WHO Vaccine Research Articles

Implementing WHO guidance on conducting and analysing vaccination coverage cluster surveys: Two examples from Nigeria.

In 2015, the World Health Organization substantially revised its guidance for vaccination coverage cluster surveys (revisions were finalized in 2018) and has since developed a set of accompanying resources, including definitions for standardized coverage indicators and software (named the Vaccination Coverage Quality Indicators-VCQI) to calculate them.-The current WHO vaccination coverage survey manual was used to design and conduct two nationally representative vaccination coverage surveys in Nigeria-one to assess routine immunization and one to measure post-measles campaign coverage. The primary analysis for both surveys was conducted using VCQI. In this paper, we describe those surveys and highlight some of the analyses that are facilitated by the new resources. In addition to calculating coverage of each vaccine-dose by age group, VCQI analyses provide insight into several indicators of program quality such as crude coverage versus valid doses, vaccination timeliness, missed opportunities for simultaneous vaccination, and, where relevant, vaccination campaign coverage stratified by several parameters, including the number of previous doses received. The VCQI software furnishes several helpful ways to visualize survey results. We show that routine coverage of all vaccines is far below targets in Nigeria and especially low in northeast and northwest zones, which also have highest rates of dropout and missed opportunities for vaccination. Coverage in the 2017 measles campaign was higher and showed less geospatial variation than routine coverage. Nonetheless, substantial improvement in both routine program performance and campaign implementation will be needed to achieve disease control goals.

35. Pneumococcal Vaccination in High-Risk Adults: An Initial Analysis Incorporating Social Determinants of Health

BackgroundDespite CDC’s recommendation, vaccination rates for adults at high-risk of invasive pneumococcal disease are below HealthyPeople 2020 goals. Comparatively little is known about influencers on vaccine-seeking behavior in this population, particularly related to social determinants of health. To address this gap, this study assessed the potential influence of select social determinants on uptake of and time to pneumococcal vaccination among a high-risk, insured US population.MethodsUsing the MarketScan commercial claims databases between 2013–2016, adult patients (aged 18–64 years) were followed from their first diagnosis for a condition deeming them high-risk for invasive pneumococcal disease through one year following the diagnosis and observed for pneumococcal vaccination in outpatient clinics and pharmacies. Publicly-available data on select social determinants of health were incorporated into analyses, guided by the WHO vaccine hesitancy matrix. Logistic regression determined predictors of vaccination and a generalized linear model compared days to being vaccinated while controlling for baseline demographic and clinical characteristics.ResultsA total of 173,712 patients were analyzed of which 25.3% were vaccinated against invasive pneumococcal disease within the first year of being deemed high risk, nearly all of which (98.5%) were received in outpatient clinics. The odds of vaccination were higher in urban areas (OR: 1.18; 95% CI: 1.144–1.223), areas of higher health literacy (OR: 1.02; 95% CI: 1.019–1.025), and more liberal-voting communities (OR: 1.5; 95% CI: 1.23–1.88). Conversely, the odds of vaccination were particularly low in areas of higher poverty (OR: 0.14; 95% CI: 0.068–0.304) and with more limited Internet access (OR: 0.14; 95% CI: 0.062–0.305) as well as among adults who did not also get a seasonal influenza vaccine (OR: 0.05; 95% CI: 0.048–0.052). Time to vaccination was longer in rural areas (B=8.3, p< 0.0001) and communities with less Internet access (B=75.6, p< 0.001).ConclusionResults suggest that some social determinants may be influencing pneumococcal vaccine-seeking behavior among those deemed high-risk. A more formal framework must be assessed to determine the full impact of these factors across vaccines recommended in adults.Disclosures Justin Gatwood, PhD,MPH, AstraZeneca (Grant/Research Support)GlaxoSmithKline (Grant/Research Support)Merck & Co. (Grant/Research Support) Tracy Hagemann, PharmD, GSK (Grant/Research Support)Merck (Grant/Research Support)

Genetic analysis of HA1 domain of influenza A/H3N2 viruses isolated in Kenya during the 2007–2013 seasons reveal significant divergence from WHO-recommended vaccine strains

