Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 38 Records) |
Query Trace: Restrepo P[original query] |
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Using regional sero-epidemiology SARS-CoV-2 Anti-S antibodies in the Dominican Republic to inform targeted public health response
Mario Martin B , Cadavid Restrepo A , Mayfield HJ , Then Paulino C , De St Aubin M , Duke W , Jarolim P , Zielinski Gutiérrez E , Skewes Ramm R , Dumas D , Garnier S , Etienne MC , Peña F , Abdalla G , Lopez B , de la Cruz L , Henríquez B , Baldwin M , Sartorius B , Kucharski A , Nilles EJ , Lau CL . Trop Med Infect Dis 2023 8 (11) Incidence of COVID-19 has been associated with sociodemographic factors. We investigated variations in SARS-CoV-2 seroprevalence at sub-national levels in the Dominican Republic and assessed potential factors influencing variation in regional-level seroprevalence. Data were collected in a three-stage cross-sectional national serosurvey from June to October 2021. Seroprevalence of antibodies against the SARS-CoV-2 spike protein (anti-S) was estimated and adjusted for selection probability, age, and sex. Multilevel logistic regression was used to estimate the effect of covariates on seropositivity for anti-S and correlates of 80% protection (PT(80)) against symptomatic infection for the ancestral and Delta strains. A total of 6683 participants from 134 clusters in all 10 regions were enrolled. Anti-S, PT80 for the ancestral and Delta strains odds ratio varied across regions, Enriquillo presented significant higher odds for all outcomes compared with Yuma. Compared to being unvaccinated, receiving ≥2 doses of COVID-19 vaccine was associated with a significantly higher odds of anti-S positivity (OR 85.94, [10.95-674.33]) and PT(80) for the ancestral (OR 4.78, [2.15-10.62]) and Delta strains (OR 3.08, [1.57-9.65]) nationally and also for each region. Our results can help inform regional-level public health response, such as strategies to increase vaccination coverage in areas with low population immunity against currently circulating strains. |
Guiding Vaccine Efficacy Trial Design During Public Health Emergencies: An interactive web-based decision support tool (preprint)
Bellan SE , Eggo RM , Gsell PS , Kucharski AJ , Dean NE , Donohue R , Zook M , Odhiambo F , Longini IM Jr , Brisson M , Mahon BE , Henao-Restrepo AM . bioRxiv 2018 252783 The design and execution of rigorous, fast, and ethical vaccine efficacy trials can be challenging during epidemics of emerging pathogens, such as the 2014-2016 Ebola virus and 2015-2016 Zika virus epidemics. Response to an urgent public health crisis requires accelerated research even as emerging epidemics themselves change rapidly and are inherently less well understood than well-established diseases. As part of the World Health Organization Research and Development Blueprint, we designed a web-based interactive decision support system (InterVax-Tool) to help diverse stakeholders navigate the epidemiological, logistical, and ethical decisions involved in designing a vaccine efficacy trial during a public health emergency. In contrast to existing literature on trial design, InterVax-Tool offers high-level visual and interactive assistance through a set of four decision trees, guiding users through selection of 1) the Primary Endpoint, (2) the Target Population, (3) Randomization, and (4) the Comparator. Guidance is provided on how each of fourteen key considerations–grouped as Epidemiological, Vaccine-related, Infrastructural, or Sociocultural–should be used to inform each decision in the trial design process. The tool is not intended to provide a black box decision framework for identifying an optimal trial design, but rather to facilitate transparent, collaborative and comprehensive discussion of the relevant decisions, while recording the decision process. The tool can also assist capacity building by providing a cross-disciplinary picture of trial design using concepts from epidemiology, study design, vaccinology, biostatistics, mathematical modeling and clinical research ethics. Here, we describe the goals and features of InterVax-Tool as well as its application to the design of a Zika vaccine efficacy trial.One Sentence Summary An interactive web-based decision support tool was developed to assist in the design of vaccine efficacy trials during emerging outbreaks. |
Potential use of antibodies to provide an earlier indication of lymphatic filariasis resurgence in post-mass drug administration surveillance, American Samoa (preprint)
Cadavid Restrepo AM , Gass K , Won KY , Sheel M , Robinson K , Graves PM , Fuimaono S , Lau CL . medRxiv 2021 02 Objectives Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted seven rounds of mass drug administration between 2000 and 2006. The territory passed transmission assessment surveys (TAS) in 2011 (TAS-1) and 2015 (TAS-2) based on World Health Organization guidelines. In 2016, the territory failed TAS-3, indicating resurgence. This study aims to determine if antibodies (Ab) may have provided a timelier indication of LF resurgence in American Samoa. Methods We examined school-level Ag and Ab status (presence/absence of Ag- and Ab-positive children) and prevalence of single and combined Ab responses to Wb123, Bm14, Bm33 Ags at each TAS. Pearson's chi-squared tests and logistic regression were used to examine associations between school-level Ab prevalence in TAS-1 and TAS-2 and school-level Ag status in TAS-3. Results Schools with higher prevalence of Wb123 Ab in TAS-2 had higher odds of being Ag-positive in TAS-3 (odds ratio [OR] 24.5, 95% CI:1.2-512.7). Schools that were Ab-positive for WB123 plus Bm14, Bm33 or both Bm14 and Bm33 in TAS-2 had higher odds of being Ag-positive in TAS-3 (OR 16.0-24.5). Conclusion Anti-filarial Abs could provide earlier signals of resurgence and enable a timelier response. The promising role of Abs in post-MDA surveillance and decision making should be further investigated in other settings. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Tackling histoplasmosis infection in people living with HIV from Latin America: From diagnostic strategy to public health solutions
Cáceres DH , Gómez BL , Tobón Á M , Restrepo Á , Chiller T , Lindsley MD , Meis JF , Verweij PE . J Fungi (Basel) 2023 9 (5) Histoplasmosis, caused by the thermally dimorphic fungus Histoplasma spp., is a disease with a broad clinical spectrum, presenting from asymptomatic/flu-like symptoms to progressive disseminated disease in people with immunosuppression. In recent years, the concept of histoplasmosis as a disease restricted to the American continent has changed, as now histoplasmosis is reported in many regions around the world. In Latin America, histoplasmosis represents a threat, especially in people with advanced HIV disease (AHD). Diagnosis of histoplasmosis in people living with HIV (PLHIV) is challenging due to the low index of suspicion of the disease, non-specificity of signs and symptoms, and limited access to specific laboratory testing, while the diagnostic delay is significantly associated with mortality. In the last decade, novel diagnostic tests have been developed for the rapid detection of histoplasmosis, such as commercial kits for antigen detection. Furthermore, advocacy groups were created that presented histoplasmosis as a public health problem, with emphasis on patients at risk of progressive disseminated disease. This review aims to discuss the impact of histoplasmosis associated with AHD in Latin America and the strategies employed to tackle histoplasmosis, from the implementation of laboratory testing to disease advocacy and public health interventions. |
A Public Health Research Agenda for Managing Infodemics: Methods and Results of the First WHO Infodemiology Conference.
