97.5% VC, 73.1% and 78.2% VE were required for < 5.0% and < 2.0% of outbreaks, respectively, to exceed 100 mumps cases. Maintaining 97.5% VC, 82.4% and 85.9% VE were required for < 5.0% and < 2.0% of outbreaks, respectively, to exceed 20 cases. We conclude that maintaining current levels of MMR2 VC, a novel vaccination strategy aimed at reducing mumps transmission must achieve at least 73.1-85.9% VE among young adults to prevent large mumps outbreaks on college campuses. |
Multisystem Inflammatory Syndrome in Children (MIS-C) During SARS-CoV-2 Delta and Omicron Variant Circulation- United States, July 2021 - January 2022.
Miller AD , Yousaf AR , Bornstein E , Wu MJ , Lindsey K , Melgar M , Oster ME , Zambrano LD , Campbell AP . Clin Infect Dis 2022 75 S303-S307 We describe 2,116 multisystem inflammatory syndrome in children (MIS-C) cases reported to CDC during Delta and Omicron circulation from July 2021-January 2022. Half of MIS-C patients were aged 5-11 years, 52% received ICU-level care, and 1.1% died. Only 3.0% of eligible patients were fully vaccinated prior to MIS-C onset. |
Isoniazid-associated pellagra during mass scale-up of tuberculosis preventive therapy: a case-control study
Nabity SA , Mponda K , Gutreuter S , Surie D , Zimba SB , Chisuwo L , Moffitt A , Williams AM , Sharma AJ , Marshall RE , Chiwaula MJ , da Silva R , Kumwenda T , Chilikutali L , Mwamale S , Nagoli E , Mwenyeheri G , Ngongonda D , Kaunda E , Mtoto F , Mhango V , Mbewe K , Melgar M , Odo M , Jahn A , Buono N , Maida A , Girma B , Kalua T , Nyirenda R , Sunguti J , Woelk G , Gunde LJ , Mekonnen TF , Maphosa T , Kim EJ , Auld AF , Muula AS , Oeltmann JE . Lancet Glob Health 2022 10 (5) e705-e714 BACKGROUND: Pellagra is caused by niacin (vitamin B3) deficiency and patients with pellagra present with a characteristic rash. Isoniazid disrupts intracellular niacin synthesis and might induce niacin deficiency. In 2017, Malawi scaled up continuous isoniazid preventive treatment (IPT) for tuberculosis prevention among people living with HIV. In addition, an under-diversified diet based on subsistence maize, as is commonly the case in Malawi, is a risk factor for pellagra. We aimed to investigate whether large-scale isoniazid exposure in Malawi contributed to the cumulative risk for pellagra in a nutritionally vulnerable population. METHODS: We did a matched case-control study to evaluate the association between daily, continuous isoniazid exposure and pellagra. We matched sequentially enrolled patients with pellagra each with four control participants by sex and age from referral dermatology centres in three IPT scale-up districts in Malawi (Lilongwe, Blantyre, and Zomba) to evaluate isoniazid as a risk for pellagra using multivariable conditional logistic regression. We established a community clinic referral system surrounding the dermatology clinic in each district to enhance case-finding and included all patients with pellagra, regardless of referral status. The primary outcome was dermatologist-diagnosed pellagra. We calculated the interval between isoniazid initiation and rash onset and assessed 30-day clinical outcomes after multi-B vitamin treatment containing 300 mg nicotinamide daily. FINDINGS: Between Feb 5 and Aug 9, 2019, we enrolled 197 patients with pellagra and 781 matched controls. Isoniazid exposure was associated with an increased risk of pellagra (adjusted odds ratio 42·6 [95% CI 13·3-136·6]). Significant covariates included HIV infection, referral status, food insecurity, underweight, excess alcohol consumption, and, among women, lactation. The median time from isoniazid initiation to rash onset was shorter during the season of food scarcity (5 months [IQR 3-7]) compared with the harvest season (9 months [8-11]; hazard ratio 7·2 [95% CI 3·2-16·2], log-rank p<0·0001). Those with isoniazid-associated pellagra who discontinued isoniazid and adhered to multi-B vitamin treatment showed 30-day clinical improvement. INTERPRETATION: Continuous IPT scale-up and the annual period of food scarcity both increased the risk of pellagra in Malawi. Use of shorter rifamycin-based regimens for tuberculosis prevention and food fortification in populations with undernutrition might reduce this risk. Niacin-containing multi-B vitamin co-administration with isoniazid as pellagra prevention is worth exploring further. FUNDING: This study was supported by the President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention under project 7173. |
Multisystem inflammatory syndrome in adults (MIS-A): case finding through systematic review of electronic medical records.
