Genetics has become a critical component of medicine over the past five to six decades. Alongside genetics, a relatively new discipline, dysmorphology, has also begun to play an important role in providing critically important diagnoses to individuals and families. Both have become indispensable to unraveling rare diseases. Almost every medical specialty relies on individuals experienced in these specialties to provide diagnoses for patients who present themselves to other doctors. Additionally, both specialties have become reliant on molecular geneticists to identify genes associated with human disorders. Many of the medical geneticists, dysmorphologists, and molecular geneticists traveled a circuitous route before arriving at the position they occupied. The purpose of collecting the memoirs contained in this article was to convey to the reader that many of the individuals who contributed to the advancement of genetics and dysmorphology since the late 1960s/early 1970s traveled along a journey based on many chances taken, replying to the necessities they faced along the way before finding full enjoyment in the practice of medical and human genetics or dysmorphology. Additionally, and of equal importance, all exhibited an ability to evolve with their field of expertise as human genetics became human genomics with the development of novel technologies.

Leptospirosis is one of the most common zoonotic diseases in the world and endemic in the Caribbean Islands. Bovine leptospirosis is an important reproductive disease. Globally, cattle are recognized as a reservoir host for L. borgpetersenii serovar Hardjo, which is transmitted via urine, semen, and uterine discharges, and can result in abortion and poor reproductive performance. The dairy industry in Puerto Rico comprises up to 25% of agriculture-related income and is historically the most financially important agricultural commodity on the island. In this study, we report the isolation of two different pathogenic Leptospira species, from two different serogroups, from urine samples collected from dairy cows in Puerto Rico: L. borgpetersenii serogroup Sejroe serovar Hardjo and L. santarosai serogroup Pyrogenes. Recovered isolates were classified using whole-genome sequencing, serotyping with reference antisera and monoclonal antibodies, and immunoblotting. These results demonstrate that dairy herds in Puerto Rico can be concurrently infected with more than one species and serovar of Leptospira, and that bacterin vaccines and serologic diagnostics should account for this when applying intervention and diagnostic strategies.

BACKGROUND: The first documented human leptospirosis cases in the U.S. Virgin Islands (USVI) occurred following 2017 Hurricanes Irma and Maria. We conducted a representative serosurvey in USVI to estimate the seroprevalence and distribution of human leptospirosis and evaluate local risk factors associated with seropositivity. METHODOLOGY/PRINCIPAL FINDINGS: A stratified, two-stage cluster sampling design was used and consisted of three island strata and random selection of census blocks and then households. All eligible members of selected households were invited to participate (≥5 years old, resided in USVI ≥6 months and ≥6 months/year). Household and individual-level questionnaires were completed, and serum collected from each enrolled individual. Microscopic agglutination test serology was conducted, and bivariate and logistic regression analyses completed to identify risk factors for seropositivity. In March 2019, 1,161 individuals were enrolled from 918 households in St. Croix, St. Thomas, and St. John. The territory-wide weighted seroprevalence was 4.0% (95% CI:2.3-5.7). Characteristics/exposures independently associated with seropositivity using logistic regression included contact with cows (OR: 39.5; 95% CI: 9.0-172.7), seeing rodents/rodent evidence or contact with rodents (OR: 2.6; 95% CI: 1.1-5.9), and increasing age (OR: 1.02; 95% CI: 1.002-1.04); full or partial Caucasian/White race was negatively correlated with seropositivity (OR: 0.02, 95% CI: 0.04-0.7). Bivariate analysis showed self-reported jaundice since the 2017 hurricanes (pRR: 5.7; 95% CI: 1.0-33.4) was associated with seropositivity and using a cover/lid on cisterns/rainwater collection containers (pRR: 0.3; 95% CI: 0.08-0.8) was protective against seropositivity. CONCLUSIONS/SIGNIFICANCE: Leptospirosis seropositivity of 4% across USVI demonstrates an important human disease that was previously unrecognized and emphasizes the importance of continued leptospirosis surveillance and investigation. Local risk factors identified may help guide future human and animal leptospirosis studies in USVI, strengthen leptospirosis public health surveillance and treatment timeliness, and inform targeted education, prevention, and control efforts.