Calleja N , AbdAllah A , Abad N , Ahmed N , Albarracin D , Altieri E , Anoko JN , Arcos R , Azlan AA , Bayer J , Bechmann A , Bezbaruah S , Briand SC , Brooks I , Bucci LM , Burzo S , Czerniak C , De Domenico M , Dunn AG , Ecker UKH , Espinosa L , Francois C , Gradon K , Gruzd A , Gülgün BS , Haydarov R , Hurley C , Astuti SI , Ishizumi A , Johnson N , Johnson Restrepo D , Kajimoto M , Koyuncu A , Kulkarni S , Lamichhane J , Lewis R , Mahajan A , Mandil A , McAweeney E , Messer M , Moy W , Ndumbi Ngamala P , Nguyen T , Nunn M , Omer SB , Pagliari C , Patel P , Phuong L , Prybylski D , Rashidian A , Rempel E , Rubinelli S , Sacco P , Schneider A , Shu K , Smith M , Sufehmi H , Tangcharoensathien V , Terry R , Thacker N , Trewinnard T , Turner S , Tworek H , Uakkas S , Vraga E , Wardle C , Wasserman H , Wilhelm E , Würz A , Yau B , Zhou L , Purnat TD . JMIR Infodemiology 2021 1 (1) e30979 BACKGROUND: An infodemic is an overflow of information of varying quality that surges across digital and physical environments during an acute public health event. It leads to confusion, risk-taking, and behaviors that can harm health and lead to erosion of trust in health authorities and public health responses. Owing to the global scale and high stakes of the health emergency, responding to the infodemic related to the pandemic is particularly urgent. Building on diverse research disciplines and expanding the discipline of infodemiology, more evidence-based interventions are needed to design infodemic management interventions and tools and implement them by health emergency responders. OBJECTIVE: The World Health Organization organized the first global infodemiology conference, entirely online, during June and July 2020, with a follow-up process from August to October 2020, to review current multidisciplinary evidence, interventions, and practices that can be applied to the COVID-19 infodemic response. This resulted in the creation of a public health research agenda for managing infodemics. METHODS: As part of the conference, a structured expert judgment synthesis method was used to formulate a public health research agenda. A total of 110 participants represented diverse scientific disciplines from over 35 countries and global public health implementing partners. The conference used a laddered discussion sprint methodology by rotating participant teams, and a managed follow-up process was used to assemble a research agenda based on the discussion and structured expert feedback. This resulted in a five-workstream frame of the research agenda for infodemic management and 166 suggested research questions. The participants then ranked the questions for feasibility and expected public health impact. The expert consensus was summarized in a public health research agenda that included a list of priority research questions. RESULTS: The public health research agenda for infodemic management has five workstreams: (1) measuring and continuously monitoring the impact of infodemics during health emergencies; (2) detecting signals and understanding the spread and risk of infodemics; (3) responding and deploying interventions that mitigate and protect against infodemics and their harmful effects; (4) evaluating infodemic interventions and strengthening the resilience of individuals and communities to infodemics; and (5) promoting the development, adaptation, and application of interventions and toolkits for infodemic management. Each workstream identifies research questions and highlights 49 high priority research questions. CONCLUSIONS: Public health authorities need to develop, validate, implement, and adapt tools and interventions for managing infodemics in acute public health events in ways that are appropriate for their countries and contexts. Infodemiology provides a scientific foundation to make this possible. This research agenda proposes a structured framework for targeted investment for the scientific community, policy makers, implementing organizations, and other stakeholders to consider. |
SARS-CoV-2 seroprevalence, cumulative infections, and immunity to symptomatic infection - A multistage national household survey and modelling study, Dominican Republic, June-October 2021.
Nilles EJ , Paulino CT , de St Aubin M , Restrepo AC , Mayfield H , Dumas D , Finch E , Garnier S , Etienne MC , Iselin L , Duke W , Jarolim P , Oasan T , Yu J , Wan H , Peña F , Iihoshi N , Abdalla G , Lopez B , Cruz L , Henríquez B , Espinosa-Bode A , Puello YC , Durski K , Baldwin M , Baez AA , Merchant RC , Barouch DH , Skewes-Ramm R , Gutiérrez EZ , Kucharski A , Lau CL . Lancet Reg Health Am 2022 16 100390 BACKGROUND: Population-level SARS-CoV-2 immunological protection is poorly understood but can guide vaccination and non-pharmaceutical intervention priorities. Our objective was to characterise cumulative infections and immunological protection in the Dominican Republic. METHODS: Household members ≥5 years were enrolled in a three-stage national household cluster serosurvey in the Dominican Republic. We measured pan-immunoglobulin antibodies against the SARS-CoV-2 spike (anti-S) and nucleocapsid glycoproteins, and pseudovirus neutralising activity against the ancestral and B.1.617.2 (Delta) strains. Seroprevalence and cumulative prior infections were weighted and adjusted for assay performance and seroreversion. Binary classification machine learning methods and pseudovirus neutralising correlates of protection were used to estimate 50% and 80% protection against symptomatic infection. FINDINGS: Between 30 Jun and 12 Oct 2021 we enrolled 6683 individuals from 3832 households. We estimate that 85.0% (CI 82.1-88.0) of the ≥5 years population had been immunologically exposed and 77.5% (CI 71.3-83) had been previously infected. Protective immunity sufficient to provide at least 50% protection against symptomatic SARS-CoV-2 infection was estimated in 78.1% (CI 74.3-82) and 66.3% (CI 62.8-70) of the population for the ancestral and Delta strains respectively. Younger (5-14 years, OR 0.47 [CI 0.36-0.61]) and older (≥75-years, 0.40 [CI 0.28-0.56]) age, working outdoors (0.53 [0.39-0.73]), smoking (0.66 [0.52-0.84]), urban setting (1.30 [1.14-1.49]), and three vs no vaccine doses (18.41 [10.69-35.04]) were associated with 50% protection against the ancestral strain. INTERPRETATION: Cumulative infections substantially exceeded prior estimates and overall immunological exposure was high. After controlling for confounders, markedly lower immunological protection was observed to the ancestral and Delta strains across certain subgroups, findings that can guide public health interventions and may be generalisable to other settings and viral strains. FUNDING: This study was funded by the US CDC. |
An introduction to the Marburg virus vaccine consortium, MARVAC
Cross RW , Longini IM , Becker S , Bok K , Boucher D , Carroll MW , Díaz JV , Dowling WE , Draghia-Akli R , Duworko JT , Dye JM , Egan MA , Fast P , Finan A , Finch C , Fleming TR , Fusco J , Geisbert TW , Griffiths A , Günther S , Hensley LE , Honko A , Hunegnaw R , Jakubik J , Ledgerwood J , Luhn K , Matassov D , Meshulam J , Nelson EV , Parks CL , Rustomjee R , Safronetz D , Schwartz LM , Smith D , Smock P , Sow Y , Spiropoulou CF , Sullivan NJ , Warfield KL , Wolfe D , Woolsey C , Zahn R , Henao-Restrepo AM , Muñoz-Fontela C , Marzi A . PLoS Pathog 2022 18 (10) e1010805 The emergence of Marburg virus (MARV) in Guinea and Ghana triggered the assembly of the MARV vaccine "MARVAC" consortium representing leaders in the field of vaccine research and development aiming to facilitate a rapid response to this infectious disease threat. Here, we discuss current progress, challenges, and future directions for MARV vaccines. |
Factors influencing the decision to receive seasonal influenza vaccination among US corporate non-healthcare workers.
