Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 50
Filtrar
1.
Nat Commun ; 12(1): 424, 2021 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-33462224

RESUMEN

There have been notable advances in the development of vaccines against active tuberculosis (TB) disease for adults and adolescents. Using mathematical models, we seek to estimate the potential impact of a post-exposure TB vaccine, having 50% efficacy in reducing active disease, on global rifampicin-resistant (RR-) TB burden. In 30 countries that together accounted for 90% of global RR-TB incidence in 2018, a future TB vaccine could avert 10% (95% credible interval: 9.7-11%) of RR-TB cases and 7.3% (6.6-8.1%) of deaths over 2020-2035, with India, China, Indonesia, Pakistan, and the Russian Federation having the greatest contribution. This impact would increase to 14% (12-16%) and 31% (29-33%) respectively, when combined with improvements in RR-TB diagnosis and treatment relative to a scenario of no vaccine and no such improvements. A future TB vaccine could have important implications for the global control of RR-TB, especially if implemented alongside enhancements in management of drug resistance.


Asunto(s)
Antituberculosos/farmacología , Carga Global de Enfermedades , Profilaxis Posexposición/métodos , Vacunas contra la Tuberculosis/administración & dosificación , Tuberculosis/epidemiología , Adolescente , Adulto , Antituberculosos/uso terapéutico , Simulación por Computador , Farmacorresistencia Bacteriana/inmunología , Humanos , Incidencia , Modelos Estadísticos , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/aislamiento & purificación , Rifampin/farmacología , Rifampin/uso terapéutico , Tuberculosis/tratamiento farmacológico , Tuberculosis/microbiología , Tuberculosis/prevención & control
2.
Epidemiology ; 32(2): 168-178, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33337670

RESUMEN

Host adaptive immune responses may protect against infection or disease when a pathogen is repeatedly encountered. The hazard ratio of infection or disease, given previous infection, is typically sought to estimate the strength of protective immunity. However, variation in individual exposure or susceptibility to infection may introduce frailty bias, whereby a tendency for infections to recur among individuals with greater risk confounds the causal association between previous infection and susceptibility. We introduce a self-matched "case-only" inference method to control for unmeasured individual heterogeneity, making use of negative-control endpoints not attributable to the pathogen of interest. To control for confounding, this method compares event times for endpoints due to the pathogen of interest and negative-control endpoints during counterfactual risk periods, defined according to individuals' infection history. We derive a standard Mantel-Haenszel (matched) odds ratio conveying the effect of prior infection on time to recurrence. We compare performance of this approach to several proportional hazards modeling frameworks and estimate statistical power of the proposed strategy under various conditions. In an example application, we use the proposed method to reestimate naturally acquired protection against rotavirus gastroenteritis using data from previously published cohort studies. This self-matched negative-control design may present a flexible alternative to existing approaches for analyzing naturally acquired immunity, as well as other exposures affecting the distribution of recurrent event times.

3.
PLoS Comput Biol ; 16(12): e1008477, 2020 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-33275606

RESUMEN

Infectious disease surveillance systems provide vital data for guiding disease prevention and control policies, yet the formalization of methods to optimize surveillance networks has largely been overlooked. Decisions surrounding surveillance design parameters-such as the number and placement of surveillance sites, target populations, and case definitions-are often determined by expert opinion or deference to operational considerations, without formal analysis of the influence of design parameters on surveillance objectives. Here we propose a simulation framework to guide evidence-based surveillance network design to better achieve specific surveillance goals with limited resources. We define evidence-based surveillance design as an optimization problem, acknowledging the many operational constraints under which surveillance systems operate, the many dimensions of surveillance system design, the multiple and competing goals of surveillance, and the complex and dynamic nature of disease systems. We describe an analytical framework-the Disease Surveillance Informatics Optimization and Simulation (DIOS) framework-for the identification of optimal surveillance designs through mathematical representations of disease and surveillance processes, definition of objective functions, and numerical optimization. We then apply the framework to the problem of selecting candidate sites to expand an existing surveillance network under alternative objectives of: (1) improving spatial prediction of disease prevalence at unmonitored sites; or (2) estimating the observed effect of a risk factor on disease. Results of this demonstration illustrate how optimal designs are sensitive to both surveillance goals and the underlying spatial pattern of the target disease. The findings affirm the value of designing surveillance systems through quantitative and adaptive analysis of network characteristics and performance. The framework can be applied to the design of surveillance systems tailored to setting-specific disease transmission dynamics and surveillance needs, and can yield improved understanding of tradeoffs between network architectures.

