Serotype epidemiology of invasive pneumococcal disease in Swiss adults: A nationwide population-based study.

BACKGROUND In Switzerland, the heptavalent (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) were recommended for all infants aged <2 years in 2007 and 2011, respectively. Due to herd effects, a protective impact on the invasive pneumococcal disease (IPD) rates in adults had been expected. METHODS Within this study, data from the nationwide mandatory surveillance was analyzed for all adult patients ≥16 years with IPD of known serotype/serogroup during 2003-2012. Trend (for IPD cases from 2003 to 2012) and logistic regression analyses (2007-2010) were performed to identify changes in serotype distribution and to identify the association of serotypes with age, clinical manifestations, comorbidities and case fatality, respectively. FINDINGS The proportion of PCV7 serotypes among all IPD cases (n=7678) significantly declined in adults from 44.7% (2003) before to 16.7% (2012) after the recommendation of PCV7 (P<0.001). In contrast, the proportion of non-PCV7 serogroup/serotypes increased for non-PCV13 but also PCV13 serotypes (not included in PCV7) at the same time. Serotype distribution varied significantly across ages, clinical manifestations and comorbidities. Serotype was furthermore associated with case fatality (P=0.001). In a multivariable logistic regression model, analyzing single serotypes showed that case-fatality was increased for the serotypes 3 (P=0.008), 19A (P=0.03) and 19F (P=0.005), compared to serotype 1 and 7F. CONCLUSION There was a significant decline in PCV7 serotypes among adults with IPD in Switzerland after introduction of childhood vaccination with PCV7. Pneumococcal serotypes were associated with case fatality, age, clinical manifestation and comorbidities of IPD in adults. These results may prove useful for future vaccine recommendations for adults in Switzerland.

Decrease in pneumococcal co-colonization following vaccination with the seven-valent pneumococcal conjugate vaccine.

Understanding the epidemiology of pneumococcal co-colonization is important for monitoring vaccine effectiveness and the occurrence of horizontal gene transfer between pneumococcal strains. In this study we aimed to evaluate the impact of the seven-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal co-colonization among Portuguese children. Nasopharyngeal samples from children up to 6 years old yielding a pneumococcal culture were clustered into three groups: pre-vaccine era (n = 173), unvaccinated children of the vaccine era (n = 169), and fully vaccinated children (4 doses; n = 150). Co-colonization, serotype identification, and relative serotype abundance were detected by analysis of DNA of the total bacterial growth of the primary culture plate using the plyNCR-RFLP method and a molecular serotyping microarray-based strategy. The plyNCR-RFLP method detected an overall co-colonization rate of 20.1%. Microarray analysis confirmed the plyNCR-RFLP results. Vaccination status was the only factor found to be significantly associated with co-colonization: co-colonization rates were significantly lower (p = 0.004; Fisher's exact test) among fully vaccinated children (8.0%) than among children from the pre-PCV7 era (17.3%) or unvaccinated children of the PCV7 era (18.3%). In the PCV7 era there were significantly less non-vaccine type (NVT) co-colonization events than would be expected based on the NVT distribution observed in the pre-PCV7 era (p = 0.024). In conclusion, vaccination with PCV7 resulted in a lower co-colonization rate due to an asymmetric distribution between NVTs found in single and co-colonized samples. We propose that some NVTs prevalent in the PCV7 era are more competitive than others, hampering their co-existence in the same niche. This result may have important implications since a decrease in co-colonization events is expected to translate in decreased opportunities for horizontal gene transfer, hindering pneumococcal evolution events such as acquisition of antibiotic resistance determinants or capsular switch. This might represent a novel potential benefit of conjugate vaccines.

Evidence for Emergency Vaccination Having Played a Crucial Role to Control the 1965/66 Foot-and-Mouth Disease Outbreak in Switzerland.