Aguolu OG , Willebrand K , Elharake JA , Qureshi HM , Kiti MC , Liu CY , Restrepo Mesa A , Nelson K , Jenness S , Melegaro A , Ahmed F , Yildirim I , Malik FA , Lopman B , Omer SB . Hum Vaccin Immunother 2022 18 (6) 2122379 Influenza causes significant mortality and morbidity in the United States (US). Employees are exposed to influenza at work and can spread it to others. The influenza vaccine is safe, effective, and prevents severe outcomes; however, coverage among US adults (50.2%) is below Healthy People 2030 target of 70%. These highlights need for more effective vaccination promotion interventions. Understanding predictors of vaccination acceptance could inform vaccine promotion messages, improve coverage, and reduce illness-related work absences. We aimed to identify factors influencing influenza vaccination among US non-healthcare workers. Using mixed-methods approach, we evaluated factors influencing influenza vaccination among employees in three US companies during April-June 2020. Survey questions were adapted from the WHO seasonal influenza survey. Most respondents (n = 454) were women (272, 59.9%), 20-39 years old (n = 250, 55.1%); white (n = 254, 56.0%); had a college degree (n = 431, 95.0%); and reported receiving influenza vaccine in preceding influenza season (n = 297, 65.4%). Logistic regression model was statistically significant, X (16, N = 450) = 31.6, p = .01. Education [(OR) = 0.3, 95%CI = 0.1-0.6)] and race (OR = 0.4, 95%CI = 0.2-0.8) were significant predictors of influenza vaccine acceptance among participants. The majority had favorable attitudes toward influenza vaccination and reported that physician recommendation would influence their vaccination decisions. Seven themes were identified in qualitative analysis: "Protecting others" (109, 24.0%), "Protecting self" (105, 23.1%), "Vaccine accessibility" (94, 20.7%), "Education/messaging" (71, 15.6%), "Policies/requirements" (15, 3.3%), "Reminders" (9, 2.0%), and "Incentives" (3, 0.7%). Our findings could facilitate the development of effective influenza vaccination promotion messages and programs for employers, and workplace vaccination programs for other diseases such as COVID-19, by public health authorities. | Influenza causes significant mortality and morbidity in the United States (US).The US working-age group (18–64-year-old) bears a huge burden of influenza annually.Influenza vaccination coverage in the working-age group is low.Physicians and employers can influence vaccine acceptance of working adults.Employers can consider practical steps, e.g., incentivizing, or offering vaccine onsite. | eng |
Progress towards the elimination of hepatitis B in children in Colombia: a novel two-phase study approach
Ríos-Hincapié CY , Murad-Rivera R , Tohme RA , Ropero AM , Gómez B , Cardona DL , Forest BN , Cuellar D , Cardenas I , Krow-Lucal E , Wannemuehler K , de la Hoz Restrepo F , Sánchez-Molano SM , Delgado CE , Rivillas-Garcia JC , Wasley A . J Viral Hepat 2022 29 (9) 737-747 The World Health Organization (WHO) has established a target to eliminate mother-to-child-transmission (EMTCT) of hepatitis B virus (HBV), defined as a prevalence of hepatitis B surface antigen (HBsAg) of ≤0.1% among children, by 2030. Using nationally representative serosurveys to verify achievement of this target requires large sample sizes and significant resources. We assessed the feasibility of a potentially more efficient two-phase method to verify EMTCT of HBV in Colombia. In the first phase, we conducted a risk assessment to identify municipalities at the highest risk of ongoing HBV transmission. We ranked the 1,122 municipalities of Colombia based on reports of HBV infection in pregnant women per 1,000 population. Municipalities with ≥0.3 reports per 1,000 persons (equating to the top quartile) were further assessed based on health facility birth rates, coverage with three doses of hepatitis B vaccine (HepB3), and seroprevalence data. Hepatitis B risk was considered to be further increased for municipalities with HepB3 coverage or health facility birth rate <90%. In the second phase, we conducted a multistage household serosurvey of children aged 5-10 years in 36 municipalities with the highest assessed HBV risk. HBsAg was not detected in any of 3,203 children tested, yielding a 90% upper confidence bound of <0.1% prevalence. Coverage with HepB3 and hepatitis B birth dose was high at 97.5% and 95.6%, respectively. These results support the conclusion that Colombia has likely achieved EMTCT of HBV. |
Potential use of antibodies to provide an earlier indication of lymphatic filariasis resurgence in post-mass drug administration surveillance, American Samoa
Restrepo AMC , Gass K , Won KY , Sheel M , Robinson K , Graves PM , Fuimaono S , Lau CL . Int J Infect Dis 2022 117 378-386 OBJECTIVES: Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted seven rounds of mass drug administration between 2000 and 2006. The territory passed transmission assessment surveys (TAS) in 2011 (TAS-1) and 2015 (TAS-2). In 2016, the territory failed TAS-3, indicating resurgence. This study aims to determine if antibodies (Ab) may have provided a timelier indication of LF resurgence in American Samoa. METHODS: We examined school-level antigen (Ag) and Ab status (presence/absence of Ag- and Ab-positive children) and prevalence of single and combined Ab responses to Wb123, Bm14, Bm33 Ags at each TAS. Pearson's chi-squared tests and logistic regression were used to examine associations between school-level Ab prevalence in TAS-1 and TAS-2 and school-level Ag status in TAS-3. RESULTS: Schools with higher prevalence of Wb123 Ab in TAS-2 had higher odds of being Ag-positive in TAS-3 (odds ratio [OR] 24.5, 95% CI:1.2-512.7). Schools that were Ab-positive for WB123 plus Bm14, Bm33 or both Bm14 and Bm33 in TAS-2 had higher odds of being Ag-positive in TAS-3 (OR 16.0-24.5). CONCLUSION: Abs could provide earlier signals of resurgence and enable a timelier response. The promising role of Abs in post-mass drug administration (MDA) surveillance and decision making should be further investigated in other settings. |
Diarrheal deaths after the introduction of rotavirus vaccination in 4 countries
Paternina-Caicedo A , Parashar U , Garcia-Calavaro C , de Oliveira LH , Alvis-Guzman N , De la Hoz-Restrepo F . Pediatrics 2021 147 (1) BACKGROUND: We aim in our analysis to estimate the reduction of diarrhea-related mortality rates after introduction of a rotavirus vaccine in subregions of 4 Latin American countries. METHODS: We selected diarrhea-related deaths from individual-level data from death certificates in Brazil, Colombia, Ecuador, and Mexico. Counts were aggregated by region, year and month, and age group for each country. We ran an interrupted time-series analysis using Poisson regression to obtain seasonal and trend-adjusted estimates of impact. Results are reported as percentages (1 - mortality rate ratio). RESULTS: We found a reduction in diarrhea-related mortality in children <5 years old of 18% (95% confidence interval [CI], 15 to 20) for Mexico, 39% (95% CI, 35 to 44) for Colombia, 19 (95% CI, 17 to 22) for Brazil, and -26% (95% CI, -40 to -14) for Ecuador. Using wavelet analyses, we found a reduction of 6- and 12-month seasonality in Brazil, Colombia, and Mexico. We also found that the increased reduction of diarrhea-related deaths was larger with greater prevaccine burden of diarrhea in infants. CONCLUSIONS: Our findings and available evidence support the recommendation from the World Health Organization for the monovalent and/or pentavalent rotavirus vaccine in countries worldwide. We found an increased benefit in those settings with a higher burden of infant diarrhea-related deaths. |