4.
Lancet Infect Dis ; 2020 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-33357507

RESUMEN

BACKGROUND: Rotavirus vaccine effectiveness is reduced among children in low-income countries. Indirect (transmission-mediated) effects of rotavirus vaccine might contribute to the total population effect of vaccination. We aimed to examine risk factors for transmission of rotavirus to household contacts in Blantyre, Malawi, and estimated the effectiveness of rotavirus vaccine in preventing transmission of infection to household contacts. METHODS: In this prospective household cohort study, we recruited children born after Sept 17, 2012, and aged at least 6 weeks (vaccine-eligible children) with acute rotavirus gastroenteritis and their household contacts, in four government health facilities in Blantyre, Malawi. Clinical data, a bulk stool sample, and 1-2 mL of serum were collected from case children at presentation. Clinical data and stool samples were also prospectively collected from household contacts over 14 days from presentation. A single stool sample was collected from control households containing asymptomatic children who were frequency age-matched to case children. Samples were tested for rotavirus using semi-quantitative real-time PCR and for anti-rotavirus IgA using a semi-quantitative sandwich ELISA. Risk factors for household transmission of rotavirus infection and clinical disease, including disease severity and faecal shedding density, were identified using mixed effects logistic regression. Vaccine effectiveness against transmission was estimated as 1 minus the ratio of secondary attack rates in vaccinated and counterfactual unvaccinated populations, using vaccine effectiveness estimates from the associated diarrhoeal surveillance platform to estimate the counterfactual secondary attack rate without vaccination. FINDINGS: Between Feb 16, 2015, and Nov 11, 2016, we recruited 196 case households (705 members) and 55 control households (153 members). Household secondary attack rate for rotavirus infection was high (434 [65%] of 665 individuals) and secondary attack rate for clinical disease was much lower (37 [5%] of 698). Asymptomatic infection in control households was common (40 [28%] of 144). Increasing disease severity in an index child (as measured by Vesikari score) was associated with increased risk of transmission of infection (odds ratio 1·17 [95% CI 1·06-1·30) and disease (1·28 [1·08-1·52]) to household contacts. Estimated vaccine effectiveness against transmission was 39% (95% CI 16-57). INTERPRETATION: Rotavirus vaccine has the potential to substantially reduce household rotavirus transmission. This finding should be considered in clinical and health economic assessments of vaccine effectiveness. FUNDING: Wellcome Trust, US National Institutes of Health, and US National Institute of Allergy and Infectious Diseases.

5.
Clin Infect Dis ; 2020 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-33346348

RESUMEN

INTRODUCTION: Streptococcus pneumoniae is a leading cause of pneumonia among children. However, owing to diagnostic limitations, the protection conferred by pneumococcal conjugate vaccines (PCVs) against pediatric pneumonia attributable to vaccine-serotype pneumococci remains unknown. METHODS: We analyzed data on vaccination and nasopharyngeal pneumococcal detection among children <5 years old with community-acquired alveolar pneumonia (CAAP; "cases") and those without respiratory symptoms ("controls"), who were enrolled in population-based prospective surveillance studies in southern Israel between 2009-18. We measured PCV-conferred protection against carriage of vaccine-serotype pneumococci via the relative risk of detecting these serotypes among vaccinated versus unvaccinated controls. We measured protection against progression of vaccine serotypes from carriage to CAAP via the relative association of vaccine-serotype detection in the nasopharynx with CAAP case status, among vaccinated and unvaccinated children. We measured PCV-conferred protection against CAAP attributable to vaccine-serotype pneumococci via the joint reduction in risks of carriage and disease progression. RESULTS: Our analyses included 1,032 CAAP cases and 7,743 controls. At ages 12-35 months, a PCV13 schedule containing two primary doses and one booster dose provided 87.2% (95% confidence interval: 8.1-100.0%) protection against CAAP attributable to PCV13-serotype pneumococci, and 92.3% (-0.9-100.0%) protection against CAAP attributable to PCV7-serotype pneumococci. Protection against PCV13-serotype and PCV7-serotype CAAP was 67.0% (-424.3-100.0%) and 67.7% (-1962.9-100.0%), respectively, at ages 36-59 months. At ages 4-11 months, two PCV13 doses provided 98.9% (-309.8-100.0%) and 91.4% (-191.4-100.0%) against PCV13-serotype and PCV7-serotype CAAP. CONCLUSIONS: Among children, PCV-conferred protection against CAAP attributable to vaccine-targeted pneumococcal serotypes resembles protection against vaccine-serotype invasive pneumococcal disease.

