Outbreak of Invasive Serratia marcescens among Persons Incarcerated in a State Prison, California, USA, March 2020-December 2022.

Serratia marcescens is an environmental gram-negative bacterium that causes invasive disease in rare cases. During 2020-2022, an outbreak of 21 invasive Serratia infections occurred in a prison in California, USA. Most (95%) patients had a history of recent injection drug use (IDU). We performed whole-genome sequencing and found isolates from 8 patients and 2 pieces of IDU equipment were closely related. We also identified social interactions among patients. We recovered S. marcescens from multiple environmental samples throughout the prison, including personal containers storing Cell Block 64 (CB64), a quaternary ammonium disinfectant solution. CB64 preparation and storage conditions were suboptimal for S. marcescens disinfection. The outbreak was likely caused by contaminated CB64 and propagated by shared IDU equipment and social connections. Ensuring appropriate preparation, storage, and availability of disinfectants and enacting interventions to counteract disease spread through IDU can reduce risks for invasive Serratia infections in California prisons.

Prevalence and Management of Sexually Transmitted Infections in Correctional Settings: A Systematic Review.

Admissions to jails and prisons in the United States number 10 million yearly; persons entering locked correctional facilities have high prevalence of sexually transmitted infections (STIs). These individuals come disproportionately from communities of color, with lower access to care and prevention, compared with the United States as a whole. Following PRISMA guidelines, the authors present results of a systematic review of literature published since 2012 on STIs in US jails, prisons, Immigration and Customs Enforcement detention centers, and juvenile facilities. This updates an earlier review of STIs in short-term facilities. This current review contributed to new recommendations in the Centers for Disease Control and Prevention 2021 treatment guidelines for STIs, advising screening for Trichomonas in women entering correctional facilities. The current review also synthesizes recommendations on screening: in particular, opt-out testing is superior to opt-in protocols. Carceral interventions-managing diagnosed cases and preventing new infections from occurring (eg, by initiating human immunodeficiency virus preexposure prophylaxis before release)-can counteract structural racism in healthcare.

Mass Testing for SARS-CoV-2 in 16 Prisons and Jails - Six Jurisdictions, United States, April-May 2020.

Preventing coronavirus disease 2019 (COVID-19) in correctional and detention facilities* can be challenging because of population-dense housing, varied access to hygiene facilities and supplies, and limited space for isolation and quarantine (1). Incarcerated and detained populations have a high prevalence of chronic diseases, increasing their risk for severe COVID-19-associated illness and making early detection critical (2,3). Correctional and detention facilities are not closed systems; SARS-CoV-2, the virus that causes COVID-19, can be transmitted to and from the surrounding community through staff member and visitor movements as well as entry, transfer, and release of incarcerated and detained persons (1). To better understand SARS-CoV-2 prevalence in these settings, CDC requested data from 15 jurisdictions describing results of mass testing events among incarcerated and detained persons and cases identified through earlier symptom-based testing. Six jurisdictions reported SARS-CoV-2 prevalence of 0%-86.8% (median = 29.3%) from mass testing events in 16 adult facilities. Before mass testing, 15 of the 16 facilities had identified at least one COVID-19 case among incarcerated or detained persons using symptom-based testing, and mass testing increased the total number of known cases from 642 to 8,239. Case surveillance from symptom-based testing has likely underestimated SARS-CoV-2 prevalence in correctional and detention facilities. Broad-based testing can provide a more accurate assessment of prevalence and generate data to help control transmission (4).

Routine Screening in a California Jail : Effect of Local Policy on Identification of Syphilis in a High-Incidence Area, 2016-2017.