BackgroundInfluenza viruses evolve rapidly and cause regular seasonal epidemics in humans challenging effective vaccination. The virus surface HA glycoprotein is the primary target for the host immune response. Here, we investigated the vaccine efficacy and evolution patterns of human influenza A/H3N2 viruses that circulated in Kenyan in the period before and after the 2009 A/H1N1 pandemic, targeting the HA1 domain. Materials and methodsA hundred and fifteen HA sequences of Kenyan virus viruses were analyzed relative to the corresponding WHO vaccine reference strains using bioinformatics approaches. ResultsOur analyses revealed varied amino acid substitutions at all the five antigenic sites (A–E) of the HA1 domain, with a majority the changes occurring at sites A and B. The Kenyan A/H3N2 viruses isolated during 2007/2008 seasons belonged to A/Brisbane/10/2007-like viruses lineage, while those circulating in 2009–2012 belonged to the lineage of A/Victoria/361/2011-like viruses. The 2013 viruses clustered in clade 3C.3 of the A/Samara/73/2013-like viruses. The mean evolutionary rate of the A/H3N2 viruses analyzed in the study was at 4.17×10−3 (95% HPD=3.09×10−3–5.31×10−3) nucleotide substitutions per site per year, whereas the TMRCA was estimated at 11.18 (95% HPD=9.00–14.12) years ago from 2013. The prediction of vaccine efficacy revealed modest vaccine efficaciousness during 2008, and 2010 influenza seasons, whilst sub-optimal effectiveness was registered in 2007, 2009, 2012 and 2013. Further, the overall selective pressure acting on the HA1 domain was estimated at 0.56 (ω<1), suggesting that a majority of codon sites in the HA1 epitopes were evolving under purifying selection. ConclusionsGenerally, our results highlight the genetic plasticity of A/H3N2 viruses and reveal considerable disparity in vaccine efficaciousness against the A/H3N2 viruses that circulated in Kenya, specifically during 2007, 2009, 2012, and 2013 influenza seasons. Our findings underscore the importance and need for consistent surveillance and molecular characterization of influenza viruses, to inform decision making and enhance early of detection of strains with epidemic/pandemic potential as well as benefit in guiding decisions regarding the appropriate annual influenza vaccine formulations.

Information sources and attitudes of Polish migrants accepting or declining vaccination in Scotland

Abstract Background Poland has the lowest EU vaccine confidence scores. The Polish are the largest migrant group in Scotland (91,000) with a high decline rate of nasal influenza vaccination. A new Polish language information leaflet in the 2018 school influenza programme saw consent form return increase but uptake remained low. We compare vaccination attitudes of accepting and declining parents. Methods A questionnaire to 365 Polish parents after vaccination asked about the leaflet, vaccination, time in UK and included WHO Vaccine Hesitancy statements. Accepting and declining parents were compared. Results 128 (37%) responded - 42% of vaccinating and 39% declining parents. 90% were long term UK resident, 72% speak Polish at home. Previous experience had most influence in vaccination decision-making, with social media and personal contacts in Poland and Scotland also key. Decliners were more likely to cite social media than accepters. Concerns about new vaccines, side effects and ’currently uncommon conditions’ are high in the Polish community and decliners hold more negative and scientifically ’incorrect’ opinions. Parents know that Polish and UK immunisation schedules differ for influenza, a condition thought less serious in Poland than UK. Conclusions Polish norms strongly influence this migrant group. Differences in how Polish migrants who accept or decline the vaccination respond to vaccine hesitancy statements plus knowing that Polish media and the Polish community shape their views can be used by health authorities to target health messages. It is important to be aware of immunisation status and vaccination beliefs of mobile migrant groups, such as the Polish, to prevent spread of vaccine preventable diseases in Europe. Linking vaccine hesitancy statement responses and behaviour can highlight national characteristics and particular concerns of vaccine hesitant parents. This information could be used to improve vaccine uptake rates among different ethnic minorities. Key messages Polish migrant children have low nasal influenza vaccine uptake. Vaccine hesitancy statements show decliners are particularly likely to distrust new vaccines and worry about vaccine side effects. Migrants access Polish social media and information and retain vaccination beliefs and norms post migration. Knowing this allows targeting of information campaigns to increase uptake.

