Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
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Query Trace: Haber P [original query] |
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Discussion of "Is group testing ready for prime-time in disease Identification?" by Haber, Malinovsky, and Albert, Statistics in Medicine, 2021
Biggerstaff BJ . Stat Med 2021 40 (17) 3887-3888 I congratulate the authors on an interesting, instructive, and timely paper. Certainly, including the testing for SARS‐CoV‐2 example in a paper on a topic—group testing—of wide interest during the current COVID‐19 pandemic emphasizes the relevance of the topic in public health and diagnostic medicine generally. But the thoughtful inclusion of the remaining examples—HIV, HPV, and cancer biomarker detection—illustrates that the issues considered are important even in less urgent times. In this note of discussion I will comment on two particular aspects in the paper that I found particularly informative, and then I will comment on two other, related areas that I believe the conclusions inform. |
Comparing statistical methods for detecting and estimating waning efficacy of rotavirus vaccines in developing countries.
Haber M , Tate JE , Lopman BA , Qi W , Ainslie KEC , Parashar UD . Hum Vaccin Immunother 2021 17 (11) 1-4 INTRODUCTION: Vaccination has significantly reduced morbidity and mortality resulting from rotavirus infection worldwide. However, rotavirus vaccine efficacy (VE) appears to wane over the first 2 years since vaccination, particularly in developing countries. Statistical methods for detecting VE waning and estimating its rate have been used in a few studies, but comparisons of methods for evaluating VE waning have not yet been performed. In this work we present and compare three methods - Durham's method, Tian's method, and time-dependent covariate (TDC) method - based on generalizations of the Cox proportional hazard model. METHODS: We developed a new stochastic agent-based simulation model to generate data from a hypothetical rotavirus vaccine trial where the protective efficacy of the vaccine may vary over time. Input parameters to the simulation model were obtained from studies on rotavirus infections in four developing countries. We applied each of the methods to four simulated datasets and compared the type-1 error probabilities and the powers of the resulting statistical tests. We also compared estimated and true values of VE over time. RESULTS: Durham's method had the highest power of detecting true VE waning of the three methods. This method also provided quite accurate estimates of VE in each period and of the per-period drop in VE. CONCLUSIONS: Durham's method is somewhat more powerful than the other two Cox proportional hazards model-based methods for detecting VE waning and provides more information about the temporal behavior of VE. |
Nonventilator hospital-acquired pneumonia: A call to action
Munro SC , Baker D , Giuliano KK , Sullivan SC , Haber J , Jones BE , Crist MB , Nelson RE , Carey E , Lounsbury O , Lucatorto M , Miller R , Pauley B , Klompas M . Infect Control Hosp Epidemiol 2021 42 (8) 1-6 In 2020 a group of U.S. healthcare leaders formed the National Organization to Prevent Hospital-Acquired Pneumonia (NOHAP) to issue a call to action to address non-ventilator-associated hospital-acquired pneumonia (NVHAP). NVHAP is one of the most common and morbid healthcare-associated infections, but it is not tracked, reported, or actively prevented by most hospitals. This national call to action includes (1) launching a national healthcare conversation about NVHAP prevention; (2) adding NVHAP prevention measures to education for patients, healthcare professionals, and students; (3) challenging healthcare systems and insurers to implement and support NVHAP prevention; and (4) encouraging researchers to develop new strategies for NVHAP surveillance and prevention. The purpose of this document is to outline research needs to support the NVHAP call to action. Primary needs include the development of better models to estimate the economic cost of NVHAP, to elucidate the pathophysiology of NVHAP and identify the most promising pathways for prevention, to develop objective and efficient surveillance methods to track NVHAP, to rigorously test the impact of prevention strategies proposed to prevent NVHAP, and to identify the policy levers that will best engage hospitals in NVHAP surveillance and prevention. A joint task force developed this document including stakeholders from the Veterans' Health Administration (VHA), the U.S. Centers for Disease Control and Prevention (CDC), The Joint Commission, the American Dental Association, the Patient Safety Movement Foundation, Oral Health Nursing Education and Practice (OHNEP), Teaching Oral-Systemic Health (TOSH), industry partners and academia. |
Safety profile of rotavirus vaccines among individuals aged 8months of age, United States, Vaccine Adverse Event Reporting System (VAERS), 2006-2019
Haber P , Tate J , Marquez PL , Moro PL , Parashar U . Vaccine 2020 39 (4) 746-750 INTRODUCTION: In 2006 and 2008, two live, oral rotavirus vaccines, RotaTeq (RV5) and Rotarix (RV1), were introduced into the routine immunization program in the United States. A previous rotavirus vaccine, RotaShield, was associated with an increased risk of intussusception, with data suggesting an age-dependent variation in risk. Advisory Committee on Immunization Practices (ACIP) currently recommends that RV5 or RV1 immunization be initiated by age 14 weeks and 6 days and completed by 8 months 0 days. METHODS: We searched for U.S. VAERS reports of RV5, RV1, or unknown rotavirus vaccine brand among individuals aged ≥8 months. We analyzed reports by 2 age groups (individuals aged ≥8 months-≤5 years and ≥6 years), vaccine brand name, adverse event (AE) reported, classification of seriousness (death, non-death serious, and non-serious) and mode of exposure (direct vs. indirect exposure). For serious reports we reviewed available medical records and assigned a primary diagnosis. RESULTS: VAERS received a total of 344 U.S. reports following rotavirus vaccination among individuals ≥8 months of age, 32 (9.3%) were serious. In the younger age-group, 307 (99%) of 309 reports followed direct vaccination of the child. In contrast, in individuals aged ≥6 years, 21 (60%) of 35 reports were via potential indirect exposure to a vaccinated child. The frequently reported AEs in the younger age-group were inappropriate schedule of drug administration 104 (34%) and drug administered to patient of inappropriate age 45 (15%); in the older group these were accidental exposure 9 (26%) and eye irritation 7 (20%). No difference in the safety profile was observed between RV1 and RV5. CONCLUSIONS: We did not identify any unexpected AEs for RV vaccines among individuals aged ≥8 months. Health care providers should adhere to the ACIP recommended schedule and older individuals should apply necessary precautions to prevent potential secondary exposure from vaccinated children. |
Association of genetic mutations and loss of ambulation in childhood-onset dystrophinopathy
Haber G , Conway KM , Paramsothy P , Roy A , Rogers H , Ling X , Kozauer N , Street N , Romitti PA , Fox DJ , Phan HC , Matthews D , Ciafaloni E , Oleszek J , James KA , Galindo M , Whitehead N , Johnson N , Butterfield RJ , Pandya S , Venkatesh S , Bhattaram VA . Muscle Nerve 2020 63 (2) 181-191 INTRODUCTION: Quantifying associations between genetic mutations and loss of ambulation (LoA) among males diagnosed with childhood-onset dystrophinopathy is important for understanding variation in disease progression and may be useful in clinical trial design. METHODS: Genetic and clinical data from the Muscular Dystrophy Surveillance, Tracking, and Research Network for 358 males born and diagnosed from 1982-2011 were analyzed. LoA was defined as the age at which independent ambulation ceased. Genetic mutations were defined by overall type (deletion/duplication/point mutation) and among deletions, those amenable to exon-skipping therapy (exons 8, 20, 44-46, 51-53) and another group. Cox proportional hazards regression modeling was used to estimate hazards ratios (HR) and 95% confidence intervals (CI). RESULTS: Mutation type did not predict time to LoA. Controlling for corticosteroids, Exons 8 (HR=0.22; 95% CI=0.08,0.63) and 44 (HR=0.30; 95% CI=0.12,0.78) were associated with delayed LOA compared to other exon deletions. DISCUSSION: Delayed LoA in males with mutations amenable to exon-skipping therapy is consistent with previous studies. These findings suggest that clinical trials including exon 8 and 44 skippable males should consider mutation information prior to randomization. |
Risk Assessment and Management of COVID-19 Among Travelers Arriving at Designated U.S. Airports, January 17-September 13, 2020.
