Prevention of respiratory virus transmission by resident memory CD8+ T cells.

An ideal vaccine both attenuates virus growth and disease in infected individuals and reduces the spread of infections in the population, thereby generating herd immunity. Although this strategy has proved successful by generating humoral immunity to measles, yellow fever and polio, many respiratory viruses evolve to evade pre-existing antibodies1. One approach for improving the breadth of antiviral immunity against escape variants is through the generation of memory T cells in the respiratory tract, which are positioned to respond rapidly to respiratory virus infections2-6. However, it is unknown whether memory T cells alone can effectively surveil the respiratory tract to the extent that they eliminate or greatly reduce viral transmission following exposure of an individual to infection. Here we use a mouse model of natural parainfluenza virus transmission to quantify the extent to which memory CD8+ T cells resident in the respiratory tract can provide herd immunity by reducing both the susceptibility of acquiring infection and the extent of transmission, even in the absence of virus-specific antibodies. We demonstrate that protection by resident memory CD8+ T cells requires the antiviral cytokine interferon-γ (IFNγ) and leads to altered transcriptional programming of epithelial cells within the respiratory tract. These results suggest that tissue-resident CD8+ T cells in the respiratory tract can have important roles in protecting the host against viral disease and limiting viral spread throughout the population.

[Immunity against SARS-CoV-2: walking to the vaccination]. / Inmunidad frente a SARS-CoV-2: caminando hacia la vacunación.

The coronavirus are a wide group of viruses among that the SARS-CoV-2 is included (family Coronaviridae, subfamily Coronavirinae, genus Betacoronavirus and subgenus Sarbecovirus). Its main structural proteins are the membrane (M), the envelope (E), the nucleocapsid (N) and spike (S). The immune response to SARS-CoV-2 involves the cellular and the humoral sides, with neutralizing antibodies fundamentally directed against the S antigen. Although the seroprevalence data are frequently assumed as protection markers, no necessarily they are. In Spain, it is estimated that, to assure the herd immunity, at least four-fifths of the population should be immunoprotected. Due the high fatality rate of COVID-19, the acquisition of the protection only by the natural infection it not assumable and other measures as the mass immunization are required. Currently, there are several vaccine prototypes (including life virus, viral vectors, peptides and proteins and nucleic acid) in different phase of clinical evaluation. Foreseeably, some of these news vaccines would be soon commercially available. In this text, aspects related to these issues are reviewed.

Geographical disparities in human papillomavirus herd protection.

BACKGROUND: Human papillomavirus (HPV) vaccination has occurred unequally across the United States, potentially contributing to uneven vaccine-type HPV prevalence between regions. We examined whether emerging vaccine-related herd protection exhibits regional differences among unvaccinated girls and women. METHODS: We evaluated the prevalence of vaginal HPV among women 14-59 years of age from 2003 to 2014 using repeated cross-sectional data from the National Health and Nutrition Examination Survey (NHANES). Women who provided an adequate vaginal swab sample were included. Vaginal prevalence of vaccine-type HPV (types 6, 11, 16, 18) were examined in four regions of the United States between 2003 and 2014. We examined vaccine-type HPV prevalence in 2007-2014 in each US census region among younger participants (14-34 years old) stratified by vaccination status to determine whether one or both groups contributed to uneven HPV prevalence. RESULTS: A total of 12 175 participants 14-59 years of age met inclusion criteria. Vaccine-type HPV prevalence decreased in all regions. Vaccine-type HPV varied by region only among unvaccinated 14-34 year olds, with a higher prevalence in the Midwest (13.8%, 95% confidence interval (CI): 10.7-17.0) and South (12.5%, 95% CI: 10.2-14.8) compared to the Northeast (8.9%, 95% CI: 6.5-11.2). No regional variation in vaccine-type HPV prevalence was observed among vaccinated participants. CONCLUSIONS: Higher prevalence of vaccine-type HPV among unvaccinated women in the South and Midwest may contribute to regional disparities in HPV-related cancer incidence, as emerging herd immunity may not be as strong in those regions.