OBJECTIVES: California is experiencing a syphilis and congenital syphilis epidemic, and many persons diagnosed with syphilis report a history of recent incarceration or sexual contact with a person who has recently been incarcerated. Fresno County's local health department and jail collaborated to implement a routine syphilis screening policy for male adults aged 18-30 and female adults aged 18-35 booked into the facility. We evaluated syphilis screening, case finding, and treatment rates after implementation of the new policy. METHODS: We linked jail census and laboratory data to syphilis surveillance data to assess screening coverage, positivity, and treatment rates for age-eligible persons who were booked into Fresno County Jail from April 1, 2016, through December 31, 2017. RESULTS: Of 24 045 age-eligible persons who were booked into the jail during the study period, 5897 (24.5%) were female and 18 148 (75.5%) were male. Of 7144 (29.7%) persons who were screened for syphilis, 611 (8.6%) had a reactive rapid plasma reagin blood test result (16.4% [253 of 1546] of female adults; 6.4% [358 of 5598] of male adults) and 238 (3.3%) were newly diagnosed with syphilis, as confirmed by matching to the surveillance system (6.9% [106 of 1546] of female adults; 2.4% [132 of 5598] of male adults). Of persons identified with syphilis, 51.7% (n = 123 of 238) received adequate recommended treatment (59.4% [63 of 106] of female adults; 45.5% [60 of 132] of male adults). CONCLUSIONS: The age-based syphilis screening policy adopted in this jail yielded high positivity, including newly identified syphilis infections among female adults of childbearing age. The targeted screening policy was formalized in the county-negotiated contract with the jail's private correctional health care company in 2018-a strategy that can be replicated.

Gaps in Chlamydia Treatment Within California Family Planning Clinics: Are Patients Filling Prescriptions?

BACKGROUND: Compared with receiving medication dispensed in a health center, patients receiving prescriptions must take additional steps for treatment. Few clinics have protocols for ensuring prescriptions are filled. This study evaluated prescription fill rates for chlamydia treatment based on claims data in California Title X clinics and examined fill rates by patient demographics and clinic type. METHODS: We collected treatment information during Title X site audits for a convenience sample of patients with a positive chlamydia test between January 2008 and March 2013. We categorized patients as receiving treatment on-site versus via prescription and matched prescriptions to pharmacy billing claims within 90 days of test date. We examined treatment rates by patient age, gender, and race/ethnicity, and by clinic type, and assessed the median time to treatment. RESULTS: Among 790 patients diagnosed with chlamydia across 79 clinics, 65% (n = 513) were treated on-site and 33% (n = 260) via prescription; 17 (2%) did not have treatment information. Sixty-seven percent of prescriptions had confirmed receipt of treatment. Prescription fill rates were lower for patients age 18 years and younger (47% vs. 71%, P < 0.01) and for patients attending federally qualified health centers compared with stand-alone family planning clinics (63% vs. 88%, P < 0.01). Median time to treatment was similar for patients treated on-site (5 days) or via prescription (4 days). CONCLUSIONS: Delays in chlamydia treatment increase risk of complications and ongoing transmission. Providing medications on-site can improve treatment rates, especially among younger patients. These insights can inform clinic treatment protocols and efforts to improve quality of chlamydia care.

Characteristics Associated With Delivery of an Infant With Congenital Syphilis and Missed Opportunities for Prevention-California, 2012 to 2014.

BACKGROUND: Congenital syphilis (CS), the transmission of Treponema pallidum from mother to fetus during pregnancy, can cause adverse birth outcomes. In 2012 to 2014, the CS rate in California increased more than 200% from 6.6 to 20.3 cases per 100,000 live births. Our objectives were to identify characteristics associated with delivering an infant with CS and missed opportunities for prevention among syphilis-infected pregnant women in California. METHODS: We linked California Department of Public Health syphilis surveillance records from women aged 15 to 45 years-diagnosed from March 13, 2012, to December 31, 2014-to birth records. We compared characteristics among mothers who delivered an infant with CS (CS mothers) with mothers who delivered an infant without CS (non-CS mothers) by using χ or Fisher exact tests. To visualize gaps in prevention among syphilis-infected pregnant women, we constructed a CS prevention cascade, a figure that shows steps to prevent CS. RESULTS: During the selected period, 2498 women were diagnosed as having syphilis, and 427 (17%) linked to birth records; 164 (38%) were defined as CS mothers and 263 (62%) as non-CS mothers. Mothers with CS were more likely than non-CS mothers to have their first prenatal care visit in the third trimester. High proportions of mothers in both groups reported high-risk sexual behaviors, methamphetamine use, or incarceration (13%-29%). The CS prevention cascade showed decrements of 5% to 11% in prenatal care receipt, testing, and treatment steps; only 62% of potential CS births were prevented. CONCLUSIONS: Multifaceted efforts are needed to address gaps in the CS prevention cascade and reduce CS cases in California.

How Good Is Your Rule of Thumb? Validating Male-to-Female Case Ratio as a Proxy for Men Who Have Sex With Men Involvement in N. gonorrhoeae Incidence at the County Level.