Antibiotic stewardship in the intensive care unit. An Official American Thoracic Society Workshop Report in Collaboration with the AACN, CHEST, CDC, and SCCM
Wunderink RG , Srinivasan A , Barie PS , Chastre J , Dela Cruz CS , Douglas IS , Ecklund M , Evans SE , Evans SR , Gerlach AT , Hicks LA , Howell M , Hutchinson ML , Hyzy RC , Kane-Gill SL , Lease ED , Metersky ML , Munro N , Niederman MS , Restrepo MI , Sessler CN , Simpson SQ , Swoboda SM , Guillamet CV , Waterer GW , Weiss CH . Ann Am Thorac Soc 2020 17 (5) 531-540 Intensive care units (ICUs) are an appropriate focus of antibiotic stewardship program efforts because a large proportion of any hospital's use of parenteral antibiotics, especially broad-spectrum, occurs in the ICU. Given the importance of antibiotic stewardship for critically ill patients and the importance of critical care practitioners as the front line for antibiotic stewardship, a workshop was convened to specifically address barriers to antibiotic stewardship in the ICU and discuss tactics to overcome these. The working definition of antibiotic stewardship is "the right drug at the right time and the right dose for the right bug for the right duration." A major emphasis was that antibiotic stewardship should be a core competency of critical care clinicians. Fear of pathogens that are not covered by empirical antibiotics is a major driver of excessively broad-spectrum therapy in critically ill patients. Better diagnostics and outcome data can address this fear and expand efforts to narrow or shorten therapy. Greater awareness of the substantial adverse effects of antibiotics should be emphasized and is an important counterargument to broad-spectrum therapy in individual low-risk patients. Optimal antibiotic stewardship should not focus solely on reducing antibiotic use or ensuring compliance with guidelines. Instead, it should enhance care both for individual patients (by improving and individualizing their choice of antibiotic) and for the ICU population as a whole. Opportunities for antibiotic stewardship in common ICU infections, including community- and hospital-acquired pneumonia and sepsis, are discussed. Intensivists can partner with antibiotic stewardship programs to address barriers and improve patient care. |
Frequency of invasive fungal disease in adults: Experience of a specialized laboratory in Medellin, Colombia (2009-2015)
Valencia Y , Caceres DH , de Bedout C , Cano LE , Restrepo A . J Fungi (Basel) 2020 6 (1) Invasive fungal diseases (IFD) contribute significantly to worldwide morbidity and mortality, but their frequency is not well-described in some countries. The present work describes the frequency of IFD in a specialized laboratory in Colombia. A retrospective, descriptive study was implemented between March 2009 and December 2015. Results: 13,071 patients with clinical suspicion of IFD were referred during the study period, from which 33,516 biological samples were processed and analyzed using 14 laboratory methods. Diagnosis was confirmed in 1425 patients (11%), distributed according to the mycoses of interest analyzed here: histoplasmosis in 641/11,756 patients (6%), aspergillosis in 331/10,985 patients (3%), cryptococcosis in 239/8172 patients (3%), pneumocystosis in 111/1651 patients (7%), paracoccidioidomycosis in 60/10,178 patients (0.6%), and invasive candidiasis in 48/7525 patients (0.6%). From the first year of the study period to the last year, there was a 53% increase in the number of cases of IFD diagnosed. Our laboratory experienced a high frequency of IFD diagnosis, possibly attributable to the availability of a greater range of diagnostic tools. Frequency of IFD in this study was atypical compared with other studies, probably as a result of the single laboratory-site analysis. This demonstrates that implementing educational strategies helps to create a high index of clinical suspicion, while the availability and utilization of appropriate diagnostic assays assure greater reliability in identification of these cases. |
Diagnosis and treatment of adults with community-acquired pneumonia. An Official Clinical Practice Guideline of the American Thoracic Society and Infectious Diseases Society of America
Metlay JP , Waterer GW , Long AC , Anzueto A , Brozek J , Crothers K , Cooley LA , Dean NC , Fine MJ , Flanders SA , Griffin MR , Metersky ML , Musher DM , Restrepo MI , Whitney CG . Am J Respir Crit Care Med 2019 200 (7) e45-e67 Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.Results: The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions.Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia. |
Quantification of 16 urinary biomarkers of exposure to flame retardants, plasticizers, and organophosphate insecticides for biomonitoring studies
Jayatilaka NK , Restrepo P , Davis Z , Vidal M , Calafat AM , Ospina M . Chemosphere 2019 235 481-491 Chlorinated alkyl and non-chlorinated aryl organophosphate flame retardants (OPFRs) and some brominated flame retardants (FR) were introduced as replacements for polybrominated diphenyl ethers (PBDEs) after PBDEs phase-out in 2004 and 2013. Organophosphorous (OP) insecticides are mainly used in agricultural settings since the Food Quality Protection Act of 1996 phased-out most residential uses of OP insecticides in the United States. Urinary metabolites of FRs and OPs are known exposure biomarkers to FRs and OP insecticides, respectively. For large population-based studies, concurrent quantification of these metabolites using a small urine volume is desirable, but until now was not possible. We developed an analytical approach to quantify in 0.2mL urine 10 FRs and six OP insecticide metabolites: diphenyl phosphate, bis(1,3-dichloro-2-propyl) phosphate, bis(1-chloro-2-propyl) phosphate, bis(2-chloroethyl) phosphate, dicresyl phosphates, dibutyl phosphate, dibenzyl phosphate, 2,3,4,5-tetrabromobenzoic acid, 2-((isopropyl)phenyl)phenyl phosphate, 4-((tert-butyl)phenyl)phenyl phosphate, dimethyl phosphate, diethyl phosphate, dimethyl thiophosphate, dimethyl dithiophosphate, diethyl thiophosphate, and diethyl dithiophosphate. The method relies on enzymatic deconjugation, automated off-line solid phase extraction, high-performance liquid chromatography, and isotope dilution tandem mass spectrometry. Detection limits ranged from 0.05 to 0.5ngmL(-1), accuracy from 89 to 118%, and imprecision was <10%. . This method is the first to quantify simultaneously trace levels of 16 biomarkers of FRs and OP insecticides in only four drops of urine. We confirmed the method suitability for use in large epidemiological studies to assess background and occupational exposures to these classes of environmental pollutants by analyzing 303 samples collected from the general population and a group of firefighters. FR metabolite and DAPs concentrations in the general population group were lower than in the firefighters group, and within the ranges reported in the U.S. general population and other non-occupationally exposed populations. |