Safety of yellow fever vaccine strain (Tiantan strain) in China and WHO vaccine strain 17D-213

Objective To study the intracerebral pathogenicity of the yellow fever vaccine strains of Tiantan strain used in China and WHO vaccine strain 17D-213 in mice. Methods Mice of different ages and strains were intracerebrally injected with same amount of Tiantan strain and 17D-213 strain. The death and survival of mice were observed and recorded. The LD50/ml and half survival time of the two vaccine strains were compared and analyzed. Results There was no difference in LD50/ml between the Tiantan strain and 17D-213 strain when used through intracerebral injection in one-day-old suckling mice, 7-9 g mice or 12-14 g mice. Moreover, no significant difference in survival trend was found in 7-9 g mice or 12-14 g mice injected with the two vaccine strains. However, the two strains had statistically different influences on the survival trend of one-day-old suckling mice. The half survival time of the Tiantan strain was 11 d, while that of the WHO vaccine strain 17D-213 was 6 d. Excepting in NIH mice, no significant differences in LD50/ml were detected between the same amount of two strains in BALB/c, KM, ICR or C57 mice. Conclusions The yellow fever Tiantan vaccine strain and WHO vaccine strain 17D-213 have no significant difference in the intracerebral pathogenicity in mice of different ages and strains with good safety. Key words: Yellow fever; Vaccine strain; Intracerebral pathogenicity; Safety

Evaluation of A(H1N1)pdm09 LAIV vaccine candidates stability and replication efficiency in primary human nasal epithelial cells

The recent reduction of live attenuated influenza vaccine (LAIV) effectiveness in multivalent formulations was particularly associated with the A(H1N1)pdm09 component. In the 2017 the WHO vaccine composition committee changed its recommendations for the A(H1N1)pdm09 component to include an A/Michigan/45/2015-like virus. We evaluated effectiveness and quality of newly developed and previous A(H1N1)pdm09 LAIV reassortants through assessment of their thermal and pH stability, receptor binding specificity and replication fitness in primary human airway epithelial cells of nasal origin (hAECN). Our analysis showed that LAIV expressed hemagglutinin (HA) and neuraminidase (NA) from an A/Michigan/45/2015-like strain A/New York/61/2015 (A/New York/61/2015-CDC-LV16A, NY-LV16A), exhibit higher thermal and pH stability compared to the previous vaccine candidates expressing HA and NA from A/California/07/2009 and A/Bolivia/559/2013 (A17/Cal09 and A17/Bol13). Reassortants A/South Africa/3626/2013-CDC-LV14A (SA-LV14A) and NY-LV16A showed preferential binding to α2,6 sialic acid (SA) receptors and replicated at higher titers and more extensively in hAECN compared to A17/Cal09 and A17/Bol13, which had an α2,3 SA receptor binding preference. Our data analysis supports selection of A/New York/61/2015-CDC-LV16A for LAIV formulation and the introduction of new assays for LAIV characterization.

Cost-effectiveness of a potential Zika vaccine candidate: a case study for Colombia

