Objectives

Patient-initiated partner STI notification, i.e., patients informing their sexual partners of diagnosis, is a cornerstone of STI prevention. Growing evidence suggests that women exposed to intimate partner violence (IPV) may fear such notification, or face negative consequences in response to STI disclosure. The current study assessed associations of IPV with fear of partner STI notification, and experiences of partner STI notification, among adolescent and young adult female family planning clinic patients.

Methods

Females patients ages 16–29 years in five family planning clinics in Northern California (n=1282) participated in a cross-sectional survey.

Results

History of physical or sexual IPV was associated with fear of partner STI notification. Moreover, participants exposed to IPV were more likely to have partners say it was not from them or otherwise accuse them of cheating in response to STI notification. Such partners were less likely to seek indicated STI treatment or testing.

Conclusions

Current findings suggest that STI partner notification may be compromised by IPV. Clinical practices and policies to support effective partner STI notification should include IPV assessment, and provide mechanisms to address related fears concerning partner notification.

In England, during pandemic 2009 H1N1, vaccine efficacy and immunogenicity population studies in priority groups were rolled out in parallel to evaluate the pandemic vaccination programme. This provided a unique opportunity to compare immunogenicity and clinical protection in the same population and thus provide insights into the correlates of protection for the pandemic H1N1 2009 vaccine in risk groups. While clinical protection from AS03-adjuvanted pandemic 2009 H1N1 vaccine was high in those aged <25 years and pregnant women, effectiveness in older adults with chronic conditions has been found to be surprisingly poor. Here we present results from the immunogenicity study derived from the same population. Individuals from priority groups eligible for pandemic vaccination attending participating general practices were recruited. Pre and post-vaccination blood samples were collected and HI antibody testing to assess immune response to vaccination performed. The final cohort consisted of 610 individuals: 60 healthy children aged <5 years; 32 healthy pregnant women; 518 individuals from risk groups. Seroconversion rate in healthy children aged <5 years (87%, 95% CI: 75% to 94%) was higher than that of risk groups combined (65%, 95% CI: 61% to 69%) (p<0.001). Multivariable analysis of risk groups showed that the size of response in those who did seroconvert was lower in those who received the 2009/10 seasonal TIV (Fold effect: 0.52, 0.35 to 0.78). Predicted immunological boosting from higher pre-vaccine titres after 2009 pandemic H1N1 vaccination only occurred in children (seroconversion rate = 92%) and not in individuals aged 10 to 39 from risk groups (seroconversion rate = 74%). The lack of clinical protection identified in the same population in older adults from risk groups could be attributed to these lower seroresponses. Current immunogenicity licensing criteria for pandemic influenza vaccine may not correlate with clinical protection in individuals with chronic disease or immunocompromised.

Adolescent sexual activity involving three or more people is an emerging public health concern. The goal of this exploratory, cross-sectional study was to describe the prevalence, correlates, and context of multiple-person sex among a sample of adolescent females seeking health care from an urban clinic. Because sex involving multiple people may either be consensual (i.e., “three-ways” or “group sex”) or forced (i.e., “gang rape”), we use the term “multi-person sex” (MPS) to encompass these experiences. Subjects were 328 females, ages 14–20 years old, who utilized a Boston-area community- or school-based health clinic between April and December of 2006, and completed an anonymous survey using computer-assisted self-interview software. Overall, 7.3% reported ever having had a MPS experience. Of these, 52% reported ever being pressured to engage in MPS and 43% reported ever being threatened or forced. Condom nonuse by at least one male participant in the most recent MPS was reported by 45%. Controlling for potential demographic confounders, MPS was associated with cigarette smoking (adjusted prevalence ratio [APR], 3.83; 95% confidence interval [CI], 1.56–9.44), sexual initiation prior to age 15 (APR, 2.50; 95% CI, 1.04–5.98), ever being diagnosed with an STI (APR, 2.55; 95% CI, 1.08–6.03), dating violence victimization (APR, 4.43; 95% CI, 1.68–11.69), childhood sexual abuse victimization (APR, 4.30; 95% CI, 1.83–10.07) and past-month pornography exposure (APR, 4.79; 95% CI, 1.91–11.98). Additional study of the perpetration and prevention of adolescent MPS is urgently needed.