Gender-neutral vaccination provides improved control of human papillomavirus types 18/31/33/35 through herd immunity: Results of a community randomized trial (III).

With optimal strategy, human papillomavirus (HPV) vaccines have the potential to control HPV. We have assessed vaccine efficacy (VE), herd effect (HE) of HPV vaccination and overall protective effectiveness (PE) against high-risk HPV infections by HPV type and vaccination strategy in a community-randomized trial using the bivalent HPV16/18 vaccine. We randomized 33 communities to gender-neutral HPV vaccination (Arm A), HPV vaccination of girls and hepatitis B-virus (HBV) vaccination of boys (Arm B) and gender-neutral HBV vaccination (Arm C). Entire 1992-1995 male (40,852) and female (39,420) birth cohorts were invited, and 11,662 males and 20,513 females vaccinated with 20-30% and 45% coverage in 2007-2010. During 2010-2014, 11,396 cervicovaginal samples were collected from 13,545 18.5-year-old attendees. HPV typing was performed by a high-throughput PCR. VE was calculated for HPV vaccinated women and HE for non-HPV-vaccinated women, using the HBV vaccinated, for HE all non-HPV vaccinated, Arm C women as controls. PE was calculated as coverage rate-weighted mean of VE + HE. HPV16/18/45 and 31/33/35 VEs varied between 86-94% and 30-66%, respectively. Only the gender-neutral vaccination provided significant HEs against HPV18 (61%) and HPV31 (72%) in the 1995 birth cohort-increased HEs against HPV33 (39%) and HPV35 (42%) were also observed. Due to the increased HEs, PEs for HPV16/18/45 and HPV31/33/35 were comparable in the gender-neutral arm 1995 birth cohort. High vaccine efficacy against HPV16/18/45 and, gender-neutral vaccination-enforced, herd effect against HPV18/31/33/35 by the bivalent vaccine rapidly provides comparable overall protective effectiveness against six oncogenic HPV types: 16/18/31/33/35/45.

Human papillomavirus vaccination and the role of herd effects in future cancer control planning: a review.

INTRODUCTION: Vaccine herd effects are the indirect protection that vaccinated persons provide to those who remain susceptible to infection, due to the reduced transmission of infections. Herd effects have been an important part of the discourse on how to best implement human papillomavirus (HPV) vaccines and prevent HPV-related diseases. AREAS COVERED: In this paper, we review the theory of HPV vaccine herd effects derived from mathematical models, give an account of observed HPV vaccine herd effects worldwide, and examine the implications of vaccine herd effects for future cervical cancer screening efforts. EXPERT COMMENTARY: HPV vaccine herd effects improve the cost-effectiveness of vaccinating preadolescent girls, but contribute to making gender-neutral vaccination less economically efficient. Vaccination coverage and sexual mixing patterns by age are strong determinants of herd effects. Many countries worldwide are starting to observe reductions in HPV-related outcomes likely attributable to herd effects, most notably declining anogenital warts in young men, and declining HPV-16/18 infection prevalence in young unvaccinated women. Policy makers making recommendations for cervical cancer screening will have to consider HPV vaccination coverage and herd effects, as these will affect the positive predictive value of screening and the risk of cervical cancer in unvaccinated women.

Differences between vaccinated and unvaccinated women explain increase in non-vaccine-type human papillomavirus in unvaccinated women after vaccine introduction.

The aim of this study was to determine whether an observed increase in non-vaccine-type human papillomavirus (HPV) in unvaccinated women during the first eight years after vaccine introduction may be explained by differences in demographics or sexual behaviors, instead of type replacement. We analyzed data from three cross-sectional surveillance studies of 13-26 year-old women (total N = 1180). For women recruited from a health department clinic, older age (OR = 1.4, 95% CI: 1.2-1.6) and consistent condom use with main partner in the past 3 months (OR = 11.6, 95% CI: 3.4-40) were associated with being unvaccinated. For women recruited from a teen health center African American race (OR = 0.2, 95% CI: 0.07-0.7) and having Medicaid health insurance (OR = 0.3, 95% CI: 0.1-0.7) were inversely associated with being unvaccinated. The observed increase in non-vaccine-type HPV prevalence in unvaccinated women may be explained by differences between unvaccinated and vaccinated women.