An online decision tree for vaccine efficacy trial design during infectious disease epidemics: The InterVax-Tool
Bellan SE , Eggo RM , Gsell PS , Kucharski AJ , Dean NE , Donohue R , Zook M , Edmunds WJ , Odhiambo F , Longini IM Jr , Brisson M , Mahon BE , Henao-Restrepo AM . Vaccine 2019 37 (31) 4376-4381 BACKGROUND: Licensed vaccines are urgently needed for emerging infectious diseases, but the nature of these epidemics causes challenges for the design of phase III trials to evaluate vaccine efficacy. Designing and executing rigorous, fast, and ethical, vaccine efficacy trials is difficult, and the decisions and limitations in the design of these trials encompass epidemiological, logistical, regulatory, statistical, and ethical dimensions. RESULTS: Trial design decisions are complex and interrelated, but current guidance documents do not lend themselves to efficient decision-making. We created InterVax-Tool (http://vaxeval.com), an online, interactive decision-support tool, to help diverse stakeholders navigate the decisions in the design of phase III vaccine trials. InterVax-Tool offers high-level visual and interactive assistance through a set of four decision trees, guiding users through selection of the: (1) Primary Endpoint, (2) Target Population, (3) Randomization Scheme, and, (4) Comparator. We provide guidance on how key considerations - grouped as Epidemiological, Vaccine-related, Infrastructural, or Sociocultural - inform each decision in the trial design process. CONCLUSIONS: InterVax-Tool facilitates structured, transparent, and collaborative discussion of trial design, while recording the decision-making process. Users can save and share their decisions, which is useful both for comparing proposed trial designs, and for justifying particular design choices. Here, we describe the goals and features of InterVax-Tool as well as its application to the design of a Zika vaccine efficacy trial. |
Global review of the age distribution of rotavirus disease in children aged <5 years before the introduction of rotavirus vaccination
Hasso-Agopsowicz M , Ladva CN , Lopman B , Sanderson C , Cohen AL , Tate JE , Riveros X , Henao-Restrepo AM , Clark A . Clin Infect Dis 2019 69 (6) 1071-1078 We sought datasets with granular age distributions of rotavirus-positive presentations among children <5 years of age, before the introduction of rotavirus vaccines. We identified 117 datasets and fit parametric age distributions to each country dataset and mortality stratum and calculated the median age, and cumulative proportion of rotavirus gastroenteritis events expected to occur at ages between birth and 5.0 years. The median age of rotavirus-positive hospital admissions was 38 weeks (inter-quartile range IQR: 25-58) in countries with very high child mortality and 65 weeks (IQR: 40-107) in countries with very low/low child mortality. In countries with very high child mortality 69% of rotavirus-positive admissions <5 years were in the first year of life, with 3% by 10 weeks, 8% by 15 weeks and 27% by 26 weeks. This information is critical for assessing the potential benefits of alternative rotavirus vaccination schedules in different countries, and for monitoring programme impact. |
Multicenter validation of commercial antigenuria reagents to diagnose progressive disseminated histoplasmosis in people living with HIV/AIDS in two Latin American countries
Caceres DH , Samayoa BE , Medina NG , Tobon AM , Guzman BJ , Mercado D , Restrepo A , Chiller T , Arathoon EE , Gomez BL . J Clin Microbiol 2018 56 (6) Histoplasmosis is an important cause of mortality in patients with AIDS, especially in countries with limited access to antiretroviral therapies and diagnostic tests. However, many disseminated infections in Latin America go undiagnosed. A simple, rapid method to detect Histoplasma capsulatum infection in endemic regions would dramatically decrease time to diagnosis and treatment, reducing morbidity and mortality. The aim of this study was to validate a commercial monoclonal Histoplasma galactomannan (HGM) ELISA (Immuno-Mycologics [IMMY], Norman, Oklahoma, USA) in two cohorts of people living with HIV/AIDS (PLHIV). We analyzed urine samples from 589 people (466 from Guatemala and 123 from Colombia), including 546 from PLHIV and 43 from non-PLHIV controls. Sixty-three of these people (35 from Guatemala and 28 from Colombia) had confirmed histoplasmosis by isolation of H. capsulatum Using the standard curve provided by the quantitative commercial test, sensitivity was 98% (95% CI, 95-100) and specificity was 97% (95% CI, 96-99) (cutoff=0.5 ng/mL). Semi-quantitative results, using a calibrator of 12.5 ng/mL of Histoplasma galactomannan to calculate an EIA Index Value (EIV) of the samples, showed a sensitivity of 95% (95% CI, 89-100%) and specificity of 98% (95% CI, 96-99%) (cutoff >/=2.6 EIV). This relatively simple-to-perform commercial antigenuria test showed a high performance, with reproducible results in both countries, suggesting that it can used to detect progressive disseminated histoplasmosis in PLHIV in a wide range of clinical laboratories in countries where histoplasmosis is endemic. |
The important role of co-infections in patients with AIDS and progressive disseminated histoplasmosis (PDH): A cohort from Colombia
Caceres DH , Tobon A M , Restrepo A , Chiller T , Gómez BL . Med Mycol Case Rep 2018 19 41-44 A total of 23/45 (51%) patients with AIDS and histoplasmosis from Medellín, Colombia had other infections. Tuberculosis was the most common (n = 16/23, 70%). Pneumocystosis and cryptococcosis were found in three patients each (13%), bacterial infection and cytomegalovirus occurred each in two patients (9%) while toxoplasmosis, herpes virus and esophageal candidiasis were recorded in one patient each (4%). Of all co-infected patients, 18/23 (78%) had one, four (17%) had two and one (4%) had three additional opportunistic infections. |
Exposure to organophosphate flame retardant chemicals in the U.S. general population: Data from the 2013-2014 National Health and Nutrition Examination Survey