Foot-and-mouth disease (FMD) is a highly contagious disease that caused several large outbreaks in Europe in the last century. The last important outbreak in Switzerland took place in 1965/66 and affected more than 900 premises and more than 50,000 animals were slaughtered. Large-scale emergency vaccination of the cattle and pig population has been applied to control the epidemic. In recent years, many studies have used infectious disease models to assess the impact of different disease control measures, including models developed for diseases exotic for the specific region of interest. Often, the absence of real outbreak data makes a validation of such models impossible. This study aimed to evaluate whether a spatial, stochastic simulation model (the Davis Animal Disease Simulation model) can predict the course of a Swiss FMD epidemic based on the available historic input data on population structure, contact rates, epidemiology of the virus, and quality of the vaccine. In addition, the potential outcome of the 1965/66 FMD epidemic without application of vaccination was investigated. Comparing the model outcomes to reality, only the largest 10% of the simulated outbreaks approximated the number of animals being culled. However, the simulation model highly overestimated the number of culled premises. While the outbreak duration could not be well reproduced by the model compared to the 1965/66 epidemic, it was able to accurately estimate the size of the area infected. Without application of vaccination, the model predicted a much higher mean number of culled animals than with vaccination, demonstrating that vaccination was likely crucial in disease control for the Swiss FMD outbreak in 1965/66. The study demonstrated the feasibility to analyze historical outbreak data with modern analytical tools. However, it also confirmed that predicted epidemics from a most carefully parameterized model cannot integrate all eventualities of a real epidemic. Therefore, decision makers need to be aware that infectious disease models are useful tools to support the decision-making process but their results are not equal valuable as real observations and should always be interpreted with caution.

Survey of VFC provider knowledge of catch-up regimens and contraindications to vaccination in Houston, Texas

In 2004, Houston had one of the lowest childhood immunization levels among major metropolitan cities in the United States at 65% for the 4:3:1:3:3 vaccination series. Delays in the receipt of scheduled vaccinations may be related to missed opportunities due to health care provider lack of knowledge about catch-up regimens and contraindications for pediatric vaccination. The objectives of this study are to identify, measure, and report on VFC provider-practice characteristics, knowledge of catch-up regimens and contraindications, and use of Reminder recall (R/R) and moved or gone elsewhere (MOGE) practices among providers with high (>80%) and low (<70%) immunization coverage among 19-35 month old children. The sampling frame consists of 187 Vaccines for Children (VFC) providers with 2004 clinic assessment software application (CASA) scores. Data were collected by personal interview with each participating practice provider. Only ten VFC providers were successful at maximizing vaccinations for every vignette and no provider administered the maximum possible number of vaccinations at visit 2 for all six vignettes. Both coverage groups administered polio conjugate vaccine (PCV), haemophilus influenza type b (Hib), and diphtheria, tetanus and acellular pertussis (DTaP) most frequently and omitted most frequently varicella zoster vaccine (VZV) and measles, mumps, and rubella (MMR) vaccine. ^

Influenza vaccination and peoples' knowledge and attitudes towards it: Factors that influenced influenza vaccination during the 2004--2005 influenza vaccine shortage

Influenza and pneumonia together comprise the seventh leading cause of death among adults in the U.S and were responsible for 65,163 deaths in 2003 and an average of 36,000 deaths per year in the United States from 1990 to 1999. Vaccination is efficacious and cost-effective in terms of preventing the infection and reducing both health care costs and productivity losses associated with influenza illness. The vaccine shortage of 2004–2005 resulted in a 39% decrease in the influenza vaccine supplies. During the fall of 2004, we conducted a nationwide, random-digit dialing, telephonic-interview survey of 1,202 adults aged 18 years and older to ascertain influenza vaccine knowledge, attitude and behavior. Of the 1,202 total interviewed subjects, 44.7% had received or intended to receive vaccine at the time of the survey (2004–05) and 39.6% had received the influenza vaccine the previous year (2003–04). Receipt of vaccine increased with previous receipt of the influenza vaccine (OR 13.17, 95% CI 8.65–20.08), increased motivation status (OR 7.58, 95% CI 4.03–14.25), subjective risk status (OR 3.33, 95% CI 2.23–4.97), age (OR 1.83, 95% CI 1.22–2.75) and previous receipt of the pneumococcal vaccine (OR 1.75, 95% CI 1.02–3.0). The influenza vaccine shortage of 2004–05 did not have a negative impact on the vaccination rates of study population. In addition to the increased rates, a large majority of respondents were also aware of the shortage of influenza vaccine during the 2004–05 season, about the indications for receiving the influenza vaccine, about alternative methods to prevent contracting the influenza and increased motivation to receive the vaccine. ^