6.
Science ; 370(6517): 691-697, 2020 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-33154136

RESUMEN

Although most cases of coronavirus disease 2019 (COVID-19) have occurred in low-resource countries, little is known about the epidemiology of the disease in such contexts. Data from the Indian states of Tamil Nadu and Andhra Pradesh provide a detailed view into severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission pathways and mortality in a high-incidence setting. Reported cases and deaths have been concentrated in younger cohorts than would be expected from observations in higher-income countries, even after accounting for demographic differences across settings. Among 575,071 individuals exposed to 84,965 confirmed cases, infection probabilities ranged from 4.7 to 10.7% for low-risk and high-risk contact types, respectively. Same-age contacts were associated with the greatest infection risk. Case fatality ratios spanned 0.05% at ages of 5 to 17 years to 16.6% at ages of 85 years or more. Primary data from low-resource countries are urgently needed to guide control measures.


Asunto(s)
Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/transmisión , Neumonía Viral/mortalidad , Neumonía Viral/transmisión , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Betacoronavirus , Niño , Preescolar , Trazado de Contacto , Femenino , Humanos , Incidencia , India/epidemiología , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Pandemias , Adulto Joven
8.
medRxiv ; 2020 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-32793934

RESUMEN

Background Large-scale school closures have been implemented worldwide to curb the spread of COVID-19. However, the impact of school closures and re-opening on epidemic dynamics remains unclear. Methods We simulated COVID-19 transmission dynamics using an individual-based stochastic model, incorporating social-contact data of school-aged children during shelter-in-place orders derived from Bay Area (California) household surveys. We simulated transmission under observed conditions and counterfactual intervention scenarios between March 17-June 1, and evaluated various fall 2020 K-12 reopening strategies. Findings Between March 17-June 1, assuming children <10 were half as susceptible to infection as older children and adults, we estimated school closures averted a similar number of infections (13,842 cases; 95% CI: 6,290, 23,040) as workplace closures (15,813; 95% CI: 9,963, 22,617) and social distancing measures (7,030; 95% CI: 3,118, 11,676). School closure effects were driven by high school and middle school closures. Under assumptions of moderate community transmission, we estimate that fall 2020 school reopenings will increase symptomatic illness among high school teachers (an additional 40.7% expected to experience symptomatic infection, 95% CI: 1.9, 61.1), middle school teachers (37.2%, 95% CI: 4.6, 58.1), and elementary school teachers (4.1%, 95% CI: -1.7, 12.0). Results are highly dependent on uncertain parameters, notably the relative susceptibility and infectiousness of children, and extent of community transmission amid re-opening. The school-based interventions needed to reduce the risk to fewer than an additional 1% of teachers infected varies by grade level. A hybrid-learning approach with halved class sizes of 10 students may be needed in high schools, while maintaining small cohorts of 20 students may be needed for elementary schools. Interpretation Multiple in-school intervention strategies and community transmission reductions, beyond the extent achieved to date, will be necessary to avoid undue excess risk associated with school reopening. Policymakers must urgently enact policies that curb community transmission and implement within-school control measures to simultaneously address the tandem health crises posed by COVID-19 and adverse child health and development consequences of long-term school closures.

9.
J R Soc Interface ; 17(169): 20200161, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32781936

RESUMEN

The fact that many pathogens can be carried or shed without causing symptoms complicates the interpretation of microbiological data when diagnosing certain infectious disease syndromes. Diagnostic criteria that attribute symptoms to a pathogen which is detectable, whether it is or is not the aetiological agent of disease, may lead to outcome misclassification in epidemiological studies. Case-control studies are commonly undertaken to estimate vaccine effectiveness (VE) and present an opportunity to compare pathogen detection among individuals with and without clinically relevant symptoms. Considering this study context, we present a mathematical framework yielding simple estimators for the direct effects of vaccination on various aspects of host susceptibility. These include protection against acquisition of the pathogen of interest and protection against progression of this pathogen to disease following acquisition. We assess the impact of test sensitivity on these estimators and extend our framework to identify a 'vaccine probe' estimator for pathogen-specific aetiological fractions. We also derive biases affecting VE estimates under the test-negative design, a special case enrolling only symptomatic persons. Our results provide strategies for estimating pathogen-specific VE in the absence of a diagnostic gold standard. These approaches can inform the design and analysis of studies addressing numerous pathogens and vaccines.