Melgar M , Haston J , DeCuir J , Cheng Q , Arnold KE , Meng L , Murphy DJ , Overton E , Hollberg J , Tobin-D'Angelo M , Patel P , Campbell AP , Godfred-Cato Do S , Belay ED . Clin Infect Dis 2022 75 (11) 1903-1911 BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) is a severe condition temporally associated with SARS-CoV-2 infection. METHODS: In this retrospective cohort study, we applied the U.S. Centers for Disease Control and Prevention (CDC) case definition to identify diagnosed and undiagnosed MIS-A cases among adults discharged April 2020-January 2021 from four Atlanta, Georgia hospitals affiliated with a single medical center. Non-MIS-A COVID-19 hospitalizations were identified using International Classification of Diseases, Tenth Revision encounter code U07.1. We calculated the ratio of MIS-A to COVID-19 hospitalizations, compared demographic characteristics of the two cohorts, and described clinical characteristics of MIS-A patients. RESULTS: We identified 11 MIS-A cases, none of which were diagnosed by the treatment team, and 5,755 COVID-19 hospitalizations (ratio 1: 523). Compared with patients with COVID-19, patients with MIS-A were more likely to be younger than 50 years (72.7% vs. 26.1%, p < 0.01) and to be non-Hispanic Black persons (81.8% vs. 50.0%, p = 0.04). Ten patients with MIS-A (90.9%) had at least one underlying medical condition. Two MIS-A patients (18.2%) had a previous episode of laboratory-confirmed COVID-19, occurring 37 and 55 days prior to admission. All MIS-A patients developed left ventricular systolic dysfunction. None had documented mucocutaneous involvement. All required intensive care, all received systemic corticosteroids, eight (72.7%) required mechanical ventilation, two (18.2%) required mechanical cardiovascular circulatory support, and none received intravenous immunoglobulin. Two (18.2%) died or were discharged to hospice. CONCLUSIONS: MIS-A is severe but likely underrecognized complication of SARS-CoV-2 infection. Improved recognition of MIS-A is needed to quantify its burden and identify populations at highest risk. |
Clinical Characteristics and Outcomes Among Adults Hospitalized with Laboratory-Confirmed SARS-CoV-2 Infection During Periods of B.1.617.2 (Delta) and B.1.1.529 (Omicron) Variant Predominance - One Hospital, California, July 15-September 23, 2021, and December 21, 2021-January 27, 2022.
Modes ME , Directo MP , Melgar M , Johnson LR , Yang H , Chaudhary P , Bartolini S , Kho N , Noble PW , Isonaka S , Chen P . MMWR Morb Mortal Wkly Rep 2022 71 (6) 217-223 In mid-December 2021, the B.1.1.529 (Omicron) variant of SARS-CoV-2, the virus that causes COVID-19, surpassed the B.1.617.2 (Delta) variant as the predominant strain in California.() Initial reports suggest that the Omicron variant is more transmissible and resistant to vaccine neutralization but causes less severe illness compared with previous variants (1-3). To describe characteristics of patients hospitalized with SARS-CoV-2 infection during periods of Delta and Omicron predominance, clinical characteristics and outcomes were retrospectively abstracted from the electronic health records (EHRs) of adults aged 18 years with positive reverse transcription-polymerase chain reaction (RT-PCR) SARS-CoV-2 test results admitted to one academic hospital in Los Angeles, California, during July 15-September 23, 2021 (Delta predominant period, 339 patients) and December 21, 2021-January 27, 2022 (Omicron predominant period, 737 patients). Compared with patients during the period of Delta predominance, a higher proportion of adults admitted during Omicron predominance had received the final dose in a primary COVID-19 vaccination series (were fully vaccinated) (39.6% versus 25.1%), and fewer received COVID-19-directed therapies. Although fewer required intensive care unit (ICU) admission and invasive mechanical ventilation (IMV), and fewer died while hospitalized during Omicron predominance, there were no significant differences in ICU admission or IMV when stratified by vaccination status. Fewer fully vaccinated Omicron-period patients died while hospitalized (3.4%), compared with Delta-period patients (10.6%). Among Omicron-period patients, vaccination was associated with lower likelihood of ICU admission, and among adults aged 65 years, lower likelihood of death while hospitalized. Likelihood of ICU admission and death were lowest among adults who had received a booster dose. Among the first 131 Omicron-period hospitalizations, 19.8% of patients were clinically assessed as admitted for non-COVID-19 conditions. Compared with adults considered likely to have been admitted because of COVID-19, these patients were younger (median age=38 versus 67 years) and more likely to have received at least one dose of a COVID-19 vaccine (84.6% versus 61.0%). Although 20% of SARS-CoV-2-associated hospitalizations during the period of Omicron predominance might be driven by non-COVID-19 conditions, large numbers of hospitalizations place a strain on health systems. Vaccination, including a booster dose for those who are fully vaccinated, remains critical to minimizing risk for severe health outcomes among adults with SARS-CoV-2 infection. |
Associations Between Eight Earth Observation-Derived Climate Variables and Enteropathogen Infection: An Independent Participant Data Meta-Analysis of Surveillance Studies With Broad Spectrum Nucleic Acid Diagnostics.