While teen pregnancy rates appear to be declining in the USA overall, the rate of decline among young Latinas has been less than other ethnic groups. Among the myriad factors associated with elevated pregnancy rates, for Latina girls living in the inner city, exposure to gang and community violence may be a critical context for increased pregnancy risk. This study explores the relationship between gang involvement and reproductive health, and the pathways through which childhood, family, and relationship violence exposure may lead to unintended pregnancy. Interviews of 20 young adult Latinas with known gang involvement in Los Angeles County were audiotaped, transcribed, and coded for key themes related to violence exposure and reproductive health. Limited access to reproductive health care compounded by male partner sexual and pregnancy coercion, as well as physical and sexual violence, emerged in the interviews. Exposures to interparental domestic violence, childhood physical and sexual abuse, and gang violence were prominent and closely associated with unhealthy and abusive intimate relationships. Adverse childhood experiences and exposure to partner, family, and community violence impact the reproductive lives and choices of young Latina women in gangs. These findings may guide targeted pregnancy prevention efforts among urban gang-affiliated Latinas as well as encourage the integration of sexual violence prevention and reproductive health promotion within gang violence intervention programs.

Nonvaccine serotypes occur more often among children with comorbid conditions.

We assessed known risk factors, clinical presentation, and outcome of invasive pneumococcal disease (IPD) in children 3–59 months of age after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in England and Wales. During September 2006–March 2010, a total of 1,342 IPD episodes occurred in 1,332 children; 14.9% (198/1,332) had comorbidities. Compared with IPD caused by PCV7 serotypes (44/248; 17.7%), comorbidities were less common for the extra 3 serotypes in the 10-valent vaccine (15/299; 5.0%) but similar to the 3 additional PCV13 serotypes (45/336; 13.4%) and increased for the 11 extra serotypes in 23-valent polysaccharide vaccine (PPV23) (39/186; 21.0%) and non-PPV23 serotypes (38/138; 27.5%). Fifty-two (3.9%) cases resulted from PCV7 failure; 9 (0.7%) case-patients had recurrent IPD. Case-fatality rate was 4.4% (58/1,332) but higher for meningitis (11.0%) and children with comorbidities (9.1%). Thus, comorbidities were more prevalent in children with IPD caused by non-PCV13 serotypes and were associated with increased case fatality.

The intense influenza activity in England during the 2010–11 winter resulted from a combination of factors. Population-based seroepidemiology confirms that the third wave of influenza A(H1N1)pdm09 virus circulation was associated with a shift in age groups affected, with the highest rate of infection in young adults.

Background

Mental disorders may increase the risk of physical violence among married couples.

Aims

To estimate associations between premarital mental disorders and marital violence in a cross-national sample of married couples.

Method

A total of 1821 married couples (3642 individuals) from 11 countries were interviewed as part of the World Health Organization's World Mental Health Survey Initiative. Sixteen mental disorders with onset prior to marriage were examined as predictors of marital violence reported by either spouse.

Results

Any physical violence was reported by one or both spouses in 20% of couples, and was associated with husbands' externalising disorders (OR = 1.7, 95% CI 1.2-2.3). Overall, the population attributable risk for marital violence related to premarital mental disorders was estimated to be 17.2%.

Conclusions

Husbands' externalising disorders had a modest but consistent association with marital violence across diverse countries. This finding has implications for the development of targeted interventions to reduce risk of marital violence.

Eukaryotic secretory proteins exit the endoplasmic reticulum via transport vesicles generated by the essential COPII coat proteins. The outer coat complex, Sec13-Sec31, forms a scaffold that is thought to enforce curvature. By exploiting yeast bypass-of-sec-thirteen (bst) mutants, where Sec13p is dispensable, we probed the relationship between a compromised COPII coat and the cellular context in which it could still function. Genetic and biochemical analyses suggested that Sec13p was required to generate vesicles from membranes that contained asymmetrically distributed cargoes that were likely to confer opposing curvature. Thus Sec13p may rigidify the COPII cage and increase its membrane-bending capacity; this function could be bypassed when a bst mutation renders the membrane more deformable.

Purpose

To estimate the proportion of U.S. parents who talked about dating abuse (DA) with their adolescent children in the past year, and explore reasons for not talking about DA among those who did not.

Methods

500 parents of 11–18 year old children were assessed via a national online survey.

