Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Louise Letley, Vanessa Rew, Rehana Ahmed, Katrine Bach Habersaat, Pauline Paterson, Tracey Chantler, Maria Saavedra-Campos, Robb Butler Introduction Due to regular vaccine preventable disease outbreaks and sub-optimal immunisation uptake in the London borough of Hackney, home to the largest Charedi Orthodox Jewish community in Europe, it was decided, in consultation with the community, to implement the WHO Tailoring Immunization Programmes approach (TIP). Design The WHO Tailoring Immunization Programmes (TIP) approach was used. TIP provides a framework based on behavioural insights methodology to identify populations susceptible to vaccine preventable diseases, diagnose supply and demand side barriers and enablers to vaccination and recommend evidence-informed responses to improve vaccination coverage. Results The results of the formative research and behavioural analysis challenged the assumption that a cultural or religious anti-vaccination sentiment existed within the community. Critical issues related to access to and convenience of immunisation services. Service providers in the area have challenges due to having to deliver immunisation services to the large numbers of children without additional resource. Where mothers were choosing to delay or refuse vaccinations their reasons were broadly similar to the wider population. The behavioural analysis identified potential categorisation of subgroups within the community enabling a more tailored approach to addressing concerns and meeting parents’ needs. Conclusion The TIP approach was an effective way of investigating factors linked to sub-optimal immunisation within the Charedi community. The use of behavioural insights enabled the categorisation of subgroups so that more targeted interventions could be developed. The comprehensive stakeholder engagement which is a key pillar of the TIP approach ensured a deeper understanding of the barriers and enablers to vaccination as well as increasing the level of ownership in the community. TIP should be considered as a useful approach to identify main facilitators and barriers to vaccination in communities with suboptimal immunisation uptake.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Walter H.B. Demczuk, Irene Martin, Shalini Desai, Averil Griffith, Laurence Caron-Poulin, Brigitte Lefebvre, Allison McGeer, Gregory J. Tyrrell, George G. Zhanel, Jonathan Gubbay, Linda Hoang, Paul N. Levett, Paul Van Caeseele, Rita Raafat Gad, David Haldane, George Zahariadis, Gregory German, Jennifer Daley Bernier, Lori Strudwick, Michael R. Mulvey The 13-valent conjugate vaccine (PCV13) was recommended for childhood immunization programs in 2010 in Canada and has decreased the incidence of invasive pneumococcal disease (IPD) in children and changed the epidemiology of IPD in adults. This study investigated the epidemiology of IPD in adults 65 years of age and older in Canada. A total of 7282 invasive S. pneumoniae isolated from adults ≥65 years old were serotyped from 2010 to 2016 and antimicrobial susceptibility was performed on 2527 isolates. Serotyping was performed by Quellung reaction using commercial antisera and antimicrobial susceptibilities were determined by broth microdilution. PCV7 serotypes decreased non-significantly from 2010 to 2016 from 9.1% (n = 96) to 6.7% (n = 72) while the additional six PCV13 serotypes declined significantly from 39.5% (n = 418) to 18.6% (n = 201) (p 〈 0.05). The 23-valent pneumococcal polysaccharide vaccine (PPV23) and non-vaccine (NVT) serotypes increased from 26.3% (n = 278) to 36.2% (n = 393) (p 〈 0.05), and from 25.1% (n = 266) to 38.4% (n = 416) (p 〈 0.05), respectively. There were no significant changes in antimicrobial resistance rates from 2011 to 2016: 24.1% of the IPD from adults ≥65 years were resistant to clarithromycin (n = 609), 10.0% to doxycycline (n = 254), 11.8% to penicillin (n = 299), 5.2% to cefuroxime (n = 131), 6.6% to clindamycin (n = 168), 6.0% to trimethoprim-sulfamethoxazole (n = 152), and 0.5% (n = 12) to ceftriaxone. Although overall incidence of IPD in adults ≥65 years has remained relatively constant from 2010 to 2016, childhood PCV13 vaccination programs have been successful in indirectly reducing IPD caused by PCV13 serotypes in adults through herd immunity effects.