BackgroundA number of Zika vaccine platforms are currently being investigated, some of which have entered clinical trials. We sought to evaluate the cost-effectiveness of a potential Zika vaccine candidate under the WHO Vaccine Target Product Profile for outbreak response, prioritizing women of reproductive age to prevent microcephaly and other neurological disorders.MethodsUsing an agent-based simulation model of ZIKV transmission dynamics in a Colombian population setting, we conducted cost-effectiveness analysis with and without pre-existing herd immunity. The model was parameterized with estimates associated with ZIKV infection, risks of microcephaly in different trimesters, direct medical costs, and vaccination costs. We assumed that a single dose of vaccine provides a protection efficacy in the range 60% to 90% against infection. Cost-effectiveness analysis was conducted from a government perspective.ResultsUnder a favorable scenario when the reproduction number is relatively low (R0 = 2.2) and the relative transmissibility of asymptomatic infection is 10% compared with symptomatic infection, a vaccine is cost-saving (with negative incremental cost-effective ratio; ICER) for vaccination costs up to US$6 per individual without herd immunity, and up to US$4 per individual with 8% herd immunity. For positive ICER values, vaccination is highly cost-effective for vaccination costs up to US$10 (US$7) in the respective scenarios with the willingness-to-pay of US$6610 per disability-adjusted life-year, corresponding to the average per capita GDP of Colombia between 2013 and 2017. Our results indicate that the effect of other control measures targeted to reduce ZIKV transmission decreases the range of vaccination costs for cost-effectiveness due to reduced returns of vaccine-induced herd immunity. In all scenarios investigated, the median reduction of microcephaly exceeded 64% with vaccination.ConclusionsOur study suggests that a Zika vaccine with protection efficacy as low as 60% could significantly reduce the incidence of microcephaly. From a government perspective, Zika vaccination is highly cost-effective, and even cost-saving in Colombia if vaccination costs per individual is sufficiently low. Efficacy data from clinical trials and number of vaccine doses will be important requirements in future studies to refine our estimates, and conduct similar studies in other at-risk populations.

Spatiotemporal analysis of tropical disease research combining Europe PMC and affiliation mapping web services

BackgroundTropical medicine appeared as a distinct sub-discipline in the late nineteenth century, during a period of rapid European colonial expansion in Africa and Asia. After a dramatic drop after World War II, research on tropical diseases have received more attention and research funding in the twenty-first century.MethodsWe used Apache Taverna to integrate Europe PMC and MapAffil web services, containing the spatiotemporal analysis workflow from a list of PubMed queries to a list of publication years and author affiliations geoparsed to latitudes and longitudes. The results could then be visualized in the Quantum Geographic Information System (QGIS).ResultsOur workflows automatically matched 253,277 affiliations to geographical coordinates for the first authors of 379,728 papers on tropical diseases in a single execution. The bibliometric analyses show how research output in tropical diseases follow major historical shifts in the twentieth century and renewed interest in and funding for tropical disease research in the twenty-first century. They show the effects of disease outbreaks, WHO eradication programs, vaccine developments, wars, refugee migrations, and peace treaties.ConclusionsLiterature search and geoparsing web services can be combined in scientific workflows performing a complete spatiotemporal bibliometric analyses of research in tropical medicine. The workflows and datasets are freely available and can be used to reproduce or refine the analyses and test specific hypotheses or look into particular diseases or geographic regions. This work exceeds all previously published bibliometric analyses on tropical diseases in both scale and spatiotemporal range.

Age-appropriate versus up-to-date coverage of routine childhood vaccinations among young children in Israel

ABSTRACTBackground and aims: Routine childhood vaccinations schedules recommend that children receive the vaccine doses at specific ages. Vaccination coverage data are conventionally reported by the up-to-date method. We aimed to assess vaccination timeliness by the age-appropriate method and compare with the up-to-date vaccination coverage. Methods: Assessment of age-appropriate and up-to-date vaccination coverage among children born in Israel in 2009 and followed to age 48 months (national representative sample, n = 3892). The vaccinations included: Hepatitis B vaccine (HBV), Diphtheria-Tetanus-acellular Pertussis-Polio-Haemophilus-influenzae-b (DTaP-IPV-Hib), Pneumococcal conjugate vaccine (PCV), Measles-mumps-rubella-varicella vaccine (MMR/MMRV) and Hepatitis A vaccine (HAV). The categories defined: age-appropriate (at the recommended age and up to 1 month), delayed less than 6 months, delayed 6 months and above and unvaccinated (48 months). Results: The age-specific vaccinations assessment showed considerable delay in receipt of routine vaccination. While most (96%, 95%, 91%, 96%, 94% and 86%) children were vaccinated up-to-date for HBV3, DTaP-IPV-Hib4, PCV3, MMR/MMRV1, HAV1and HAV2 vaccine doses; only 26%, 29%, 47%, 64%, 55% and 12% were vaccinated age-appropriate. Vaccination delay was more common in vaccines with multiple doses. Vaccination delay was associated with high child's birth order, low socio-economic rank, ethnicity (delay more common in Jews vs. Arabs), season of birth (winter) and delayed receipt of DTaP-IPV-Hib vaccine 1st dose. Conclusions: This study assessed age-appropriate childhood vaccination coverage in a national cohort of children. While the overall vaccination coverage stands in line with the WHO goals, vaccination timeliness and equity are inadequate and targeted public health intervention programs aimed at vaccination timeliness are necessary.