Population-Level Herd Protection of Males From a Female Human Papillomavirus Vaccination Program: Evidence from Australian Serosurveillance.

BACKGROUND: Australia instituted funded female human papillomavirus (HPV) immunization in 2007, followed by a targeted male vaccination program in 2013. To date, Australia is one of only several countries with a funded male HPV immunization program. In 2012-2013, we conducted a survey of HPV seroprevalence in males to assess whether or not a herd impact of female vaccination could be observed. METHODS: We conducted a cross-sectional study of de-identified residual diagnostic test serum samples from males aged 15-39 years from laboratories in 3 Australian states and calculated the proportion seropositive to HPV types 6, 11, 16, and 18. We compared type-specific results by age group against those from a baseline 2005 Australian HPV serosurvey. RESULTS: There were decreases in proportion seropositive for every HPV type across all age groups, many statistically significant. The largest decrease was observed for HPV-11, with decreases of 8- and 9-fold for ages 20-29 and 30-39 years, respectively. Despite substantial reductions in seroprevalence, at least 9% of males were seropositive for at least 1 of the 4 HPV types. CONCLUSIONS: This is the first serosurvey confirming broad population-level impact in males from female HPV vaccination. Our research may assist policy makers considering implementing HPV vaccination programs.

Different Challenges in Eliminating HPV16 Compared to Other Types: A Modeling Study.

Background: Human papillomavirus (HPV) vaccination is still not reaching many high-risk populations. HPV16/18 vaccines offer cross-protection against other types, for example, HPV45. Both direct vaccine efficacy and indirect herd protection contribute to vaccination effectiveness. Methods: We used a dynamic transmission model, calibrated to cervical screening data from Italy, to estimate vaccination effectiveness against HPV16 and HPV45 infection, assuming for HPV45 either 95% or lower cross-protection. Results: Basic reproductive number was smaller (2.1 vs 4.0) and hence vaccine effectiveness and herd protection stronger for HPV45 than for HPV16. The largest difference in the reduction of infection prevalence in women <35 years old was found at 70% coverage in girls-only vaccination programs (99% vs 83% for total protection for HPV45 and HPV16, respectively, mainly owing to stronger herd protection, ie, 37% vs 16%). In gender-neutral vaccination, the largest difference was at 40% coverage (herd protection, 54% vs 28% for HPV16 and HPV45, respectively). With ≥80% coverage, even 50% cross-protection would reduce HPV45 by ≥94%. Conclusions: The characteristics of individual high-risk HPV types strongly influence herd protection and determine the level of coverage and cross-protection required to reduce or eliminate the infection through HPV vaccination. HPV16 infection and related cancers are the most difficult to eliminate.

Human Papillomavirus Prevalence and Herd Immunity after Introduction of Vaccination Program, Scotland, 2009-2013.

In 2008, a national human papillomavirus (HPV) immunization program using a bivalent vaccine against HPV types 16 and 18 was implemented in Scotland along with a national surveillance program designed to determine the longitudinal effects of vaccination on HPV infection at the population level. Each year during 2009-2013, the surveillance program conducted HPV testing on a proportion of liquid-based cytology samples from women undergoing their first cervical screening test for precancerous cervical disease. By linking vaccination, cervical screening, and HPV testing data, over the study period we found a decline in HPV types 16 and 18, significant decreases in HPV types 31, 33, and 45 (suggesting cross-protection), and a nonsignificant increase in HPV 51. In addition, among nonvaccinated women, HPV types 16 and 18 infections were significantly lower in 2013 than in 2009. Our results preliminarily indicate herd immunity and sustained effectiveness of the bivalent vaccine on virologic outcomes at the population level.

Population-level impact, herd immunity, and elimination after human papillomavirus vaccination: a systematic review and meta-analysis of predictions from transmission-dynamic models.