10.
PLoS Negl Trop Dis ; 14(8): e0008520, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32776938

RESUMEN

Diarrhea is a leading cause of antibiotic consumption among children in low- and middle-income countries. While vaccines may prevent diarrhea infections for which children often receive antibiotics, the contribution of individual enteropathogens to antibiotic use is minimally understood. We used data from the Global Enteric Multicenter Study (GEMS) to estimate pathogen-specific incidence of antibiotic-treated diarrhea among children under five years old residing in six countries of sub-Saharan Africa and South Asia before rotavirus vaccine implementation. GEMS was an age-stratified, individually-matched case-control study. Stool specimens were obtained from children presenting to sentinel health clinics with newly-onset, acute diarrhea (including moderate-to-severe and less-severe diarrhea) as well as matched community controls without diarrhea. We used data from conventional and quantitative molecular diagnostic assays applied to stool specimens to estimate the proportion of antibiotic-treated diarrhea cases attributable to each pathogen. Antibiotics were administered or prescribed to 9,606 of 12,109 moderate-to-severe cases and 1,844 of 3,174 less-severe cases. Across all sites, incidence rates of clinically-attended, antibiotic-treated diarrhea were 12.2 (95% confidence interval: 9.0-17.8), 10.2 (7.4-13.9) and 1.9 (1.3-3.0) episodes per 100 child-years at risk at ages 6 weeks to 11 months, 12-23 months, and 24-59 months, respectively. Based on the recommendation for antibiotic treatment to be reserved for cases with dysentery, we estimated a ratio of 12.6 (8.6-20.8) inappropriately-treated diarrhea cases for each appropriately-treated case. Rotavirus, adenovirus serotypes 40/41, Shigella, sapovirus, Shiga toxin-producing Escherichia coli, and Cryptosporidium were the leading antibiotic-treated diarrhea etiologies. Rotavirus caused 29.2% (24.5-35.2%) of antibiotic-treated cases, including the largest share in both the first and second years of life. Shigella caused 14.9% (11.4-18.9%) of antibiotic-treated cases, and was the leading etiology at ages 24-59 months. Our findings should inform the prioritization of vaccines with the greatest potential to reduce antibiotic exposure among children.


Asunto(s)
Antibacterianos/uso terapéutico , Países en Desarrollo , Diarrea/tratamiento farmacológico , Diarrea/epidemiología , Diarrea/etiología , Adenoviridae , África del Sur del Sahara/epidemiología , Antibacterianos/administración & dosificación , Asia/epidemiología , Estudios de Casos y Controles , Preescolar , Criptosporidiosis/tratamiento farmacológico , Criptosporidiosis/epidemiología , Criptosporidiosis/etiología , Cryptosporidium , Disentería/tratamiento farmacológico , Disentería/epidemiología , Disentería/etiología , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/etiología , Heces/virología , Femenino , Encuestas Epidemiológicas , Hospitalización , Humanos , Incidencia , Renta , Lactante , Masculino , Vacunas contra Rotavirus , Escherichia coli Shiga-Toxigénica , Shigella
11.
Nature ; 581(7806): 94-99, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32376956