Rabies Vaccination Targets for Stray Dog Populations.

The role of stray dogs in the persistence of domestic dog rabies, and whether removal of such dogs is beneficial, remains contentious issues for control programs seeking to eliminate rabies. While a community might reach the WHO vaccination target of 70% for dogs that can be handled, the stray or neighborhood dogs that are too wary of humans to be held are a more problematic population to vaccinate. Here, we present a method to estimate vaccination targets for stray dogs when the dog population is made up of stray, free-roaming, and confined dogs, where the latter two types are considered to have an identifiable owner. The control effort required for stray dogs is determined by the type-reproduction number, T1, the number of stray dogs infected by one rabid stray dog either directly or via any chain of infection involving owned dogs. Like the basic reproduction number R0 for single host populations, T1 determines the vaccination effort required to control the spread of disease when control is targeted at one host type, and there is a mix of host types. The application of T1 to rabies in mixed populations of stray and owned dogs is novel. We show that the outcome is sensitive to the vaccination coverage in the owned dog population, such that if vaccination rates of owned dogs were too low then no control effort targeting stray dogs is able to control or eliminate rabies. The required vaccination level also depends on the composition of the dog population, where a high proportion of either stray or free-roaming dogs implies unrealistically high vaccination levels are required to prevent rabies. We find that the required control effort is less sensitive to continuous culling that increases the death rate of stray dogs than to changes in the carrying capacity of the stray dog population.

HCG Found in WHO Tetanus Vaccine in Kenya Raises Concern in the Developing World

In 1993, WHO announced a “birth-control vaccine” for “family planning”. Published research shows that by 1976 WHO researchers had conjugated tetanus toxoid (TT) with human chorionic gonadotropin (hCG) producing a “birth-control” vaccine. Conjugating TT with hCG causes pregnancy hormones to be attacked by the immune system. Expected results are abortions in females already pregnant and/or infertility in recipients not yet impregnated. Repeated inoculations prolong infertility. Currently WHO researchers are working on more potent anti-fertility vaccines using recombinant DNA. WHO publications show a long-range purpose to reduce population growth in unstable “less developed countries”. By November 1993 Catholic publications appeared saying an abortifacient vaccine was being used as a tetanus prophylactic. In November 2014, the Catholic Church asserted that such a program was underway in Kenya. Three independent Nairobi accredited biochemistry laboratories tested samples from vials of the WHO tetanus vaccine being used in March 2014 and found hCG where none should be present. In October 2014, 6 additional vials were obtained by Catholic doctors and were tested in 6 accredited laboratories. Again, hCG was found in half the samples. Subsequently, Nairobi’s AgriQ Quest laboratory, in two sets of analyses, again found hCG in the same vaccine vials that tested positive earlier but found no hCG in 52 samples alleged by the WHO to be vials of the vaccine used in the Kenya campaign 40 with the same identifying batch numbers as the vials that tested positive for hCG. Given that hCG was found in at least half the WHO vaccine samples known by the doctors involved in administering the vaccines to have been used in Kenya, our opinion is that the Kenya “anti-tetanus” campaign was reasonably called into question by the Kenya Catholic Doctors Association as a front for population growth reduction.