Results

55% of parents had discussed DA with their children in the past year. Mothers were more likely than fathers to discuss DA with both male and female children (59.0% vs. 50.2%, p<.05). Parents' age, income, and region of the U.S. were not related to having discussed DA. DA was substantially less likely to be discussed than school work, drugs, alcohol, family finances, the economy, money management, dating relationships in general, and sex. Parents who did not discuss DA reported that their children were not dating, too young, that their children would learn about it through experience, that they would not know what to say, or that it was too embarrassing to discuss.

Conclusions

Programs that equip parents to talk with children about DA are needed.

Background

Differences in pathogenicity between pneumococcal serotypes are important when assessing the potential benefit of different valency vaccines. We investigated the effect of serotype on clinical presentation, outcome, and quality of life lost from invasive pneumococcal disease (IPD) in the context of the 7, 10, and 13 valent pneumococcal conjugate vaccines (PCV7, PCV10, PCV13).

Method

Serotyped IPD cases in England were linked to the national dataset of hospital admissions for April 2002 to March 2011. Based on patients’ diagnostic codes and vital status at the end of the admission, disease focus (meningitis, empyema, sepsis, or respiratory disease) and case fatality rates by serotype and age group (5, 5–64, and 65 years and over) were obtained. Using these data the quality adjusted life years (QALY) lost from the IPD remaining when use of PCV7 stopped in 2010 was estimated for the serotypes covered by higher valency vaccines.

Results

The linked dataset contained 23,688 cases with information on diagnosis, mortality, and serotype. There were significant differences between serotypes in the propensity to cause meningitis, death, and QALY loss in each of the investigated age groups. As a result, vaccines’ coverage of disease burden differed by endpoint. For example, in children under 5 years in 2009/10, PCV10 covered 39% of meningitis, 19% of deaths and 28% of the QALY loss of attributable to IPD, whereas the respective percentages for PCV13 were 65%, 67%, and 66%. The highest QALY loss per serotype in this age group was for 6A. Non-PCV serotypes causing the highest QALY loss were 22F and 33F in <5 year olds and 31 in older individuals.

Conclusion

Marked differences exist between serotypes in clinical presentation and outcome, and these should be considered when evaluating the potential impact of higher valency vaccines on overall disease burden and associated QALY loss.

Introduction

England and Wales recently replaced the 7-valent pneumococcal conjugate vaccine (PCV7) with its 13-valent equivalent (PCV13), partly based on projections from mathematical models of the long-term impact of such a switch compared to ceasing pneumococcal conjugate vaccination altogether.

Methods

A compartmental deterministic model was used to estimate parameters governing transmission of infection and competition between different groups of pneumococcal serotypes prior to the introduction of PCV13. The best-fitting parameters were used in an individual based model to describe pneumococcal transmission dynamics and effects of various options for the vaccination programme change in England and Wales. A number of scenarios were conducted using (i) different assumptions about the number of invasive pneumococcal disease cases adjusted for the increasing trend in disease incidence prior to PCV7 introduction in England and Wales, and (ii) a range of values representing serotype replacement induced by vaccination of the additional six serotypes in PCV13.

Results

Most of the scenarios considered suggest that ceasing pneumococcal conjugate vaccine use would cause an increase in invasive pneumococcal disease incidence, while replacing PCV7 with PCV13 would cause an overall decrease. However, the size of this reduction largely depends on the level of competition induced by the additional serotypes in PCV13. The model estimates that over 20 years of PCV13 vaccination, around 5000–62000 IPD cases could be prevented compared to stopping pneumococcal conjugate vaccination altogether.

Conclusion

Despite inevitable uncertainty around serotype replacement effects following introduction of PCV13, the model suggests a reduction in overall invasive pneumococcal disease incidence in all cases. Our results provide useful evidence on the benefits of PCV13 to countries replacing or considering replacing PCV7 with PCV13, as well as data that can be used to evaluate the cost-effectiveness of such a switch.