INTRODUCTION: Community Healthy Start program evaluations are often limited by a lack of robust data and rigorous study designs. This study describes an enhanced methodological approach using local program data linked with existing population-level datasets for external comparison to evaluate the Enterprise Community Healthy Start (ECHS) program in two rural Georgia counties and presents results from the evaluation. METHODS: ECHS program data were linked to birth records and the Pregnancy Risk Assessment Monitoring System (PRAMS) for 869 women who delivered a live birth in Burke and McDuffie counties from 2010 to 2011. Multivariate logistic regressions with and without propensity score methods modeled the association between ECHS participation and maternal health indicators and pregnancy outcomes. RESULTS: 107 ECHS participants and 726 non-participants responded to PRAMS and met eligibility criteria. Compared with non-participants, ECHS participants were younger, completed fewer years of education, and were more likely to be non-Hispanic Black, unmarried, insured with Medicaid, participating in WIC, and having an unintended pregnancy. Models with and without propensity score weighting derived similar results: there was a positive association between ECHS participation and receiving adequate or adequate plus prenatal care (p < 0.05); no statistically significant associations were observed between ECHS participation and any other health behaviors, health care access and utilization measures or pregnancy outcomes. DISCUSSION: Rigorous evaluation of a local Healthy Start program using linked PRAMS and birth records with a population-based external comparison group and propensity score methods is an enhanced and feasible approach that can be applied in other local and state jurisdictions.

BACKGROUND: Life's Simple 7 (LS7; nutrition, physical activity, cigarette use, body mass index, blood pressure, cholesterol, glucose) predicts cardiovascular health. The principal objective of our study was to define demographic and socioeconomic factors associated with LS7 to better inform programs addressing cardiovascular health and health equity. METHODS: National Health and Nutrition Examination Surveys 1999-2016 data were analyzed on non-Hispanic White [NHW], NH Black [NHB], and Hispanic adults aged ≥20 years without cardiovascular disease. Each LS7 variable was assigned 0, 1, or 2 points for poor, intermediate, and ideal levels, respectively. Composite LS7 scores were grouped as poor (0-4 points), intermediate (5-9), and ideal (10-14). RESULTS: 32,803 adults were included. Mean composite LS7 scores were below ideal across race/ethnicity groups. After adjusting for confounders, NHBs were less likely to have optimal LS7 scores than NHW (multivariable odds ratios (OR .44; 95% CI .37-.53), whereas Hispanics tended to have better scores (1.18; .96-1.44). Hispanics had more ideal LS7 scores than NHBs, although Hispanics had lower incomes and less education, which were independently associated with fewer ideal LS7 scores. Adults aged ≥45 years were less likely to have ideal LS7 scores (.11; .09-.12) than adults aged <45 years. CONCLUSIONS: NHBs were the least likely to have optimal scores, despite higher incomes and more education than Hispanics, consistent with structural racism and Hispanic paradox. Programs to optimize lifestyle should begin in childhood to mitigate precipitous age-related declines in LS7 scores, especially in at-risk groups. Promoting higher education and reducing poverty are also important.

Importance: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). Objective: To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. Design, Setting, and Participants: This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. Exposures: A panel of several established cardiovascular risk factors. Main Outcomes and Measures: Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). Results: Of the 731728 participants from the ERFC, 403396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421537 participants from the UK Biobank, 233699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. Conclusions and Relevance: Older age, smoking, and adiposity were consistently associated with higher VTE risk.

We report a fatal case of Lassa fever diagnosed in the United States in a Liberian traveler. We describe infection control protocols and public health response. One contact at high risk became symptomatic, but her samples tested negative for Lassa virus; no secondary cases occurred among health care, family, and community contacts.

Objective: The prevalence of sub-dermal contraceptive implant use in Jamaica is low, despite growing international acceptance of long-acting reversible contraception. This study assessed the availability, effectiveness, side-effects and utilization of sub-dermal contraceptive implants and described the characteristics of users over a one-year period. Methods: We reviewed the medical records of women aged 15-45 years who utilized contraceptive implant-related services at any of the six included public health centres in Jamaica during 2013, and surveyed 20 available reproductive healthcare providers. Results: In 2013, 738 women attended a Jamaican public health centre for contraceptive implant services: 493 (66.8%) for insertion, 202 (27.4%) for removal and 53 (7.2%) for follow- up visits (10 women had the same implant inserted and removed in 2013). The women's median age was 26.0 years, 24.3% were <= 18 years, and 85.9% had >= 1 child. Most women (68.5%) did not have documented side-effects; irregular bleeding, the most commonly documented side-effect, was recorded for 24%. Of the 493 women who had implants inserted, three (0.6%) were identified to be pregnant within three months of insertion. Among the 202 women who had implants removed, 11 (5.4%) experienced complications with removal. Reproductive healthcare providers highlighted the need for an expansion of contraceptive implant availability and provider training. Conclusion: Sub-dermal implants have few insertion complications and side-effects and are effective, but were underutilized in Jamaica. Increased implant availability and enhanced reproductive healthcare provider training may improve implant utilization and reduce unintended pregnancy rates in Jamaica.