Dollard P , Griffin I , Berro A , Cohen NJ , Singler K , Haber Y , de la Motte Hurst C , Stolp A , Atti S , Hausman L , Shockey CE , Roohi S , Brown CM , Rotz LD , Cetron MS , Alvarado-Ramy F . MMWR Morb Mortal Wkly Rep 2020 69 (45) 1681-1685 In January 2020, with support from the U.S. Department of Homeland Security (DHS), CDC instituted an enhanced entry risk assessment and management (screening) program for air passengers arriving from certain countries with widespread, sustained transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). The objectives of the screening program were to reduce the importation of COVID-19 cases into the United States and slow subsequent spread within states. Screening aimed to identify travelers with COVID-19-like illness or who had a known exposure to a person with COVID-19 and separate them from others. Screening also aimed to inform all screened travelers about self-monitoring and other recommendations to prevent disease spread and obtain their contact information to share with public health authorities in destination states. CDC delegated postarrival management of crew members to airline occupational health programs by issuing joint guidance with the Federal Aviation Administration.* During January 17-September 13, 2020, a total of 766,044 travelers were screened, 298 (0.04%) of whom met criteria for public health assessment; 35 (0.005%) were tested for SARS-CoV-2, and nine (0.001%) had a positive test result. CDC shared contact information with states for approximately 68% of screened travelers because of data collection challenges and some states' opting out of receiving data. The low case detection rate of this resource-intensive program highlighted the need for fundamental change in the U.S. border health strategy. Because SARS-CoV-2 infection and transmission can occur in the absence of symptoms and because the symptoms of COVID-19 are nonspecific, symptom-based screening programs are ineffective for case detection. Since the screening program ended on September 14, 2020, efforts to reduce COVID-19 importation have focused on enhancing communications with travelers to promote recommended preventive measures, reinforcing mechanisms to refer overtly ill travelers to CDC, and enhancing public health response capacity at ports of entry. More efficient collection of contact information for international air passengers before arrival and real-time transfer of data to U.S. health departments would facilitate timely postarrival public health management, including contact tracing, when indicated. Incorporating health attestations, predeparture and postarrival testing, and a period of limited movement after higher-risk travel, might reduce risk for transmission during travel and translocation of SARS-CoV-2 between geographic areas and help guide more individualized postarrival recommendations. |
Prevention of hepatitis A virus infection in the United States: Recommendations of the Advisory Committee on Immunization Practices, 2020
Nelson NP , Weng MK , Hofmeister MG , Moore KL , Doshani M , Kamili S , Koneru A , Haber P , Hagan L , Romero JR , Schillie S , Harris AM . MMWR Recomm Rep 2020 69 (5) 1-38 Hepatitis a is a vaccine-preventable, communicable disease of the liver caused by the hepatitis a virus (hav). The infection is transmitted via the fecal-oral route, usually from direct person-to-person contact or consumption of contaminated food or water. Hepatitis a is an acute, self-limited disease that does not result in chronic infection. Hav antibodies (immunoglobulin g [igg] anti-hav) produced in response to hav infection persist for life and protect against reinfection; igg anti-hav produced after vaccination confer long-term immunity. This report supplants and summarizes previously published recommendations from the advisory committee on immunization practices (acip) regarding the prevention of hav infection in the united states. Acip recommends routine vaccination of children aged 12-23 months and catch-up vaccination for children and adolescents aged 2-18 years who have not previously received hepatitis a (hepa) vaccine at any age. Acip recommends hepa vaccination for adults at risk for hav infection or severe disease from hav infection and for adults requesting protection against hav without acknowledgment of a risk factor. These recommendations also provide guidance for vaccination before travel, for postexposure prophylaxis, in settings providing services to adults, and during outbreaks. |
Longer-term direct and indirect effects of infant rotavirus vaccination across all ages in the United States in 2000-2013: Analysis of a large hospital discharge data set
Baker JM , Tate JE , Steiner CA , Haber MJ , Parashar UD , Lopman BA . Clin Infect Dis 2019 68 (6) 976-983 BACKGROUND: Rotavirus disease rates dramatically declined among children <5 years of age since the rotavirus vaccine was introduced in 2006; population-level impacts remain to be fully elucidated. METHODS: Data from the Healthcare Cost and Utilization Project State Inpatient Databases were used to conduct a time-series analysis of monthly hospital discharges across age groups for acute gastroenteritis and rotavirus from 2000 to 2013. Rate ratios were calculated comparing prevaccine and postvaccine eras. RESULTS: Following vaccine introduction, a decrease in rotavirus hospitalizations occurred with a shift toward biennial patterns across all ages. The 0-4-year age group experienced the largest decrease in rotavirus hospitalizations (rate ratio, 0.14; 95% confidence interval, .09-.23). The 5-19-year and 20-59-year age groups experienced significant declines in rotavirus hospitalization rates overall; the even postvaccine calendar years were characterized by progressively lower rates, and the odd postvaccine years were associated with reductions in rates that diminished over time. Those aged >/=60 years experienced the smallest change in rotavirus hospitalization rates overall, with significant reductions in even postvaccine years compared with prevaccine years (rate ratio, 0.51; 95% confidence interval, .39-.66). CONCLUSIONS: Indirect impacts of infant rotavirus vaccination are apparent in the emergence of biennial patterns in rotavirus hospitalizations that extend to all age groups ineligible for vaccination. These observations are consistent with the notion that young children are of primary importance in disease transmission and that the initial postvaccine period of dramatic population-wide impacts will be followed by more complex incidence patterns across the age range in the long term. |