BACKGROUND: Lacking information on men who have sex with men (MSM) for most reported cases, sexually transmitted disease (STD) programs in the United States have used crude measures such as male-to-female case ratios (MFCR) as a rule of thumb to gauge MSM involvement at the local level, primarily with respect to syphilis cases in the past. Suitability of this measure for gonorrhea incidence has not previously been investigated. METHODS: A random sample of gonorrhea cases reported from January 2010 through June 2013 were interviewed in selected counties participating in the STD Surveillance Network to obtain gender of sex partners and history of transactional sex. Weighted estimates of proportion of cases among MSM and proportion reporting transactional sex were developed; correlation between MFCR and proportion MSM was assessed. RESULTS: Male-to-female case ratio ranged from 0.66 to 8.7, and the proportion of cases occurring among MSM varied from 2.5% to 62.3%. The MFCR was strongly correlated with proportion of cases among MSM after controlling for transactional sex (Pearson partial r = 0.754, P < 0.0001). CONCLUSIONS: Male-to-female case ratio for gonorrhea at the county level is a reliable proxy measure indicating MSM involvement in gonorrhea case incidence and should be used by STD programs to tailor their programmatic mix to include MSM-specific interventions.

Contraceptive Method Use and Chlamydia Positivity Among California Family Planning Clients: The Case for New Multipurpose Prevention Technologies.

BACKGROUND: Adolescent girls and young women experience high rates of sexually transmitted infection (STI) with currently available contraceptive methods, yet few studies examine the burden of chlamydial infection by contraceptive method used. MATERIALS AND METHODS: In this cross-sectional analysis, we linked July 2012-June 2013 claims from a publicly-funded family planning program in California to chlamydia laboratory test results. Female clients were classified by the most effective contraceptive method reported by providers during the year: tier 1 (high-efficacy permanent or long-acting reversible methods), tier 2 (shorter-acting hormonal methods), or tier 3 (barrier methods, emergency contraception, or natural family planning). In addition, we identified clients who received condoms from providers. We used log-binomial models to estimate adjusted prevalence ratios comparing chlamydia positivity by contraceptive method(s). RESULTS: Of 74,636 female clients of ages 15-29 years with chlamydia test results, 5.1% had at least one positive test during the year. Chlamydia positivity was highest among tier 2 users (5.3%) compared with 4.5% and 4.9% among tiers 1 and 3 users, respectively (p < 0.001). Positivity was higher among clients who received condoms from providers than those who did not (6.3% vs. 4.3%, p < 0.001). In adjusted analyses, there were no significant differences in positivity by contraceptive tier. However, clients who received condoms had 1.32 (95% confidence interval: 1.24-1.40) times the positivity of those who did not. CONCLUSIONS: We found high chlamydia positivity among young female family planning clients regardless of contraceptive method. The development and provision of additional Multipurpose Prevention Technologies that confer protection against both pregnancy and STIs may help to address unmet need for STI prevention.

Increases in the Rate of Neisseria gonorrhoeae Among Gay, Bisexual and Other Men Who Have Sex With Men-Findings From the Sexually Transmitted Disease Surveillance Network 2010-2015.

BACKGROUND: Inequalities in Neisseria gonorrhoeae (gonorrhea) burden by sexual minority status in the United States are difficult to quantify. Sex of sex partner is not routinely collected for reported cases. Population estimates of men who have sex with men (MSM) necessary to calculate case rates have not been available until recently. For these reasons, trends in reported gonorrhea rates among MSM have not been described across multiple jurisdictions. METHODS: We estimated of the number of MSM cases reported in 6 jurisdictions continuously participating in the STD Surveillance Network 2010-2015 based on interviews with a random sample of cases. Data were obtained for Baltimore, Philadelphia, New York City, San Francisco, California (excluding San Francisco), and Washington State. Estimates of the MSM, heterosexual male (MSW) and female populations were obtained from recently published estimates and census data. Case rates and rate-ratios were calculated comparing trends in reported cases among MSM, heterosexual males and women. RESULTS: The proportion of male gonorrhea cases among MSM varied by jurisdiction (range: 20% to 98%). Estimated MSM rate increased from 1369 cases per 100,000 in 2010 to 3435 cases per 100,000 in 2015. Between 2010 and 2015, the MSM-to-Women gonorrhea rate ratio increased from 13:1 to 24:1, and the MSM-to-MSW gonorrhea rate ratio increased from 16:1 to 31:1. CONCLUSIONS: Estimated gonorrhea rate among MSM increased in a network of 6 geographically diverse US jurisdictions. Estimating the size of this population, determining MSM among reported cases and estimating rates are essential first steps for better understanding the changing epidemiology of gonorrhea.