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Shaun H. Pennington, Daniela M. Ferreira, Jesús Reiné, Tonney S. Nyirenda, Ameeka L. Thompson, Carole A. Hancock, Angela D. Wright, Stephen B. Gordon, Melita A. Gordon Background We have previously demonstrated that polyfunctional Ty21a-responsive CD4 + and CD8 + T cells are generated at the duodenal mucosa 18 days following vaccination with live-attenuated S . Typhi (Ty21a). The longevity of cellular responses has been assessed in peripheral blood, but persistence of duodenal responses is unknown. Methods We vaccinated eight healthy adults with Ty21a. Peripheral blood and duodenal samples were acquired after a median of 1.5 years (ranging from 1.1 to 3.7 years) following vaccination. Cellular responses were assessed in peripheral blood and at the duodenal mucosa by flow cytometry. Levels of IgG and IgA were also assessed in peripheral blood by enzyme-linked immunosorbent assay. Results No T-cell responses were observed at the duodenal mucosa, but CD4 + T-cell responses to Ty21a and FliC were observed in peripheral blood. Peripheral anti-lipopolysaccharide IgG and IgA responses were also observed. Early immunoglobulin responses were not associated with the persistence of long-term cellular immune responses. Conclusions Early T-cell responses which we have previously observed at the duodenal mucosa 18 days following oral vaccination with Ty21a could not be detected at a median of 1.5 years. Peripheral responses were observed at this time. Immunoglobulin responses observed shortly after vaccination were not associated with cellular immune responses at 1.5 years, suggesting that the persistence of cellular immunity is not associated with the strength of the initial humoral response to vaccination.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Saber Yezli, Philippe Gautret, Abdullah M. Assiri, Bradford D. Gessner, Badriah Alotaibi Meningococcal disease is a serious public health threat given the seriousness of the illness, its disabling sequelae and its potential for epidemic spread. The disease is a concern during mass gatherings which provide conditions that facilitate transmission of infectious agents including Neisseria meningitidis . Implementation of appropriate meningococcal disease preventive measures during at-risk mass gatherings is crucial to prevent illness and outbreaks which may result in significant morbidity and mortality as well as local and international spread of the disease. These preventive measures should be informed by comprehensive risk assessments of the disease at those events and may include the use of vaccination, chemoprophylaxis and health awareness and educational campaigns, supported by efficient disease surveillance and response systems. The Hajj and Umrah religious mass gatherings in the Kingdom of Saudi Arabia are examples of how the implementation of such preventive measures was successful in reducing the incidence of meningococcal disease during these events as well as controlling and preventing outbreaks. Lessons learned from the Hajj and Umrah experience can inform meningococcal disease preventive strategies for other mass gatherings worldwide.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Al-Mamoon Badahdah, Harunor Rashid, Ameneh Khatami, Robert Booy Background Mass gatherings (MGs) such as the Hajj and Umrah pilgrimages are known to amplify the risk of invasive meningococcal disease (IMD) due to enhanced transmission of the organism between attendees. The burden of IMD at MGs other than Hajj and Umrah has not previously been quantified through a systematic review. Methods A systematic search for relevant articles in PubMed and Embase was conducted using MeSH terms; this was buttressed by hand searching. Following data abstraction, a narrative synthesis was conducted to quantify the burden of IMD at MGs and identify potential risk factors and mitigation measures. Results Thirteen studies reporting occurrence of IMD at MGs or similar crowded settings were identified. Eight studies reported cases or outbreaks in MGs of ≥1000 people; five others reported IMD in other crowded settings; all occurred between 1991 and 2015. All age groups were involved in the identified studies; however the majority of cases (∼80%) were young people aged 15–24 years. The number of affected people ranged from one to 321 cases and the overall crude estimate of incidence was calculated as 66 per 100,000 individuals. Serogroups A, C, B and W were identified, with serogroups A and C being most common. Of 450 cases of IMD reported in non-Hajj/Umrah MGs, 67 (14.9%) had fatal outcomes. Conclusion IMD outbreaks at non-Hajj/Umrah MGs are generally much smaller than Hajj-related outbreaks and affect mainly young people. Health education and vaccination should be considered for attendees of high risk non-Hajj/Umrah MGs, especially those involving adolescents and young adults.