Colston JM , Zaitchik BF , Badr HS , Burnett E , Ali SA , Rayamajhi A , Satter SM , Eibach D , Krumkamp R , May J , Chilengi R , Howard LM , Sow SO , JahangirHossain M , Saha D , ImranNisar M , Zaidi AKM , Kanungo S , Mandomando I , Faruque ASG , Kotloff KL , Levine MM , Breiman RF , Omore R , Page N , Platts-Mills JA , Ashorn U , Fan YM , Shrestha PS , Ahmed T , Mduma E , Yori PP , Bhutta Z , Bessong P , Olortegui MP , Lima AAM , Kang G , Humphrey J , Prendergast AJ , Ntozini R , Okada K , Wongboot W , Gaensbauer J , Melgar MT , Pelkonen T , Freitas CM , Kosek MN . Geohealth 2022 6 (1) e2021GH000452 Diarrheal disease, still a major cause of childhood illness, is caused by numerous, diverse infectious microorganisms, which are differentially sensitive to environmental conditions. Enteropathogen-specific impacts of climate remain underexplored. Results from 15 studies that diagnosed enteropathogens in 64,788 stool samples from 20,760 children in 19 countries were combined. Infection status for 10 common enteropathogens-adenovirus, astrovirus, norovirus, rotavirus, sapovirus, Campylobacter, ETEC, Shigella, Cryptosporidium and Giardia-was matched by date with hydrometeorological variables from a global Earth observation dataset-precipitation and runoff volume, humidity, soil moisture, solar radiation, air pressure, temperature, and wind speed. Models were fitted for each pathogen, accounting for lags, nonlinearity, confounders, and threshold effects. Different variables showed complex, non-linear associations with infection risk varying in magnitude and direction depending on pathogen species. Rotavirus infection decreased markedly following increasing 7-day average temperatures-a relative risk of 0.76 (95% confidence interval: 0.69-0.85) above 28C-while ETEC risk increased by almost half, 1.43 (1.36-1.50), in the 20-35C range. Risk for all pathogens was highest following soil moistures in the upper range. Humidity was associated with increases in bacterial infections and decreases in most viral infections. Several virus species' risk increased following lower-than-average rainfall, while rotavirus and ETEC increased with heavier runoff. Temperature, soil moisture, and humidity are particularly influential parameters across all enteropathogens, likely impacting pathogen survival outside the host. Precipitation and runoff have divergent associations with different enteric viruses. These effects may engender shifts in the relative burden of diarrhea-causing agents as the global climate changes. |
Identification and description of patients with multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection using the Premier Healthcare Database.
DeCuir J , Baggs J , Melgar M , Patel P , Wong KK , Schwartz NG , Bamrah Morris S , Godfred-Cato S , Belay ED . Epidemiol Infect 2022 150 1-22 Multisystem inflammatory syndrome in adults (MIS-A) is a hyperinflammatory illness related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The characteristics of patients with this syndrome and the frequency with which it occurs among patients hospitalised after SARS-CoV-2 infection are unclear. Using the Centers for Disease Control and Prevention case definition for MIS-A, we created ICD-10-CM code and laboratory criteria to identify potential MIS-A patients in the Premier Healthcare Database Special COVID-19 Release, a database containing patient-level information on hospital discharges across the United States. Modified MIS-A criteria were applied to hospitalisations with discharge from March to December 2020. The proportion of hospitalisations meeting electronic health record criteria for MIS-A and descriptive statistics for patients in the potential MIS-A cohort were calculated. Of 34 515 SARS-CoV-2-related hospitalisations with complete clinical and laboratory data, 53 met modified criteria for MIS-A (0.15%). The median age was 62 years (IQR 52-74). Most patients met the severe cardiac illness criterion through either myocarditis (66.0%) or new-onset heart failure (35.8%). A total of 79.2% of patients required ICU admission, while 43.4% of patients in the cohort died. MIS-A appears to be a rare but severe outcome of SARS-CoV-2 infection. Additional studies are needed to investigate how this syndrome differs from severe coronavirus disease 2019 (COVID-19) in adults. |
Multisystem Inflammatory Syndrome in Children-United States, February 2020-July 2021.