Post-vaccination serum anti-rotavirus immunoglobulin A as a correlate of protection against rotavirus gastroenteritis across settings
Baker JM , Tate JE , Leon J , Haber MJ , Pitzer VE , Lopman BA . J Infect Dis 2020 222 (2) 309-318 BACKGROUND: A correlate of protection for rotavirus gastroenteritis would facilitate rapid assessment of vaccination strategies and the next generation of rotavirus vaccines. We aimed to quantify a threshold of post-vaccine serum anti-rotavirus immunoglobulin A (IgA) that serves as an individual-level immune correlate of protection against rotavirus gastroenteritis. METHODS: Individual-level data on 5,074 infants enrolled in nine GlaxoSmithKline Rotarix Phase II/III clinical trials from 16 countries were pooled. Cox proportional hazard models were fit to estimate hazard ratios (HRs) describing the relationship between IgA thresholds and occurrence of rotavirus gastroenteritis. RESULTS: Seroconversion (IgA >/=20 U/mL) conferred substantial protection against any and severe rotavirus gastroenteritis up to 1 year of age. In low child mortality settings, seroconversion provided near perfect protection against severe rotavirus gastroenteritis (HR=0.04, 95% confidence interval (CI)=0.01-0.31). In high child mortality settings, seroconversion dramatically reduced the risk of severe rotavirus gastroenteritis (0.46, 0.25-0.86). As the IgA threshold increased, the risk of rotavirus gastroenteritis generally decreased. A given IgA threshold provided better protection in low compared to high child mortality settings. DISCUSSION: Post-vaccination anti-rotavirus IgA is a valuable correlate of protection against rotavirus gastroenteritis up to 1 year of age. Seroconversion provides an informative threshold for assessing rotavirus vaccine performance. |
Antirotavirus IgA seroconversion rates in children who receive concomitant oral poliovirus vaccine: A secondary, pooled analysis of Phase II and III trial data from 33 countries
Baker JM , Tate JE , Leon J , Haber MJ , Lopman BA . PLoS Med 2019 16 (12) e1003005 BACKGROUND: Despite the success of rotavirus vaccines over the last decade, rotavirus remains a leading cause of severe diarrheal disease among young children. Further progress in reducing the burden of disease is inhibited, in part, by vaccine underperformance in certain settings. Early trials suggested that oral poliovirus vaccine (OPV), when administered concomitantly with rotavirus vaccine, reduces rotavirus seroconversion rates after the first rotavirus dose with modest or nonsignificant interference after completion of the full rotavirus vaccine course. Our study aimed to identify a range of individual-level characteristics, including concomitant receipt of OPV, that affect rotavirus vaccine immunogenicity in high- and low-child-mortality settings, controlling for individual- and country-level factors. Our central hypothesis was that OPV administered concomitantly with rotavirus vaccine reduced rotavirus vaccine immunogenicity. METHODS AND FINDINGS: Pooled, individual-level data from GlaxoSmithKline's Phase II and III clinical trials of the monovalent rotavirus vaccine (RV1), Rotarix, were analyzed, including 7,280 vaccinated infants (5-17 weeks of age at first vaccine dose) from 22 trials and 33 countries/territories (5 countries/territories with high, 13 with moderately low, and 15 with very low child mortality). Two standard markers for immune response were examined including antirotavirus immunoglobulin A (IgA) seroconversion (defined as the appearance of serum antirotavirus IgA antibodies in subjects initially seronegative) and serum antirotavirus IgA titer, both collected approximately 4-12 weeks after administration of the last rotavirus vaccine dose. Mixed-effect logistic regression and mixed-effect linear regression of log-transformed data were used to identify individual- and country-level predictors of seroconversion (dichotomous) and antibody titer (continuous), respectively. Infants in high-child-mortality settings had lower odds of seroconverting compared with infants in low-child-mortality settings (odds ratio [OR] = 0.48, 95% confidence interval [CI] 0.43-0.53, p < 0.001). Similarly, among those who seroconverted, infants in high-child-mortality settings had lower IgA titers compared with infants in low-child-mortality settings (mean difference [beta] = 0.83, 95% CI 0.77-0.90, p < 0.001). Infants who received OPV concomitantly with both their first and their second doses of rotavirus vaccine had 0.63 times the odds of seroconverting (OR = 0.63, 95% CI 0.47-0.84, p = 0.002) compared with infants who received OPV but not concomitantly with either dose. In contrast, among infants who seroconverted, OPV concomitantly administered with both the first and second rotavirus vaccine doses was found to be positively associated with antirotavirus IgA titer (beta = 1.28, 95% CI 1.07-1.53, p = 0.009). Our findings may have some limitations in terms of generalizability to routine use of rotavirus vaccine because the analysis was limited to healthy infants receiving RV1 in clinical trial settings. CONCLUSIONS: Our findings suggest that OPV given concomitantly with RV1 was a substantial contributor to reduced antirotavirus IgA seroconversion, and this interference was apparent after the second vaccine dose of RV1, as with the original clinical trials that our reanalysis is based on. However, our findings do suggest that the forthcoming withdrawal of OPV from the infant immunization schedule globally has the potential to improve RV1 performance. |
Erythema multiforme, Stevens Johnson syndrome, and toxic epidermal necrolysis reported after vaccination, 1999-2017.