The epidemiology of Hepatitis B and Hepatitis C virus infection among college students who are not US/Canadian born in Houston

Introduction. A vast majority of studies conducted in both developed and developing nations have focused on the epidemiology of HBV (Hepatitis B virus) and HCV (Hepatitis C virus) in high-risk populations; low-risk populations have been neglected. Recently Hwang et al conducted a unique large cross-sectional study in American university students that focused on cosmetic procedures and drug use for acquiring these infections among a low-risk young adult population In Houston. ^ Methods. This study is a secondary data analysis of the cross-sectional study conducted by Hwang et al. Data for this anonymous study were collected from 7,960 college students, among whom were the 2,561 non US/Canadian born students included in this study. All students completed a self-administered questionnaire and provided a blood sample. The epidemiology of HBV/HCV and risk factors for acquiring HBV/HCV infection was studied by comparing those with HBV/HCV infection versus those without. Both univariate and multivariate logistic regression was used to analyze the data. ^ Results. Overall prevalence of HBV and HCV infections were 22% and 0.8% respectively. By multivariable analysis, the factors that were independently associated with increased prevalence of HBV infection were increasing age per year (OR=1.06, 95% C.I=1.04-1.08), Black or Asian race (OR=6.21, 95% C.I=3.14-12.27), history of household contact with hepatitis (OR=1.87, 95% C.I=1.15-3.05), and having sexual partner with hepatitis (OR=5.20, 95% C.I=1.5-18.00). For HCV these factors included increasing age per year (OR= 1.08, 95% C.I=1.03-1.14), history of blood transfusion prior to 1991 (OR=25.45, 95% C.I=7.58-85.40), and Injection drug use. (OR=78.15, 95% C.I=12.19-500.85). Cosmetic procedures like tattooing were not significant risk factors for either HBV or HCV infection. ^ Conclusions. In a low-risk adult foreign born population, cosmetic procedures are not significant risk factors for HBV or HCV infection. The prevention strategies of these infections in this population should focus on safe sexual practices/abstinence and HBV vaccination should be provided to adolescents and sexually active adults. ^

Associations between vaccination and childhood cancers in Texas counties

Background. In Dr. Mel Greaves "delayed-infection hypothesis," postponed exposure to common infections increases the likelihood of childhood cancer. Hygienic advancements in developed countries have reduced children's exposure to pathogens and children encounter common infectious agents at an older age with an immune system unable to deal with the foreign antigens. Vaccinations may be considered to be simulated infections as they prompt an antigenic response by the immune system. Vaccinations may regulate the risk of childhood cancer by modulating the immune system. The aim of the study was to determine if children born in Texas counties with higher levels of vaccination coverage were at a reduced risk for childhood cancer.^ Methods. We conducted a case-control study to examine the risk of childhood cancers, specifically leukemia, brain tumors, and non-Hodgkin lymphoma, in relation to vaccination rates in Texas counties. We utilized a multilevel mixed-effects regression model of the individual data from the Texas Cancer Registry (TCR) with group-level exposure data (i.e., the county- and public health region-level vaccination rates).^ Results. Utilizing county-level vaccination rates and controlling for child's sex, birth year, ethnicity, birth weight, and mother's age at child's birth the hepatitis B vaccine revealed negative associations with developing all cancer types (OR = 0.81, 95% CI: 0.67–0.98) and acute lymphoblastic leukemia (ALL) (OR = 0.63, 95% CI: 0.46–0.88). The decreased risk for ALL was also evident for the inactivated polio vaccine (IPV) (OR = 0.67, 95% CI: 0.49–0.92) and 4-3-1-3-3 vaccination series (OR = 0.62, 95% CI: 0.44-0.87). Using public health region vaccine coverage levels, an inverse association between the Haemophilus influenzae type b (Hib) vaccine and ALL (OR: 0.58; 95% CI: 0.42–0.82) was present. Conversely, the measles, mumps, and rubella (MMR) vaccine resulted in a positive association with developing non-Hodgkin lymphoma (OR = 2.81, 95% CI: 1.27–6.22). ^

