Ali Rowhani-Rahbar

Waning Protection after Fifth Dose of Acellular Pertussis Vaccine in Children

BACKGROUND In the United States, children receive five doses of diphtheria, tetanus, and acellular pertussis (DTaP) vaccine before 7 years of age. The duration of protection after five doses of DTaP is unknown. METHODS We assessed the risk of pertussis in children in California relative to the time since the fifth dose of DTaP from 2006 to 2011. This period included a large outbreak in 2010. We conducted a case-control study involving members of Kaiser Permanente Northern California who were vaccinated with DTaP at 47 to 84 months of age. We compared children with pertussis confirmed by a positive polymerase-chain-reaction (PCR) assay with two sets of controls: those who were PCR-negative for pertussis and closely matched controls from the general population of health-plan members. We used logistic regression to examine the risk of pertussis in relation to the duration of time since the fifth DTaP dose. Children who received whole-cell pertussis vaccine during infancy or who received any pertussis-containing vaccine after their fifth dose of DTaP were excluded. RESULTS We compared 277 children, 4 to 12 years of age, who were PCR-positive for pertussis with 3318 PCR-negative controls and 6086 matched controls. PCR-positive children were more likely to have received the fifth DTaP dose earlier than PCR-negative controls (P<0.001) or matched controls (P=0.005). Comparison with PCR-negative controls yielded an odds ratio of 1.42 (95% confidence interval, 1.21 to 1.66), indicating that after the fifth dose of DTaP, the odds of acquiring pertussis increased by an average of 42% per year. CONCLUSIONS Protection against pertussis waned during the 5 years after the fifth dose of DTaP. (Funded by Kaiser Permanente).

Comparative Effectiveness of Acellular Versus Whole-Cell Pertussis Vaccines in Teenagers

BACKGROUND: During the 1990s, the United States switched from combined diphtheria, tetanus toxoids, whole-cell pertussis (DTwP) vaccines to combined acellular pertussis (DTaP) vaccines because of safety concerns. After a 2010–2011 pertussis outbreak, we sought to evaluate whether disease risk in 10 to 17 year olds differed between those who previously received DTwP from those who received DTaP. METHODS: A case-control study among individuals born from 1994 to 1999 who received 4 pertussis-containing vaccines during the first 2 years of life at Kaiser Permanente Northern California (KPNC). We separately compared pertussis polymerase chain reaction (PCR)-positive cases with PCR-negative and KPNC-matched controls. We assessed risk of pertussis relative to vaccine type in early childhood (4 DTwPs, mixed DTwP/DTaP, or 4 DTaPs) by using conditional logistic regression stratified for calendar time and adjusted for gender, race, medical clinic, and receipt of reduced antigen content acellular pertussis (Tdap) vaccine. RESULTS: We compared 138 PCR-positive cases with 899 PCR-negative and 54 339 KPNC-matched controls. Teenagers who had received 4 DTwPs were much less likely to be pertussis PCR-positive than those who had received 4 DTaPs (odds ratio 5.63, 95% confidence interval 2.55–12.46) or mixed DTwP/DTaP vaccines (odds ratio 3.77, 95% confidence interval 1.57–9.07). Decreasing number of DTwP doses was significantly associated with increased pertussis risk (P < .0001). CONCLUSIONS: Teenagers who received DTwP vaccines in childhood were more protected during a pertussis outbreak than were those who received DTaP vaccines.

Mycoplasma genitalium Infection and Female Reproductive Tract Disease: A Meta-analysis

To determine the association between Mycoplasma genitalium infection and female reproductive tract syndromes through meta-analysis, English-language, peer-reviewed studies were identified via PubMed, Embase, Biosis, Cochrane Library, and reference review. Two reviewers independently extracted data. Random-effects models were employed to calculate summary estimates, between-study heterogeneity was evaluated using I(2) statistics, publication bias was assessed via funnel plots and the Begg and Egger tests, and methodologic quality was rated. Mycoplasma genitalium infection was significantly associated with increased risk of cervicitis (pooled odds ratio [OR], 1.66 [95% confidence interval {CI}, 1.35-2.04]), pelvic inflammatory disease (pooled OR, 2.14 [95% CI, 1.31-3.49]), preterm birth (pooled OR, 1.89 [95% CI, 1.25-2.85]), and spontaneous abortion (pooled OR, 1.82 [95% CI, 1.10-3.03]). Risk of infertility was similarly elevated (pooled OR, 2.43 [95% CI, .93-6.34]). In subanalyses accounting for coinfections, all associations were stronger and statistically significant. Testing of high-risk symptomatic women for M. genitalium may be warranted.