Su JR , Haber P , Ng CS , Marquez PL , Dores GM , Perez-Vilar S , Cano MV . Vaccine 2019 38 (7) 1746-1752 BACKGROUND: Since the last review of vaccine safety surveillance data for erythema multiforme (EM), Stevens Johnson syndrome (SJS), SJS/TEN, and toxic epidermal necrolysis (TEN) (EM/SJS/TEN), over 37 new vaccines have been introduced in the United States. We sought to describe reported EM/SJS/TEN after vaccines during 1999-2017. METHODS: We identified U.S. reports of EM/SJS/TEN received by the Vaccine Adverse Event Reporting System (VAERS) during 1999-2017. We stratified analysis by condition (EM, SJS, or TEN), and analyzed reports by serious or non-serious status, sex, age group, time from vaccination to symptom onset, exposure to known causes of EM/SJS/TEN, and vaccines administered. We used Empirical Bayesian data mining to detect vaccine-AE pairs reported more frequently than expected. RESULTS: Of 466,027 reports to VAERS during 1999-2017, we identified 984 reports of EM, 89 reports of SJS, 6 reports of SJS/TEN, and 7 reports of TEN. Few reports of EM (9%), and most reports of SJS (52%), SJS/TEN (100%), and TEN (100%) were serious. Overall, 55% of reports described males, 48% described children aged < 4 years; 58% of EM/SJS/TEN occurred </= 7 days after vaccination. Few reports (</=5%) described exposure to known causes of EM/SJS/TEN. Overall, childhood vaccines (e.g., combined measles, mumps, and rubella vaccine) were most commonly reported. We identified 6 deaths; 4 were exposed to medications associated with EM/SJS/TEN. EM after smallpox vaccine was reported disproportionately among people aged 19-49 years. CONCLUSIONS: EM/SJS/TEN were rarely reported after vaccination; data mining identified a known association between EM and smallpox vaccine. |
Safety review of tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccines (Tdap) in adults aged ≥65 years, Vaccine Adverse Event reporting System (VAERS), United States, September 2010-December 2018.
Haber P , Moro PL , Ng C , Dores GM , Perez-Vilar S , Marquez PL , Cano M . Vaccine 2019 38 (6) 1476-1480 INTRODUCTION: The Advisory Committee on Immunization Practices (ACIP) recommends vaccination with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) in persons >/=65years of age. To date, few studies have assessed the safety of Tdap in this population. We aimed to summarize reports submitted to the Vaccine Adverse Event Reporting System (VAERS) following receipt of Tdap in this age group. METHODS: We searched for and analyzed U.S. VAERS reports of Tdap among individuals >/=65years of age submitted from September 1, 2010 through December 31, 2018. We classified reports according to concurrent vaccination, seriousness, and outcome (death, non-death) and determined the frequency of reported adverse events (AEs). For serious reports, we reviewed available medical records. Data mining analyses were undertaken to detect disproportionality in reporting. RESULTS: VAERS received a total of 1,798 reports following Tdap, of which 104 (6%) were serious. The most common AEs were injection site erythema (26%; n=468), injection site pain (19%; n=335), injection site swelling (18%; n=329), and erythema (18%; n=321). We identified seven deaths; none were attributed to Tdap. Among serious non-death reports, nervous system disorders (35.1%; n=34) and infections and infestations (n=18.6%; n=18) were most commonly reported. Data mining did not identify any vaccine-AE combination reported more frequently than expected. CONCLUSIONS: We did not identify any new safety concern over nearly a decade of recommended Tdap use among adults >/=65years of age. Findings from this post-marketing review are consistent with prior post-marketing observations and pre-licensure studies. |
Challenges in evaluating post-licensure vaccine safety: Observations from the Centers for Disease Control and Prevention
Moro PL , Haber P , McNeil MM . Expert Rev Vaccines 2019 18 (10) 1091-1101 Introduction: Vaccination is one of the most successful and cost-effective public health interventions. Although vaccines undergo extensive safety and efficacy evaluations prior to licensure, vaccine safety assessment post-licensure is essential for detecting rare and longer-term adverse events (AEs) and maintaining public confidence in vaccines and recommended immunization programs. Despite the proven effect of vaccines to save lives and prevent disease and overwhelming evidence of vaccines' safety and societal benefit, like any drug, no vaccine can be considered as completely safe and completely effective. New vaccines continue to be introduced and require rapid safety assessment post-licensure through pharmacovigilance reports as well as epidemiologic studies to investigate any potential safety signals. Areas covered: We discuss selected challenges for conducting pharmacovigilance and epidemiologic studies of AEs after vaccination in the United States using the post-licensure safety surveillance infrastructure of the Centers for Disease Control and Prevention (CDC). Expert opinion: The availability of specific post-licensure surveillance systems to monitor and study AEs after vaccination such as the Vaccine Adverse Event Reporting System, the Vaccine Safety Datalink, and the Clinical Immunization Safety Assessment Project, each with its unique set of strengths and limitations, provide a harmonized and supportive approach to meet several of these barriers. |
Effect of propensity of seeking medical care on the bias of the estimated effectiveness of rotavirus vaccines from studies using a test-negative case-control design
Haber M , Lopman BA , Tate JE , Shi M , Parashar UD . Vaccine 2019 37 (24) 3229-3233 BACKGROUND: Rotavirus is the leading cause of severe diarrhea among children worldwide, and vaccines can reduce morbidity and mortality by 50-98%. The test-negative control (TNC) study design is increasingly used for evaluating the effectiveness of vaccines against rotavirus and other vaccine-preventable diseases. In this study design, symptomatic patients who seek medical care are tested for the pathogen of interest. Those who test positive (negative) are classified as cases (controls). METHODS: We use a probability model to evaluate the bias of estimates of rotavirus vaccine effectiveness (VE) against rotavirus diarrhea resulting in hospitalization in the presence of possible confounding and selection biases due to differences in the propensity of seeking medical care (PSMC) between vaccinated and unvaccinated children. RESULTS: The TNC-based VE estimate corrects for confounding bias when the confounder's effects on the probabilities of rotavirus and non-rotavirus related hospitalizations are equal. If this condition is not met, then the estimated VE may be substantially biased. The bias is more severe in low-income countries, where VE is known to be lower. Under our model, differences in PSMC between vaccinated and unvaccinated children do not result in selection bias when the TNC study design is used. CONCLUSIONS: In practice, one can expect the association of PSMC (or other potential confounders) with the probabilities of rotavirus and non-rotavirus related hospitalization to be similar, in which case the confounding effects will only result in small bias in the VE estimate from TNC studies. The results of this work, along with those of our previous paper, confirm the TNC design can be expected to provide reliable estimates of rotavirus VE in both high- and low-income countries. |
Post-licensure surveillance of trivalent adjuvanted influenza vaccine (aIIV3; Fluad), Vaccine Adverse Event Reporting System (VAERS), United States, July 2016-June 2018.