This study aims to examine the link between male perpetration of teen dating violence (TDV) and neighborhood violence, as well as associations with gender attitudes and perceived peer and neighborhood norms related to violence among a sample of urban adolescent boys. Participants of this cross-sectional study (N = 275) were between the ages of 14 and 20 years and recruited from urban community health centers. Crude and adjusted logistic and linear regression models were used to examine TDV perpetration in relation to (a) neighborhood violence involvement, (b) perceptions of peer violence, (c) perceptions of neighborhood violence, and (d) gender attitudes. Slightly more than one in four (28%) boys reported at least one form of TDV perpetration; among boys who have ever had sex, almost half (45%) reported at least one form of TDV perpetration. In logistic and linear regression models adjusted for demographics, boys who reported TDV perpetration were more likely to report involvement in neighborhood violence (odds ratio (OR) = 3.1; 95% confidence interval (CI) = 1.7–5.5), beliefs that their friends have perpetrated TDV (OR = 2.7; 95%CI = 1.4–5.1), perceptions of violent activity within their neighborhood (OR = 3.0; 95%CI = 1.4–6.3), and greater support of traditional gender norms (β = 3.2, p = 0.002). The findings suggest that efforts are needed to address boys’ behaviors related to the perpetration of multiple forms of violence and require explicit efforts to reduce perceived norms of violence perpetration as well as problematic gender attitudes (e.g., increasing support for gender equity) across boys’ life contexts.

Background

This study examined the efficacy of a family planning clinic-based intervention to address intimate partner violence (IPV) and reproductive coercion.

Study Design

Four free-standing urban family planning clinics in Northern California were randomized to intervention (trained family planning counselors) or standard-of-care. English-and Spanish-speaking females ages 16-29 years (N=906) completed audio computer-assisted surveys prior to a clinic visit and 12 to 24 weeks later (75% retention rate). Analyses included assessment of intervention effects on recent IPV, awareness of IPV services, and reproductive coercion.

Results

Among women reporting past 3-month IPV at baseline, there was a 71% reduction in the odds of pregnancy coercion among participants in intervention clinics compared to participants from the control clinics that provided standard of care. Women in the intervention arm were more likely to report ending a relationship because the relationship was unhealthy or unsafe regardless of IPV status (AOR 1.63, 95% CI 1.01 – 2.63).

Conclusions

Results of this pilot study suggest that this intervention may reduce risk for reproductive coercion from abusive male partners among family planning clients and support such women to leave unsafe relationships.

We examined the joint predictive effects of childhood and adolescent onset psychiatric and substance use disorders on failure to graduate high school (HS) on time. Structured diagnostic interviews were conducted with a US national sample of adults (18 and over). The analysis sample included respondents with at least 8 years of education who were born in the US or arrived in the US prior to age 13 (N=29,662). Psychiatric disorders, substance use and substance use disorders were examined as predictors of termination or interruption of educational progress prior to HS graduation, with statistical adjustment for demographic characteristics and childhood adversities. Failure to graduate HS on time was more common among respondents with any of the psychiatric and substance use disorders examined, ranging from 18.1% (specific phobia) to 33.2% (ADHD-combined type), compared with respondents with no disorder (15.2%). After adjustment for co-occurring disorders, significant associations with failure to graduate on time remained only for conduct disorder (OR=1.89, 95%CI 1.57–2.26) and the three ADHD subtypes (Inattentive OR=1.78, 95%CI 1.44–2.20, Hyperactive-Impulsive OR=1.38, 95%CI 1.14–1.67, and Combined OR=2.06, 95%CI 1.66–2.56). Adjusting for prior disorders, tobacco use was associated with failure to graduate on time (OR=1.97, 95%CI 1.80–2.16). Among substance users, substance use disorders were not associated with on time graduation. The findings suggest that the adverse impact of childhood and adolescent onset psychiatric disorders on HS graduation is largely accounted for by problems of conduct and inattention. Adjusting for these disorders, smoking remains strongly associated with failure to graduate HS on time.

Unintended pregnancy is common, disproportionately affects younger women and is associated with intimate partner violence. Forced sex, fear of negotiating condom and contraceptive use, inconsistent condom use and partner interference with access to healthcare all contribute to this association between unintended pregnancy and intimate partner violence. A growing body of literature on male partner influences on contraception and pregnancy decision-making has identified a range of male partner pregnancy-controlling behaviors which we have termed reproductive coercion, defined as male partners’ attempts to promote pregnancy in their female partners through verbal pressure and threats to become pregnant (pregnancy coercion), direct interference with contraception (birth-control sabotage), and threats and coercion related to pregnancy continuation or termination (control of pregnancy outcomes). This article examines recent studies on male partner reproductive coercion, underscores the link between unintended pregnancy and intimate partner violence and highlights future directions for research as well as implications for clinical practice.

Two doses of AS03B-adjuvanted pandemic influenza vaccine may be sufficient to maintain seroprotection across 2 influenza seasons. Administration of trivalent influenza vaccine to children who previously received 2 doses of pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain.

Background. We investigated antibody persistence in children 1 year after 2 doses of either an AS03B-adjuvanted split-virion or nonadjuvanted whole-virion monovalent pandemic influenza vaccine and assessed the immunogenicity and reactogenicity of a subsequent dose of trivalent influenza vaccine (TIV).

Methods. Children previously immunized at age 6 months to 12 years in the original study were invited to participate. After a blood sample was obtained to assess persistence of antibody against swine influenza A/H1N1(2009) pandemic influenza, children received 1 dose of 2010/2011 TIV, reactogenicity data were collected for 7 days, and another blood sample was obtained 21 days after vaccination.

Results. Of 323 children recruited, 302 received TIV. Antibody persistence (defined as microneutralization [MN] titer ≥1:40) 1 year after initial vaccination was significantly higher in the AS03B-adjuvanted compared with the whole-virion vaccine group, 100% (95% confidence interval [CI], 94.1%–100%) vs 32.4% (95% CI, 21.5%–44.8%) in children immunized <3 years old and 96.9% (95% CI, 91.3%–99.4%) vs 65.9% (95% CI, 55.3%–75.5%) in those 3–12 years old at immunization, respectively (P < .001 for both groups). All children receiving TIV had post-vaccination MN titers ≥1:40. Although TIV was well tolerated in all groups, reactogenicity in children <5 years old was slightly greater in those who originally received AS03B-adjuvanted vaccine.

Conclusions. This study provides serological evidence that 2 doses of AS03B-adjuvanted pandemic influenza vaccine may be sufficient to maintain protection across 2 influenza seasons. Administration of TIV to children who previously received 2 doses of either pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain.

Pertussis incidence among infants can be reduced by early completion of the primary vaccination schedule.

Background

The 7-valent pneumococcal conjugate vaccine (PCV-7) was introduced in the United Kingdom in 2006 with a 2,3 and 13month schedule, and has led to large decreases in invasive pneumococcal disease (IPD) caused by the vaccine serotypes in both vaccinated and unvaccinated cohorts. We estimated the effectiveness of PCV-7 against IPD.

Methods and Findings

We used enhanced surveillance data, collated at the Health Protection Agency, on vaccine type (n = 153) and non vaccine type (n = 919) IPD cases eligible for PCV-7. The indirect cohort method, a case-control type design which uses non vaccine type cases as controls, was used to estimate effectiveness of various numbers of doses as well as for each vaccine serotype. Possible bias with this design, caused by differential serotype replacement in vaccinated and unvaccinated individuals, was estimated after deriving formulae to quantify the bias. The results showed good effectiveness, increasing from 56% (95% confidence interval (CI): -7-82) for a single dose given under one year of age to 93% (95% CI: 70-98) for two doses under one year of age plus a booster dose in the second year of life. Serotype specific estimates indicated higher effectiveness against serotypes 4, 14 and 18C and lower effectiveness against 6B. Under the assumption of complete serotype replacement by non vaccine serotypes in carriage, we estimated that effectiveness estimates may be overestimated by about 2 to 5%.

Conclusions

This study shows high effectiveness of PCV-7 under the reduced schedule used in the UK. This finding agrees with the large reductions seen in vaccine type IPD in recent years in England and Wales. The formulae derived to assess the bias of the indirect cohort method for PCV-7 can also be used when using the design for other vaccines that affect carriage such as the recently introduced 13 valent pneumococcal conjugate vaccine.

In a cluster-randomized trial conducted in Gambian villages, Anna Roca and colleagues find that vaccination of children with pneumococcal conjugate vaccines reduced vaccine-type pneumococcal carriage even among nonvaccinated older children and adults.

Background

Introduction of pneumococcal conjugate vaccines (PCVs) of limited valency is justified in Africa by the high burden of pneumococcal disease. Long-term beneficial effects of PCVs may be countered by serotype replacement. We aimed to determine the impact of PCV-7 vaccination on pneumococcal carriage in rural Gambia.

Methods and Findings

A cluster-randomized (by village) trial of the impact of PCV-7 on pneumococcal nasopharyngeal carriage was conducted in 21 Gambian villages between December 2003 to June 2008 (5,441 inhabitants in 2006). Analysis was complemented with data obtained before vaccination. Because efficacy of PCV-9 in young Gambian children had been shown, it was considered unethical not to give PCV-7 to young children in all of the study villages. PCV-7 was given to children below 30 mo of age and to those born during the trial in all study villages. Villages were randomized (older children and adults) to receive one dose of PCV-7 (11 vaccinated villages) or meningococcal serogroup C conjugate vaccine (10 control villages). Cross-sectional surveys (CSSs) to collect nasopharyngeal swabs were conducted before vaccination (2,094 samples in the baseline CSS), and 4–6, 12, and 22 mo after vaccination (1,168, 1,210, and 446 samples in CSS-1, -2, and -3, respectively).

A time trend analysis showed a marked fall in the prevalence of vaccine-type pneumococcal carriage in all age groups following vaccination (from 23.7% and 26.8% in the baseline CSS to 7.1% and 8.5% in CSS-1, in vaccinated and control villages, respectively). The prevalence of vaccine-type pneumococcal carriage was lower in vaccinated than in control villages among older children (5 y to <15 y of age) and adults (≥15 y of age) at CSS-2 (odds ratio [OR] = 0.15 [95% CI 0.04–0.57] and OR = 0.32 [95% CI 0.10–0.98], respectively) and at CSS-3 (OR = 0.37 [95% CI 0.15–0.90] for older children, and 0% versus 7.6% for adults in vaccinated and control villages, respectively). Differences in the prevalence of non-vaccine-type pneumococcal carriage between vaccinated and control villages were small.

Conclusions

Vaccination of Gambian children reduced vaccine-type pneumococcal carriage across all age groups, indicating a “herd effect” in non-vaccinated older children and adults. No significant serotype replacement was detected.

Please see later in the article for the Editors' Summary

Editors' Summary

Background

The prevention of pneumococcal disease, especially in children in developing countries, is a major international public health priority. Despite all the international attention on the UN's Millennium Development Goal 4—to reduce deaths in children under five years by two-thirds between 1990 and 2015—pneumonia, sepsis, and meningitis together compose more than 25% of the 10 million deaths occurring in children less than five years of age. Streptococcus pneumoniae is a leading bacterial cause of these diseases, and the World Health Organization estimates that approximately 800,000 children die each year of invasive pneumococcal disease.

Pneumococcal conjugate vaccines are currently available and protect against the serotypes that most commonly cause invasive pneumococcal disease in young children in North America and Europe. Such vaccines have been highly successful in reducing the incidence of invasive pneumococcal disease in both vaccinated children and in the non-vaccinated older population by reducing nasopharyngeal carriage (presence of pneumococcal bacteria in the back of the nose) in vaccinated infants, resulting in decreased transmission to contacts—the so-called herd effect. However, few countries with the highest burden of invasive pneumococcal disease, especially those in sub-Saharan Africa, have introduced the vaccine into their national immunization programs.

Why Was This Study Done?

The features of pneumococcal nasopharyngeal carriage and invasive pneumococcal disease in sub-Saharan Africa are different than in other regions. Therefore, careful evaluation of the immune effects of vaccination requires long-term, longitudinal studies. As an alternative to such long-term observational studies, and to anticipate the potential long-term effects of the introduction of pneumococcal conjugate vaccination in sub-Saharan Africa, the researchers conducted a cluster-randomized (by village) trial in The Gambia in which the whole populations of some villages were immunized with the vaccine PCV-7, and other villages received a control.

What Did the Researchers Do and Find?

With full consent from communities, the researchers randomized 21 similar villages in a rural region of western Gambia to receive pneumococcal conjugate vaccine or a control—meningococcal serogroup C conjugated vaccine, which is unlikely to affect pneumococcal carriage rates. For ethical reasons, the researchers only randomized residents aged over 30 months—all young infants received PCV-7, as a similar vaccine had already been shown to be effective in young infants. Before immunization began, the researchers took nasopharyngeal swabs from a random selection of village residents to determine the baseline pneumococcal carriage rates of both the serotypes of pneumococci covered by the vaccine (vaccine types, VTs) and the serotypes of pneumococci not covered in the vaccine (non-vaccine types, NVTs). The researchers then took nasopharyngeal swabs from a random sample of 1,200 of village residents in both groups of villages in cross-sectional surveys at 4–6, 12, and 22 months after vaccination. Villagers and laboratory staff were unaware of which vaccine was which (that is, they were blinded).

Before immunization, the overall prevalence of pneumococcal carriage in both groups was high, at 71.1%, and decreased with age. After vaccination, the overall prevalence of pneumococcal carriage in all three surveys was similar between vaccinated and control villages, showing a marked fall. However, the prevalence of carriage of VT pneumococci was significantly lower in vaccinated than in control villages in all surveys for all age groups. The prevalence of carriage of NVT pneumococci was similar in vaccinated and in control villages, except for a slightly higher prevalence of NVT pneumococci among vaccinated communities in adults at 4–6 months after vaccination. The researchers also found that the overall prevalence of pneumococcal carriage fell markedly after vaccination and reached minimum levels at 12 months in both study arms and in all age groups.

What Do These Findings Mean?

These findings show that vaccination of young Gambian children reduced carriage of VT pneumococci in vaccinated children but also in vaccinated and non-vaccinated older children and adults, revealing a potential herd effect from vaccination of young children. Furthermore, the immunological pressure induced by vaccinating whole communities did not lead to a community-wide increase in carriage of NVT pneumococci during a two-year period after vaccination. The researchers plan to conduct more long-term follow-up studies to determine nasopharyngeal carriage in these communities.

Additional Information

Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001107.

The World Health Organization has information about pneumococcus

The US Centers for Disease Control and Prevention provides information about pneumococcal conjugate vaccination

Background

The UK introduced the 7-valent pneumococcal conjugate vaccine (PCV7) into the national vaccination program in September 2006. Previous modelling assumed that the likely impact of PCV7 on invasive pneumococcal disease (IPD) would be similar to the US experience with PCV7. However, recent surveillance data show a more rapid replacement of PCV7 IPD cases by non-PCV7 IPD cases than was seen in the US.

Methods and Findings

A previous model of pneumococcal vaccination was re-parameterised using data on vaccine coverage and IPD from England and Wales between 2006 and 2009. Disease incidence was adjusted for the increasing trend in reported IPD cases prior to vaccination. Using this data we estimated that individuals carrying PCV7 serotypes have much higher protection (96%;95% CI 72%-100%) against acquisition of NVT carriage than the 15% previously estimated from US data, which leads to greater replacement. However, even with this level of replacement, the annual number of IPD cases may be 560 (95% CI, -100 to 1230) lower ten years after vaccine introduction compared to what it may have been without vaccination. A particularly marked fall of 39% in children under 15 years by 2015/6 is predicted.

Conclusion

Our model suggests that PCV7 vaccination could result in a decrease in overall invasive pneumococcal disease, particularly in children, even in an environment of rapid replacement with non-PCV7 serotypes within 5 years of vaccine introduction at high coverage.

The coadministration of the combined meningococcal serogroup C conjugate (MCC)/Haemophilus influenzae type b (Hib) vaccine with pneumococcal conjugate vaccine (PCV7) and measles, mumps, and rubella (MMR) vaccine at 12 months of age was investigated to assess the safety and immunogenicity of this regimen compared with separate administration of the conjugate vaccines. Children were randomized to receive MCC/Hib vaccine alone followed 1 month later by PCV7 with MMR vaccine or to receive all three vaccines concomitantly. Immunogenicity endpoints were MCC serum bactericidal antibody (SBA) titers of ≥8, Hib-polyribosylribitol phosphate (PRP) IgG antibody concentrations of ≥0.15 μg/ml, PCV serotype-specific IgG concentrations of ≥0.35 μg/ml, measles and mumps IgG concentrations of >120 arbitrary units (AU)/ml, and rubella IgG concentrations of ≥11 AU/ml. For safety assessment, the proportions of children with erythema, swelling, or tenderness at site of injection or fever or other systemic symptoms for 7 days after immunization were compared between regimens. No adverse consequences for either safety or immunogenicity were demonstrated when MCC/Hib vaccine was given concomitantly with PCV and MMR vaccine at 12 months of age or separately at 12 and 13 months of age. Any small differences in immunogenicity were largely in the direction of a higher response when all three vaccines were given concomitantly. For systemic symptoms, there was no evidence of an additive effect; rather, any differences between schedules showed benefit from the concomitant administration of all three vaccines, such as lower overall proportions with postvaccination fevers. The United Kingdom infant immunization schedule now recommends that these three vaccines may be offered at one visit at between 12 and 13 months of age.

Many eukaryotic secretory proteins are selected for export from the endoplasmic reticulum (ER) through their interaction with the Sec24p subunit of the COPII coat. Three distinct cargo-binding sites on yeast Sec24p have been described by biochemical, genetic, and structural studies. Each site recognizes a limited set of peptide motifs or a folded structural domain, however, the breadth of cargo recognized by a given site and the dynamics of cargo engagement remain poorly understood. We aimed to gain further insight into the broader molecular function of one of these cargo-binding sites using a non-biased genetic approach. We exploited the in vivo lethality associated with mutation of the Sec24p B-site to identify genes that suppress this phenotype when overexpressed. We identified SMY2 as general suppressor that rescued multiple defects in Sec24p, and SEC22 as a specific suppressor of two adjacent cargo-binding sites, raising the possibility of allosteric regulation of these domains. We generated a novel set of mutations in Sec24p that distinguish these two sites and examined the ability of Sec22p to rescue these mutations. Our findings suggest that cooperativity does not influence cargo capture at these sites, and that Sec22p rescue occurs via its function as a retrograde SNARE.

Summary of Recent Advances

The small GTPase Sar1 resides at the core of a regulatory cycle that controls protein export from the ER in COPII vesicles. Recent advances in minimally reconstituted systems indicate continual flux of Sar1 through GTPase cycles facilitates cargo concentration into forming vesicles that ultimately bud from membranes. During export from ER membranes, this GTPase cycle is harnessed through the combinatorial power of multiple coat subunits and cargo adaptors to sort an expanding array of proteins into ER-derived vesicles. The COPII budding machinery is further organized into higher-order structures at transitional zones on the ER surface where the large multi-domain Sec16 protein appears to perform a central function.

Objective

To examine the relationship of primary caregivers’ literacy with children's oral health outcomes.

Design

We performed a cross-sectional study of children ages six and younger who presented for an initial dental appointment in the teaching clinics at the University of North Carolina at Chapel Hill School of Dentistry. Caregiver literacy was measured using the Rapid Estimate of Adult Literacy in Dentistry (REALD-30). The outcome measures included oral health knowledge, oral health behaviors, primary caregiver's reports of their child's oral health status, and the clinical oral health status of the child as determined by a clinical exam completed by trained, calibrated examiners.

Results

Among the 106 caregiver/child dyads enrolled, 59% of the children were male, 52% were white, and 86% caregivers were the biological mothers. The bivariate results showed no significant relationships between literacy and oral health knowledge (p=0.16) and behaviors (p=0.24); however, there was an association between literacy and oral health status (p<0.05). The multivariate analysis controlled for race, and income; this analysis revealed a significant relationship between caregiver literacy scores and clinical oral health status as determined using a standardized clinical exam. Caregivers of children with mild to moderate treatment needs were more likely to have higher REALD-30 scores than those with severe treatment needs (OR=1.14; 95%CI 1.05:1.25, p=0.003).

Conclusions

Caregiver literacy is significantly associated with children's dental disease status.

Hph1 and Hph2 are homologous integral endoplasmic reticulum (ER) membrane proteins required for Saccharomyces cerevisiae survival under environmental stress conditions. To investigate the molecular functions of Hph1 and Hph2, we carried out a split-ubiquitin-membrane-based yeast two-hybrid screen and identified their interactions with Sec71, a subunit of the Sec63/Sec62 complex, which mediates posttranslational translocation of proteins into the ER. Hph1 and Hph2 likely function in posttranslational translocation, as they interact with other Sec63/Sec62 complex subunits, i.e., Sec72, Sec62, and Sec63. hph1Δ hph2Δ cells display reduced vacuole acidification; increased instability of Vph1, a subunit of vacuolar proton ATPase (V-ATPase); and growth defects similar to those of mutants lacking V-ATPase activity. sec71Δ cells exhibit similar phenotypes, indicating that Hph1/Hph2 and the Sec63/Sec62 complex function during V-ATPase biogenesis. Hph1/Hph2 and the Sec63/Sec62 complex may act together in this process, as vacuolar acidification and Vph1 stability are compromised to the same extent in hph1Δ hph2Δ and hph1Δ hph2Δ sec71Δ cells. In contrast, loss of Pkr1, an ER protein that promotes posttranslocation assembly of Vph1 with V-ATPase subunits, further exacerbates hph1Δ hph2Δ phenotypes, suggesting that Hph1 and Hph2 function independently of Pkr1-mediated V-ATPase assembly. We propose that Hph1 and Hph2 aid Sec63/Sec62-mediated translocation of specific proteins, including factors that promote efficient biogenesis of V-ATPase, to support yeast cell survival during environmental stress.