RESUMEN

Vaccines may reduce the burden of antimicrobial resistance, in part by preventing infections for which treatment often includes the use of antibiotics1-4. However, the effects of vaccination on antibiotic consumption remain poorly understood-especially in low- and middle-income countries (LMICs), where the burden of antimicrobial resistance is greatest5. Here we show that vaccines that have recently been implemented in the World Health Organization's Expanded Programme on Immunization reduce antibiotic consumption substantially among children under five years of age in LMICs. By analysing data from large-scale studies of households, we estimate that pneumococcal conjugate vaccines and live attenuated rotavirus vaccines confer 19.7% (95% confidence interval, 3.4-43.4%) and 11.4% (4.0-18.6%) protection against antibiotic-treated episodes of acute respiratory infection and diarrhoea, respectively, in age groups that experience the greatest disease burden attributable to the vaccine-targeted pathogens6,7. Under current coverage levels, pneumococcal and rotavirus vaccines prevent 23.8 million and 13.6 million episodes of antibiotic-treated illness, respectively, among children under five years of age in LMICs each year. Direct protection resulting from the achievement of universal coverage targets for these vaccines could prevent an additional 40.0 million episodes of antibiotic-treated illness. This evidence supports the prioritization of vaccines within the global strategy to combat antimicrobial resistance8.


Asunto(s)
Antibacterianos , Países en Desarrollo/economía , Utilización de Medicamentos/estadística & datos numéricos , Vacunas , Antibacterianos/administración & dosificación , Antibacterianos/economía , Preescolar , Diarrea/tratamiento farmacológico , Diarrea/prevención & control , Diarrea/virología , Farmacorresistencia Microbiana , Utilización de Medicamentos/economía , Humanos , Incidencia , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/inmunología , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/prevención & control , Vacunas contra Rotavirus/administración & dosificación , Vacunas contra Rotavirus/inmunología , Vacunas/administración & dosificación , Vacunas/economía , Vacunas/inmunología , Organización Mundial de la Salud/organización & administración
12.
Clin Infect Dis ; 2020 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-32374829

RESUMEN

BACKGROUND: Group A Streptococcus (GAS) is a leading cause of acute respiratory infections frequently resulting in antibiotic prescribing. Vaccines against GAS are currently in development. METHODS: We estimated the incidence of healthcare visits and antibiotic prescribing for pharyngitis, sinusitis, and acute otitis media (AOM) in the United States using nationally-representative surveys of outpatient care provision, supplemented by insurance claims data. We estimated the proportion of these episodes attributable to GAS, and to GAS emm types included in a proposed 30-valent vaccine. We used these outputs to estimate the incidence of outpatient visits and antibiotic prescribing preventable by GAS vaccines with various efficacy profiles under infant and school-age dosing schedules. RESULTS: GAS pharyngitis causes 19.1 (95%CI: 17.3-21.1) outpatient visits and 10.2 (9.0-11.5) antibiotic prescriptions per 1,000 US persons aged 0-64 years, annually. GAS pharyngitis causes 93.2 (82.3-105.3) visits and 53.2 (45.2-62.5) antibiotic prescriptions per 1,000 children ages 3-9 years, annually, representing 5.9% (5.1-7.0%) of all outpatient antibiotic prescribing in this age group. Collectively, GAS-attributable pharyngitis, sinusitis, and AOM cause 26.9 (23.9-30.8) and 16.1 (14.0-18.7) outpatient visits and antibiotic prescriptions per 1,000 population, annually. A 30-valent GAS vaccine meeting the WHO 80% efficacy target could prevent 5.4% (4.6-6.4%) of outpatient antibiotic prescriptions among children aged 3-9 years. If vaccine prevention of GAS pharyngitis made routine antibiotic treatment of pharyngitis unnecessary, up to 17.1% (15.0-19.6%) of outpatient antibiotic prescriptions among children aged 3-9 years could be prevented. CONCLUSIONS: An efficacious GAS vaccine could prevent substantial incidence of pharyngitis infections and associated antibiotic prescribing in the United States.

