Heidi M. Bauer

Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis.

BACKGROUNDnHuman papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether or not the high efficacy reported in randomised controlled clinical trials are materialising in real-world situations.nnnMETHODSnWe searched the Medline and Embase databases (between Jan 1, 2007 and Feb 28, 2014) and conference abstracts for time-trend studies that analysed changes, between the pre-vaccination and post-vaccination periods, in the incidence or prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts, and high-grade cervical lesions. We used random-effects models to derive pooled relative risk (RR) estimates. We stratified all analyses by age and sex. We did subgroup analyses by comparing studies according to vaccine type, vaccination coverage, and years since implementation of the vaccination programme. We assessed heterogeneity across studies using I(2) and χ(2) statistics and we did trends analysis to examine the dose-response association between HPV vaccination coverage and each study effect measure.nnnFINDINGSnWe identified 20 eligible studies, which were all undertaken in nine high-income countries and represent more than 140 million person-years of follow-up. In countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the pre-vaccination and post-vaccination periods by 68% (RR 0·32, 95% CI 0·19-0·52) and anogenital warts decreased significantly by 61% (0·39, 0·22-0·71) in girls 13-19 years of age. Significant reductions were also recorded in HPV types 31, 33, and 45 in this age group of girls (RR 0·72, 95% CI 0·54-0·96), which suggests cross-protection. Additionally, significant reductions in anogenital warts were also reported in boys younger than 20 years of age (0·66 [95% CI 0·47-0·91]) and in women 20-39 years of age (0·68 [95% CI 0·51-0·89]), which suggests herd effects. In countries with female vaccination coverage lower than 50%, significant reductions in HPV types 16 and 18 infection (RR 0·50, 95% CI 0·34-0·74]) and in anogenital warts (0·86 [95% CI 0·79-0·94]) occurred in girls younger than 20 years of age, with no indication of cross-protection or herd effects.nnnINTERPRETATIONnOur results are promising for the long-term population-level effects of HPV vaccination programmes. However, continued monitoring is essential to identify any signals of potential waning efficacy or type-replacement.nnnFUNDINGnThe Canadian Institutes of Health Research.

Impact of human papillomavirus (HPV) vaccination on HPV 16/18-related prevalence in precancerous cervical lesions

BACKGROUNDnVaccination against human papillomavirus (HPV) types 16 and 18 is recommended for girls aged 11 or 12 years with catch-up vaccination through age 26 in the U.S. Cervical intraepithelial neoplasia (CIN) grade 2 or 3 and adenocarcinoma in situ (CIN2+) are used to monitor HPV vaccine impact on cervical disease. This report describes vaccination status in women diagnosed with CIN2+ and examines HPV vaccine impact on HPV 16/18-related CIN2+.nnnMETHODSnAs part of a vaccine impact monitoring project (HPV-IMPACT), females 18-31 years with CIN2+ were reported from pathology laboratories in CA, CT, NY, OR, TN from 2008 to 2011. One diagnostic block was selected for HPV DNA typing with Roche Linear Array. Demographic, abnormal Papanicolaou (Pap) test dates and vaccine status information were collected. The abnormal Pap test immediately preceding the CIN2+ diagnosis was defined as the trigger Pap.nnnRESULTSnAmong 5083 CIN2+ cases reported to date, 3855 had vaccination history investigated; 1900 had vaccine history documented (vaccinated, with trigger Pap dates, or unvaccinated). Among women who initiated vaccination >24 months before their trigger Pap, there was a significantly lower proportion of CIN2+ lesions due to 16/18 compared to women who were not vaccinated (aPR=.67, 95% CI: .48-.94). Among the 1900 with known vaccination status, 20% initiated vaccination on/after their trigger screening. Women aged 21-23 years were more likely to initiate vaccination on/after the trigger Pap compared to 24-26 year olds (29.0% vs. 19.6%, p=.001), as were non-Hispanic blacks compared to non-Hispanic whites (27.3% vs. 19.0%, p=.001) and publicly compared to privately insured women (38.1% vs. 17.4%, p<.0001).nnnCONCLUSIONnWe found a significant reduction in HPV 16/18-related lesions in women with CIN2+ who initiated vaccination at least 24 months prior to their trigger Pap. These preliminary results suggest early impact of the HPV vaccine on vaccine-type disease, but further evaluation is warranted.