Haber P , Moro PL , Ng C , Dores GM , Lewis P , Cano M . Vaccine 2019 37 (11) 1516-1520 BACKGROUND: Trivalent adjuvanted influenza vaccine (aIIV3; Fluad(R)) was approved in the United States (U.S.) in 2015 for adults aged >/=65years and has been in use since the 2016-17 influenza season. METHODS: We analyzed U.S. reports for aIIV3 submitted from July 1, 2016 through June 30, 2018 to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system. Medical records were reviewed for serious reports. Among individuals >/=65years of age, the relative frequency of the most commonly reported adverse events (AEs) after aIIV3 were compared with non-adjuvanted inactivated influenza vaccines given to adults aged >/=65years, high-dose trivalent influenza vaccine (IIV3-HD) and trivalent or quadrivalent vaccines (IIV3/IIV4). Data mining analyses were undertaken to identify whether AEs for aIIV3 occurred disproportionately more than expected compared to all influenza vaccines. RESULTS: VAERS received 630 reports after aIIV3, of which 521 (83%) were in adults aged >/=65years; 79 (13%) in persons <65years and in 30 (5%) reports age was missing; 19 (3%) reports were serious, including two deaths (0.4%) related to myocardial infarction and Sjogren's syndrome. The most common AEs reported in adults aged >/=65years were injection site pain (21%) and erythema (18%), with similar proportions reported for IIV3-HD (17% and 19%, respectively) and for IIV3/IIV4 (15%, each). Except for reports related to vaccination of inappropriate age (n=79) and syringe malfunction (n=6), data mining did not identify other disproportionately reported AEs. CONCLUSIONS: Although our review of aIIV3 in VAERS did not identify any unexpected health conditions of concern, we observed more than twice the expected number of reports with administration of the vaccine to persons outside of the age range for which the vaccine is approved in the U.S. Health care providers should be educated on the age groups for whom aIIV3 is recommended. |
A comparison of the test-negative and traditional case-control study designs with respect to the bias of estimates of rotavirus vaccine effectiveness
Haber M , Lopman BA , Tate JE , Shi M , Parashar UD . Vaccine 2018 36 (33) 5071-5076 Estimation of the effectiveness of rotavirus vaccines via the test-negative control study design has gained popularity over the past few years. In this study design, children with severe diarrhea who test positive for rotavirus infection are considered as cases, while children who test negative serve as controls. We use a simple probability model to evaluate and compare the test-negative control and the traditional case-control designs with respect to the bias of resulting estimates of rotavirus vaccine effectiveness (VE). Comparisons are performed under two scenarios, corresponding to studies performed in high-income and low-income countries. We consider two potential sources of bias: (a) misclassification bias resulting from imperfect sensitivity and specificity of the test used to diagnose rotavirus infection, and (b) selection bias associated with possible effect of rotavirus vaccination on the probability of contracting severe non-rotavirus diarrhea. Our results suggest that both sources of bias may produce VE estimates with substantial bias. Particularly, lack of perfect specificity is associated with severe negative bias. For example, if the specificity of the diagnostic test is 90% then VE estimates from both types of case-control studies may under-estimate the true VE by more than 20%. If the vaccine protects children against non-rotavirus diarrhea then VE estimates from test-negative control studies may be close to zero even though the true VE is 50%. However, the sensitivity and specificity of the enzyme immunoassay test currently used to diagnose rotavirus infections are both over 99%, and there is no solid evidence that the existing rotavirus vaccines affect the rates of non-rotavirus diarrhea. We therefore conclude that the test-negative control study design is a convenient and reliable alternative for estimation of rotavirus VE. |
Reports of lower respiratory tract infection following dose 1 of RotaTeq and Rotarix vaccines to the Vaccine Adverse Event Reporting System (VAERS), 2008-2016
Haber P , Amin M , Carmen N , Weintraub E , McNeil M . Hum Vaccin Immunother 2018 14 (11) 1-20 A 2018 manufacturer post-licensure safety study identified a possible association between Rotarix (RV1) rotavirus vaccine and lower respiratory tract infections (LRTI) in infants within 0-6 days following receipt of RV1 dose 1. We reviewed reports to the Vaccine Adverse Event Reporting System (VAERS) of LRTI occurring 0-6 days and 0-29 days post vaccination following RotaTeq (RV5) or Rotarix (RV1) vaccinations in conjunction with either Prevnar (PCV7) or Prevnar 13 (PCV13), in infants aged 6 to 15 weeks. There was no significant difference in LRTI reports to VAERS in the 0-6 days and 0-29 days following receipt of either RV5 or RV1 given with either pneumococcal vaccine. |
Prevention of hepatitis B virus infection in the United States: Recommendations of the Advisory Committee on Immunization Practices
Schillie S , Vellozzi C , Reingold A , Harris A , Haber P , Ward JW , Nelson NP . MMWR Recomm Rep 2018 67 (1) 1-31 Hepatitis B virus (HBV) is transmitted via blood or sexual contact. Persons with chronic HBV infection are at increased risk for cirrhosis and liver cancer and require medical care. This report updates and summarizes previously published recommendations from the Advisory Committee on Immunization Practices (ACIP) and CDC regarding the prevention of HBV infection in the United States. ACIP recommends testing all pregnant women for hepatitis B surface antigen (HBsAg), and testing HBsAg-positive pregnant women for hepatitis B virus deoxyribonucleic acid (HBV DNA); administration of HepB vaccine and hepatitis B immune globulin (HBIG) for infants born to HBV-infected women within 12 hours of birth, followed by completion of the vaccine series and postvaccination serologic testing; universal hepatitis B vaccination within 24 hours of birth, followed by completion of the vaccine series; and vaccination of children and adolescents aged < 19 years who have not been vaccinated previously. ACIP recommends vaccination of adults at risk for HBV infection, including universal vaccination of adults in settings in which a high proportion have risk factors for HBV infection and vaccination of adults requesting protection from HBV without acknowledgment of a specific risk factor. These recommendations also provide CDC guidance for postexposure prophylaxis following occupational and other exposures. This report also briefly summarizes previously published American Association for the Study of Liver Diseases guidelines for maternal antiviral therapy to reduce perinatal HBV transmission. |
Safety of currently licensed hepatitis B surface antigen vaccines in the United States, Vaccine Adverse Event Reporting System (VAERS), 2005-2015.