A decade of adaptation: Regulatory contributions of the World Health Organization to the Global Action Plan for Influenza Vaccines (2006–2016)

The Global Action Plan (GAP) for Influenza Vaccines is a decade-long initiative that brings together a diverse range of stakeholders to work towards reducing anticipated global shortage of influenza vaccines and ensuring more equitable access to vaccines during the next influenza pandemic. Since its inception in 2006, significant progress has been made towards all the main objectives of GAP, namely: (1) an increase in seasonal vaccine use, (2) an increase in vaccine production, and (3) progress in research and development of more effective vaccines. The Technology Transfer Initiative (TTI), conceived and managed by WHO under the GAP, contributed to increasing regional influenza vaccine production capacity. This was achieved by facilitating technology transfer in 14 low- and middle-income countries, through grants to manufacturers to establish or strengthen influenza vaccine production capacity and support to their national regulatory authorities. Five of the countries subsequently licensed locally produced influenza vaccines; two pandemic and three seasonal vaccines received WHO prequalification. The success of GAP can be largely attributed to the regulatory support provided by WHO to both manufacturers and regulators. This support had two components: (1) direct regulatory support to GAP/TTI, and (2) support to GAP-related WHO programmes, such as the Pandemic Influenza Vaccine Deployment Initiative in 2010 and the Pandemic Influenza Preparedness Framework since 2013, especially in non-vaccine-producing countries. Temporary adaptation of the assessment process for influenza vaccines in the WHO Vaccine Prequalification Programme to the A(H1N1) pandemic situation in 2009 was instrumental to the success of the WHO Pandemic Influenza Vaccine Deployment Initiative in its attempt to meet the demand for pandemic vaccines in countries that received donated vaccines.

From current vaccine recommendations to everyday practices: An analysis in five sub-Saharan African countries

BackgroundEstimates of WHO and UNICEF vaccination coverage may provide little insight into the extent to which vaccinations are administered on time. Yet, lack of adherence to the recommended age to receive a specific vaccination may have detrimental health consequences. For example, delays in receiving vaccination will prolong the risk of lack of protection, often when disease risk is highest, such as during early infancy. We estimated the reported age at vaccination, and vaccine coverage at different ages in children from five sub-Saharan African countries. MethodsWe analyzed data from the latest Demographic and Health Programme databases available for Burkina Faso 2010 (n=15,044 observations), Ghana 2008 (n=2992), Kenya 2008–9 (n=6079), Senegal 2010–11 (n=12,326), and Tanzania 2010 (n=8023). We assessed, amongst vaccinees, the exact age when vaccine was administered for the three infant doses of pentavalent vaccine (DTP) and the first dose of measles-containing-vaccine (MCV), as well as the proportion of children immunized with these antigens by a certain age. Vitamin A supplementation (VAS) coverage was evaluated as a potential contact visit for vaccine introduction. ResultsFor all DTP doses, the median intervals between recommended and actual ages of receiving vaccination ranged from 12, 17 and 23 days in Kenya, to 22, 33 and 45 days in Senegal. MCV was mostly given during the recommended age of 9 months. In each country, there was a large discrepancy in the median age at DTP vaccination between regions. VAS coverage in young children ranged from 30.3% in Kenya to 78.4% in Senegal, with large variations observed between areas within each study country. ConclusionIn the context of new vaccine introduction, age of children at vaccination should be monitored to interpret data on vaccine-preventable disease burden, vaccine effectiveness, and vaccine safety, and to adapt targeted interventions and messages.

Long-term impact of pneumococcal polysaccharide vaccination on nasopharyngeal carriage in children previously vaccinated with various pneumococcal conjugate vaccine regimes

Previously, the Fiji Pneumococcal Project (FiPP) evaluated reduced dose immunization schedules that incorporated pneumococcal protein conjugate and/or polysaccharide vaccine (PCV7 and 23vPPV, respectively). Immune hyporesponsiveness was observed in children vaccinated with 23vPPV at 12 months of age compared with children who did not receive 23vPPV.Here we assess the long-term impact of 23vPPV vaccination on nasopharyngeal carriage rates and densities of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. Nasopharyngeal swabs (n=194) were obtained from healthy children who participated in FiPP (now aged 5–7 years). S. pneumoniae were isolated and identified by standard culture-based methods, and serotyped using latex agglutination and the Quellung reaction. Carriage rates and densities of S. pneumoniae, H. influenzae, S. aureus and M. catarrhalis were determined using real-time quantitative PCR.There were no differences in the rate or density of S. pneumoniae, H. influenzae or M. catarrhalis carriage by PCV7 dose or 23vPPV vaccination in the vaccinated participants overall. However, differences were observed between the two main ethnic groups: Fijian children of Indian descent (Indo-Fijian) were less likely to carry S. pneumoniae, H. influenzae and M. catarrhalis, and there was evidence of a higher carriage rate of S. aureus compared with indigenous Fijian (iTaukei) children. Polysaccharide vaccination appeared to have effects that varied between ethnic groups, with 23vPPV vaccination associated with a higher carriage rate of S. aureus in iTaukei children, while there was a lower carriage rate of S. pneumoniae associated with 23vPPV vaccination in Indo-Fijian children.Overall, polysaccharide vaccination had no long-term impact on pneumococcal carriage, but may have impacted on S. aureus carriage and have varying effects in ethnic groups, suggesting current WHO vaccine schedule recommendations against the use of 23vPPV in children under two years of age are appropriate.