Human papillomavirus genotypes in high grade cervical lesions in the United States

BACKGROUNDnTwo vaccines protect against human papillomaviruses (HPV) 16 and 18, which cause 70% of cervical cancer and 50% of cervical intraepithelial neoplasia 2/3 and adenocarcinoma in situ (CIN2+). Monitoring HPV types in CIN2+ may be used to assess HPV vaccine impact.nnnMETHODSnAs part of a multisite vaccine impact monitoring project (HPV-IMPACT), biopsy specimens used to diagnose CIN2+ were obtained for HPV DNA typing for women aged 18-39 years.nnnRESULTSnAmong 4,121 CIN2+ cases reported during 2008-2009 in 18- to 39-year-old women 3058 (74.2%) were tested; 96% were HPV DNA positive. HPV 16 was most common (49.1%), followed by HPV 31 (10.4%) and HPV 52 (9.7%). HPV 18 prevalence was 5.5% overall. Proportion of CIN2+ cases associated with HPV 16/18 was highest (56.3%) in 25- to 29-year-old women. HPV 16/18-associated lesions were less common in non-Hispanic blacks (41.9%) and Hispanics (46.3%) compared with non-Hispanic whites (59.1%) (P < .0001); the difference remained significant when adjusted for covariates. Compared to non-Hispanic whites, HPV 35 and 58 were significantly more common in non-Hispanic blacks (14.5% vs 4.2%; 12.3% vs 3.4%) and HPV 45 was higher in Hispanics (3.7% vs 1.5%).nnnCONCLUSIONSnAge and racial/ethnic differences in HPV type distribution may have implications for vaccine impact and should be considered in monitoring trends.

Population-Based Trends in High-Grade Cervical Lesions in the Early Human Papillomavirus Vaccine Era in the United States

Cervical intraepithelial neoplasia grade 2, 3, and adenocarcinoma in situ (CIN2+) lesions can be monitored as early indicators of human papillomavirus (HPV) vaccine impact. Changes to screening utilization will affect observed reductions in CIN2+ rates and complicate the interpretation of vaccine impact.

Home-based chlamydia and gonorrhoea screening: a systematic review of strategies and outcomes

BackgroundIn many countries, low Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) screening rates among young people in primary-care have encouraged screening programs outside of clinics. Nucleic acid amplification tests (NAATs) make it possible to screen people in homes with self-collected specimens. We systematically reviewed the strategies and outcomes of home-based CT/NG screening programs.MethodsElectronic databases were searched for home-based CT and/or NG screening studies published since January 2005. Screening information (e.g. target group, recruitment and specimen-collection method) and quantitative outcomes (e.g. number of participants, tests and positivity) were extracted. The screening programs were classified into seven groups on the basis of strategies used.ResultsWe found 29 eligible papers describing 32 home-based screening programs. In seven outreach programs, people were approached in their homes: a median of 97% participants provided specimens and 76% were tested overall (13717 tests). In seven programs, people were invited to receive postal test-kits (PTKs) at their homes: a median of 37% accepted PTKs, 79% returned specimens and 19% were tested (46225 tests). PTKs were sent along with invitation letters in five programs: a median of 33% returned specimens and 29% of those invited were tested (15126 tests). PTKs were requested through the internet or phone without invitations in four programs and a median of 32% returned specimens (2666 tests). Four programs involved study personnel directly inviting people to receive PTKs: a median of 46% accepted PTKs, 21% returned specimens and 9.1% were tested (341 tests). PTKs were picked-up from designated locations in three programs: a total of 6765 kits were picked-up and 1167 (17%) specimens were returned for screening. Two programs used a combination of above strategies (2395 tests) but the outcomes were not reported separately. The overall median CT positivity was 3.6% (inter-quartile range: 1.7-7.3%).ConclusionsA variety of strategies have been used in home-based CT/NG screening programs. The screening strategies and their feasibility in the local context need to be carefully considered to maximize the effectiveness of home-based screening programs.