BACKGROUND: Modelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta-analysis of model predictions of the long-term population-level effectiveness of vaccination against HPV 16, 18, 6, and 11 infection in women and men, to examine the variability in predicted herd effects, incremental benefit of vaccinating boys, and potential for HPV-vaccine-type elimination. METHODS: We searched MEDLINE and Embase for transmission-dynamic modelling studies published between Jan 1, 2009, and April 28, 2015, that predicted the population-level impact of vaccination on HPV 6, 11, 16, and 18 infections in high-income countries. We contacted authors to determine whether they were willing to produce new predictions for standardised scenarios. Strategies investigated were girls-only vaccination and girls and boys vaccination at age 12 years. Base-case vaccine characteristics were 100% efficacy and lifetime protection. We did sensitivity analyses by varying vaccination coverage, vaccine efficacy, and duration of protection. For all scenarios we pooled model predictions of relative reductions in HPV prevalence (RRprev) over time after vaccination and summarised results using the median and 10th and 90th percentiles (80% uncertainty intervals [UI]). FINDINGS: 16 of 19 eligible models from ten high-income countries provided predictions. Under base-case assumptions, 40% vaccination coverage and girls-only vaccination, the RRprev of HPV 16 among women and men was 0·53 (80% UI 0·46-0·68) and 0·36 (0·28-0·61), respectively, after 70 years. With 80% girls-only vaccination coverage, the RRprev of HPV 16 among women and men was 0·93 (0·90-1·00) and 0·83 (0·75-1·00), respectively. Vaccinating boys in addition to girls increased the RRprev of HPV 16 among women and men by 0·18 (0·13-0·32) and 0·35 (0·27-0·39) for 40% coverage, and 0·07 (0·00-0·10) and 0·16 (0·01-0·25) for 80% coverage, respectively. The RRprev were greater for HPV 6, 11, and 18 than for HPV 16 for all scenarios investigated. Finally at 80% coverage, most models predicted that girls and boys vaccination would eliminate HPV 6, 11, 16, and 18, with a median RRprev of 1·00 for women and men for all four HPV types. Variability in pooled findings was low, but increased with lower vaccination coverage and shorter vaccine protection (from lifetime to 20 years). INTERPRETATION: Although HPV models differ in structure, data used for calibration, and settings, our population-level predictions were generally concordant and suggest that strong herd effects are expected from vaccinating girls only, even with coverage as low as 20%. Elimination of HPV 16, 18, 6, and 11 is possible if 80% coverage in girls and boys is reached and if high vaccine efficacy is maintained over time. FUNDING: Canadian Institutes of Health Research.

Gender-neutrality, herd effect and resilient immune response for sustainable impact of HPV vaccination.

PURPOSE OF REVIEW: This review summarize the impact of various strategies of human papillomavirus (HPV) vaccination, such as vaccinating only girls or both girls and boys. RECENT FINDINGS: Slow and inefficient implementation of HPV vaccination programmes has delayed the impact of the first human cancer vaccine. Vaccinating only girls, with a rather low coverage, has led to a limited herd effect and, thus, not full use of the HPV vaccine potential. SUMMARY: Gender-neutral vaccination based on comparative effectiveness research will hopefully soon tackle the whole spectrum of HPV cancers in both sexes. The remaining challenges are how to ensure resilience of HPV vaccine-induced immunity and herd effect to guarantee population-level impact of HPV vaccination, and how to guard against HPV type replacement.

Characteristics of a cluster-randomized phase IV human papillomavirus vaccination effectiveness trial.