Impact of maternal Tdap vaccination on pertussis infection in young infants

Undiagnosed infected mothers often are the source of pertussis illness in young infants. The Centers for Disease Control and Prevention (CDC) recommends Tdap vaccine for post-partum women before hospital discharge. This intervention has been implemented at Ben Taub General Hospital (BTGH) in Houston, TX since January 2008. Our objective was to compare the proportion of infants born at BTGH and developing pertussis to the total number of pertussis cases before and after the intervention. Methods. We conducted a cross-sectional comparative study between the pre-intervention (7/2000 to 12/2007) and post-intervention (1/2008 to 5/2009) periods. Information on pertussis diagnosis was determined using ICD-9 codes, infection control records, and molecular microbiology reports from Texas Children's Hospital (TCH) and BTGH. Only patients ≤ 6 months of age with laboratory-confirmed B. pertussis infection were included in the study. Results. 481 infants had pertussis illness; 353 (73.3%) during pre-intervention and 128 (26.6%) during post-intervention years. The groups were comparable in all measures including age (median 73 vs. 62.5 days; p=0.08), gender (males 54.2%; p=0.47), length of hospitalization (median 9.8 vs. 4 9.5 days; p=0.5), outcomes (2 deaths in each period; p=0.28) and pertussis illness at TCH (95.2% vs. 95.3%; p=0.9). The proportion of pertussis patients born at BTGH, and thus amenable to protection by the intervention, was not statically different between the two periods after adjusting for age, gender and ethnicity (7.3% vs. 9.3%; an OR=1.05, 95% CI 0.5-2.1, p=0.88). Conclusions. Vaccinating only mothers with Tdap in the post-partum period does not reduce the proportion of pertussis in infants age ≤ 6 months. Efforts should be directed at Tdap immunization of not only mothers, but also all household and key contacts of newborns to protect them against pertussis illness before the primary DTaP series is completed.^

Immune response to hepatitis B vaccination in drug using populations: A systematic review and meta-regression analysis

Hepatitis B virus (HBV) is a significant cause of liver diseases and related complications worldwide. Both injecting and non-injecting drug users are at increased risk of contracting HBV infection. Scientific evidence suggests that drug users have subnormal response to HBV vaccination and the seroprotection rates are lower than that in the general population; potentially due to vaccine factors, host factors, or both. The purpose of this systematic review is to examine the rates of seroprotection following HBV vaccination in drug using populations and to conduct a meta-analysis to identify the factors associated with varying seroprotection rates. Seroprotection is defined as developing an anti-HBs antibody level of ≥ 10 mIU/ml after receiving the HBV vaccine. Original research articles were searched using online databases and reference lists of shortlisted articles. HBV vaccine intervention studies reporting seroprotection rates in drug users and published in English language during or after 1989 were eligible. Out of 235 citations reviewed, 11 studies were included in this review. The reported seroprotection rates ranged from 54.5 – 97.1%. Combination vaccine (HAV and HBV) (Risk ratio 12.91, 95% CI 2.98-55.86, p = 0.003), measurement of anti-HBs with microparticle immunoassay (Risk ratio 3.46, 95% CI 1.11-10.81, p = 0.035) and anti-HBs antibody measurement at 2 months after the last HBV vaccine dose (RR 4.11, 95% CI 1.55-10.89, p = 0.009) were significantly associated with higher seroprotection rates. Although statistically nonsignificant, the variables mean age>30 years, higher prevalence of anti-HBc antibody and anti-HIV antibody in the sample population, and current drug use (not in drug rehabilitation treatment) were strongly associated with decreased seroprotection rates. Proportion of injecting drug users, vaccine dose and accelerated vaccine schedule were not predictors of heterogeneity across studies. Studies examined in this review were significantly heterogeneous (Q = 180.850, p = 0.000) and factors identified should be considered when comparing immune response across studies. The combination vaccine showed promising results; however, its effectiveness compared to standard HBV vaccine needs to be examined systematically. Immune response in DUs can possibly be improved by the use of bivalent vaccines, booster doses, and improving vaccine completion rates through integrated public programs and incentives.^

Influenza vaccination as a primary or secondary prevention for cardiovascular diseases: A systematic review of the literature