Longer-term efficacy of a prophylactic monovalent human papillomavirus type 16 vaccine

We conducted an extended follow-up study (March 2006-May 2008) to assess the longer term efficacy of a prophylactic monovalent human papillomavirus (HPV) type 16 L1 virus-like particle vaccine in women (n=290) who had enrolled in a randomized controlled trial of this vaccine (October 1998-November 1999) in Seattle and remained HPV-16 DNA negative during the course of that trial. During the extended follow-up period, in the per-protocol susceptible population, none of the vaccine recipients was found to be infected with HPV-16 or developed HPV-16-related cervical lesions; among placebo recipients, 6 women were found to be infected with HPV-16 (vaccine efficacy [VE]=100%; 95% confidence interval [CI]: 29-100%) and 3 women developed HPV-16-related cervical lesions (VE=100%; 95% CI: <0-100%). Approximately 86% of vaccine recipients remained HPV-16 competitive Luminex immunoassay seropositive at an average of 8.5 years of follow-up. During the combined original trial and extended follow-up period, in the intention-to-treat population, 20 and 22 women developed any cervical lesion regardless of HPV type among the vaccine and placebo recipients, respectively (VE=15%; 95% CI: <0-56%). The results suggest that this monovalent HPV-16 vaccine remains efficacious through 8.5 years after its administration.

Sports- and Recreation-Related Concussions in US Youth

OBJECTIVE: The incidence of sports- and recreation-related concussions (SRRCs) in the United States is unknown. More than 44 million youth participate in sports annually, thus understanding the frequency of SRRCs in children is important on a population level. Our objective was to determine the number of SRRCs occurring annually among US youth ≤18 years old. METHODS: We identified SRRCs using 3 national databases: MarketScan, National Electronic Injury Surveillance System, and National High School Sports Related Injury Surveillance System, Reporting Injury Online. We determined the number of SRRCs seen in health care settings (outpatient, inpatient, and emergency department) and SRRCs reported to certified high school athletic trainers (ATCs). We used these data and findings in recently published literature to generate a national estimate of SRRCs. RESULTS: We estimate that between 1.1 and 1.9 million SRRCs occur annually in US children aged ≤18 years. Most children with SRRCs, 511 590 to 1 240 972, were not seen in health care settings. Of children with SRRCs seen in health care settings, most were seen as outpatients with 377 978 visits, compared with between 115 479 and 166 929 ED visits, and between 2886 and 4936 hospitalizations. CONCLUSIONS: This study provides the most accurate and precise estimate to date of the number of concussions among US children annually. SRRCs are a common injury in children. Providers in all health care settings need to be trained in concussion care. There is a need for better surveillance to enhance our understanding of the epidemiology of concussions in youth.

The Impact of HIV Status and Type on the Clearance of Human Papillomavirus Infection among Senegalese Women