The influence of performance-based payment on childhood immunisation coverage

BackgroundPay-for-performance, also called the quality system (QS) in Estonia, was implemented in 2006 and one indicator for achievement is the childhood immunisation coverage rate. The WHO vaccination coverage in Europe for diphtheria, tetanus and pertussis, and measles in children aged around one year old should meet or exceed 90 per cent. MethodsThe study was conducted using a database from the Estonian Health Insurance Fund. The study compared childhood immunisation coverage rates of all Estonian family physicians in two groups, joined and not joined to the quality system during the observation period 2006–2012. Immunisation coverage was calculated as the percentage of persons in the target age group who received a vaccine dose by a given age. The target level of immunisations in Estonia is set at 90 per cent and higher. ResultsImmunisation coverage rates of family doctors (FD) in Estonia showed significant differences between two groups of doctors: joined to the quality system and not joined. Doctors joined to the quality system met the 90 per cent vaccination criterion more frequently compared to doctors not joined to the quality system. Doctors not joined to the quality system were below the 90 per cent vaccination criterion in all vaccinations listed in the Estonian State Immunisation Schedule. ConclusionPay-for-performance as a financial incentive encourages higher levels of childhood immunisations.

Prospective Surveillance and Molecular Characterization of Seasonal Influenza in a University Cohort in Singapore

BackgroundSoutheast Asia is believed to be a potential locus for the emergence of novel influenza strains, and therefore accurate sentinel surveillance in the region is critical. Limited information exists on sentinel surveillance of influenza-like illness (ILI) in young adults in Singapore in a University campus setting. The objective of the present study was to determine the proportion of ILI caused by influenza A and B viruses in a university cohort in Singapore.Methodology/Principal FindingsWe conducted a prospective surveillance study from May through October 2007, at the National University of Singapore (NUS). Basic demographic information and nasopharyngeal swabs were collected from students and staff with ILI. Reverse-transcriptase PCR (RT-PCR) and viral isolation were employed to detect influenza viruses. Sequencing of hemagglutinin (HA) and neuraminidase (NA) genes of some representative isolates was also performed. Overall proportions of influenza A and B virus infections were 47/266 (18%) and 9/266 (3%) respectively. The predominant subtype was A/H3N2 (55%) and the rest were A/H1N1 (45%). The overall sensitivity difference for detection of influenza A viruses using RT-PCR and viral isolation was 53%. Phylogenetic analyses of HA and NA gene sequences of Singapore strains showed identities higher than 98% within both the genes. The strains were more similar to strains included in the WHO vaccine recommendation for the following year (2008). Genetic markers of oseltamivir resistance were not detected in any of the sequenced Singapore isolates.Conclusions/SignificanceHA and NA gene sequences of Singapore strains were similar to vaccine strains for the upcoming influenza season. No drug resistance was found. Sentinel surveillance on university campuses should make use of molecular methods to better detect emerging and re-emerging influenza viral threats.