High-risk human papillomaviruses (hrHPV) cause anogenital and oropharyngeal cancers. HPV-16/18 virus-like particle vaccine formulated with an AS04 adjuvant is very efficacious against hrHPV associated precancers but the herd effects of different vaccination scenarios are not known. Our cluster randomized trial (NCT00534638) assesses the overall and herd effects of vaccinating girls vs. girls and boys. In two school-years (2007-2008 and 2008-2009) we invited 80,272 1992-1995 born early adolescents to a CRT in 33 communities a priori stratified by low, intermediate and high HPV-16/18 seroprevalence. In 11 Arm A communities 90% of participating girls and boys were assigned to receive HPV-16/18 vaccine, in 11 Arm B communities 90% of girls were assigned to receive HPV-16/18 vaccine - boys were assigned to receive hepatitis B-virus (HBV) vaccine, and in 11 Arm C communities all were assigned to receive HBV-vaccine. Prevalence of HPV in vaccinated and unvaccinated girls is studied at age 18.5 years. Recruitment resulted in equal enrolment of four birth cohorts (born 1992-1995) comprising altogether 32,175 (40% response) early adolescents: 20,514 girls (50.5-53.0% response by arm) and 11,661 boys (21.9-31.6%% response by arm). At the age of 15 years, 79.3% of the vaccinees completed a questionnaire. Among them >98% were living at, and during the week-ends 1.3-1.6% stayed outside, the study site communities. Smoking habit and alcohol consumption were similar in the different trial arms, also mean-age of menarche (12.4 years) and 1st ejaculation (12.6 years), and sexual behaviour (among those <25%, who had had sexual debut) did not differ by arm: mean-age at the sexual debut 14.3 and 14.4 in girls and boys, and proportions of those with multiple (≥5) life-time sexual partners (6.5-7.5%) at the age of 15 years. Uniform residential, life-style and sexual behaviour characteristics indicate successful randomization/enrolment of the CRT. Our CRT will verify modelled predictions on up to 31% herd effect of vaccinating both girls and boys with moderate vaccine coverage - quantifying overall effectiveness of different strategies which will soon guide how to implement HPV vaccination.

Assessment of herd immunity and cross-protection after a human papillomavirus vaccination programme in Australia: a repeat cross-sectional study.

BACKGROUND: After the introduction of a quadrivalent human papillomavirus (HPV) vaccination programme in Australia in April, 2007, we measured the prevalence of vaccine-targeted and closely related HPV types with the aim of assessing direct protection, cross-protection, and herd immunity. METHODS: In this repeat cross-sectional study, we recruited women aged 18-24 years who attended Pap screening between October, 2005, and July, 2007, in three major metropolitan areas of Australia to form our prevaccine-implementation sample. For our postvaccine-implementation sample, we recruited women aged 18-24 years who attended Pap screening in the same three metropolitan areas from August, 2010, to November, 2012. We compared the crude prevalence of HPV genotypes in cervical specimens between the prevaccine and the postvaccine implementation groups, with vaccination status validated against the National HPV Vaccination Program Register. We estimated adjusted prevalence ratios using log linear regression. We estimated vaccine effectiveness both for vaccine-targeted HPV types (16, 18, 6, and 11) and non-vaccine but related HPV types (31, 33, and 45). FINDINGS: 202 women were recruited into the prevaccine-implementation group, and 1058 were recruited into the postvaccine-implementation group. Crude prevalence of vaccine-targeted HPV genotypes was significantly lower in the postvaccine-implementation sample than in the prevaccine-implementation sample (58 [29%] of 202 vs 69 [7%] of 1058; p<0·0001). Compared with the prevaccine-implementation sample, adjusted prevalence ratios for vaccine-targeted HPV genotypes were 0·07 (95% CI 0·04-0·14; p<0·0001) in fully vaccinated women and 0·65 (0·43-0·96; p=0·03) in unvaccinated women, which suggests herd immunity. No significant declines were noted for non-vaccine-targeted HPV genotypes. However, within the postvaccine-implementation sample, adjusted vaccine effectiveness against vaccine-targeted HPV types for fully vaccinated women compared with unvaccinated women was 86% (95% CI 71-93), and was 58% (26-76) against non-vaccine-targeted but related genotypes (HPV 31, 33, and 45). INTERPRETATION: 6 years after the initiation of the Australian HPV vaccination programme, we have detected a substantial fall in vaccine-targeted HPV genotypes in vaccinated women; a lower prevalence of vaccine-targeted types in unvaccinated women, suggesting herd immunity; and a possible indication of cross-protection against HPV types related to the vaccine-targeted types in vaccinated women. FUNDING: Australian National Health and Medical Research Council and Cancer Council Victoria.