BACKGROUND Persistent infection with human papillomavirus (HPV) is associated with the development and progression of HPV-related disease, including cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. METHODS We examined the impact of human immunodeficiency virus (HIV) status and type on the clearance of HPV infection among 614 Senegalese women enrolled in a longitudinal study of HPV and CIN. Women were examined every 4 months for HPV DNA. Clearance was defined as 2 consecutive negative HPV DNA test results. RESULTS Cox proportional hazard regression with time-dependent covariates indicated that HIV-positive women were less likely to clear HPV infection (adjusted hazard ratio [HR], 0.31 [95% confidence interval {CI}, 0.21-0.45]) than HIV-negative women. Among HIV-positive women, those with CD4 cell counts <200 or from 200 to 500 cells/microL showed a 71% (adjusted HR, 0.29 [95% CI, 0.11-0.76]) and 32% (adjusted HR, 0.68 [95% CI, 0.31-1.48]) reduction in the likelihood of HPV clearance, respectively, compared with those with CD4 cell counts >500 cells/microL. HIV-2 infection was associated with an increased likelihood of HPV clearance (adjusted HR, 2.46 [95% CI, 1.17-5.16]), compared with that for HIV-1 infection. CONCLUSIONS HIV infection reduces the likelihood of HPV clearance. Among HIV-positive women, immunosuppression, as measured by CD4 cell count, reduces the likelihood of HPV clearance, and HIV type appears to be associated with HPV clearance.

Effectiveness of pertussis vaccines for adolescents and adults: case-control study

Objective To assess the effectiveness of reduced acellular pertussis (Tdap) vaccines in adolescents and adults. Setting Kaiser Permanente Northern California. Design Case-control study. Participants All polymerase chain reaction (PCR) confirmed cases of pertussis in members aged 11 years and older from January 2006 to December 2011. We compared the Tdap vaccination status of PCR positive cases with two control groups: people testing negative for pertussis by PCR and closely matched people from the general Kaiser Permanente Northern California population. Main outcome measure PCR confirmed pertussis. The association of Tdap vaccination with the odds of pertussis infection was estimated by conditional logistic regression, with adjustment for calendar time, pertussis vaccine type received in early childhood, age, sex, race or ethnic group, and medical clinic. We calculated Tdap vaccine effectiveness as 1 minus the adjusted odds ratio. Results The study population included 668 PCR positive cases, 10 098 PCR negative controls, and 21 599 Kaiser Permanente Northern California matched controls. Tdap vaccination rates were 24.0% in PCR positive cases and 31.9% in PCR negative controls (P<0.001). The adjusted estimate of effectiveness of Tdap vaccination against pertussis was 53.0% (95% confidence interval 41.9% to 62.0%) in the comparison with PCR controls, and 64.0% (55.5% to 70.9%) in the comparison with Kaiser Permanente Northern California controls. Conclusion Tdap vaccination was moderately effective at preventing PCR confirmed pertussis among adolescents and adults.

Effect of Age on the Risk of Fever and Seizures Following Immunization With Measles-Containing Vaccines in Children

IMPORTANCE The first dose of live attenuated measles-containing vaccines is associated with an increased risk of febrile seizures 7 to 10 days following immunization among 12- to 23-month-old children. The combination measles, mumps, rubella, and varicella vaccine is associated with a 2-fold increased risk of febrile seizures 7 to 10 days following immunization compared with the separately administered measles, mumps, and rubella and varicella vaccines. It is unknown whether the magnitude of these increased risks depends on age at immunization. OBJECTIVE To examine the potential modifying effect of age on the risk of fever and seizures following immunization with measles-containing vaccines. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study at 8 Vaccine Safety Datalink sites of a total of 840,348 children 12 to 23 months of age who had received a measles-containing vaccine from 2001 through 2011. EXPOSURES Any measles-containing vaccines and measles-containing vaccines by type. MAIN OUTCOMES AND MEASURES Fever and seizure events occurring during a 42-day postimmunization observation period. RESULTS In the analysis of any measles-containing vaccines, the increased risk of seizures during the 7- to 10-day risk interval, using the remainder of the observation period as the control interval, was significantly greater among older children (relative risk, 6.5; 95% CI, 5.3-8.1; attributable risk, 9.5 excess cases per 10,000 doses; 95% CI, 7.6-11.5) than among younger children (relative risk, 3.4; 95% CI, 3.0-3.9; attributable risk = 4.0 excess cases per 10,000 doses; 95% CI, 3.4-4.6). The relative risk of postimmunization fever was significantly greater among older children than among younger children; however, its attributable risk was not. In the analysis of vaccine type, measles, mumps, rubella, and varicella vaccine was associated with a 1.4-fold increase in the risk of fever and 2-fold increase in the risk of seizures compared with measles, mumps, and rubella vaccine administered with or without varicella vaccine in both younger and older children. CONCLUSIONS AND RELEVANCE Measles-containing vaccines are associated with a lower increased risk of seizures when administered at 12 to 15 months of age. Findings of this study that focused on safety outcomes highlight the importance of timely immunization of children with the first dose of measles-containing vaccines.