Ocular Syphilis - Eight Jurisdictions, United States, 2014-2015.

Ocular syphilis, a manifestation of Treponema pallidum infection, can cause a variety of ocular signs and symptoms, including eye redness, blurry vision, and vision loss. Although syphilis is nationally notifiable, ocular manifestations are not reportable to CDC. Syphilis rates have increased in the United States since 2000. After ocular syphilis clusters were reported in early 2015, CDC issued a clinical advisory (1) in April 2015 and published a description of the cases in October 2015 (2). Because of concerns about an increase in ocular syphilis, eight jurisdictions (California, excluding Los Angeles and San Francisco, Florida, Indiana, Maryland, New York City, North Carolina, Texas, and Washington) reviewed syphilis surveillance and case investigation data from 2014, 2015, or both to ascertain syphilis cases with ocular manifestations. A total of 388 suspected ocular syphilis cases were identified, 157 in 2014 and 231 in 2015. Overall, among total syphilis surveillance cases in the jurisdictions evaluated, 0.53% in 2014 and 0.65% in 2015 indicated ocular symptoms. Five jurisdictions described an increase in suspected ocular syphilis cases in 2014 and 2015. The predominance of cases in men (93%), proportion of those who are men who have sex with men (MSM), and percentage who are HIV-positive (51%) are consistent with the epidemiology of syphilis in the United States. It is important for clinicians to be aware of potential visual complications related to syphilis infections. Prompt identification of potential ocular syphilis, ophthalmologic evaluation, and appropriate treatment are critical to prevent or manage visual symptoms and sequelae of ocular syphilis.

Comparison of sidestream treatment technologies: post aerobic digestion and Anammox.

Post aerobic digestion (PAD) and anaerobic ammonium oxidation (Anammox) are sidestream treatment technologies which are both excellent options for the reduction of nitrogen recycled back to the liquid stream without the need for supplemental carbon or alkalinity. However, the achievement of this goal is where the similarities between the two technologies end. PAD is an advanced digestion process where aerobic digestion is designed to follow anaerobic digestion. Other benefits of PAD include volatile solids reduction, odor reduction, and struvite formation reduction. Anammox harnesses a specific species of autotrophic bacteria that can help achieve partial nitritation/deammonification. Other benefits of Anammox include lower energy consumption due to requiring less oxygen compared with conventional nitrification. This manuscript describes the unique benefits and challenges of each technology. Example installations are presented with a narrative of how and why the technology was selected. A whole plant simulator is used to compare and contrast the mass balances and net present value costs on an 'apples to apples' basis. The discussion includes descriptions of conditions under which each technology would potentially be the most beneficial and cost-effective against a baseline facility without sidestream treatment.

Occupational HIV Transmission Among Male Adult Film Performers - Multiple States, 2014.

In 2014, the California Department of Public Health was notified by a local health department of a diagnosis of acute human immunodeficiency virus (HIV) infection* and rectal gonorrhea in a male adult film industry performer, aged 25 years (patient A). Patient A had a 6-day history of rash, fever, and sore throat suggestive of acute retroviral syndrome at the time of examination. He was informed of his positive HIV and gonorrhea test results 6 days after his examination. Patient A had a negative HIV-1 RNA qualitative nucleic acid amplification test (NAAT)(†) 10 days before symptom onset. This investigation found that during the 22 days between the negative NAAT and being informed of his positive HIV test results, two different production companies directed patient A to have condomless sex with a total of 12 male performers. Patient A also provided contact information for five male non-work-related sexual partners during the month before and after his symptom onset. Patient A had additional partners during this time period for which no locating information was provided. Neither patient A nor any of his interviewed sexual partners reported taking HIV preexposure prophylaxis (PrEP). Contact tracing and phylogenetic analysis of HIV sequences amplified from pretreatment plasma revealed that a non-work-related partner likely infected patient A, and that patient A likely subsequently infected both a coworker during the second film production and a non-work-related partner during the interval between his negative test and receipt of his positive HIV results. Adult film performers and production companies, medical providers, and all persons at risk for HIV should be aware that testing alone is not sufficient to prevent HIV transmission. Condom use provides additional protection from HIV and sexually transmitted infections (STIs). Performers and all persons at risk for HIV infection in their professional and personal lives should discuss the use of PrEP with their medical providers.