Ospina M , Jayatilaka NK , Wong LY , Restrepo P , Calafat AM . Environ Int 2018 110 32-41 BACKGROUND: Use of organophosphate flame retardants (OPFRs) including tris(1,3-dichloro-2-propyl) phosphate, triphenyl phosphate, tris(1-chloro-2-propyl) phosphate, and tris-2-chloroethyl phosphate, in consumer products is on the rise because of the recent phase out of polybrominated diphenyl ether (PBDE) flame retardants. Some of these chemicals are also used as plasticizers or lubricants in many consumer products. OBJECTIVES: To assess human exposure to these chlorinated and non-chlorinated organophosphates, and non-PBDE brominated chemicals in a representative sample of the U.S. general population 6years and older from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). METHODS: We used solid-phase extraction coupled to isotope dilution high-performance liquid chromatography-tandem mass spectrometry after enzymatic hydrolysis of conjugates to analyze 2666 NHANES urine samples for nine biomarkers: diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis-(1-chloro-2-propyl) phosphate (BCIPP), bis-2-chloroethyl phosphate (BCEP), di-n-butyl phosphate (DNBP), di-p-cresylphosphate (DpCP), di-o-cresylphosphate (DoCP), dibenzyl phosphate (DBzP), and 2,3,4,5-tetrabromobenzoic acid (TBBA). We calculated the geometric mean (GM) and distribution percentiles for the urinary concentrations (both in micrograms per liter [mug/L] and in micrograms per gram of creatinine). We only calculated GMs for analytes with an overall weighted frequency of detection >60%. For those analytes, we also a) determined weighted Pearson correlations among the log10-transformed concentrations, and b) used regression models to evaluate associations of various demographic parameters with urinary concentrations of these biomarkers. RESULTS: We detected BDCIPP and DPHP in approximately 92% of study participants, BCEP in 89%, DNBP in 81%, and BCIPP in 61%. By contrast, we detected the other biomarkers much less frequently: DpCP (13%), DoCP (0.1%), TBBA (5%), and did not detect DBzP in any of the participants. Concentration ranges were highest for DPHP (<0.16-193mug/L), BDCIPP (<0.11-169mug/L), and BCEP (<0.08-110mug/L). Regardless of race/ethnicity, 6-11year old children had significantly higher BCEP adjusted GMs than other age groups. Females had significantly higher DPHP and BDCIPP adjusted GM than males, and were more likely than males to have DPHP concentrations above the 95th percentile (odds ratio=3.61; 95% confidence interval, 2.01-6.48). CONCLUSIONS: Our results confirm findings from previous studies suggesting human exposure to OPFRs, and demonstrate, for the first time, widespread exposure to several OPFRs among a representative sample of the U.S. general population 6years of age and older. The observed differences in concentrations of certain OPFRs biomarkers by race/ethnicity, in children compared to other age groups, and in females compared to males may reflect differences in lifestyle and exposure patterns. These NHANES data can be used to stablish a nationally representative baseline of exposures to OPFRs and when combined with future 2-year survey data, to evaluate exposure trends. |
Challenges and opportunities to scale up cardiovascular disease secondary prevention in Latin America and the Caribbean
Avezum A , Perel P , Oliveira GBF , Lopez-Jaramillo P , Restrepo G , Loustalot F , Srur A , de La Noval R , Connell KI , Cruz-Flores S , de Moura L , Castellac G , Mattos AC , Ordunez P . Glob Heart 2017 13 (2) 83-91 Cardiovascular disease (CVD) is the leading cause of death throughout the world; however, a reduction of 21% (age-standardized cardiovascular mortality rates per 100,000 inhabitants) was observed between 1990 and 2010, with more substantial reductions in CVD mortality evident in high-income countries (~42% reduction in CVD deaths) (Table 1) [1,2]. |
Molecular Epidemiology of Giardia, Blastocystis and Cryptosporidium among Indigenous Children from the Colombian Amazon Basin.
Sanchez A , Munoz M , Gomez N , Tabares J , Segura L , Salazar A , Restrepo C , Ruiz M , Reyes P , Qian Y , Xiao L , Lopez MC , Ramirez JD . Front Microbiol 2017 8 248 The incidence and prevalence of intestinal parasites in children is most likely due to lack of natural or acquired resistance and differences in behavior and habits closely related to environmental and socioeconomic determinants. The most important protozoa that parasitize humans are Giardia, Entamoeba, Blastocystis, and Cryptosporidium. These parasites present wide intraspecific genetic diversity and subsequently classified into assemblages and subtypes. The Amazon basin is the largest in the world and is the fifth freshwater reserve on the planet. Contradictorily, people living in these areas (Indigenous populations) have poor quality of life, which favors the infection of diseases of fecal-oral transmission. The aim of this work was to unravel the molecular epidemiology of Giardia, Blastocystis and Cryptosporidium across four communities (Puerto Narino, San Juan del Soco, Villa Andrea and Nuevo Paraiso). We obtained 284 fecal samples from children under 15 years old that were analyzed by direct microscopy (261 samples) and Real Time PCR (qPCR) (284 samples). The positive samples for these protozoa were further characterized by several molecular markers to depict assemblages and subtypes. We observed a frequency of Giardia infection by microscopy of 23.7% (62 samples) and by qPCR of 64.8% (184 samples); for Blastocystis by microscopy of 35.2% (92 samples) and by qPCR of 88.7% (252 samples) and for Cryptosporidium only 1.9% (5 samples) were positive by microscopy and qPCR 1.8% (5 samples). Regarding the Giardia assemblages, using the glutamate dehydrogenase (gdh) marker we observed AI, BIII and BIV assemblages and when using triose phosphate isomerase (tpi) we observed assemblages AI, AII, BIII and BIV. In contrast, Blastocystis STs detected were 1, 2, 3, 4, and 6. Lastly, the species C. viatorum, C. hominis (with the subtypes IdA19 and IaA12R8) and C. parvum (with the subtype IIcA5G3c) were identified. We observed a high profile of zoonotic transmission regarding the Giardia assemblages and Blastocystis STs/alleles. Also, we highlight the elevated frequency of infection by these two protozoans suggesting an active transmission in the area. Our findings reinforces the need to deploy better epidemiological surveillance systems for enteric pathogens in the area. |
Quantification of three chlorinated dialkyl phosphates, diphenyl phosphate, 2,3,4,5-tetrabromobenzoic acid, and four other organophosphates in human urine by solid phase extraction-high performance liquid chromatography-tandem mass spectrometry