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Moran Ki, Hwa Young Choi, Minji Han, Jin-Kyoung Oh Background This prevalence-based, cost-of-illness study estimated the health care costs of human papillomavirus (HPV) infection-associated diseases in the era before the introduction of organized HPV vaccination for 12-year-old girls in 2016, South Korea. Methods The claims data provided by the National Health Insurance Service was used to estimate the prevalence of HPV-associated diseases and their direct medical costs, including costs related to hospitalizations, outpatient visits, and medications. Results A total of 1.3 million men and women used medical services for HPV-attributed diseases between 2002 and 2015. Among women, the most common diseases attributable to HPV were cervical dysplasia (64.4%), anogenital warts (12.9%), cervical carcinoma in situ (10.7%) and cervical cancer (2.6%), whereas anogenital warts (80.6%), benign neoplasms of larynx (14.3%), and anal cancers (8.9%) were most common among men. In 2015, the healthcare cost attributable to HPV was 124.9 million US dollars (USD) representing 69.0% of the annual cost of all HPV-associated diseases. At a cost of 75.1 million USD, cervical cancer contributed the largest economic burden in 2015 followed by cervical dysplasia (19.4 million USD) and cervical carcinoma in situ (10.7 million USD). These three conditions represented 58.2% of the total annual cost of all HPV-associated diseases, while 84.2% of the total annual cost was attributable to HPV. Annual health care costs increased from 42.6 million USD in 2002 to 180.9 million USD in 2015. Conclusion The healthcare costs associated with HPV-related diseases in Korea are substantial and increased between 2002 and 2015 mainly caused by increased number of patients. Expanding the target age for HPV vaccination of girls and introducing HPV vaccination for boys are possible ways of reducing the economic burden of HPV-associated disease and should be considered.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Xinyu Liu, Danhua Zhao, Lili Jia, Hongshan Xu, Rui Na, Yonghong Ge, Shaoxiang Liu, Yongxin Yu, Yuhua Li Japanese encephalitis (JE) live attenuated vaccine SA14-14-2 is the most widely used JE vaccine in the world. Large-scale clinical trials have demonstrated satisfactory safety and efficacy profiles. The establishment of genetic and attenuated neurovirulence characteristics and their stabilities of SA14-14-2 virus are important in relation to vaccine safety in humans. Therefore, several researchers have studied and analyzed the full-length gene sequences of the SA14-14-2 virus strain. However, sequencing results have shown a significant difference. Here, we further studied the full-length sequence of three class seed virus banks of the vaccine as well as two vaccine viruses with different passages in primary hamster kidney cells, and compared them with our original stored SA14 parent virus (low passage in mouse brain). The full-length gene sequence determined in this study indicates there were 57 nucleotide and 25 amino acid substitutions of the SA14-14-2 strain compared to its parental SA14 virus strain. The full-length sequences of the three class seed bank viruses and the vaccine virus PHKC8 were completely identical among them, but the working seed virus passaged in primary hamster kidney cells for 17 generations (PHKC17) had a single nucleotide change at the 5′ NCR. Both KM and ICR mice tested by intracerebral (i.c.) or subcutaneous (s.c.) routes with the three class seed viruses and vaccine viruses with ≥5.7 lgpfu/mL remained healthy, but all the mice inoculated with the SA14 parental virus strain died as early as day 5 post-inoculation. The present study provided new information on the full-length gene sequence and attenuated neurovirulence of SA14-14-2. They can be used as a reference sequence for vaccine quality control and surveillance of neurovirulence reversion following vaccination. Moreover, the present results further demonstrated the high genetic and phenotypic stabilities of the SA14-14-2 virus, suggesting the neurovirulence reversion of the vaccine strain will be highly unlikely.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): M.S. Boukhvalova, A. Mbaye, S. Kovtun, K.C. Yim, T. Konstantinova, T. Getachew, S. Khurana, A.R. Falsey, J.C.G. Blanco Respiratory syncytial virus (RSV) is a significant cause of bronchiolitis and pneumonia. Protection against RSV is associated with neutralizing antibodies against the fusion (F) and attachment (G) glycoproteins. Several RSV vaccine candidates are in development, but their immunogenicity is hard to compare due to the little-understood differences between multiple RSV neutralizing antibody assays used. Existing assays utilize primarily Vero or HEp-2 cells, but their ability to detect G-neutralizing antibodies or antibodies against specific RSV strains is unclear. In this work, we developed an RSV microneutralization assay (MNA) using unmodified RSV and immortalized cell line derived from human airway epithelial cells (A549). Performance of A549-, HEp-2- and Vero-based MNA was compared under the same assay