Haber P , Moro PL , Ng C , Lewis PW , Hibbs B , Schillie SF , Nelson NP , Li R , Stewart B , Cano MV . Vaccine 2017 36 (4) 559-564 INTRODUCTION: Currently four recombinant hepatitis B (HepB) vaccines are in use in the United States. HepB vaccines are recommended for infants, children and adults. We assessed adverse events (AEs) following HepB vaccines reported to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system. METHODS: We searched VAERS for reports of AEs following single antigen HepB vaccine and HepB-containing vaccines (either given alone or with other vaccines), from January 2005 - December 2015. We conducted descriptive analyses and performed empirical Bayesian data mining to assess disproportionate reporting. We reviewed serious reports including reports of special interest. RESULTS: VAERS received 20,231 reports following HepB or HepB-containing vaccines: 10,291 (51%) in persons <2years of age; 2588 (13%) in persons 2-18years and 5867 (29%) in persons >18years; for 1485 (7.3%) age was missing. Dizziness and nausea (8.4% each) were the most frequently reported AEs following a single antigen HepB vaccine: fever (23%) and injection site erythema (11%) were most frequent following Hep-containing vaccines. Of the 4444 (22%) reports after single antigen HepB vaccine, 303 (6.8%) were serious, including 45 deaths. Most commonly reported cause of death was Sudden Infant Death Syndrome (197). Most common non-death serious reports following single antigen HepB vaccines among infants aged <1month, were nervous system disorders (15) among children aged 1-23months; infections and infestation (8) among persons age 2-18years blood and lymphatic systemic disorders; and general disorders and administration site conditions among persons age >18years. Most common vaccination error following single antigen HepB was incorrect product storage. CONCLUSIONS: Review current U.S.-licensed HepB vaccines administered alone or in combination with other vaccines did not reveal new or unexpected safety concerns. Vaccination errors were identified which indicate the need for training and education of providers on HepB vaccine indications and recommendations. |
Estimating direct and indirect protective effect of influenza vaccination in the United States
Arinaminpathy N , Kim IK , Gargiullo P , Haber M , Foppa IM , Gambhir M , Bresee J . Am J Epidemiol 2017 186 (1) 1-9 With influenza vaccination rates in the United States recently exceeding 45% of the population, it is important to understand the impact that vaccination is having on influenza transmission. In this study, we used a Bayesian modeling approach, combined with a simple dynamical model of influenza transmission, to estimate this impact. The combined framework synthesized evidence from a range of data sources relating to influenza transmission and vaccination in the United States. We found that, for seasonal epidemics, the number of infections averted ranged from 9.6 million in the 2006-2007 season (95% credible interval (CI): 8.7, 10.9) to 37.2 million (95% CI: 34.1, 39.6) in the 2012-2013 season. Expressed in relative terms, the proportion averted ranged from 20.8% (95% CI: 16.8, 24.3) of potential infections in the 2011-2012 season to 47.5% (95% CI: 43.7, 50.8) in the 2008-2009 season. The percentage averted was only 1.04% (95% CI: 0.15, 3.2) for the 2009 H1N1 pandemic, owing to the late timing of the vaccination program in relation to the pandemic in the Northern hemisphere. In the future, further vaccination coverage, as well as improved influenza vaccines (especially those offering better protection in the elderly), could have an even stronger effect on annual influenza epidemics. |
Surveillance systems and methods for monitoring the post-marketing safety of influenza vaccines at the Centers for Disease Control and Prevention
Moro PL , Li R , Haber P , Weintraub E , Cano M . Expert Opin Drug Saf 2016 15 (9) 1175-83 INTRODUCTION: Annual influenza vaccine safety monitoring is an important component of the influenza vaccination program in the United States to ensure that vaccines are safe, which is important for maintaining public trust in the national vaccination program. This is specially the case for influenza vaccines since the antigen composition of the viruses of which the vaccine is made often changes from one season to the next, based on the circulating strain of influenza virus. AREAS COVERED: This review describes the two surveillance systems used by the Centers for Disease Control and Prevention (CDC) to monitor the safety of influenza vaccines: 1) the Vaccine Adverse Event Reporting System (VAERS); and 2) the Vaccine Safety datalink (VSD). EXPERT OPINION: VAERS and VSD are used routinely to monitor the safety of influenza vaccines in the United States, and over the years they have demonstrated their value in monitoring vaccine safety since their implementation in 1990. Both systems, although different, complemented each other well to study febrile seizures in young children following influenza vaccination during the 2010-2011 influenza season. Other examples of potential safety concerns after influenza vaccines are also presented and discussed. |
Safety of Second-Dose Single-Antigen Varicella Vaccine.