Jayatilaka NK , Restrepo P , Williams L , Ospina M , Valentin-Blasini L , Calafat AM . Anal Bioanal Chem 2016 409 (5) 1323-1332 Polybrominated diphenyl ethers (PBDEs), produced as flame retardants worldwide, have been phased-out in many countries, and chlorinated and non-chlorinated organophosphates and non-PBDE brominated formulations (e.g., Firemaster 550 (FM550)) have entered the consumers' market. Recent studies show that components of organophosphate esters and FM550 are frequently detected in many products common to human environments. Therefore, urinary metabolites of these compounds can be used as human exposure biomarkers. We developed a method to quantify nine compounds in 0.4 mL urine: diphenyl phosphate (DPhP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis-(1-chloro-2-propyl) phosphate, bis-2-chloroethyl phosphate, di-p-cresylphosphate, di-o-cresylphosphate (DoCP), di-n-butyl phosphate, dibenzyl phosphate (DBzP), and 2,3,4,5-tetrabromobenzoic acid. The method relies on an enzymatic hydrolysis of urinary conjugates of the target analytes, automated off-line solid phase extraction, reversed phase high performance liquid chromatography separation, and isotope dilution-electrospray ionization tandem mass spectrometry detection. The method is high-throughput (96 samples/day) with detection limits ranging from 0.05 to 0.16 ng mL-1. Spiked recoveries were 90-113 %, and interday imprecision was 2-8 %. We assessed the suitability of the method by analyzing urine samples collected from a convenience sample of adults (n = 76) and from a group of firefighters (n = 146). DPhP (median, 0.89; range, 0.26-5.6 ng mL-1) and BDCPP (median, 0.69; range, 0.31-6.8 ng mL-1) were detected in all of the non-occupationally exposed adult samples and all of the firefighter samples (DPhP [median, 2.9; range, 0.24-28 ng mL-1], BDCPP [median, 3.4; range, 0.30-44 ng mL-1]); DBzP and DoCP were not detected in any samples. |
Clinical and laboratory profile of persons living with human immunodeficiency virus/acquired immune deficiency syndrome and histoplasmosis from a Colombian hospital
Caceres DH , Tobon AM , Cleveland AA , Scheel CM , Berbesi DY , Ochoa J , Restrepo A , Brandt ME , Chiller T , Gomez BL . Am J Trop Med Hyg 2016 95 (4) 918-924 Histoplasmosis is common among persons living with human immunodeficiency virus/acquired immune deficiency syndrome (PLWHA) in Latin America, but its diagnosis is difficult and often nonspecific. We conducted prospective screening for histoplasmosis among PLWHA with signs or symptoms suggesting progressive disseminated histoplasmosis (PDH) and hospitalized in Hospital La Maria in Medellin, Colombia. The study's aim was to obtain a clinical and laboratory profile of PLWHA with PDH. During 3 years (May 2008 to August 2011), we identified 89 PLWHA hospitalized with symptoms suggestive of PDH, of whom 45 (51%) had histoplasmosis. We observed tuberculosis (TB) coinfection in a large proportion of patients with PDH (35%), so all analyses were performed adjusting for this coinfection and, alternatively, excluding histoplasmosis patients with TB. Results showed that the patients with PDH were more likely to have Karnofsky score ≤ 30 (prevalence ratio [PR] = 1.98, 95% confidence interval [CI] = 0.97-4.06), liver compromised with hepatomegaly and/or splenomegaly (PR = 1.77, CI = 1.03-3.06) and elevation in serum of alanine aminotransferase and aspartate aminotransferase to values > 40 mU/mL (PR = 2.06, CI = 1.09-3.88 and PR = 1.53, CI = 0.99-2.35, respectively). Using multiple correspondence analyses, we identified in patients with PDH a profile characterized by the presence of constitutional symptoms, namely weight loss and Karnofsky classification ≤ 30, gastrointestinal manifestations with alteration of liver enzymes and hepatosplenomegaly and/or splenomegaly, skin lesions, and hematological alterations. Study of the profiles is no substitute for laboratory diagnostics, but identifying clinical and laboratory indicators of PLWHA with PDH should allow development of strategies for reducing the time to diagnosis and thus mortality caused by Histoplasma capsulatum. |
Effect of rotavirus vaccine on childhood diarrhea mortality in five Latin American countries
Paternina-Caicedo A , Parashar UD , Alvis-Guzman N , De Oliveira LH , Castano-Zuluaga A , Cotes-Cantillo K , Gamboa-Garay O , Coronell-Rodriguez W , De la Hoz-Restrepo F . Vaccine 2015 33 (32) 3923-8 BACKGROUND: The aim of this study was to estimate the association between rotavirus vaccine (RV) introduction and reduction of all-cause diarrhea death rates among children in five Latin American countries that introduced RV in 2006. METHODS: Diarrhea mortality data was gathered from 2002 until 2009 from the Pan American Health Organization Mortality Database for five "vaccine adopter" countries (Brazil, El Salvador, Mexico, Nicaragua, and Panama) that introduced RV in 2006 and four "control" countries (Argentina, Chile, Costa Rica, and Paraguay) that did not introduce RV by 2009. Time trend analyses were carried out, and effects and 95% confidence intervals (CI) were estimated. RESULTS: Each of the five vaccine adopter countries, except Panama, showed a significant trend in declining mortality rates during the post-vaccine period from 2006 to 2009, whereas no decline was seen in control countries during these years. Furthermore, trends of reduction of all-cause diarrhea mortality in both children <1 year of age and <5 years of age were greater in the post-vaccination period compared with the pre-vaccine period in all vaccine adopter countries (except for Nicaragua), whereas in control countries, a reverse pattern was seen with greater reduction in the early years from 2002 to 2005 versus 2006-2009. An estimatedtotal of 1777 of annual under-5 deaths were avoided in Brazil, El Salvador, Mexico, and Nicaragua during the post-vaccination period. CONCLUSION: All vaccine adopter countries, except Panama, showed a significant decrease in all-cause diarrhea-related deaths after RV implementation, even after adjusting for declining trends over time in diarrhea mortality. These data strongly support continuous efforts to increase vaccination coverage of RV vaccines, particularly in countries with high levels of child mortality from diarrhea. |
A qualitative study of vaccine acceptability and decision making among pregnant women in Morocco during the A (H1N1) pdm09 pandemic