conditions (fixed amount of virus and cells) with regards to detection of neutralizing antibodies against RSV A or B viruses, G-reactive neutralizing antibodies, and effect of complement. Our results indicate that A549 cells yield the highest MNA titers, particularly in the RSV A/A2 MNA, are least susceptible to complement-enhancing effect of neutralizing titer readout and are superior to Vero or HEp-2 MNA at recognizing G-reactive neutralizing antibodies when no complement is used. Vero cells, however, can be more consistent at recognizing neutralizing antibodies against multiple RSV strains. The choice of substrate cells thus affects the outcome of MNA, as some immortalized cells better support detection of broader range of neutralizing antibodies, while others facilitate detection of G-targeting neutralizing antibodies, a long-thought prerogative of primary airway epithelial cells.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Luciana Gomes Pedro Brandão, Guilherme Santoro-Lopes, Silas de Souza Oliveira, Edson Elias da Silva, Pedro Emmanuel Alvarenga Americano do Brasil Objectives To assess the prevalence of protective antibody titers to polioviruses in adults candidates for solid organ transplant (SOT), and to assess the immunogenic response to inactivated polio vaccine in this population. Methods The study included SOT candidates referred to Immunization Reference Centre of Evandro Chagas National Institute of Infectious Diseases from March 2013 to January 2016. It was conducted in 2 phases. The first one, a cross-sectional seroprevalence study, followed by an uncontrolled analysis of vaccine response among patients without protective antibody titers at baseline. Antibody titers to poliomyelitis were determined by microneutralization assay. Results Among 206 SOT candidates included, 156 (76%) had protective antibody titers to all poliovirus serotypes (95% CI: 70–81%). Proven history of oral vaccination in childhood was not associated with higher seroprevalence of protective antibody. In 97% of individuals without protective antibody titers at baseline, there was adequate vaccine response with one dose of inactivated polio vaccine. Conclusions A relevant proportion of adult candidates for SOT does not have protective titers of antibodies to one or more poliovirus serotype. One dose of inactivated vaccine elicited protective antibody titers in 97% of these subjects and should be routinely prescribed prior to SOT.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Amit Saha, Andrew Hayen, Mohammad Ali, Alexander Rosewell, C. Raina MacIntyre, John D. Clemens, Firdausi Qadri Background Evaluations of oral cholera vaccines (OCVs) have demonstrated their effectiveness in diverse settings. However, low vaccine uptake in some settings reduces the opportunity for prevention. This paper identifies the socioeconomic factors associated with vaccine uptake in a mass vaccination program. Methods This was a three-arm (vaccine, vaccine plus behavioral change, and non-intervention) cluster randomized trial conducted in Dhaka, Bangladesh. Socio-demographic and vaccination data were collected from 268,896 participants. A geographical information system (GIS) was used to design and implement the vaccination program. A logistic regression model was used to assess the association between vaccine uptake and socioeconomic characteristics. Results The GIS supported the implementation of the vaccination program by identifying ideal locations of vaccination centres for equitable population access, defining catchment areas of daily activities, and providing daily coverage maps during the campaign. Among 188,206 individuals in the intervention arms, 123,686 (66%) received two complete doses, and 64,520 (34%) received one or no doses of the OCV. The vaccine uptake rate was higher in females than males (aOR: 1.80; 95% CI = 1.75–1.84) and in younger (〈15 years) than older participants (aOR: 2.19; 95% CI = 2.13–3.26). Individuals living in their own house or having a higher monthly family expenditure were more likely to receive the OCV (aOR: 1.60; 95% CI = 1.50–1.70 and aOR: 1.14; 95% CI = 1.10–1.18 respectively). Individuals using treated water for drinking or using own tap as the source of water were more likely to receive the OCV (aOR: 1.23; 95% CI = 1.17–1.29 and aOR: 1.14; 95% CI = 1.02–1.25 respectively) than their counterpart. Vaccine uptake was also significantly higher in participants residing farther away from health facilities (aOR: 95% 1.80; CI = 1.36–2.37). Conclusion The GIS was useful in designing field activities, facilitating vaccine delivery and identifying socioeconomic drivers of vaccine uptake in the urban area of Bangladesh. Addressing these socioeconomic drivers may help improve OCV uptake, thereby effectiveness of the OCV in a community.