Su JR , Leroy Z , Lewis PW , Haber P , Marin M , Leung J , Woo EJ , Shimabukuro TT . Pediatrics 2017 139 (3) BACKGROUND AND OBJECTIVE: In 2006, routine 2-dose varicella vaccination for children was recommended to improve control of varicella. We assessed the safety of second-dose varicella vaccination. METHODS: We identified second-dose single-antigen varicella vaccine reports in the Vaccine Adverse Event Reporting System during 2006 to 2014 among children aged 4 to 18 years. We analyzed reports by age group (4-6 and 7-18 years), sex, serious or nonserious status, most common adverse events (AEs), and whether other vaccines were administered concomitantly with varicella vaccine. We reviewed serious reports of selected AEs and conducted empirical Bayesian data mining to detect disproportional reporting of AEs. RESULTS: We identified 14 641 Vaccine Adverse Event Reporting System reports after second-dose varicella vaccination, with 494 (3%) classified as serious. Among nonserious reports, injection site reactions were most common (48% of children aged 4-6 years, 38% of children aged 7-18 years). The most common AEs among serious reports were pyrexia (31%) for children aged 4 to 6 years and headache (28%) and vomiting (27%) for children aged 7 to 18 years. Serious reports of selected AEs included anaphylaxis (83), meningitis (5), encephalitis (16), cellulitis (52), varicella (6), herpes zoster (6), and deaths (7). One immunosuppressed adolescent was reported with vaccine-strain herpes zoster. Only previously known AEs were reported more frequently after second-dose varicella vaccination compared with other vaccines. CONCLUSIONS: We identified no new or unexpected safety concerns for second-dose varicella vaccination. Robust safety monitoring remains an important component of the national varicella vaccination program. |
Travel volume to the United States from countries and U.S. territories with local Zika virus transmission
Nelson B , Morrison S , Joseph H , Wojno A , Lash RR , Haber Y , Berro A , Cetron M , Grills A . PLoS Curr 2016 8 INTRODUCTION: Air, land, and sea transportation can facilitate rapid spread of infectious diseases. In May 2015 the Pan American Health Organization (PAHO) issued an alert regarding the first confirmed Zika virus infection in Brazil. As of March 8, 2016, the U.S. Centers for Disease Control and Prevention (CDC) had issued travel notices for 33 countries and 3 U.S. territories with local Zika virus transmission. METHODS: Using data from five separate datasets from 2014 and 2015, we estimated the annual number of passenger journeys by air and land border crossings to the United States from the 33 countries and 3 U.S. territories listed in the CDC's Zika travel notices as of March 8, 2016. We also estimated the annual number of passenger journeys originating in and returning to the United States (primarily on cruises) with visits to seaports in areas with local Zika virus transmission. Because of the adverse pregnancy and birth outcomes that have been associated with Zika virus disease, the number of passenger journeys completed by women of childbearing age and pregnant women was also estimated. RESULTS: An estimated 216.3 million passenger journeys by air, land, and sea are made annually to the United States from areas with local Zika virus transmission (as of March 8). The destination states with the largest numbers of arrivals were Texas (by land) and Florida (by air and sea). An estimated 51.7 million passenger journeys were made by women of childbearing age and an estimated 2.3 million were made by pregnant women. CONCLUSION: Travel volume analyses provide important information that can be used to effectively target public health interventions as well as direct public health resources and efforts at local, regional, and country-specific levels. |
Post-licensure surveillance of 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ⩾19years old in the United States, Vaccine Adverse Event Reporting System (VAERS), June 1, 2012-December 31, 2015.
Haber P , Arana J , Pilishvili T , Lewis P , Moro PL , Cano M . Vaccine 2016 34 (50) 6330-6334 BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) was first recommended for use in adults aged 19years with immunocompromising conditions in June 2012. On August 2014, the Advisory Committee on Immunization Practices (ACIP) recommended routine use of PCV13 among adults aged 65 years. METHODS: We assessed adverse events (AEs) reports following PCV13 in adults aged 19 years reported to the Vaccine Adverse Event Reporting System (VAERS) from June 2012 to December 2015. VAERS is a national spontaneous reporting system for monitoring AEs following vaccination. Our assessment included automated data analysis, clinical review of all serious reports and reports of special interest. We conducted empirical Bayesian data mining to assess for disproportionate reporting. RESULTS: VAERS received 2976 US PCV13 adult reports; 2103 (71%) of these reports were from PCV13 administered alone. Fourteen percent were in persons aged 19-64 years and 86% were in persons aged 65 years. Injection site erythema (28%), injection site pain (24%) and fever (22%) were the most frequent AEs among persons aged 19-64 years; injection site erythema (30%), erythema (20%) and injection site swelling (18%) were the most frequent among persons aged 65 years who were given the vaccine alone. The most frequently reported AEs among non-death serious reports were injection site reactions and general malaise among persons 19-64 years old; injection site reactions, general malaise and Guillain-Barre syndrome among those 65 years. Data mining did not detect disproportional reporting for any unexpected AE. CONCLUSIONS: The results of this study were consistent with safety data from pre-licensure studies of PCV13. We did not detect any new or unexpected AEs. |
Estimation of severe Middle East Respiratory Syndrome cases in the Middle East, 2012-2016
O'Hagan JJ , Carias C , Rudd JM , Pham HT , Haber Y , Pesik N , Cetron MS , Gambhir M , Gerber SI , Swerdlow DL . Emerg Infect Dis 2016 22 (10) 1797-9 Using data from travelers to 4 countries in the Middle East, we estimated 3,250 (95% CI 1,300-6,600) severe cases of Middle East respiratory syndrome occurred in this region during September 2012-January 2016. This number is 2.3-fold higher than the number of laboratory-confirmed cases recorded in these countries. |
Exportations of symptomatic cases of MERS-CoV infection to countries outside the Middle East
Carias C , O'Hagan JJ , Jewett A , Gambhir M , Cohen NJ , Haber Y , Pesik N , Swerdlow DL . Emerg Infect Dis 2016 22 (3) 723-5 In 2012, an outbreak of infection with Middle East respiratory syndrome coronavirus (MERS-CoV), was detected in the Arabian Peninsula. Modeling can produce estimates of the expected annual number of symptomatic cases of MERS-CoV infection exported and the likelihood of exportation from source countries in the Middle East to countries outside the region. |
Post-licensure surveillance of quadrivalent inactivated influenza (IIV4) vaccine in the United States, Vaccine Adverse Event Reporting System (VAERS), July 1, 2013-May 31, 2015.