The recent article describing apparent artemether-lumefantrine (AL) treatment failure in four travelers returning to the United Kingdom (1) is well detailed. Passive surveillance for treatment failures, particularly in countries where malaria is not endemic and where greater attention and resources can be directed at individual malaria cases, is an important tool for antimalarial resistance monitoring. In fact, chloroquine resistance in sub-Saharan Africa was first documented in travelers returning to Europe and North America prior to being confirmed through efficacy trials at clinical sites in Africa (2). Toward this goal, the U.S. Centers for Disease Control and Prevention performs molecular resistance testing of samples from passively reported imported cases and investigates cases of suspected treatment failure. | However, treatment failures detected passively must be interpreted with caution and an attempt should be made to estimate the relevant denominator—the total number of cases treated with an antimalarial during the same period. Without denominator information, it is difficult to know whether the four cases reported by Sutherland et al. are indicative of a trend of decreasing AL efficacy or are consistent with the known background rate of AL treatment failure.

Malaria in humans is caused by six species of Plasmodium parasites, of which the nuclear genome sequences for the two Plasmodium ovale spp., P. ovale curtisi and P. ovale wallikeri, and Plasmodium malariae have not yet been analyzed. Here we present an analysis of the nuclear genome sequences of these three parasites, and describe gene family expansions therein. Plasmodium ovale curtisi and P. ovale wallikeri are genetically distinct but morphologically indistinguishable and have sympatric ranges through the tropics of Africa, Asia and Oceania. Both P. ovale spp. show expansion of the surfin variant gene family, and an amplification of the Plasmodium interspersed repeat (pir) superfamily which results in an approximately 30% increase in genome size. For comparison, we have also analyzed the draft nuclear genome of P. malariae, a malaria parasite causing mild malaria symptoms with a quartan life cycle, long-term chronic infections, and wide geographic distribution. Plasmodium malariae shows only a moderate level of expansion of pir genes, and unique expansions of a highly diverged transmembrane protein family with over 550 members and the gamete P25/27 gene family. The observed diversity in the P. ovale wallikeri and P. ovale curtisi surface antigens, combined with their phylogenetic separation, supports consideration that the two parasites be given species status.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 degreeC) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

Francisella tularensis causes disease (tularemia) in a large number of mammals, including man. We previously demonstrated enhanced efficacy of conventional antibiotic therapy for tularemia by postexposure passive transfer of immune sera developed against a F. tularensis LVS membrane protein fraction (MPF). However, the protein composition of this immunogenic fraction was not defined. Proteomic approaches were applied to define the protein composition and identify the immunogens of MPF. MPF consisted of at least 299 proteins and 2-D Western blot analyses using sera from MPF-immunized and F. tularensis LVS-vaccinated mice coupled to liquid chromatography-tandem mass spectrometry identified 24 immunoreactive protein spots containing 45 proteins. A reverse vaccinology approach that applied labeling of F. tularensis LVS surface proteins and bioinformatics was used to reduce the complexity of potential target immunogens. Bioinformatics analyses of the immunoreactive proteins reduced the number of immunogen targets to 32. Direct surface labeling of F. tularensis LVS resulted in the identification of 31 surface proteins. However, only 13 of these were reactive with MPF and/or F. tularensis LVS immune sera. Collectively, this use of orthogonal proteomic approaches reduced the complexity of potential immunogens in MPF by 96% and allowed for prioritization of target immunogens for antibody-based immunotherapies against tularemia.

Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the artemisinin component and the partner drug. Polymorphisms in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance 1 (pfmdr1) genes are associated with decreased sensitivity to amodiaquine and lumefantrine, but effects of these polymorphisms on therapeutic responses to artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 clinical trials were harmonized and pooled by using standardized methods from the WorldWide Antimalarial Resistance Network. Data for more than 7,000 patients were analyzed to assess relationships between parasite polymorphisms in pfcrt and pfmdr1 and clinically relevant outcomes after treatment with AL or ASAQ. Presence of the pfmdr1 gene N86 (adjusted hazards ratio = 4.74, 95% confidence interval = 2.29 - 9.78, P < 0.001) and increased pfmdr1 copy number (adjusted hazards ratio = 6.52, 95% confidence interval = 2.36-17.97, P < 0.001: were significant independent risk factors for recrudescence in patients treated with AL. AL and ASAQ exerted opposing selective effects on single-nucleotide polymorphisms in pfcrt and pfmdr1. Monitoring selection and responding to emerging signs of drug resistance are critical tools for preserving efficacy of artemisinin combination therapies; determination of the prevalence of at least pfcrt K76T and pfmdr1 N86Y should now be routine.