Analysis of risk-structured vaccination model for the dynamics of oncogenic and warts-causing HPV types.

A new deterministic model is designed and used to assess the community-wide impact of mass vaccination of new sexually active individuals on the dynamics of the oncogenic and warts-causing HPV types. Rigorous qualitative analyses of the model, which incorporates the two currently available anti-HPV vaccines, reveal that it undergoes competitive exclusion when the reproduction of one HPV risk type (low/high) exceeds unity, while that of the other HPV risk type is less than unity. For the case when the reproduction numbers of the two HPV risk types (low/high) exceed unity, the two risk types co-exist. It is shown that the sub-model with the low-risk HPV types only has at least one endemic equilibrium whenever the associated reproduction threshold exceeds unity. Furthermore, this sub-model undergoes a re-infection-induced backward bifurcation under certain conditions. In the absence of the re-infection of recovered individuals and cancer-induced mortality in males, the associated disease-free equilibrium of the full (risk-structured) model is shown to be globally asymptotically stable whenever the reproduction number of the model is less than unity (that is, the full model does not undergo backward bifurcation under this setting). It is shown, via numerical simulations, that the use of the Gardasil vaccine could lead to the effective control of HPV in the community if the coverage rate is in the range of 73-95 % (84 %). If 70 % of the new sexually active susceptible females are vaccinated with the Gardasil vaccine, additionally vaccinating 34-56 % (45 %) of the new sexually active susceptible males can lead to the effective community-wide control (or elimination) of the HPV types.

Herd immunity effect of the HPV vaccination program in Australia under different assumptions regarding natural immunity against re-infection.

Deterministic dynamic compartmental transmission models (DDCTMs) of human papillomavirus (HPV) transmission have been used in a number of studies to estimate the potential impact of HPV vaccination programs. In most cases, the models were built under the assumption that an individual who cleared HPV infection develops (life-long) natural immunity against re-infection with the same HPV type (this is known as SIR scenario). This assumption was also made by two Australian modelling studies evaluating the impact of the National HPV Vaccination Program to assist in the health-economic assessment of male vaccination. An alternative view denying natural immunity after clearance (SIS scenario) was only presented in one study, although neither scenario has been supported by strong evidence. Some recent findings, however, provide arguments in favour of SIS. We developed HPV transmission models implementing life-time (SIR), limited, and non-existent (SIS) natural immunity. For each model we estimated the herd immunity effect of the ongoing Australian HPV vaccination program and its extension to cover males. Given the Australian setting, we aimed to clarify the extent to which the choice of model structure would influence estimation of this effect. A statistically robust and efficient calibration methodology was applied to ensure credibility of our results. We observed that for non-SIR models the herd immunity effect measured in relative reductions in HPV prevalence in the unvaccinated population was much more pronounced than for the SIR model. For example, with vaccine efficacy of 95% for females and 90% for males, the reductions for HPV-16 were 3% in females and 28% in males for the SIR model, and at least 30% (females) and 60% (males) for non-SIR models. The magnitude of these differences implies that evaluations of the impact of vaccination programs using DDCTMs should incorporate several model structures until our understanding of natural immunity is improved.

Inmunidad colectiva contra la rubéola según una encuesta poblacional en Medellín, Colombia / Herd immunity against rubella according to a survey of the population in Medellin, Colombia