Trends in Chlamydia Screening, Test Positivity, and Treatment Among Females in California Juvenile Detention Facilities, 2003-2014.

BACKGROUND: Juvenile detention facilities house adolescents at high risk for sexually transmitted diseases. Collaboration between health departments and juvenile detention authorities can provide routine, cost-efficient chlamydia screening and treatment to females with limited access to care. We describe trends in screening, positivity, treatment, and associated costs in a well-established juvenile detention chlamydia screening program. METHODS: In the California Chlamydia Screening Project, juvenile detention facilities in 12 counties collected quarterly aggregate data on female census and line-listed chlamydia test results and treatment data from fiscal year (FY) 2003-2004 to FY 2013-2014. Trends in the proportion of females screened, positivity, and treatment by age, race/ethnicity, and facility volume were evaluated by Cochran-Armitage test. The median cost of the program per chlamydia positive identified was compared by facility in FY 2013-2014. RESULTS: Data from 59,518 test records among juvenile females indicated high screening rates (75.1%-79.4%). Chlamydia positivity, although consistently high, decreased from 14.8% in 2003-2004 to 11.5% in 2013-2014 (P < 0.001). Documented treatment decreased (88.8% in 2005-2006 to 79.0% in 2013-2014, P < 0.001); of those treated, treatment within 7 days increased (80.1% in 2005-2006 to 88.8% in 2013-2014, P < 0.001). The median cost per chlamydia positive identified was $708 (interquartile range, $669-$894) and was lowest for facilities with high chlamydia positivity. CONCLUSIONS: The California Chlamydia Screening Project demonstrated consistently high rates of chlamydia screening and positivity among adolescent females while keeping costs low for high-volume facilities. Further improvement in timely treatment rates remains a challenge for extending the impact of screening in this high-risk population.

Patient-Reported Expedited Partner Therapy for Gonorrhea in the United States: Findings of the STD Surveillance Network 2010-2012.

BACKGROUND: Expedited partner therapy (EPT) has been shown to prevent reinfection in persons with gonorrhea and to plausibly reduce incidence. The Centers for Disease Control and Prevention recommends EPT as an option for treating sex partners of heterosexual patients. Few studies that examine how the reported use of this valuable intervention differs by patient and provider characteristics and by geography across multiple jurisdictions in the United States are currently available. METHODS: Case and patient interview data were obtained for a random sample of reported cases from 7 geographically disparate US jurisdictions participating in the Sexually Transmitted Disease (STD) Surveillance Network. These data were weighted to be representative of all reported gonorrhea cases in the 7 study sites. Patient receipt of EPT was estimated, and multivariate models were constructed separately to examine factors associated with receipt of EPT for heterosexuals and for men who have sex with men. RESULTS: Overall, 5.4% of patients diagnosed and reported as having gonorrhea reported receiving EPT to treat their sex partners. Heterosexual patients were more likely to have received EPT than men who have sex with men at 6.6% and 2.6% of patients, respectively. Receipt of EPT did not vary significantly by race, Hispanic ethnicity, or age for either group, although significant variation was observed in different provider settings, with patients from family planning/reproductive health and STD clinic settings more likely to report receiving EPT. Jurisdiction variations were also observed with heterosexual patients in Washington State most likely (35.5%), and those in New York City, Connecticut, and Philadelphia least likely to report receiving EPT (<2%). CONCLUSIONS: With the exception of one jurisdiction in the STD Surveillance Network actively promoting EPT use, patient-reported receipt of the intervention remains suboptimal across the network. Additional efforts to promote EPT, especially for patients diagnosed in private provider and hospital settings, are needed to realize the full potential of this valuable gonorrhea control intervention.