Neisseria gonorrhoeae and extended-spectrum cephalosporins in California: surveillance and molecular detection of mosaic penA

BackgroundThe spread of Neisseria gonorrhoeae strains with mosaic penA alleles and reduced susceptibility to extended-spectrum cephalosporins is a major public health problem. While much work has been performed internationally, little is known about the genetics or molecular epidemiology of N. gonorrhoeae isolates with reduced susceptibility to extended-spectrum cephalosporins in the United States. The majority of N. gonorrhoeae infections are diagnosed without a live culture. Molecular tools capable of detecting markers of extended-spectrum cephalosporin resistance are needed.MethodsUrethral N. gonorrhoeae isolates were collected from 684 men at public health clinics in California in 2011. Minimum inhibitory concentrations (MICs) to ceftriaxone, cefixime, cefpodoxime and azithromycin were determined by Etest and categorized according to the U.S. Centers for Disease Control 2010 alert value breakpoints. 684 isolates were screened for mosaic penA alleles using real-time PCR (RTPCR) and 59 reactive isolates were subjected to DNA sequencing of their penA alleles and Neisseria gonorrhoeae multi-antigen sequence typing (NG-MAST). To increase the specificity of the screening RTPCR in detecting isolates with alert value extended-spectrum cephalosporin MICs, the primers were modified to selectively amplify the mosaic XXXIV penA allele.ResultsThree mosaic penA alleles were detected including two previously described alleles (XXXIV, XXXVIII) and one novel allele (LA-A). Of the 29 isolates with an alert value extended-spectrum cephalosporin MIC, all possessed the mosaic XXXIV penA allele and 18 were sequence type 1407, an internationally successful strain associated with multi-drug resistance. The modified RTPCR detected the mosaic XXXIV penA allele in urethral isolates and urine specimens and displayed no amplification of the other penA alleles detected in this study.ConclusionN. gonorrhoeae isolates with mosaic penA alleles and reduced susceptibility to extended-spectrum cephalosporins are currently circulating in California. Isolates with the same NG-MAST ST, penA allele and extended-spectrum cephalosporin MICs have caused treatment failures elsewhere. The RTPCR assay presented here may be useful for the detection of N. gonorrheoae isolates and clinical specimens with reduced extended-spectrum cephalosporin MICs in settings where antimicrobial susceptibility testing is unavailable. In an era of increasing antimicrobial resistance and decreasing culture capacity, molecular assays capable of detecting extended-spectrum cephalosporin of resistance are essential to public health.

Monitoring Effect of Human Papillomavirus Vaccines in US Population, Emerging Infections Program, 2008–2012

Methods for surveillance of cervical precancers and associated types were developed to monitor effect of HPV vaccination.

Neisseria gonorrhoeae strain with reduced susceptibilities to extended-spectrum cephalosporins.

The spread of Neisseria gonorrhoeae strains with reduced susceptibility to extended-spectrum cephalosporins is an increasing public health threat. Using Etest and multiantigen sequence typing, we detected sequence type 1407, which is associated with reduced susceptibilities to extended-spectrum cephalosporins, in 4 major populated regions in California, USA, in 2012.

Comparison of Neisseria gonorrhoeae MICs Obtained by Etest and Agar Dilution for Ceftriaxone, Cefpodoxime, Cefixime and Azithromycin.

We evaluated Neisseria gonorrhoeae Etest minimum inhibitory concentrations (MICs) relative to agar dilution MICs for 664 urethral isolates for ceftriaxone (CRO) and azithromycin (AZM), 351 isolates for cefpodoxime (CPD) and 315 isolates for cefixime (CFM). Etest accurately determined CPD, CFM and AZM MICs, but resulted in higher CRO MICs.

Chlamydia Prevalence Among Adolescent Females and Males in Juvenile Detention Facilities in California

With the advent of urine–based chlamydia tests, screening can be conducted in juvenile detention facilities. To determine chlamydia infection rates among female and male juvenile detainees in seven detention facilities in California, urine–based chlamydia testing was conducted from September 2000 through July 2002. Participants provided data on demographics and use of health care services. Among the 1,284 females, chlamydia prevalence was 12.9%; among the 4,778 males, prevalence was 6.0%. Overall, 54.3% of females and 70.5% of males reported not having received primary care in the previous year. High chlamydia prevalence combined with poor access to primary care among adolescents in detention warrants screening for chlamydia in juvenile detention facilities.