A study of West Nile virus (WNV) ecology was conducted in St. Tammany Parish, Louisiana, from 2002 to 2004. Mosquitoes were collected weekly throughout the year using Centers for Disease Control and Prevention (CDC) light traps placed at 1.5 and 6 m above the ground and gravid traps. A total of 379,466 mosquitoes was collected. WNV was identified in 33 pools of mosquitoes comprising five species; 23 positive pools were from Culex nigripalpus collected during 2003. Significantly more positive pools were obtained from Cx. nigripalpus collected in traps placed at 6 m than 1.5 m that year, but abundance did not differ by trap height. In contrast, Cx. nigripalpus abundance was significantly greater in traps placed at 6 m in 2002 and 2004. Annual temporal variation in Cx. nigripalpus peak seasonal abundance has significant implications for WNV transmission in Louisiana. Two WNV-positive pools, one each from Anopheles crucians s.l. and Cx. erraticus, were collected during the winter of 2004, showing year-round transmission. The potential roles of additional mosquito species in WNV transmission in southeastern Louisiana are discussed.

The HIV drug resistance (HIVDR) prevention and assessment strategy, developed by the World Health Organization (WHO) in partnership with HIVResNet, includes monitoring of HIVDR early warning indicators, surveys to assess acquired and transmitted HIVDR, and development of an accredited HIVDR genotyping laboratory network to support survey implementation in resource-limited settings. As of June 2011, 52 countries had implemented at least 1 element of the strategy, and 27 laboratories had been accredited. As access to antiretrovirals expands under the WHO/Joint United Nations Programme on HIV/AIDS Treatment 2.0 initiative, it is essential to strengthen HIVDR surveillance efforts in the face of increasing concern about HIVDR emergence and transmission.

Just as treatment guidelines for diabetes care were at the forefront of medical guideline development (1), diabetes has been a prominent focus of performance measurement and quality improvement initiatives for well over a decade. However, the constraints of pre-electronic health records (EHRs) data systems have consistently limited the clinical scope and sophistication of current diabetes quality measures. The U.S. health care system is nearing a tipping point in the use of more sophisticated EHR-based information systems, and widespread use of these systems will usher in a new era for diabetes quality measurement. New information system capabilities will enable improvements to existing measures and enable development of much more sophisticated measures that can accommodate personalization of clinical goals, patient preferences, and patient-reported data, thus moving both guidelines and measures toward personalization based on sophisticated assessment of the risks and benefits of certain clinical actions for a given patient at a given clinical encounter. | To facilitate discussion of the future of performance measurement in diabetes in this era of rapid transition to EHRs, the American Diabetes Association (ADA) convened a consensus development conference in December 2010. Participating experts identified and discussed the following questions: | 1. | What is the evidence that measuring quality, benchmarking, and providing feedback or incentives improve diabetes care? | 2. | What are the limitations, burdens, and consequences (intended or unintended) of diabetes quality measures as currently structured? | 3. | What should be the role of shared decision making, patient preferences, and patient-reported data in quality measures? | 4. | What is the future of quality measurement in diabetes? | 5. | How can quality monitoring be integrated into population surveillance efforts? | This report summarizes the consensus meeting, and represents the expert opinion of its authors and not the official position of the ADA or any other participating organization.

OBJECTIVE: The objective of the study was to characterize reports to the Vaccine Adverse Event Reporting System (VAERS) in pregnant women who received seasonal influenza vaccines to assess for potential vaccine safety concerns. STUDY DESIGN: We searched VAERS for reports of adverse events (AEs) in pregnant women who received trivalent inactivated influenza vaccine (TIV) from July 1, 1990 through June 30, 2009, or live attenuated influenza vaccine (LAIV) from July 1, 2003, through June 30, 2009. RESULTS: A total of 148 reports after TIV and 27 reports after LAIV were identified. Twenty TIV (13.5%) and 1 LAIV (4%) reports were classified as serious. No specific AEs were reported in 30 TIV (20.3%) and 16 LAIV (59%) reports. The most common pregnancy-specific AE was spontaneous abortion: 17 after TIV (11.5%) and 3 after LAIV (11%). The reporting rate of spontaneous abortion was 1.9 per million pregnant women vaccinated. CONCLUSION: No unusual patterns of pregnancy complications or fetal outcomes were observed in the VAERS reports of pregnant women after the administration of TIV or LAIV.