Association Between Undervaccination With Diphtheria, Tetanus Toxoids, and Acellular Pertussis (DTaP) Vaccine and Risk of Pertussis Infection in Children 3 to 36 Months of Age

IMPORTANCE Undervaccination is an increasing trend that potentially places children and their communities at an increased risk for serious infectious diseases. OBJECTIVE To examine the association between undervaccination and pertussis in children 3 to 36 months of age. DESIGN Matched case-control study with conditional logistic regression analysis. SETTING Eight managed care organizations of the Vaccine Safety Datalink between 2004 and 2010. PARTICIPANTS Each laboratory-confirmed case of pertussis (72 patients) was matched to 4 randomly selected controls (for a total of 288 controls). The case patients were matched to controls by managed care organization site, sex, and age at the index date. The index date was defined as the date of pertussis diagnosis for the case patients. EXPOSURE Undervaccination for the diphtheria, tetanus toxoids, and acellular pertussis (DTaP) vaccine. Undervaccination was defined as the number of doses of DTaP vaccine that was either missing or delayed by the index date. Case patients and controls could be undervaccinated by 0, 1, 2, 3, or 4 doses of DTaP vaccine. Children undervaccinated by 0 doses were considered age-appropriately vaccinated by the index date. MAIN OUTCOME AND MEASURE Pertussis. RESULTS Of the 72 case patients with pertussis, 12 (16.67%) were hospitalized, and 34 (47.22%) were undervaccinated for DTaP vaccine by the date of pertussis diagnosis. Of the 288 matched controls, 64 (22.22%) were undervaccinated for DTaP vaccine. Undervaccination was strongly associated with pertussis. Children undervaccinated for 3 or 4 doses of DTaP vaccine were 18.56 (95% CI, 4.92-69.95) and 28.38 (95% CI, 3.19-252.63) times more likely, respectively, to have received a diagnosis of pertussis than children who were age-appropriately vaccinated. CONCLUSIONS AND RELEVANCE Undervaccination with DTaP vaccine increases the risk of pertussis among children 3 to 36 months of age.

Epidemiology of human papillomavirus infection among fishermen along Lake Victoria Shore in the Kisumu District, Kenya.

Objectives: The epidemiology of human papillomavirus (HPV) infection in men in Kenya is largely uncharacterised. We set out to determine the prevalence and determinants of HPV infection among sexually active fishermen along Lake Victoria in the Kisumu district of Kenya. Methods: Genital swabs were obtained from 250 consenting fishermen from 18 beaches and a detailed sociodemographic questionnaire was administered. HPV positivity was determined by polymerase chain reaction amplification and detected by dot blot hybridisation with generic HPV and β-globin probes. HPV positive samples were genotyped using the Roche Linear array assay. Results: Overall, 144 (57.6%) fishermen had detectable HPV DNA, 106 (42.4%) were infected with oncogenic HPV types, with HPV-16 being the most frequent type (12.4%). Among HPV positive men, 105 (72.9%) were infected with more than one HPV type and 20 (13.9%) were infected with more than six different types. HIV seropositive men (PR 1.49, 95% CI 1.19 to 1.86) and those divorced or separated (PR 1.62, 95% CI 1.13 to 2.33) were more likely to be infected with HPV. HIV infection (PR 1.22, 95% CI 1.01 to 1.47) was the only factor independently associated with infection with multiple types of HPV. Conclusion: The prevalence of oncogenic HPV infection is high among this population and is associated with HIV serostatus and marital status. This community could benefit from enhanced sexually transmitted infection and HIV prevention interventions.