Antigenic sites of H1N1 influenza virus hemagglutinin revealed by natural isolates and inhibition assays

The antigenic sites of hemagglutinin (HA) are crucial for understanding antigenic drift and vaccine strain selection for influenza viruses. In 1982, 32 epitope residues (called laboratory epitope residues) were proposed for antigenic sites of H1N1 HA based on the monoclonal antibody-selected variants. Interestingly, these laboratory epitope residues only cover 28% (23/83) mutation positions for 9 H1N1 vaccine strain comparisons (from 1977 to 2009). Here, we propose the entropy and likelihood ratio to model amino acid diversity and antigenic variant score for inferring 41 H1N1 HA epitope residues (called natural epitope residues) with statistically significant scores according to 1572 HA sequences and 197 pairs of HA sequences with hemagglutination inhibition (HI) assays of natural isolates. By combining both natural and laboratory epitope residues, we identified 62 (11 overlapped) residues clustered into five antigenic sites (i.e., A–E) which are highly correlated to the antigenic sites of H3N2 HA. Our method recognizes sites A, B and C as critical sites for escaping from neutralizing antibodies in H1N1 virus. Experimental results show that the accuracies of our models are 81.2% and 82.2% using 41 and 62 epitope residues, respectively, for predicting antigenic variants on 197 paring HA sequences. In addition, our model can detect the emergence of epidemic strains and reflect the genetic diversity and antigenic variant between the vaccine and circulating strains. Finally, our model is theoretically consistent with the evolution rates of H3N2 and H1N1 viruses and is often consistent to WHO vaccine strain selections. We believe that our models and the inferred antigenic sites of HA are useful for understanding the antigenic drift and evolution of influenza A H1N1 virus.

Book: Academics, Epidemics, Politics by Idris Mohammed

Book: <i>Academics, Epidemics, Politics</i> by Idris Mohammed

Changed epitopes drive the antigenic drift for influenza A (H3N2) viruses

BackgroundIn circulating influenza viruses, gradually accumulated mutations on the glycoprotein hemagglutinin (HA), which interacts with infectivity-neutralizing antibodies, lead to the escape of immune system (called antigenic drift). The antibody recognition is highly correlated to the conformation change on the antigenic sites (epitopes), which locate on HA surface. To quantify a changed epitope for escaping from neutralizing antibodies is the basis for the antigenic drift and vaccine development.ResultsWe have developed an epitope-based method to identify the antigenic drift of influenza A utilizing the conformation changes on epitopes. A changed epitope, an antigenic site on HA with an accumulated conformation change to escape from neutralizing antibody, can be considered as a "key feature" for representing the antigenic drift. According to hemagglutination inhibition (HI) assays and HA/antibody complex structures, we statistically measured the conformation change of an epitope by considering the number of critical position mutations with high genetic diversity and antigenic scores. Experimental results show that two critical position mutations can induce the conformation change of an epitope to escape from the antibody recognition. Among five epitopes of HA, epitopes A and B, which are near to the receptor binding site, play a key role for neutralizing antibodies. In addition, two changed epitopes often drive the antigenic drift and can explain the selections of 24 WHO vaccine strains.ConclusionsOur method is able to quantify the changed epitopes on HA for predicting the antigenic variants and providing biological insights to the vaccine updates. We believe that our method is robust and useful for studying influenza virus evolution and vaccine development.

Establishing global policy recommendations: the role of the Strategic Advisory Group of Experts on immunization

The vaccine landscape has changed considerably over the last decade with many new vaccines and technological developments, unprecedented progress in reaching out to children and the development of new financing mechanisms. At the same time, there are more demands and additional expectations of national policy makers, donors and other interested parties for increased protection through immunization. The Global Immunization Vision and Strategy (GIVS), which broadens the previous scope of immunization efforts, sets a number of goals to be met by countries. The WHO has recently reviewed and adjusted both its policy making structure and processes for vaccines and immunization to include an enlarged consultation process to generate evidence-based recommendations, thereby ensuring the transparency of the decision making process and improving communications. This article describes the process of development of immunization policy recommendations at the global level and some of their impacts. It focuses on the roles and modes of operating of the Strategic Advisory Group of Experts on immunization, which is the overarching advisory group involved with the issuance of policy recommendations, monitoring and facilitating the achievement of the GIVS goals. The article also describes the process leading to the publication of WHO vaccine position papers, which provide WHO recommendations on vaccine use. WHO vaccine-related recommendations have become a necessary step in the pathway to the introduction and use of vaccines, especially in developing countries and, consequently, have a clear and significant impact.