BACKGROUND: Malaria in humans is caused by apicomplexan parasites belonging to 5 species of the genus Plasmodium. Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease is not known. Dimorphism in defined genes has led to P. ovale parasites being divided into classic and variant types. We hypothesized that these dimorphs represent distinct parasite species. METHODS: Multilocus sequence analysis of 6 genetic characters was carried out among 55 isolates from 12 African and 3 Asia-Pacific countries. RESULTS: Each genetic character displayed complete dimorphism and segregated perfectly between the 2 types. Both types were identified in samples from Ghana, Nigeria, Sao Tome, Sierra Leone, and Uganda and have been described previously in Myanmar. Splitting of the 2 lineages is estimated to have occurred between 1.0 and 3.5 million years ago in hominid hosts. CONCLUSIONS: We propose that P. ovale comprises 2 nonrecombining species that are sympatric in Africa and Asia. We speculate on possible scenarios that could have led to this speciation. Furthermore, the relatively high frequency of imported cases of symptomatic P. ovale infection in the United Kingdom suggests that the morbidity caused by ovale malaria has been underestimated.

In contrast with the majority of children with Down syndrome (DS) that have a full trisomy 21 in every cell [Gardner and Sutherland, 2004; Sherman et al., 2007], children with trisomy 21 mosaicism (herein referred to as mosaic DS) exhibit considerable variation in the proportion of cells with trisomy 21, both as a whole and among tissues [Sherman et al., 2007; Ringman et al., 2008]. The clinical characteristics of children with mosaic DS are generally milder compared with those of children with non-mosaic DS, as reflected by a lower frequency of clinical diagnosis at birth for children with mosaic DS (37.5%) compared with non-mosaic DS (90–100%) [Devlin and Morrison, 2004a]. Whether this variability in phenotypes for children with mosaic DS translates into a higher survival experience than that reported for children with non-mosaic DS is unclear. | We obtained data on 6,300 cytogenetically confirmed livebirths with DS born during 1993–2003 from seven U.S. population-based birth defects registries and verified vital status through December 31, 2004 using medical records, state vital records, and the National Death Index. All registries used a 6-digit International Classification of Diseases, 9th Revision, Clinical Modification or the modified codes from the British Paediatric Association Classification of Diseases; however, the period of ascertainment varied among registries, from 1 to 6 years of age [National Birth Defects Prevention Network, 2008]. We estimated the survival probability among children with mosaic DS and compared survival rates among those with and those without major congenital heart defects (CHD) using the Kaplan–Meier method and the log-rank test.

CONTEXT: In June 2006, the Food and Drug Administration licensed the quadrivalent human papillomavirus (types 6, 11, 16, and 18) recombinant vaccine (qHPV) in the United States for use in females aged 9 to 26 years; the Advisory Committee on Immunization Practices then recommended qHPV for routine vaccination of girls aged 11 to 12 years. OBJECTIVE: To summarize reports to the Vaccine Adverse Event Reporting System (VAERS) following receipt of qHPV. DESIGN, SETTING, AND PARTICIPANTS: Review and describe adverse events following immunization (AEFIs) reported to VAERS, a national, voluntary, passive surveillance system, from June 1, 2006, through December 31, 2008. Additional analyses were performed for some AEFIs in prelicensure trials, those of unusual severity, or those that had received public attention. Statistical data mining, including proportional reporting ratios (PRRs) and empirical Bayesian geometric mean methods, were used to detect disproportionality in reporting. MAIN OUTCOME MEASURES: Numbers of reported AEFIs, reporting rates (reports per 100,000 doses of distributed vaccine or per person-years at risk), and comparisons with expected background rates. RESULTS: VAERS received 12 424 reports of AEFIs following qHPV distribution, a rate of 53.9 reports per 100,000 doses distributed. A total of 772 reports (6.2% of all reports) described serious AEFIs, including 32 reports of death. The reporting rates per 100,000 qHPV doses distributed were 8.2 for syncope; 7.5 for local site reactions; 6.8 for dizziness; 5.0 for nausea; 4.1 for headache; 3.1 for hypersensitivity reactions; 2.6 for urticaria; 0.2 for venous thromboembolic events, autoimmune disorders, and Guillain-Barre syndrome; 0.1 for anaphylaxis and death; 0.04 for transverse myelitis and pancreatitis; and 0.009 for motor neuron disease. Disproportional reporting of syncope and venous thromboembolic events was noted with data mining methods. CONCLUSIONS: Most of the AEFI rates were not greater than the background rates compared with other vaccines, but there was disproportional reporting of syncope and venous thromboembolic events. The significance of these findings must be tempered with the limitations (possible underreporting) of a passive reporting system.