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

In 2007, five Emerging Infections Program (EIP) sites were funded to determine the feasibility of establishing a population-based surveillance system for monitoring the effect of human papillomavirus (HPV) vaccine on pre-invasive cervical lesions. The project involved active population-based surveillance of cervical intraepithelial neoplasia grades 2 and 3 and adenocarcinoma in situ as well as associated HPV types in women >18 years of age residing in defined catchment areas; collecting relevant clinical information and detailed HPV vaccination histories for women 18-39 years of age; and estimating the annual rate of cervical cancer screening among the catchment area population. The first few years of the project provided key information, including data on HPV type distribution, before expected effect of vaccine introduction. The project's success exemplifies the flexibility of EIP's network to expand core activities to include emerging surveillance needs beyond acute infectious diseases. Project results contribute key information regarding the impact of HPV vaccination in the United States.

Population-based trends in high-grade cervical lesions in the early human papillomavirus vaccine era in the United States.

BACKGROUND: 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. METHODS: From 2008 to 2012, 9119 cases of CIN2+ among 18- to 39-year-old residents of catchment areas in California, Connecticut, New York, and Oregon were reported to the HPV-IMPACT Project, a sentinel system for monitoring the population impact of HPV vaccine. Age-stratified CIN2+ incidence rates were calculated for each catchment. Annual cervical screening was estimated for California, New York, and Oregon catchments with administrative and survey data. The Cochran-Armitage test was used to examine trends. RESULTS: From 2008 to 2012, the incidence of CIN2+ significantly decreased among 18- to 20-year-olds (California, from 94 to 5 per 100,000 women; Connecticut, from 450 to 57 per 100,000 women; New York, from 299 to 43 per 100,000 women; and Oregon, from 202 to 37 per 100,000 women; Ptrend < .0001) and among 21- to 29-year-olds in Connecticut (from 762 to 589 per 100,000 women) and New York (from 770 to 465 per 100,000 women; Ptrend < .001); rates did not differ among 30- to 39-year-olds. During the same period, screening rates also declined, with the largest decreases among 18- to 20-year-olds (from 67% in Oregon to 88% in California) and with smaller declines among 21- to 29-year-olds (13%-27%) and 30- to 39-year-olds (3%-21%). CONCLUSIONS: The declines in CIN2+ detection in young women were likely due to reduced screening but could also reflect the impact of vaccination. These data illustrate challenges in interpreting CIN2+ ecologic trends in the new era of cervical cancer prevention and emphasize the importance of information such as HPV types detected in lesions to assess the impact of HPV vaccine on cervical precancers.

Failure of azithromycin 2.0 g in the treatment of gonococcal urethritis caused by high-level resistance in California.

We report a treatment failure to azithromycin 2.0 g caused by a urethral Neisseria gonorrhoeae isolate with high-level azithromycin resistance in California. This report describes the epidemiological case investigation and phenotypic and genetic characterization of the treatment failure isolate.

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

BACKGROUND: Human 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. METHODS: We 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. FINDINGS: We 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. INTERPRETATION: Our 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. FUNDING: The Canadian Institutes of Health Research.

Cytology and human papillomavirus co-test results preceding incident high-grade cervical intraepithelial neoplasia.

OBJECTIVE: High-risk HPV (hrHPV) and cytology co-testing is utilized for primary cervical cancer screening and for enhanced follow-up of women who are hrHPV-positive, cytology negative. However, data are lacking on the utility of this method to detect pre-cancer or cancer in community-based clinical practice. This study describes cytology and hrHPV results preceding high-grade cervical intraepithelial neoplasia, adenocarcinoma in situ, or cervical cancer (i.e., CIN2+) in an integrated health system employing routine co-testing among women aged 30 years and older. METHODS: We conducted a cross-sectional analysis of adult female members of Kaiser Permanente Northern California (KPNC) with incident CIN2+ between July 2008 and June 2009. The primary outcome was the proportions of cytologic diagnoses and hrHPV co-test results preceding a diagnosis of CIN2+. Cervical cytology and hrHPV testing results were abstracted from electronic medical records. RESULTS: Of 1283 CIN2+ cases among adult women, 880 (68.5%) were among women aged 30 years and older and 145/880 (16.5%, 95% CI 14.1-19.1) had only normal cytology during the 12 months prior to diagnosis. Furthermore, 133/880 (15.1%, 95% 12.9-17.7) were preceded by only normal cytology and persistent hrHPV infection (at least 2 positive hrHPV tests) during the 6-36 months preceding CIN2+ diagnosis. CONCLUSIONS: Incident CIN2+ is frequently preceded by normal cytology and persistent hrHPV infection among women aged 30 years and older; screening strategies that employ HPV testing and cytology may improve the detection of CIN2+ compared with cytology alone.