Background: Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide. CVD mainly comprise of coronary heart disease and stroke and were ranked first and fourth respectively amongst leading causes of death in the United States. Influenza (flu) causes annual outbreaks and pandemics and is increasingly recognized as an important trigger for acute coronary syndromes and stroke. Influenza vaccination is an inexpensive and effective strategy for prevention of influenza related complications in high risk individuals. Though it is recommended for all CVD patients, Influenza vaccine is still used at suboptimal levels in these patients owing to prevailing controversy related to its effectiveness in preventing CVD. This review was undertaken to critically assess the effectiveness of influenza vaccination as a primary or secondary prevention method for CVD. ^ Methods: A systematic review was conducted using electronic databases OVID MEDLINE, PUBMED (National Library of Medicine), EMBASE, GOOGLE SCHOLAR and TRIP (Turning Research into Practice). The study search was limited to peer-reviewed articles published in English language from January 1970 through May 2012. The case control studies, cohort studies and randomized controlled trials related to influenza vaccination and CVD, with data on at least one of the outcomes were identified. In the review, only population-based epidemiologic studies in all ethnic groups and of either sex and with age limitation of 30 yrs or above, with clinical CVD outcomes of interest were included. ^ Results: Of the 16 studies (8 case control studies, 6 cohort studies and 2 randomized controlled trials) that met the inclusion criteria, 14 studies reported that there was a significant benefit in u influenza vaccination as primary or secondary prevention method for preventing new cardiovascular events. In contrary to the above findings, two studies mentioned that there was no significant benefit of vaccination in CVD prevention. ^ Conclusion: The available body of evidence in the review elucidates that vaccination against influenza is associated with reduction in the risk of new CVD events, hospitalization for coronary heart disease and stroke and as well as the risk of death. The study findings disclose that the influenza vaccination is very effective in CVD prevention and should be encouraged for the high risk population. However, larger and more future studies like randomized control trials are needed to further evaluate and confirm these findings. ^

Mass vaccination to control chickenpox: the influence of zoster.

The impact of transmission events from patients with shingles (zoster) on the epidemiology of varicella is examined before and after the introduction of mass immunization by using a stochastic mathematical model of transmission dynamics. Reactivation of the virus is shown to damp stochastic fluctuations and move the dynamics toward simple annual oscillations. The force of infection due to zoster cases is estimated by comparison of simulated and observed incidence time series. The presence of infectious zoster cases reduces the tendency for mass immunization to increase varicella incidence at older ages when disease severity is typically greater.

Time to Extinction in Branching Processes and its Application in Epidemiology

2010 Mathematics Subject Classification: Primary 60J80; Secondary 92D30.

Digital Epidemiology Reveals Global Childhood Disease Seasonality and the Effects of Immunization

ACKNOWLEDGMENTS. We would like to thank Fernando Gonzalez-Dominguez and Gilberto Vaughan for providing the chicken pox case reports from Mexico, and the Estonia Health Board, Department of Communicable Disease Surveillance and Control, for Estonian chicken pox case reports. KB would like to thank Mercedes Pascual, her lab, and Marisa Eisenberg for helpful comments. Jesus Cantu (research assistant, Princeton University) translated and categorized chicken pox searches from Mexico, Thailand, Australia, and the US.

Molecular epidemiology of sexually transmitted human papillomavirus in a self referred group of women in Ireland

Background: Human papillomavirus (HPV) causes cervical cancer and external genital warts. The purpose of this study is to document the genotype distribution of HPV in females aged between 18 and 34 who self-referred to an STI clinic with visible external genital warts (EGW). Scrapings were taken from visible external genital warts (EGW). These scrapings were analysed by PCR for the presence of HPV DNA. Positive samples were then genotyped by means of a commercially available assay (LiPA). A comparison of genotyping results determined by the LiPA assay and direct amplicon DNA sequencing was also performed. Results: Ninety-two patients out of 105 samples (88%) had detectable levels of HPV DNA. The majority of individuals with EGW (66%) showed the presence of two or more genotypes. The most common HPV genotypes present in the study population were HPV-6, HPV-11, HPV-16, HPV-18, HPV-33 and HPV-53. Potential effects of vaccination on HPV molecular epidemiology indicate that 40% of the patients could have been protected from the high risk genotypes HPV-16 and HPV-18.Conclusion: This is the first report of the molecular epidemiology of external genital warts in women aged between 18 and 34 from Ireland based on results from a LiPA assay. The study shows that most individuals are infected with multiple genotypes including those with high oncogenic potential and that the newly available HPV vaccines could have a significant impact on prevalence of the most common HPV genotypes in this study population.