Lohiniva AL , Barakat A , Dueger E , Restrepo S , El Aouad R . PLoS One 2014 9 (10) e96244 Vaccination uptake of pregnant women in Morocco during the A (H1N1) pdm09 pandemic was lower than expected. A qualitative study using open-ended questions was developed to explore the main determinants of acceptance and non-acceptance of the monovalent A (H1N1) pdm09 vaccine among pregnant women in Morocco and to identify information sources that influenced their decision-making process. The study sample included 123 vaccinated and unvaccinated pregnant women who were in their second or third trimester between December 2009 and March 2010. They took part in 14 focus group discussions and eight in-depth interviews in the districts of Casablanca and Kenitra. Thematic qualitative analysis identified reasons for vaccine non-acceptance: (1) fear of the monovalent A (H1N1) pdm09 vaccine, (2) belief in an A (H1N1) pdm09 pandemic conspiracy, (3) belief in the inapplicability of the monovalent A (H1N1) pdm09 vaccine to Moroccans, (4) lack of knowledge of the monovalent A (H1N1) pdm09 vaccine, and (5) challenges of vaccination services/logistics. Reasons for vaccine acceptance included: (1) perceived benefits and (2) modeling. Decision-making was strongly influenced by family, community, mass media, religious leaders and health providers suggesting that broad communication efforts should also be used to advocate for vaccination. Meaningful communication for future vaccine campaigns must consider these context-specific findings. As cultural and religious values are shared across many Arab countries, these findings may also provide valuable insights for seasonal influenza vaccine planning in the Middle East and North Africa region at large. |
Validation of a histoplasma ELISA antigenuria test in Colombian patients with AIDS for diagnosis and follow-up during therapy
Caceres DH , Scheel CM , Tobon AM , Ahlquist Cleveland A , Restrepo A , Brandt ME , Chiller T , Gomez BL . Clin Vaccine Immunol 2014 We validated an antigen capture ELISA test in Colombian persons with AIDS and proven histoplasmosis, and evaluated the correlation between antigenuria and clinical improvement during follow up. The sensitivity of the H. capsulatum ELISA was 86% and the overall specificity was 94%. The antigen test successfully monitored response to therapy. |
Characterization of rotavirus genotypes before and after the introduction of a monovalent rotavirus vaccine in Colombia
Pelaez-Carvajal D , Cotes-Cantillo K , Paternina-Caicedo A , Gentsch J , de la Hoz-Restrepo F , Patel M . J Med Virol 2014 86 (6) 1083-6 Strain monitoring for emergence of novel strains after the introduction of rotavirus vaccine is an integral component of routine rotavirus immunization programs. Using a laboratory based strain surveillance system between 2008 and 2012, a wide variation in strain pattern in Colombia was founded both before and after the introduction of a monovalent rotavirus vaccine in 2009. G2P[4], a strain fully heterotypic to the vaccine was predominant before vaccine introduction in 2008 (47%) and after vaccine introduction in 2010 (54%), 2011 (86%), and 2012 (32%). The presence of this strain before the introduction of vaccine and decreasing prevalence during the most recent surveillance year suggests secular variation rather than vaccine pressure as a cause for this fluctuation. While strain monitoring can be valuable after vaccine introduction, these surveillance data alone without information on disease incidence or strain specific vaccine effectiveness can be prone to misinterpretation with regard to the role of vaccine pressure on emergence of new or persistent strains. |
Association of blood lead level with neurological features in 972 children affected by an acute severe lead poisoning outbreak in Zamfara State, northern Nigeria
Greig J , Thurtle N , Cooney L , Ariti C , Ahmed AO , Ashagre T , Ayela A , Chukwumalu K , Criado-Perez A , Gomez-Restrepo C , Meredith C , Neri A , Stellmach D , Sani-Gwarzo N , Nasidi A , Shanks L , Dargan PI . PLoS One 2014 9 (4) e93716 BACKGROUND: In 2010, Medecins Sans Frontieres (MSF) investigated reports of high mortality in young children in Zamfara State, Nigeria, leading to confirmation of villages with widespread acute severe lead poisoning. In a retrospective analysis, we aimed to determine venous blood lead level (VBLL) thresholds and risk factors for encephalopathy using MSF programmatic data from the first year of the outbreak response. METHODS AND FINDINGS: We included children aged ≤5 years with VBLL ≥45 microg/dL before any chelation and recorded neurological status. Odds ratios (OR) for neurological features were estimated; the final model was adjusted for age and baseline VBLL, using random effects for village of residence. 972 children met inclusion criteria: 885 (91%) had no neurological features; 34 (4%) had severe features; 47 (5%) had reported recent seizures; and six (1%) had other neurological abnormalities. The geometric mean VBLLs for all groups with neurological features were >100 microg/dL vs 65.9 microg/dL for those without neurological features. The adjusted OR for neurological features increased with increasing VBLL: from 2.75, 95%CI 1.27-5.98 (80-99.9 microg/dL) to 22.95, 95%CI 10.54-49.96 (≥120 microg/dL). Neurological features were associated with younger age (OR 4.77 [95% CI 2.50-9.11] for 1-<2 years and 2.69 [95%CI 1.15-6.26] for 2-<3 years, both vs 3-5 years). Severe neurological features were seen at VBLL <105 microg/dL only in those with malaria. INTERPRETATION: Increasing VBLL (from ≥80 microg/dL) and age 1-<3 years were strongly associated with neurological features; in those tested for malaria, a positive test was also strongly associated. These factors will help clinicians managing children with lead poisoning in prioritising therapy and developing chelation protocols. |
A missed tuberculosis diagnosis resulting in hospital transmission
Medrano BA , Salinas G , Sanchez C , Miramontes R , Restrepo BI , Haddad MB , Lambert LA . Infect Control Hosp Epidemiol 2014 35 (5) 534-7 OBJECTIVE: To find the source of tuberculin skin test conversions among 38 hospital employees on 1 floor during routine testing January-February 2010. METHODS: Record review of patients at a private hospital during September-December 2009 and interviews with hospital employees. Names of patients from the state tuberculosis (TB) registry were cross-referenced with hospital records for admissions. Mycobacterium tuberculosis genotype results in the county and adjacent counties were examined, and contacts were evaluated for TB infection and disease. RESULTS: One of the 38 employees, a nurse, was diagnosed with pulmonary TB with a matching M. tuberculosis genotype and drug resistance pattern (isoniazid monoresistant) to those of a county jail inmate also recently diagnosed with pulmonary TB. The nurse had no known contact with that inmate; however, another inmate in his 20's from the same jail had been hospitalized under that nurse's care in October 2009. That young man died, and a postmortem examination result subsequently confirmed TB, which had not been suspected. Exposure to this man with undiagnosed TB could explain the transmission: 87 (27%) of the 318 hospital-based contacts without previous positive tuberculin skin test results were infected, and 9 contacts had active TB. CONCLUSIONS: This investigation demonstrated M. tuberculosis transmission in a hospital due to a missed diagnosis and nonadherence to national TB infection control guidelines. Routine TB screening of employees allowed early detection of this missed TB diagnosis, facilitating prompt evaluation of contacts. Healthcare providers should suspect TB in symptomatic persons and adhere to TB control policies. |
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