Haber P , Moro PL , Lewis P , Woo EJ , Jankosky C , Cano M . Vaccine 2016 34 (22) 2507-12 BACKGROUND: Quadrivalent inactivated influenza vaccines (IIV4) were first available for use during 2013-14 influenza season for individuals aged ≥6 months. IIV4 is designed to protect against four different flu viruses; two influenza A viruses and two influenza B viruses. METHODS: We searched the Vaccine Adverse Event Reporting System (VAERS) for US reports after IIV4 and trivalent inactivated influenza vaccine (IIV3) from 7/1/2013-5/31/2015. Medical records were requested for non-manufacturer reports classified as serious (i.e. death, hospitalization, prolonged hospitalization, life-threatening illness, permanent disability). The review included automated data analysis, clinical review of all serious reports, reports of special interest, and empirical Bayesian data mining. RESULTS: VAERS received 1,838 IIV4 reports; 512 (28%) in persons aged 6 months-17 years of which 42 (8.2%) were serious reports; 1,265 (69%) in persons aged >18 years of which 84 (6.6%) were serious reports; two in children <6 months and 59 in persons of unknown age. Injection site erythema (24%), fever (14%) and injection site swelling (17%) were the most frequent adverse events among persons aged 6 months-17 years, while injection site pain (16%), pain (15%) and pain in extremity (13%) were the most frequent among persons aged 18-64 years given the vaccine alone. Among non-death serious reports, injection site reactions, constitutional symptoms, Guillain-Barre syndrome, seizures, and anaphylaxis were the most frequently reported adverse events. Data mining detected disproportional reporting for incorrect vaccine administration with no associated adverse events. Adverse events following IIV4 reported to VAERS were similar to those following IIV3. CONCLUSIONS: In our review of VAERS reports, IIV4 had a similar safety profile to IIV3. Most of the reported AEs were non-serious. Our findings are consistent with data from pre-licensure studies of IIV4. |
The case test-negative design for studies of the effectiveness of influenza vaccine in inpatient settings
Foppa IM , Ferdinands JM , Chaves SS , Haber MJ , Reynolds SB , Flannery B , Fry AM . Int J Epidemiol 2016 45 (6) 2052-2059 BACKGROUND: The test-negative design (TND) to evaluate influenza vaccine effectiveness is based on patients seeking care for acute respiratory infection, with those who test positive for influenza as cases and the test-negatives serving as controls. This design has not been validated for the inpatient setting where selection bias might be different from an outpatient setting. METHODS: We derived mathematical expressions for vaccine effectiveness (VE) against laboratory-confirmed influenza hospitalizations and used numerical simulations to verify theoretical results exploring expected biases under various scenarios. We explored meaningful interpretations of VE estimates from inpatient TND studies. RESULTS: VE estimates from inpatient TND studies capture the vaccine-mediated protection of the source population against laboratory-confirmed influenza hospitalizations. If vaccination does not modify disease severity, these estimates are equivalent to VE against influenza virus infection. If chronic cardiopulmonary individuals are enrolled because of non-infectious exacerbation, biased VE estimates (too high) will result. If chronic cardiopulmonary disease status is adjusted for accurately, the VE estimates will be unbiased. If chronic cardiopulmonary illness cannot be adequately be characterized, excluding these individuals may provide unbiased VE estimates. CONCLUSIONS: The inpatient TND offers logistic advantages and can provide valid estimates of influenza VE. If highly vaccinated patients with respiratory exacerbation of chronic cardiopulmonary conditions are eligible for study inclusion, biased VE estimates will result unless this group is well characterized and the analysis can adequately adjust for it. Otherwise, such groups of subjects should be excluded from the analysis. |
Post-Licensure Surveillance of Trivalent Live-Attenuated Influenza Vaccine in Children Aged 2-18 Years, Vaccine Adverse Event Reporting System, United States, July 2005-June 2012.
Haber P , Moro PL , Cano M , Vellozzi C , Lewis P , Woo EJ , Broder K . J Pediatric Infect Dis Soc 2015 4 (3) 205-13 BACKGROUND: The first trivalent live-attenuated influenza vaccine (LAIV3) was licensed in 2003 for use in healthy persons 5-49 years of age. In 2007, the US Food and Drug Administration expanded its indication to healthy children 2-4 years of age. METHODS: We searched the Vaccine Adverse Event Reporting System (VAERS) for US reports after LAIV3 from July 1, 2005 to June 30, 2012 in children aged 2-18 years. Medical records were requested for nonmanufacturer reports coded as serious (ie, death, hospitalization, prolonged hospitalization, life-threatening illness, disability). We characterized electronic data and clinically reviewed all serious reports and reports of special interest. Empirical Bayesian data mining was used to identify new or unexpected adverse events (AEs). RESULTS: During the study period, VAERS received 2619 US LAIV3 reports for children aged 2-18 years; 197 (7.5%) reports were serious, including 5 deaths. The 2 most frequent nonfatal serious reports involved neurological and respiratory systems, with 56 (29.2%) and 43 (22.4%) reports, respectively. The most frequent neurological diagnoses were seizures and Guillain-Barre Syndrome, and the most frequent respiratory conditions were pneumonia and asthma or reactive airway disease. Data mining showed increased proportions for reports of medication errors, most commonly vaccine administration errors not associated with an AE. CONCLUSIONS: In this VAERS analysis of reports following LAIV3, we found no new or unexpected AEs patterns. Reports of LAIV3 administration to persons, for whom it is not recommended, including children with a history of asthma or reactive airway disease or wheezing, indicate that ongoing monitoring and education in vaccine indications are needed. |
A simulation study of nonparametric total deviation index as a measure of agreement based on quantile regression
Lin L , Pan Y , Hedayat AS , Barnhart HX , Haber M . J Biopharm Stat 2015 26 (5) 937-50 Total deviation index (TDI) captures a pre-specified quantile of the absolute deviation of paired observations from raters, observers, methods, assays, instruments, etc. We compare the performance of total deviation index (TDI) using nonparametric quantile regression to the TDI assuming normality (Lin 2000). This simulation study considers 3 distributions: normal, Poisson, and uniform at quantile levels of 0.8 and 0.9 for cases with and without contamination. Study endpoints include the bias of TDI estimates (compared to their respective theoretical values), standard error of TDI estimates (compared to their true simulated standard errors), and test size (compared to 0.05) and power. Nonparametric TDI using quantile regression, although it slightly underestimates and delivers slightly less power for data without contamination, works satisfactorily under all simulated cases even for moderate (say, ≥40) sample sizes. The performance of the TDI based on a quantile of 0.8 is in general superior to that of 0.9. The performances of nonparametric and parametric TDI methods are compared with a real data example. Nonparametric TDI can be very useful when the underlying distribution on the difference is not normal, especially when it has a heavy tail. |
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