13.
BMJ ; 369: m1923, 2020 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-32444358

RESUMEN

OBJECTIVE: To understand the epidemiology and burden of severe coronavirus disease 2019 (covid-19) during the first epidemic wave on the west coast of the United States. DESIGN: Prospective cohort study. SETTING: Kaiser Permanente integrated healthcare delivery systems serving populations in northern California, southern California, and Washington state. PARTICIPANTS: 1840 people with a first acute hospital admission for confirmed covid-19 by 22 April 2020, among 9 596 321 healthcare plan enrollees. Analyses of hospital length of stay and clinical outcomes included 1328 people admitted by 9 April 2020 (534 in northern California, 711 in southern California, and 83 in Washington). MAIN OUTCOME MEASURES: Cumulative incidence of first acute hospital admission for confirmed covid-19, and subsequent probabilities of admission to an intensive care unit (ICU) and mortality, as well as duration of hospital stay and ICU stay. The effective reproduction number (RE ) describing transmission dynamics was estimated for each region. RESULTS: As of 22 April 2020, cumulative incidences of a first acute hospital admission for covid-19 were 15.6 per 100 000 cohort members in northern California, 23.3 per 100 000 in southern California, and 14.7 per 100 000 in Washington. Accounting for censoring of incomplete hospital stays among those admitted by 9 April 2020, the estimated median duration of stay among survivors was 9.3 days (with 95% staying 0.8 to 32.9 days) and among non-survivors was 12.7 days (1.6 to 37.7 days). The censoring adjusted probability of ICU admission for male patients was 48.5% (95% confidence interval 41.8% to 56.3%) and for female patients was 32.0% (26.6% to 38.4%). For patients requiring critical care, the median duration of ICU stay was 10.6 days (with 95% staying 1.3 to 30.8 days). The censoring adjusted case fatality ratio was 23.5% (95% confidence interval 19.6% to 28.2%) among male inpatients and 14.9% (11.8% to 18.6%) among female inpatients; mortality risk increased with age for both male and female patients. Reductions in RE were identified over the study period within each region. CONCLUSIONS: Among residents of California and Washington state enrolled in Kaiser Permanente healthcare plans who were admitted to hospital with covid-19, the probabilities of ICU admission, of long hospital stay, and of mortality were identified to be high. Incidence rates of new hospital admissions have stabilized or declined in conjunction with implementation of social distancing interventions.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Betacoronavirus , California/epidemiología , Infecciones por Coronavirus/transmisión , Cuidados Críticos , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Incidencia , Unidades de Cuidados Intensivos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/transmisión , Estudios Prospectivos , Washingtón/epidemiología , Adulto Joven
17.
PLoS Biol ; 18(2): e3000611, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32045407

RESUMEN

Unusually large outbreaks of mumps across the United States in 2016 and 2017 raised questions about the extent of mumps circulation and the relationship between these and prior outbreaks. We paired epidemiological data from public health investigations with analysis of mumps virus whole genome sequences from 201 infected individuals, focusing on Massachusetts university communities. Our analysis suggests continuous, undetected circulation of mumps locally and nationally, including multiple independent introductions into Massachusetts and into individual communities. Despite the presence of these multiple mumps virus lineages, the genomic data show that one lineage has dominated in the US since at least 2006. Widespread transmission was surprising given high vaccination rates, but we found no genetic evidence that variants arising during this outbreak contributed to vaccine escape. Viral genomic data allowed us to reconstruct mumps transmission links not evident from epidemiological data or standard single-gene surveillance efforts and also revealed connections between apparently unrelated mumps outbreaks.


Asunto(s)
Brotes de Enfermedades , Genoma Viral/genética , Virus de la Parotiditis/genética , Paperas/epidemiología , Paperas/transmisión , Genotipo , Humanos , Epidemiología Molecular , Paperas/virología , Virus de la Parotiditis/clasificación , Mutación , Filogenia , Análisis de Secuencia de ADN , Estados Unidos/epidemiología , Vacunación/estadística & datos numéricos , Proteínas Virales/genética
18.
Clin Infect Dis ; 71(8): e244-e254, 2020 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-31955205

RESUMEN

BACKGROUND: Pharyngitis due to group A Streptococcus (GAS) represents a major cause of outpatient visits and antibiotic use in the United States. A leading vaccine candidate targets 30 of the > 200 emm types of GAS. We aimed to assess natural protection conferred by GAS against respiratory symptoms. METHODS: In a 5-year study among school-aged children in Pittsburgh, Pennsylvania, pharyngeal cultures were obtained from children at 2-week intervals, and active surveillance was conducted for respiratory illnesses. We assessed protection via the relative odds of previous detection of homologous strains (defined by field-inversion gel electrophoresis banding pattern), emm types, and emm clusters at visits where GAS was detected with symptoms, vs visits where GAS was detected without symptoms. We used a cluster bootstrap of children to adjust estimates for repeated sampling. RESULTS: At visits where previously detected GAS emm types were identified, we estimated 81.8% (95% confidence interval [CI], 67.1%-91.7%) protection against typical pharyngitis symptoms among children reacquiring the same strain, and 94.5% (95% CI, 83.5%-98.6%) protection among children acquiring a distinct strain. We estimated 77.1% (95% CI, 33.7%-96.3%) protection against typical symptoms among children acquiring partially heterologous emm types belonging to a previously detected emm cluster. Protection was evident after both symptomatic and asymptomatic detections of GAS. We did not identify strong evidence of protection against atypical respiratory symptoms. CONCLUSIONS: Within a 5-year longitudinal study, previous detection of GAS emm types was associated with protection against typical symptoms when homologous strains were subsequently detected. Naturally acquired protection against partially heterologous types suggests that emm type-based vaccines may have broader strain coverage than what has been previously assumed.