Objetivo. Calcular la proporción crítica (Pc) para el logro de la inmunidad colectiva a partir de un estudio poblacional realizado en el 2009 en Medellín, Colombia, por edad, en forma global y desagregada por sexo, zona de procedencia y estrato socioeconómico. Métodos. Se realizó una encuesta de seroprevalencia poblacional, con una muestra aleatoria de 2 124 individuos de 6 a 64 años, representativa por edad, sexo y zona. Se estimó el número básico de reproducción utilizando una regresión cuadrática de los títulos promedio de IgG contra la rubéola por edad en los individuos no vacunados con títulos mayores o iguales a 15 UI/ml. Se calculó el número efectivo de reproducción (Re ) con los datos de la proporción ponderada de protección por edad, sexo, zona y estrato socioeconómico. Resultados. En forma global, la Pc fue de 90,0% (IC95% 88,6­95,2) y el Re de 0,95 (IC95% 0,8­1,8), para una proporción ponderada de protección de 89,4% (IC95% 86,8­91,6). La protección fue menor que la Pc esperada en ambos sexos, en los estratos socioeconómicos alto y bajo, y en la zona rural. En la zona urbana la protección fue mayor que la Pc (89,4%, IC95% 86,6­91,7 en comparación con 87,4%, IC95% 85,2­87,8). Conclusiones. En la zona urbana se ha avanzado hacia la inmunidad colectiva, pero se requiere aumentar la proporción de protección en forma global, en las mujeres, en la zona rural y en los individuos de estrato socioeconómico alto. El número efectivo puede tener un valor mayor de uno, lo que indica el potencial de propagación de la enfermedad.

Objective. Calculate the critical proportion (Pc ) for achieving herd immunity based on a 2009 population study conducted in Medellin, Colombia, by age, globally and disaggregated by sex, location, and socioeconomic stratum. Methods. A survey of seroprevalence in the population was conducted by means of a random sample of 2 124 individuals aged 6 to 64 that was representative of age, sex, and location. The basic reproduction number was estimated using a quadratic regression of the average IgG titers for rubella by age in unvaccinated individuals with titers greater than or equal to 15 IU/ml. The effective reproduction number (Re) was calculated with the data on the weighted proportion of protection by age, sex, location, and socioeconomic stratum. Results. Overall, the Pc was 90.0% (95% CI, 88.6­95.2%) and the Re was 0.95 (95% CI, 0.8­1.8), for a weighted proportion of protection of 89.4% (95% CI, 86.8­ 91.6%). Protection was lower than the expected Pc in both sexes, in high and low socioeconomic strata, and in the rural area. In the urban area, protection was greater than the Pc (89.4%, with a 95% CI, 86.6­91.7%, compared to 87.4% and a 95% CI, 85.2­87.8%). Conclusions. The urban area has made progress toward herd immunity, but the overall proportion of protection in women, the rural area, and the high socioeconomic strata must be increased. The effective number may be greater than one, indicating the potential for the spread of the disease.

Vaccine-type human papillomavirus and evidence of herd protection after vaccine introduction.

OBJECTIVES: The aims of this study were to compare prevalence rates of human papillomavirus (HPV) in young women before and after HPV vaccine introduction to determine the following: (1) whether vaccine-type HPV infection decreased, (2) whether there was evidence of herd protection, and (3) whether there was evidence for type-replacement (increased prevalence of nonvaccine-type HPV). METHODS: Young women 13 to 26 years of age who had had sexual contact were recruited from 2 primary care clinics in 2006-2007 for a prevaccination surveillance study (N = 368, none were vaccinated) and 2009-2010 for a postvaccination surveillance study (N = 409, 59% were vaccinated). Participants completed a questionnaire and were tested for cervicovaginal HPV DNA. HPV prevalence rates were compared in the pre- versus postsurveillance studies by using χ(2) tests. Propensity score weighting was used to balance differences in covariates between the 2 surveillance studies. RESULTS: The mean age was ∼19 years for both groups of participants and most were African American and non-Hispanic. After propensity score weighting, the prevalence rate for vaccine-type HPV decreased substantially (31.7%-13.4%, P < .0001). The decrease in vaccine-type HPV not only occurred among vaccinated (31.8%-9.9%, P < .0001) but also among unvaccinated (30.2%-15.4%, P < .0001) postsurveillance study participants. Nonvaccine-type HPV increased (60.7%-75.9%, P < .0001) for vaccinated postsurveillance study participants. CONCLUSIONS: Four years after licensing of the quadrivalent HPV vaccine, there was a substantial decrease in vaccine-type HPV prevalence and evidence of herd protection in this community. The increase in nonvaccine-type HPV in vaccinated participants should be interpreted with caution but warrants further study.