Miller AD , Zambrano LD , Yousaf AR , Abrams JY , Meng L , Wu MJ , Melgar M , Oster ME , Godfred Cato SE , Belay ED , Campbell AP . Clin Infect Dis 2021 75 (1) e1165-e1175 BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory condition in persons aged <21 years associated with antecedent SARS-CoV-2 infection. Our objective was to describe MIS-C cases reported to CDC's national surveillance since the COVID-19 pandemic began. METHODS: We included patients meeting the MIS-C case definition with onset date from February 19, 2020 through July 31, 2021, using CDC's MIS-C case report form, which collects information on demographics, clinical presentation, and laboratory results. Trends over time across 3 MIS-C pandemic waves were assessed using Cochran-Armitage test for categorical and Jonckheere-Terpstra test for continuous variables. RESULTS: Of 4,901 reported cases, 4,470 met inclusion criteria. Median patient age increased over time (P<0.001), with a median of 9 years (interquartile range, 5-13 years) during the most recent (third) wave. Male predominance also increased (62% in third wave, P<0.001). A significant (P<0.001) increase in severe hematologic and gastrointestinal involvement was observed across the study period. Frequency of several cardiovascular complications (i.e., cardiac dysfunction, myocarditis, and shock/ vasopressor receipt) and renal failure declined (P<0.001). Provision of critical care including mechanical ventilation (P<0.001) and extracorporeal membrane oxygenation (ECMO; P=0.046) decreased, as did duration of hospitalization and mortality (each P<0.001). CONCLUSIONS: Over the first 3 pandemic waves of MIS-C in the United States, cardiovascular complications and clinical outcomes including length of hospitalization, receipt of ECMO, and death decreased over time. These data serve as a baseline for monitoring future trends associated with SARS-CoV-2 B.1.617.2 (Delta) or other variants and increased COVID-19 vaccination among children. |
Multisystem Inflammatory Syndrome in Adults After Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Coronavirus Disease 2019 (COVID-19) Vaccination.
Belay ED , Godfred Cato S , Rao AK , Abrams J , Wilson WW , Lim S , Newton-Cheh C , Melgar M , DeCuir J , Webb B , Marquez P , Su JR , Meng L , Grome HN , Schlaudecker E , Talaat K , Edwards K , Barnett E , Campbell AP , Broder KR , Bamrah Morris S . Clin Infect Dis 2021 75 (1) e741-e748 BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) was reported in association with the COVID-19 pandemic. MIS-A was included in the list of adverse events to be monitored as part of the emergency use authorizations issued for COVID-19 vaccines. METHODS: Reports of MIS-A patients received by the Centers for Disease Control and Prevention (CDC) after COVID-19 vaccines became available were assessed. Data collected on the patients included clinical and demographic characteristics and their vaccine status. The Vaccine Adverse Events Reporting System (VAERS) was also reviewed for possible cases of MIS-A. RESULTS: From December 14, 2020 to April 30, 2021, 20 patients who met the case definition for MIS-A were reported to CDC. Their median age was 35 years (range, 21-66 years), and 13 (65%) were male. Overall, 16 (80%) patients had a preceding COVID-19-like illness a median of 26 days (range 11-78 days) before MIS-A onset. All 20 patients had laboratory evidence of SARS-CoV-2 infection. Seven MIS-A patients (35%) received COVID-19 vaccine a median of 10 days (range, 6-45 days) before MIS-A onset; 3 patients received a second dose of COVID-19 vaccine 4, 17, and 22 days before MIS-A onset. Patients with MIS-A predominantly had gastrointestinal and cardiac manifestations and hypotension or shock. CONCLUSIONS: Although 7 patients were reported to have received COVID-19 vaccine, all had evidence of prior SARS-CoV-2 infection. Given the widespread use of COVID-19 vaccines, the lack of reporting of MIS-A associated with vaccination alone, without evidence of underlying SARS-CoV-2 infection, is reassuring. |
Assessment of the tuberculosis case-finding and prevention cascade among people living with HIV in Zambia - 2018: a cross-sectional cluster survey
Melgar M , Shiraishi RW , Tende C , Mwanza S , Mulenga J , Khondowe S , Mwakazanga D , Kapungu K , Tembo M , Nota A , Lungu P , Moore B , Podewils LJ . BMC Public Health 2021 21 (1) 859 BACKGROUND: The Ministry of Health Zambia recommends tuberculosis preventive treatment (TPT) with 6 months daily isoniazid for all people living with human immunodeficiency virus (HIV) after ruling out active tuberculosis disease. We sought to estimate the percentage of people living with HIV who progress through each stage of the tuberculosis case-finding and prevention cascade in two provinces with the highest tuberculosis burden in Zambia. METHODS: In this cross-sectional survey, we used a two-stage cluster sampling method. We sampled 12 healthcare facilities with probability proportional to size. Patient volume determined facility cluster size. During October 2018, from each facility we systematically sampled medical records of adults and children living with HIV. Our primary outcome of interest was TPT initiation rate among eligible people living with HIV, weighted for complex survey design. The Rao-Scott adjusted chi-square test was used to test for differences in TPT initiation rate and other indicators from the tuberculosis prevention cascade by age group and province of residence. Additionally, we conducted semi-structured interviews with healthcare workers at each facility to assess TPT knowledge and identify challenges to its implementation. RESULTS: We sampled 482 records of people living with HIV (including 128 children living with HIV). Excluding two people diagnosed with tuberculosis disease before enrollment in HIV care, 93.4% underwent tuberculosis symptom screening. Of those, 4.7% were diagnosed with tuberculosis disease and 95.3% were TPT-eligible, of whom 24.7% initiated TPT. TPT initiation was lower among eligible children (7.7%) compared with adults (25.2%, p = 0.03) and Copperbelt residents (3.1%) compared with Lusaka residents (35.8%, p < 0.01). TPT completion rate was 38.4% among people living with HIV who initiated the 6-month course. Among interviewed healthcare workers, 58.3% (unweighted) incorrectly relayed the number of symptoms needed for a positive tuberculosis symptom screen, 83.3% (unweighted) reported insufficient isoniazid stockpile for completion at the time of TPT initiation, and only 27.3% (unweighted) reported receiving TPT-specific training. CONCLUSIONS: TPT uptake among people living with HIV in Zambia is challenged by inconsistent tuberculosis screening, lack of TPT training for healthcare workers, and supply chain inefficiencies. Addressing these barriers may increase TPT initiations and improve outcomes among people living with HIV. |
Global Reports of Intussusception in Infants With SARS-CoV-2 Infection.
Giovanni JE , Hrapcak S , Melgar M , Godfred-Cato S . Pediatr Infect Dis J 2020 40 (1) e35-e36 Idiopathic intussusception is a common cause of bowel obstruction in infants, presenting as refractory abdominal pain or mass, vomiting, lethargy, and currant jelly stool. Coronavirus disease 2019 is not well characterized in children, especially infants, but symptoms in children have included nausea, vomiting, diarrhea, and abdominal pain. From January to July 2020, intussusception was reported in 5 infants 4-10 months of age who had laboratory-confirmed SARS-CoV-2 infection. All 5 infants presented with currant jelly stool and at least 1 other abdominal symptom, and none presented with respiratory symptoms. Four infants recovered but the fifth infant progressed to a critical illness and death. While an association between SARS-CoV-2 infection and intussusception has not been established, infants with symptoms consistent with intussusception may warrant testing for viral pathogens, including SARS-CoV-2, especially if presenting to healthcare with a history of SARS-CoV-2 exposure or with signs and symptoms of COVID-19. More investigation is needed to determine whether intussusception is part of the clinical spectrum of COVID-19 in infants or a coincidental finding among infants with SARS-CoV-2 infection. |
Serious Adverse Health Events, Including Death, Associated with Ingesting Alcohol-Based Hand Sanitizers Containing Methanol - Arizona and New Mexico, May-June 2020.
Yip L , Bixler D , Brooks DE , Clarke KR , Datta SD , Dudley S Jr , Komatsu KK , Lind JN , Mayette A , Melgar M , Pindyck T , Schmit KM , Seifert SA , Shirazi FM , Smolinske SC , Warrick BJ , Chang A . MMWR Morb Mortal Wkly Rep 2020 69 (32) 1070-1073 Alcohol-based hand sanitizer is a liquid, gel, or foam that contains ethanol or isopropanol used to disinfect hands. Hand hygiene is an important component of the U.S. response to the emergence of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). If soap and water are not readily available, CDC recommends the use of alcohol-based hand sanitizer products that contain at least 60% ethyl alcohol (ethanol) or 70% isopropyl alcohol (isopropanol) in community settings (1); in health care settings, CDC recommendations specify that alcohol-based hand sanitizer products should contain 60%-95% alcohol (≥60% ethanol or ≥70% isopropanol) (2). According to the Food and Drug Administration (FDA), which regulates alcohol-based hand sanitizers as an over-the-counter drug, methanol (methyl alcohol) is not an acceptable ingredient. Cases of ethanol toxicity following ingestion of alcohol-based hand sanitizer products have been reported in persons with alcohol use disorder (3,4). On June 30, 2020, CDC received notification from public health partners in Arizona and New Mexico of cases of methanol poisoning associated with ingestion of alcohol-based hand sanitizers. The case reports followed an FDA consumer alert issued on June 19, 2020, warning about specific hand sanitizers that contain methanol. Whereas early clinical effects of methanol and ethanol poisoning are similar (e.g., headache, blurred vision, nausea, vomiting, abdominal pain, loss of coordination, and decreased level of consciousness), persons with methanol poisoning might develop severe anion-gap metabolic acidosis, seizures, and blindness. If left untreated methanol poisoning can be fatal (5). Survivors of methanol poisoning might have permanent visual impairment, including complete vision loss; data suggest that vision loss results from the direct toxic effect of formate, a toxic anion metabolite of methanol, on the optic nerve (6). CDC and state partners established a case definition of alcohol-based hand sanitizer-associated methanol poisoning and reviewed 62 poison center call records from May 1 through June 30, 2020, to characterize reported cases. Medical records were reviewed to abstract details missing from poison center call records. During this period, 15 adult patients met the case definition, including persons who were American Indian/Alaska Native (AI/AN). All had ingested an alcohol-based hand sanitizer and were subsequently admitted to a hospital. Four patients died and three were discharged with vision impairment. Persons should never ingest alcohol-based hand sanitizer, avoid use of specific imported products found to contain methanol, and continue to monitor FDA guidance (7). Clinicians should maintain a high index of suspicion for methanol poisoning when evaluating adult or pediatric patients with reported swallowing of an alcohol-based hand sanitizer product or with symptoms, signs, and laboratory findings (e.g., elevated anion-gap metabolic acidosis) compatible with methanol poisoning. Treatment of methanol poisoning includes supportive care, correction of acidosis, administration of an alcohol dehydrogenase inhibitor (e.g., fomepizole), and frequently, hemodialysis. |
Estimated Community Seroprevalence of SARS-CoV-2 Antibodies - Two Georgia Counties, April 28-May 3, 2020.
Biggs HM , Harris JB , Breakwell L , Dahlgren FS , Abedi GR , Szablewski CM , Drobeniuc J , Bustamante ND , Almendares O , Schnall AH , Gilani Z , Smith T , Gieraltowski L , Johnson JA , Bajema KL , McDavid K , Schafer IJ , Sullivan V , Punkova L , Tejada-Strop A , Amiling R , Mattison CP , Cortese MM , Ford SE , Paxton LA , Drenzek C , Tate JE , CDC Field Surveyor Team , Brown Nicole , Chang Karen T , Deputy Nicholas P , Desamu-Thorpe Rodel , Gorishek Chase , Hanchey Arianna , Melgar Michael , Monroe Benjamin P , Nielsen Carrie F , Pellegrini Gerald JJr , Shamout Mays , Tison Laura I , Vagi Sara , Zacks Rachael . MMWR Morb Mortal Wkly Rep 2020 69 (29) 965-970 Transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is ongoing in many communities throughout the United States. Although case-based and syndromic surveillance are critical for monitoring the pandemic, these systems rely on persons obtaining testing or reporting a COVID-19-like illness. Using serologic tests to detect the presence of SARS-CoV-2 antibodies is an adjunctive strategy that estimates the prevalence of past infection in a population. During April 28-May 3, 2020, coinciding with the end of a statewide shelter-in-place order, CDC and the Georgia Department of Public Health conducted a serologic survey in DeKalb and Fulton counties in metropolitan Atlanta to estimate SARS-CoV-2 seroprevalence in the population. A two-stage cluster sampling design was used to randomly select 30 census blocks in each county, with a target of seven participating households per census block. Weighted estimates were calculated to account for the probability of selection and adjusted for age group, sex, and race/ethnicity. A total of 394 households and 696 persons participated and had a serology result; 19 (2.7%) of 696 persons had SARS-CoV-2 antibodies detected. The estimated weighted seroprevalence across these two metropolitan Atlanta counties was 2.5% (95% confidence interval [CI] = 1.4-4.5). Non-Hispanic black participants more commonly had SARS-CoV-2 antibodies than did participants of other racial/ethnic groups (p<0.01). Among persons with SARS-CoV-2 antibodies, 13 (weighted % = 49.9; 95% CI = 24.4-75.5) reported a COVID-19-compatible illness,* six (weighted % = 28.2; 95% CI = 11.9-53.3) sought medical care for a COVID-19-compatible illness, and five (weighted % = 15.7; 95% CI = 5.1-39.4) had been tested for SARS-CoV-2 infection, demonstrating that many of these infections would not have been identified through case-based or syndromic surveillance. The relatively low seroprevalence estimate in this report indicates that most persons in the catchment area had not been infected with SARS-CoV-2 at the time of the survey. Continued preventive measures, including social distancing, consistent and correct use of face coverings, and hand hygiene, remain critical in controlling community spread of SARS-CoV-2. |
Tuberculosis preventive treatment scale-up among antiretroviral therapy patients - 16 countries supported by the U.S. President's Emergency Plan for AIDS Relief, 2017-2019
Melgar M , Nichols C , Cavanaugh JS , Kirking HL , Surie D , Date A , Ahmedov S , Maloney S , Fukunaga R . MMWR Morb Mortal Wkly Rep 2020 69 (12) 329-334 Tuberculosis (TB) is the leading cause of death among persons living with human immunodeficiency virus (HIV) infection. In 2018, an estimated 251,000 persons living with HIV infection died from TB, accounting for one third of all HIV-related deaths and one sixth of all TB deaths (1). TB preventive treatment (TPT) is recommended by the World Health Organization (WHO) for persons living with HIV infection without active TB disease (i.e., adults with a negative clinical symptom screen for cough, fever, night sweats, or weight loss; and children with a negative clinical screen for cough, fever, contact with a person with TB, or poor weight gain) and either without* a tuberculin skin test result or with a known positive result (2). TPT decreases morbidity and mortality among persons living with HIV infection, independent of antiretroviral therapy (ART) (3); however, in 2017, fewer than 1 million of the estimated 21.3 million ART patients started TPT worldwide. Most patients receiving TPT were treated with 6 months of daily isoniazid (1,4). This report summarizes data on TB symptom screening and TPT initiation and completion among ART patients in 16 countries supported by the U.S. President's Emergency Plan for AIDS(dagger) Relief (PEPFAR) during April 1, 2017-March 31, 2019. During this period, these 16 countries accounted for approximately 90% of PEPFAR-supported ART patients. During April 1, 2017-September 30, 2018, TB symptom screening increased from 54% to 84%. Overall, nearly 2 million ART patients initiated TPT, and 60% completed treatment during October 1, 2017-March 31, 2019. Although TPT initiations increased substantially, completion among those who initiated TPT increased only from 55% to 66%. In addition to continuing gains in initiation, improving retention after initiation and identifying barriers to TPT completion are important to increase TPT scale-up and reduce global TB mortality. |
Impact of maternal antibody on the immunogenicity of inactivated polio vaccine in infants immunized with bivalent oral polio vaccine: Implications for the polio eradication endgame
Gaensbauer JT , Gast C , Bandyopadhyay AS , O'Ryan M , Saez-Llorens X , Rivera L , Lopez-Medina E , Melgar M , Weldon WC , Oberste MS , Ruttimann R , Clemens R , Asturias EJ . Clin Infect Dis 2018 67 S57-s65 Background: Quantifying interference of maternal antibodies with immune responses to varying dose schedules of inactivated polio vaccine (IPV) is important for the polio endgame as IPV replaces oral polio vaccine (OPV). Methods: Type 2 poliovirus humoral and intestinal responses were analyzed using pre-IPV type 2 seropositivity as proxy for maternal antibodies from 2 trials in Latin America. Infants received 1 or 2 doses of IPV in sequential IPV-bivalent oral polio vaccine (bOPV) or mixed bOPV-IPV schedules. Results: Among infants vaccinated with bOPV at age 6, 10, and 14 weeks of age and IPV at 14 weeks, those with type 2 pre-IPV seropositivity had lower seroprotection rates than seronegative infants at 4 weeks (92.7% vs 83.8%; difference, 8.9% [95% confidence interval, 0.6%-19.9%]; n = 260) and 22 weeks (82.7% vs 60.4%; difference, 22.3 [12.8%-32.4%]; n = 481) post-IPV. A second IPV at age 36 weeks resulted in 100% seroprotection in both groups. Among infants vaccinated with 1 IPV at age 8 weeks followed by 2 doses of bOPV, pre-IPV type 2-seropositive infants had lower seroprotection at age 28 weeks than those who were seronegative (93.0% vs 73.9%; difference, 19.6% [95% confidence interval, 7.3%-29.4%]; n = 168). A second dose of IPV at 16 weeks achieved >97% seroprotection at age 24 or 28 weeks, regardless of pre-IPV status. Poliovirus shedding after challenge with monovalent OPV, serotype 2, was higher in pre-IPV seropositive infants given sequential IPV-bOPV. No differences were observed in the mixed bOPV-IPV schedule. Conclusions: The presence of maternal antibody is associated with lower type 2 post-IPV seroprotection rates among infants who receive a single dose of IPV. This impact persists until late in infancy and is overcome by a second IPV dose. |
Inactivated polio vaccines from three different manufacturers have equivalent safety and immunogenicity when given as 1 or 2 additional doses after bivalent OPV: Results from a randomized controlled trial in Latin America
Lopez-Medina E , Melgar M , Gaensbauer JT , Bandyopadhyay AS , Borate BR , Weldon WC , Ruttimann R , Ward J , Clemens R , Asturias EJ . Vaccine 2017 35 (28) 3591-3597 BACKGROUND: Since April 2016 inactivated poliovirus vaccine (IPV) has been the only routine source of polio type 2 protection worldwide. With IPV supply constraints, data on comparability of immunogenicity and safety will be important to optimally utilize available supplies from different manufacturers. METHODS: In this multicenter phase IV study, 900 Latin American infants randomly assigned to six study groups received three doses of bOPV at 6, 10 and 14weeks and either one IPV dose at 14weeks (groups SP-1, GSK-1 and BBio-1) or two IPV doses at 14 and 36weeks (groups SP-2, GSK-2 and BBio-2) from three different manufacturers. Children were challenged with mOPV2 at either 18 (one IPV dose) or 40weeks (two IPV doses) and stools were collected weekly for 4weeks to assess viral shedding. Serum neutralizing antibodies were measured at various time points pre and post vaccination. Serious adverse events and important medical events (SAE and IME) were monitored for 6months after last study vaccine. RESULTS: At week 18, 4weeks after one dose of IPV, overall type 2 seroconversion rates were 80.4%, 80.4% and 73.3% for SP-1, GSK-1 and BBio-1 groups, respectively; and 92.6%, 96.8% and 88.0% in those who were seronegative before IPV administration. At 40weeks, 4weeks after a second IPV dose, type 2 seroconversion rates were ≥99% for any of the three manufacturers. There were no significant differences in fecal shedding index endpoint (SIE) after one or two IPV doses (SP: 2.3 [95% CI: 2.1-2.6]); GSK: 2.2 [1.7-2.5]; BBio 1.8 [1.5-2.3]. All vaccines appeared safe, with no vaccine-related SAE or IME. CONCLUSION: Current WHO prequalified IPV vaccines are safe and induce similar humoral and intestinal immunity after one or two doses. The parent study was registered with ClinicalTrials.gov, number NCT01831050. |
Humoral and intestinal immunity induced by new schedules of bivalent oral poliovirus vaccine and one or two doses of inactivated poliovirus vaccine in Latin American infants: an open-label randomised controlled trial
Asturias EJ , Bandyopadhyay AS , Self S , Rivera L , Saez-Llorens X , Lopez E , Melgar M , Gaensbauer JT , Weldon WC , Oberste MS , Borate BR , Gast C , Clemens R , Orenstein W , O'Ryan M , Jimeno J , Clemens SA , Ward J , Ruttimann R . Lancet 2016 388 (10040) 158-69 BACKGROUND: Replacement of the trivalent oral poliovirus vaccine (tOPV) with bivalent types 1 and 3 oral poliovirus vaccine (bOPV) and global introduction of inactivated poliovirus vaccine (IPV) are major steps in the polio endgame strategy. In this study, we assessed humoral and intestinal immunity in Latin American infants after three doses of bOPV combined with zero, one, or two doses of IPV. METHODS: This open-label randomised controlled multicentre trial was part of a larger study. 6-week-old full-term infants due for their first polio vaccinations, who were healthy on physical examination, with no obvious medical conditions and no known chronic medical disorders, were enrolled from four investigational sites in Colombia, Dominican Republic, Guatemala, and Panama. The infants were randomly assigned by permuted block randomisation (through the use of a computer-generated list, block size 36) to nine groups, of which five will be discussed in this report. These five groups were randomly assigned 1:1:1:1 to four permutations of schedule: groups 1 and 2 (control groups) received bOPV at 6, 10, and 14 weeks; group 3 (also a control group, which did not count as a permutation) received tOPV at 6, 10, and 14 weeks; group 4 received bOPV plus one dose of IPV at 14 weeks; and group 5 received bOPV plus two doses of IPV at 14 and 36 weeks. Infants in all groups were challenged with monovalent type 2 vaccine (mOPV2) at 18 weeks (groups 1, 3, and 4) or 40 weeks (groups 2 and 5). The primary objective was to assess the superiority of bOPV-IPV schedules over bOPV alone, as assessed by the primary endpoints of humoral immunity (neutralising antibodies-ie, seroconversion) to all three serotypes and intestinal immunity (faecal viral shedding post-challenge) to serotype 2, analysed in the per-protocol population. Serious and medically important adverse events were monitored for up to 6 months after the study vaccination. This study is registered with ClinicalTrials.gov, number NCT01831050, and has been completed. FINDINGS: Between May 20, 2013, and Aug 15, 2013, 940 eligible infants were enrolled and randomly assigned to the five treatment groups (210 to group 1, 210 to group 2, 100 to group 3, 210 to group 4, and 210 to group 5). One infant in group 1 was not vaccinated because their parents withdrew consent after enrolment and randomisation, so 939 infants actually received the vaccinations. Three doses of bOPV or tOPV elicited type 1 and 3 seroconversion rates of at least 97.7%. Type 2 seroconversion occurred in 19 of 198 infants (9.6%, 95% CI 6.2-14.5) in the bOPV-only groups, 86 of 88 (97.7%, 92.1-99.4) in the tOPV-only group (p<0.0001 vs bOPV-only), and 156 of 194 (80.4%, 74.3-85.4) infants in the bOPV-one dose of IPV group (p<0.0001 vs bOPV-only). A further 20 of 193 (10%) infants in the latter group seroconverted 1 week after mOPV2 challenge, resulting in around 98% of infants being seropositive against type 2. After a bOPV-two IPV schedule, all 193 infants (100%, 98.0-100; p<0.0001 vs bOPV-only) seroconverted to type 2. IPV induced small but significant decreases in a composite serotype 2 viral shedding index after mOPV2 challenge. 21 serious adverse events were reported in 20 patients during the study, including two that were judged to be possibly related to the vaccines. Most of the serious adverse events (18 [86%] of 21) and 24 (80%) of the 30 important medical events reported were infections and infestations. No deaths occurred during the study. INTERPRETATION: bOPV provided humoral protection similar to tOPV against polio serotypes 1 and 3. After one or two IPV doses in addition to bOPV, 80% and 100% of infants seroconverted, respectively, and the vaccination induced a degree of intestinal immunity against type 2 poliovirus. FUNDING: Bill & Melinda Gates Foundation. |
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