19.
Epidemiology ; 31(1): 43-64, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31609860

RESUMEN

BACKGROUND: The test-negative design is an increasingly popular approach for estimating vaccine effectiveness (VE) due to its efficiency. This review aims to examine published test-negative design studies of VE and to explore similarities and differences in methodological choices for different diseases and vaccines. METHODS: We conducted a systematic search on PubMed, Web of Science, and Medline, for studies reporting the effectiveness of any vaccines using a test-negative design. We screened titles and abstracts and reviewed full texts to identify relevant articles. We created a standardized form for each included article to extract information on the pathogen of interest, vaccine(s) being evaluated, study setting, clinical case definition, choices of cases and controls, and statistical approaches used to estimate VE. RESULTS: We identified a total of 348 articles, including studies on VE against influenza virus (n = 253), rotavirus (n = 48), pneumococcus (n = 24), and nine other pathogens. Clinical case definitions used to enroll patients were similar by pathogens of interest but the sets of symptoms that defined them varied substantially. Controls could be those testing negative for the pathogen of interest, those testing positive for nonvaccine type of the pathogen of interest, or a subset of those testing positive for alternative pathogens. Most studies controlled for age, calendar time, and comorbidities. CONCLUSIONS: Our review highlights similarities and differences in the application of the test-negative design that deserve further examination. If vaccination reduces disease severity in breakthrough infections, particular care must be taken in interpreting vaccine effectiveness estimates from test-negative design studies.

20.
Clin Infect Dis ; 71(8): e289-e300, 2020 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-31784753

RESUMEN

BACKGROUND: Reduced-dose pneumococcal conjugate vaccine (PCV) schedules are under consideration in countries where children are recommended to receive 3 doses. Whereas PCV-derived protection against vaccine-serotype colonization is responsible for herd effects of vaccination, dose-specific PCV effectiveness against colonization endpoints is not known. We aimed to assess the performance of differing PCV schedules against vaccine-serotype colonization in children. METHODS: From 2009-2016, we monitored pneumococcal carriage in southern Israel, where children should receive PCV at ages 2 months, 4 months, and 12 months (2 primary [p] +1 booster [b] schedule). We analyzed nasopharyngeal swabs and vaccination histories from 5928 children aged 0-59 months without symptoms of diseases potentially attributable to pneumococci. Matching individuals on age, sex, ethnicity, visit timing, and recent antibiotic receipt, we measured schedule-specific 7-valent PCV (PCV7) and 13-valent PCV (PCV13) effectiveness against vaccine-serotype colonization in a modified case-control framework. We sampled from the distribution of all possible case-control match assignments for statistical analyses. RESULTS: Receiving 2 primary-series PCV13 doses conferred 53% (95% confidence interval [CI], 32-67%) protection against PCV13-serotype colonization at ages ≤12 months; 1 primary-series dose was not protective. A 2p+1b PCV13 series conferred 40% (95% CI, 4-67%) and 62% (95% CI, 33-83%) protection against PCV13-serotype colonization at ages 13-24 months and 25-59 months, respectively. Estimates suggested greater PCV13-conferred protection against PCV7-targeted serotypes than the 6 PCV13-only serotypes. As compared to children receiving 2p+1b PCV13 dosing, those receiving 1p+1b and 2p+0b schedules experienced 2.05-fold (95% CI, 1.12-5.00) and 3.33-fold (95% CI, 2.28-4.93) greater odds, respectively, of vaccine-serotype pneumococcal colonization at ages 13-24 months. CONCLUSIONS: Our results demonstrate real-world effectiveness of 2p+1b PCV dosing against vaccine-serotype colonization. Reduced-dose schedules may confer lower protection against vaccine-serotype carriage during and beyond the first year of life.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA