Prevalence and annual risk of tuberculosis infection in the school population aged 7 years old in Ceuta (Spain)

Objective

To determine the prevalence of tuberculosis infection and annual risk of infection in the school population of Ceuta.

Method

A cross-sectional study was conducted. A tuberculin test (2UT RT-23 Tween 80) was given to 7-year-old schoolchildren in Ceuta in 2008. A positive result was considered as an induration of ≥5 mm at 72 hours in unvaccinated children.

Results

A total of 612 children were studied. The prevalence of tuberculosis infection was 0.98% (95% confidence interval with a 2.5% margin of error). The distribution showed differences among three health areas, and was greatest in the most deprived area (2.07%). The annual risk of infection was 0.15%.

Conclusions

According to the most recent studies, the prevalence of tuberculosis infection in Ceuta is one of the highest of Spain. Our results do not agree with the epidemiological data for tuberculosis in Ceuta, which also includes imported cases.     

The end of the Australia antigen? An ecological study of the impact of universal newborn hepatitis B vaccination two decades on

Background

A universal newborn hepatitis B (HBV) vaccination program was introduced in the Northern Territory of Australia in 1990, followed by a school-based catch-up program. We evaluated the prevalence of hepatitis B infection in birthing women up to 20 years after vaccination and compared this to women born before the programs commenced.

Methods

A cohort of birthing mothers was defined from Northern Territory public hospital birth records between 2005 and 2010 and linked to laboratory confirmed notifications of chronic HBV, based principally on a record of hepatitis B surface antigen detection. Prevalence of HBV was compared between women born before or after implementation of the newborn and catch-up vaccination programs.

Findings

Among 10797 birthing mothers, 138 (1.3%) linked to a chronic HBV record. HBV prevalence was substantially higher in Aboriginal women compared to non-Indigenous women (2.4% versus 0.04%; p < 0.001). Among 5678 Aboriginal women, those eligible for catch-up and newborn HBV vaccination programs had a significantly lower HBV prevalence than older women born prior to the programs: HBV prevalence respectively 2.2% versus 3.5%, (OR 0.61, 95%CI 0.43–0.88) and 0.8% versus 3.5% (OR 0.21, 95%CI 0.11–0.43). This represents a risk reduction of respectively 40% and 80% compared to unvaccinated women.

Interpretation

The progressively greater reduction in the prevalence of chronic HBV in adult Aboriginal women co-inciding with eligibility for catch-up and newborn vaccination programs is consistent with a significant impact from both programs. The use of data derived from antenatal screening to track ongoing vaccine impact is applicable to a range of settings globally.     

Inhibition of IFN-γ promotes anti-asthma effect of Mycobacterium bovis Bacillus Calmette-Guerin neonatal vaccination: A murine asthma model

Objective

The Mycobacterium bovis Bacillus Calmette-Guerin (BCG) neonatal vaccination inhibits allergy-induced pathologic changes. However, the mechanisms underlying this process are unclear. This study aimed to investigate the role of interferon (IFN)-γ and interleukin (IL)-17 in the protective effects of the BCG neonatal vaccination on allergic pulmonary inflammation and airway hyperresponsiveness (AHR).

Methods

Wild type (WT)-neonate and IL-17 knock out (KO) neonate mice were vaccinated with BCG. A murine asthma model was developed by sensitization and then challenging with ovalbumin (OVA). Recombinant IL-17 or recombinant IFN-γ was delivered to the airway to overexpress IL-17 or IFN-γ. An anti-IFN-γ neutralizing antibody was used to block the effects of IFN-γ.

Results

We found exogenous IL-17 delivered to the airway reversed the anti-asthma effects of the neonatal BCG vaccination. BCG neonatal vaccination further reduced OVA-induced inflammation and AHR in IL-17 KO mice. Inhibition of IFN-γ in BCG neonatal vaccinated OVA-induced asthma model mice led to a further reduction in airway inflammation and AHR. In addition, airway inflammation and AHR were robust following treatment with exogenous IFN-γ. Neutralizing IL-17 was not sufficient to block OVA-induced airway inflammation and AHR. In IL-17 KO mice, airway inflammation and AHR did not occur following treatment with an anti-IFN-γ neutralizing antibody.

Conclusions

In an OVA-induced murine asthma model, inhibition of IFN-γ enhanced the anti-asthma effects of BCG neonatal vaccination.     

Safety and reactogenicity of BCG revaccination with isoniazid pretreatment in TST positive adults

Rationale

Global tuberculosis (TB) control may require mass vaccination with a new TB vaccine, such as a recombinant bacille Calmette Guerin (BCG) or attenuated Mycobacterium tuberculosis (MTB). The safety profile of live mycobacterial vaccines in latently infected adults with prior infant BCG vaccination is unknown.

Objectives

Evaluate safety and reactogenicity of BCG revaccination, with or without isoniazid (INH) pretreatment, in adults with latent MTB infection (LTBI).

Methods

Eighty-two healthy, HIV uninfected, South African adults, with a BCG scar and tuberculin skin test (TST) diameter ≥15 mm, were randomized to receive 6 months of INH, starting either before, or 6 months after, intradermal revaccination with BCG Vaccine SSI (Statens Serum Institut, Copenhagen). Safety and reactogenicity data are reported through 3 months post BCG revaccination.

Results

Baseline characteristics were similar between treatment arms. Mean baseline TST diameter was 20 ± 4 mm. Seventy-two subjects received BCG revaccination. Injection site erythema (68%) and induration (86%) peaked 1 week after revaccination. Ulceration (76%) peaked at 2 weeks, and resolved by 3 months in all but 3 subjects. Diameter of ulceration was >10 mm in only 8%, but a residual scar was common (85%). No regional lymphadenitis or serious morbidity related to BCG was seen. Reactogenicity was not affected by INH pretreatment.

Conclusion

BCG revaccination of MTB infected adults is safe, well tolerated, and reactogenicity is similar to that of primary BCG vaccination. Clinical trials of live recombinant BCG or attenuated MTB vaccines may be considered in latently infected adults, with or without INH pretreatment (ClinicalTrials.gov identifier: NCT01119521).     

Comparison of antibody and cell-mediated immune responses of foals and adult horses after vaccination with live Mycobacterium bovis BCG

Background

Equine neonates have reduced humoral and cell-mediated immune responses compared to adult horses after administration of killed vaccines. As a basis for this study, we hypothesized that newborn foals can mount strong immune responses after vaccination with live Mycobacterium bovis BCG.

Methods

Healthy 4-day-old foals (n = 7), 4-month-old foals (n = 7) and adult horses (n = 6) were vaccinated once with live M. bovis BCG. Age-matched animals (n = 5 per group) were used as unvaccinated controls. Relative vaccine-specific immunoglobulin concentrations and whole blood mRNA expression of IFN-γ, IL-4, and IL-10 were measured prior to and 2, 4, 6, and 8 weeks after vaccination. Eight weeks after vaccination, delayed type hypersensitivity (DTH) responses were assessed by measuring the increase in double skin thickness after intradermal injection of purified protein derivative.

Results

Both groups of foals and adult horses responded with a significant increase in vaccine-specific total IgG, IgGa, IgGc, IgG(T), and IgM concentrations. In contrast, only adult horses mounted significant IgGb responses. Vaccine-specific concentrations of total IgG and IgGa were significantly higher in adult horses than in 4-day-old foals whereas IgGc responses were significantly higher in 4-day-old foals than in the other two age groups. Adult horses had significantly higher basal IFN-γ and IL-4 mRNA expression than both groups of foals but vaccination with M. bovis BCG did not significantly increase expression of these cytokines, regardless of age group. Immunized horses had significantly higher DTH responses than age-matched unvaccinated controls. DTH responses were significantly greater in both groups of vaccinated foals than in vaccinated adult horses.

Conclusion

Despite a naïve immune system, newborn foals have the ability to mount robust antibody and cell-mediated immune responses to M. bovis BCG.     

Delaying BCG vaccination from birth to 10 weeks of age may result in an enhanced memory CD4 T cell response

Background

In most tuberculosis (TB) endemic countries, bacillus Calmette–Guérin (BCG) is usually given around birth to prevent severe TB in infants. The neonatal immune system is immature. Our hypothesis was that delaying BCG vaccination from birth to 10 weeks of age would enhance the vaccine-induced immune response.

Methods

In a randomized clinical trial, BCG was administered intradermally either at birth (n = 25) or at 10 weeks of age (n = 21). Ten weeks after vaccination, and at 1 year of age, vaccine-specific CD4 and CD8 T cell responses were measured with a whole blood intracellular cytokine assay.

Results

Infants who received delayed BCG vaccination demonstrated higher frequencies of BCG-specific CD4 T cells, particularly polyfunctional T cells co-expressing IFN-γ, TNF-α and IL-2, and most strikingly at 1 year of age.

Conclusions

Delaying BCG vaccination from birth to 10 weeks of age enhances the quantitative and qualitative BCG-specific T cell response, when measured at 1 year of age.     

Sustained protection against tuberculosis conferred to a wildlife host by single dose oral vaccination

Background

Vaccination of wildlife against bovine tuberculosis (TB) is being considered by several countries to reduce the transmission of Mycobacterium bovis infection to livestock. In New Zealand, where introduced brushtail possums (Trichosurus vulpecula) are the major wildlife hosts, we have previously shown that repeat applications of a lipid-encapsulated oral bacille Calmette-Guerin (BCG) vaccine reduce the incidence of naturally acquired TB in wild possums. Here we extend this conceptual demonstration to an operational level, assessing long-term protection against TB conferred to free-living possums by a single oral immunisation.

Methods

Possums in a non-TB area were randomly allocated to receive lipid-formulated BCG vaccine or remained unvaccinated. After initial trials to assess vaccine immunogenicity and establishment of protection within the first year post-vaccination, 13 individuals of each treatment group were relocated to a biosecurity facility and challenged (at 28 months post-vaccination) by subcutaneous injection of virulent M. bovis.

Results

Vaccine immunogenicity and short-term protection were confirmed at 2 months and 12 months post-vaccination, respectively. In the long-term assessment, vaccinated possums had significantly reduced bacterial counts in peripheral lymph nodes compared to controls, with 0.6–2.3 log₁₀-fold reductions in M. bovis burdens.

Discussion

The magnitude of protective response by possums to experimental challenge at 28 months post-vaccination is known to equate to a high degree of protection against natural infection in this species. With techniques for oral bait delivery well advanced, the longevity of protection demonstrated here shows that an operable wildlife vaccine against TB is feasible.     

Comparative varicella vaccine effectiveness during outbreaks in day-care centres

Background

Routine varicella vaccination for children >11 months was introduced in Germany in 2004 with three different vaccine brands available. In 2008 and 2009, we investigated seven varicella outbreaks in day-care centres (DCC).

Methods

Varicella disease and vaccination status of 1084 children was reviewed to evaluate vaccination coverage (VC), brand-specific varicella vaccine effectiveness (VE), and risk factors of breakthrough varicella (BV, >42 days after vaccination). A case was defined as a child with acute onset of varicella attending one of the respective DCC at the time of outbreak. Children with a previous history of varicella, age < 11 months, vaccinated at age < 11 months or <42 days before disease onset or during the outbreak were excluded from VE and BV risk factors analyses (adjusted for gender, age and DCC).

Findings

Of 631 children with available vaccination information, 392 (62%) were vaccinated at least once. Overall VE among 352 children eligible was 71% (95% confidence interval (CI) 57–81, p < 0.001) and differed significantly by disease severity and number of doses administered. Risk for BV was higher for 1 dose of Varilrix^® (RR = 2.8, 95%CI 1.0–7.8, p = 0.05) or Priorix-Tetra^® (RR = 2.4, 95%CI 0.7–8.3, p = 0.18) but lower for 2 doses of Priorix-Tetra^® (RR = 0.5, 95%CI 0.1–2.7, p = 0.41) than for 1 dose of Varivax^®.

Interpretation

Enhanced efforts to increase VC in Germany and 2 doses varicella vaccine might be successful to reduce the risk for BV. The evidence that VE and risk of BV are associated with vaccine brand needs further investigation.     

Socio-demographic determinants of timely adherence to BCG,Penta3, measles,and complete vaccination schedule in Burkina Faso

Objective

To identify the determinants of timely vaccination among young children in the North-West of Burkina Faso.

Methods

This study included 1665 children between 12 and 23 months of age from the Nouna Health and Demographic Surveillance System, born between September 2006 and December 2008. The effect of socio-demographic variables on timely adherence to the complete vaccination schedule was studied in multivariable ordinal logistic regression with 3 distinct endpoints: (i) complete timely adherence, (ii) failure, and (iii) missing vaccination. Three secondary endpoints were timely vaccination with BCG, Penta3, and measles, which were studied with standard multivariable logistic regression.

Results

Mothers’ education, socio-economic status, season of birth, and area of residence were significantly associated with failure of timely adherence to the complete vaccination schedule. Year of birth, ethnicity, and the number of siblings was significantly related to timely vaccination with Penta3 but not with BCG or measles vaccination. Children living in rural areas were more likely to fail timely vaccination with BCG than urban children (OR = 1.79, 95%CI = 1.24–2.58 (proximity to health facility), OR = 3.02, 95%CI = 2.18–4.19 (long distance to health facility)). In contrast, when looking at Penta3 and measles vaccination, children living in rural areas were far less likely to have failed timely vaccinations than urban children. Mother's education positively influenced timely adherence to the vaccination schedule (OR = 1.42, 95%CI 1.06–1.89). There was no effect of household size or the age of the mother.

Conclusions

Additional health facilities and encouragement of women to give birth in these facilities could improve timely vaccination with BCG. Rural children had an advantage over the urban children in timely vaccination, which is probably attributable to outreach vaccination teams amongst other factors. As urban children rely on their mothers’ own initiative to get vaccinated, urban mothers should be encouraged more strongly to get their children vaccinated in time.     

The immunological effect of revaccination with Bacille Calmette-Guérin vaccine at 19 months of age

Background

Bacille Calmette-Guérin (BCG) vaccination has important non-specific immune effects. In a randomized trial in Guinea-Bissau, BCG revaccination was associated with significantly increased survival in children who received diphtheria-tetanus-pertussis (DTP)-booster vaccine before enrolment and in children who did not receive micronutrient supplementation (MN). Within the trial we assessed the immunological effects of BCG revaccination.

Methods

Children were randomized to BCG or nothing. Blood was sampled 6–11 weeks after randomization (early sample group) or 5–9 months later (late sample group). In vitro cytokine responses (interferon (IFN)-γ, interleukin (IL)-13, tumor-necrosis-factor (TNF)-α, and IL-10) were assessed in whole blood cultures stimulated with lipopolysaccharide (LPS), purified protein derivative (PPD) or phytohaemagglutinin (PHA). Effect-modification by sex, DTP-booster vaccination and MN was studied.

Results

Cytokines were measured in 345 infants. BCG was associated with significantly increased IFN-γ (geometric mean ratio (GMR) = 4.54 (95% confidence interval: 3.13–6.58)) and IL-13 (GMR = 1.43 (1.00–2.05)) PPD responses, the effect being strongest in the early sample group. Across all three conditions BCG tended to increase IL-10 (LPS, PHA, PPD: GMR = 1.20, 1.12, 1.20), most pronounced in the late sample group. BCG reduced the TNF-α/IL-10 ratio in boys with DTP-booster at bleeding and increased it in those without (interaction test: p = 0.03). In children without MN, BCG was associated with reduced TNF-α response in the early sample group (p = 0.006), and increased IL-10 in the late sample group (p = 0.03).

Conclusion

BCG revaccination resulted in a strong IFN-γ response to PPD, which waned slightly over time. BCG also affected the pro-/anti-inflammatory balance, with reduced TNF-α and increased IL-10 responses to LPS, PHA and PPD. This effect depended on sex, DTP-booster vaccination and micronutrient supplementation, being most pronounced in children who had received DTP-booster before enrolment and children who had not received MN, i.e. the group of children which also had lower mortality after BCG revaccination.     

Social inequalities in vaccination uptake among children aged 0–59 months living in Madagascar: An analysis of Demographic and Health Survey data from 2008 to 2009

Background

Socioeconomic inequalities in vaccination can reduce the ability and efficiency of global efforts to reduce the burden of disease. Vaccination is particularly critical because the poorest children are often at the greatest risk of contracting preventable infectious diseases, and unvaccinated children may be clustered geographically, jeopardizing herd immunity. Without herd immunity, these children are at even greater risk of contracting disease and social inequalities in associated morbidity and mortality are amplified.

Methods

Data on vaccination for children under five came from the most recent Demographic and Health Survey in Madagascar (2008–2009). Vaccination status was available for diptheria, pertussis, tetanus, hepatitis B, measles, tuberculosis, poliomyelitis, and H. influenza type-B. Multilevel logistic regression was used to analyze childhood vaccination by parental socioeconomic status while accounting for shared district, cluster, and household variation. Maps were created to serve as a roadmap for efforts to increase vaccination.

Findings

Geographic variation in vaccination rates was substantial. Districts that were less covered were near other districts with limited coverage. Most districts lacked herd immunity for diphtheria, pertussis, poliomyelitis and measles. Full herd immunity was reached in a small number of districts clustered near the capital. While within-district variation in coverage was substantial; parental education and wealth were independently associated with vaccination.

Interpretation

Socioeconomic inequalities in vaccination reduce herd immunity and perpetuate inequalities by allowing infectious diseases to disproportionately affect the most vulnerable populations. Findings indicated that most districts had low immunization coverage rates and unvaccinated children were geographically clustered. The result was inequalities in vaccination and reduced herd immunity. To further improve coverage, interventions must take a multilevel approach that focuses on both supply- and demand-side barriers to delivering vaccination to underserved regions, and to the poorest children in those regions.     

Is vaccination coverage a good indicator of age-appropriate vaccination? A prospective study from Uganda

Background

Timely vaccination is important to protect children from common infectious diseases. We assessed vaccination timeliness and vaccination coverage as well as coverage of vitamin A supplementation in a Ugandan setting.

Methods and findings

This study used vaccination information gathered during a cluster-randomized trial promoting exclusive breastfeeding in Eastern Uganda between 2006 and 2008 (ClinicalTrials.gov no. NCT00397150). Five visits were carried out from birth up to 2 years of age (median follow-up time 1.5 years), and 765 children were included in the analysis. We used Kaplan-Meier time-to-event analysis to describe vaccination coverage and timeliness. Vaccination coverage at the end of follow-up was above 90% for all vaccines assessed individually that were part of the Expanded Program on Immunization (EPI), except for the measles vaccine which had 80% coverage (95%CI 76-83). In total, 75% (95%CI 71-79) had received all the recommended vaccines at the end of follow-up. Timely vaccination according to the recommendations of the Ugandan EPI was less common, ranging from 56% for the measles vaccine (95%CI 54-57) to 89% for the Bacillus Calmette-Guérin (BCG) vaccine (95%CI 86-91). Only 18% of the children received all vaccines within the recommended time ranges (95%CI 15-22). The children of mothers with higher education had more timely vaccination. The coverage for vitamin A supplementation at end of follow-up was 84% (95%CI 81-87).

Conclusions

Vaccination coverage was reasonably high, but often not timely. Many children were unprotected for several months despite being vaccinated at the end of follow-up. There is a need for continued efforts to optimise vaccination timeliness.     

Loss of anti-mycobacterial efficacy in mice over time following vaccination with Mycobacterium bovis bacillus Calmette-Guérin

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the most often used vaccine worldwide and sole vaccine against tuberculosis. BCG is protective against severe form of childhood tuberculosis but less or not protective to adult pulmonary tuberculosis. Therefore, improved vaccination strategies and development of new tuberculosis vaccines are urgent demands. For those purposes, appropriate animal models that reflect human are critically useful. However, in animal models, BCG vaccination protects well against subsequent challenge of Mycobacterium tuberculosis. In this study we evaluated the duration of protective efficacy of the BCG vaccination in mice over time and found that efficacy was diminished 40 weeks after vaccination. The aged mice older than 45 weeks are protected sufficiently after the vaccination with BCG, suggesting that loss of its efficacy is not dependent on the age of mice but rather depends on the period from vaccination. The loss of protection occurred in TH1 polarized STAT6 deficient mice despite the maintenance of interferon (IFN)-gamma production activity of lymph node cells and splenic CD4⁺ T cells against M. tuberculosis antigens. Our data suggest that the duration from vaccination may explain the variation in BCG efficacy against adult pulmonary tuberculosis.     

Non-specific and sex-differential effects of vaccinations on child survival in rural western India

Background

Studies from Africa have suggested marked non-specific effects (NSEs) of routine vaccinations with effects on child survival. There have been few studies from Asia. We re-analyzed a study from Maharashtra, India, which had collected information on vaccinations during infancy and survival until 5 years of age.

Design

4138 children born between 1987 and 1989 were visited at home every three months to collect information on nutritional status and vaccinations. Since nutritional status was a determinant of time to vaccinations, we adjusted for nutritional status in the analyzes of the association between vaccinations and mortality.

Setting

45 contiguous villages in Shirur Administrative Block in Pune District.

Main outcome measures

Mortality rate ratios (MRR) for different vaccination status groups.

Results

The study area has male preferential treatment, but the female–male mortality ratio varied between age groups with different pre-dominant vaccines; it was high in the age group in which diphtheria–tetanus–pertussis (DTP) vaccine predominates and low in the age group in which measles vaccine (MV) is given. Children who followed the WHO recommended schedule of first BCG and then DTP vaccination were vaccinated earlier than other children (p < 0.01). Two-thirds of the children had received BCG and DTP out-of-sequence, i.e. BCG and DTP simultaneously or BCG after DTP. Children who received BCG and DTP simultaneously or BCG as most recent vaccination had significantly lower mortality than children having DTP as the most recent vaccination, the mortality rate ratio being 0.15 (0.03–0.70).

Conclusions

BCG out-of-sequence may be associated with lower mortality than DTP as the most recent vaccination. Given the public health implications, this possibility should be tested in randomized trials. Excess female mortality may also be related to vaccination policy.     

Intent to receive HPV vaccine and reasons for not vaccinating among unvaccinated adolescent and young women: findings from the 2006-2008 National Survey of Family Growth

Background and purpose

HPV vaccine coverage for females has increased in the U.S., although challenges to achieving high coverage remain. HPV vaccine coverage continues to lag behind that of other routinely recommended adolescent vaccines and these gaps in coverage are widening. To inform strategies to improve uptake, we explore correlates of vaccine intention and describe reasons for refusing HPV vaccination among unvaccinated females in a nationally representative sample of adolescents and young adults during early stages of HPV vaccine availability.

Methods

In 2007–2008, 1243 females aged 15–24 years were asked about HPV vaccination in the National Survey of Family Growth (NSFG). For unvaccinated women (n = 955), we evaluated demographic and sexual behavior correlates of likelihood to receive the vaccine in the next 12 months in bivariate and multivariable analyses by age. Correlates to the main reasons for foregoing vaccination are described.

Results

A minority (42.5%) of unvaccinated respondents said they intended to receive HPV vaccine in the next 12 months: 37.6% of adolescents (15–19 years) and 42.0% of young adults (20–24 years). Sexually experienced women were more than twice as likely as non-sexually experienced women to intend to receive HPV vaccine (15–19 years: aOR = 2.39, 95% CI = 1.15, 4.94; 20–24 years: aOR = 2.17, 95% CI = 1.08, 4.33). Having health insurance was associated with being likely to receive HPV vaccine among adolescents. Hispanic young adults were more likely than non-Hispanic Whites to be likely to receive HPV vaccine. The belief of not being at risk for HPV and institutional barriers were the two most commonly cited reasons for foregoing vaccination.Among unvaccinated women who did not intend to get vaccinated, respondents who never had sex were more likely to report not being at risk as the main reason for not needing the vaccine compared to women with sexual experience (44.5 vs. 24.4%) but this finding was only marginally significant in our limited sample.

Conclusion

In the first years immediately post-licensure of an HPV vaccine, the majority of unvaccinated women indicated that they were unlikely to seek vaccination. Intent to receive the HPV vaccine is tied to sexual experience and most women who do not intend to get vaccinated and have never had sex believe they are not at risk of HPV or do not need an HPV vaccine. These findings highlight the need to better communicate information regarding lifetime risk for HPV and the importance of receiving HPV vaccine prior to sexual initiation. These findings should inform strategies to increase vaccine uptake.     

Safety and immunogenicity of the recombinant BCG vaccine VPM1002 in a phase 1 open-label randomized clinical trial

Background

Current vaccination using Mycobacterium bovis bacillus Calmette-Guérin (BCG), fails to prevent pulmonary tuberculosis (TB). New vaccination strategies are essential for reducing the global incidence of TB. We assessed the safety and immunogenicity of VPM1002, a recombinant BCG vaccine candidate. EudraCT (2007-002789-37) and ClinicalTrials.gov (NCT00749034).

Methods

Healthy volunteers were enrolled in a phase 1 open-label, dose escalation randomized clinical trial, and received one intradermal dose of VPM1002 (Mycobacterium bovis BCG ΔureC::hly Hm^R) or BCG. Immunogenicity was assessed by interferon-gamma (IFN-γ) production, cellular immune response markers by flow cytometry and serum antibodies against mycobacterial antigens.

Results

Eighty volunteers were randomized into two groups according to previous BCG vaccination and mycobacterial exposure (BCG-naïve, n = 40 and BCG-immune, n = 40). In each group, 30 individuals were vaccinated with VPM1002 (randomized to three escalating doses) and 10 with BCG. VPM1002 was safe and stimulated IFN-γ-producing and multifunctional T cells, as well as antibody-producing B cells in BCG-naïve and BCG-immune individuals.

Conclusions

VPM1002 was safe and immunogenic for B-cell and T-cell responses and hence will be brought forward through the clinical trial pipeline.     

Declining incidence of hepatitis A in Amsterdam (The Netherlands), 1996–2011: Second generation migrants still an important risk group for virus importation

Background

The Netherlands is a very low endemic country for hepatitis A virus infections (HAV, notification rate of <1/100,000). Historically in Amsterdam, a large proportion of infections are imported from Turkey and Morocco in children returning from summer holiday. Annually since 1998, the public health service of Amsterdam has targeted these children for HAV vaccination before the summer. As the population of non-western immigrants and their descendents increases, we describe recent trends in HAV in ethnic groups in Amsterdam (1996–2011), identifying current risk groups and recommending targeted prevention through vaccination.

Methods

We studied all cases of (non-homosexually acquired) HAV infection notified in the Amsterdam region (1996–2011, n = 819) by ethnic group and generation (first/second generation migrants: FGM and SGM respectively). Incidence rates were estimated as the average number of cases per 100,000/year. Using Poisson regression, we calculated incidence rate ratios (IRR) by ethnic group and generation adjusted for age and calendar year, and modeled seasonal variation using a smoothed time series.

Results

Incidence of HAV in Amsterdam dropped from 24.8/100,000 population in 1996 (178 cases) to 1.0/100,000 in 2011 (8 cases). Since 2005, 56% of cases are imported, the majority (62%) in second generation migrant (SGM) children of Moroccan, or other non-western ethnic backgrounds. The adjusted IRR in SGM relative to the ethnic Dutch population was 3.7 (95% CI: 2.3–6.1) in Moroccan SGM, 4.3 (95%CI: 2.6–7.2) in SGM of other non-western backgrounds and 1.9 (95%CI: 0.8–4.1) in Turkish SGM.

Conclusion

Though incidence of HAV in Amsterdam has declined substantially since 1996, it is still higher in SGM children of Moroccan & other non-western ethnic backgrounds. In line with WHO recommendations of June 2012, introduction of single-dose HAV vaccination, targeted at SGM children from HAV endemic countries, could be considered within the routine childhood vaccination schedule.     

Efficacy of Trivalent Seasonal Influenza Vaccination in Reducing Mortality and Hospitalization in Chinese Nursing Home Older Adults

Objective

To examine the clinical efficacy of the trivalent seasonal influenza vaccination among Chinese older adults residing in a nursing home.

Design

A 12-month prospective cohort study. Participants were divided into 2 groups based on their own choice on vaccination of trivalent seasonal influenza vaccine: vaccinated group and unvaccinated group.

Setting

Fifty-eight nursing homes in Hong Kong.

Participants

A total of 1859 older adults residing in a nursing home.

Measurements

All-cause mortality, pneumonia-related mortality, all-cause hospitalization, and pneumonia-related hospitalization.

Results

A total of 1859 older adults residing in a nursing home were included: 1214 (65.3%) in the vaccinated group and 645 (34.7%) in the unvaccinated group. At 12 months of study, for all-cause mortality, 14.6% (177 of 1214) of the vaccinated group and 20.2% (130 of 645) of the unvaccinated group had died (P < .001). Multivariate analysis showed the hazard ratio for the vaccinated group was 0.72 (95% confidence interval [CI]: 0.54–0.95; P < .01). For pneumonia-related mortality, 9.4% (114 of 1214) of the vaccinated group and 12.7% (82 of 645) of the unvaccinated group died (P = .033). Multivariate analysis showed the hazard ratio for the vaccinated group was 0.80 (CI: 0.62–0.98; P < .05). The median number of all-cause hospitalizations per 1000 person-months was 55 (0–111) for the vaccinated group and 55 (0–167) for the unvaccinated group (P < .01). The median number of pneumonia-related hospitalizations per 1000 person-months was 0 (0–55) for the vaccinated group and 0 (0–111) for the unvaccinated group (P < .01).

Conclusions

Vaccination of trivalent seasonal influenza vaccine in Chinese nursing home older adults significantly reduced all-cause and pneumonia-related mortality and hospitalization.     

Pandemic influenza A(H1N1)pdm09 improves vaccination routine in subsequent years: A cohort study from 2009 to 2011

Background

In 2009 the pandemic influenza virus A(H1N1)pdm09 emerged with guidance that people at risk should be vaccinated. It is unclear how this event affected the underlying seasonal vaccination rate in subsequent years.

Purpose

To investigate the association of pandemic influenza A(H1N1)pdm09 and seasonal flu vaccination status in 2009 with vaccination rates in 2010 and 2011.

Methods

Data were collected in 40 Dutch family practices on patients at risk for influenza during 2009–2011; data analysis was conducted in 2012.

Results

A multilevel logistic regression model (n = 41,843 patients) adjusted for practice and patient characteristics (age and gender, as well as those patient groups at risk), showed that people who were vaccinated against A(H1N1)pdm09 in 2009 were more likely to have been vaccinated in 2010 (OR 6.02; 95%CI 5.62–6.45, p < .0001). This likelihood was even more for people who were vaccinated against seasonal flu in 2009 (OR 13.83; 95%CI 12.93–14.78, p < .0001). A second analysis on the uptake rate in 2011 (n = 39,468 patients) showed that the influence of the vaccination state in 2009 declined after two years, but the diminishing effect was smaller for people vaccinated against A(H1N1)pdm09 than for seasonal flu (OR 5.50; 95%CI 5.13–5.90, p < .0001; OR 10.98; 95%CI 10.26–11.75, p < .0001, respectively).

Conclusion

Being vaccinated against A(H1N1)pdm09 and seasonal influenza in the pandemic year 2009 enhanced the probability of vaccination in the next year and this was still effective in 2011. This suggests that peoples’ vaccination routines were not changed by the rumor around the outbreak of A(H1N1)pdm09, but rather confirmed underlying behavior.     

Disseminated bacille Calmette�CGu��rin disease in HIV-infected South African infants

Objective

To determine the population-based incidence of disseminated bacille Calmette–Guérin (BCG) disease in HIV-infected infants (aged ≤ 1 year) in a setting with a high burden of tuberculosis and HIV infection coupled with a well-functioning programme for the prevention of HIV infection in infants.

Methods

The numerator, or number of new cases of disseminated BCG disease, was derived from multicentre surveillance data collected prospectively on infants with a confirmed HIV infection during 2004–2006. The denominator, or total number of HIV-infected infants who were BCG-vaccinated, was derived from population-based estimates of the number of live infants and from reported maternal HIV infection prevalence, vertical HIV transmission rates and BCG vaccination rates.

Findings

The estimated incidences of disseminated BCG disease per 100 000 BCG-vaccinated, HIV-infected infants were as follows: 778 (95% confidence interval, CI: 361–1319) in 2004 (vertical HIV transmission rate: 10.4%); 1300 (95% CI: 587–2290) in 2005 (transmission rate: 6.1%); and 1013 (95% CI: 377–1895) in 2006 (transmission rate: 5.4%). The pooled incidence over the study period was 992 (95% CI: 567–1495) per 100 000.

Conclusion

Multicentre surveillance data showed that the risk of disseminated BCG disease in HIV-infected infants is considerably higher than previously estimated, although likely to be under-estimated. There is an urgent need for data on the risk–benefit ratio of BCG vaccination in HIV-infected infants to inform decision-making in settings where HIV infection and tuberculosis burdens are high. Safe and effective tuberculosis prevention strategies are needed for HIV-infected infants.