Rebecca Martin

Lessons learnt from pandemic A(H1N1) 2009 influenza vaccination. Highlights of a European workshop in Brussels (22 March 2010).

This European workshop identified a number of lessons learnt in the field of vaccine licensure, prioritization of target groups, communication on pandemic vaccines, implementation of vaccination and safety monitoring. The mild severity of the pandemic A(H1N1) 2009 influenza virus influenced the perception of pandemic vaccines, as previous pandemic preparedness had anticipated a more virulent virus. This vaccination experience provides an important opportunity for research on the long-term immunogenicity and safety of pandemic vaccines in pregnant women and children, as well as on the long-term safety of adjuvants. Preparedness for future pandemics could involve improved decision-making on target groups and increased communication on vaccine safety.

Molecular Genotyping and Epidemiology of Measles Virus Transmission in the World Health Organization European Region, 2007–2009

BACKGROUND In 2002, the World Health Organization (WHO) adopted a goal to eliminate measles in the European Region by 2010. Measles elimination is defined as the interruption of indigenous measles virus (MV) transmission. The molecular epidemiology of MV transmission in the WHO European Region was studied through the investigation of reported cases and outbreaks to monitor the regions progress toward its measles elimination goal. METHODS National and regional laboratories performed molecular characterization of MV detected between 2007 and 2009 in the WHO European Region. To document indigenous transmission and importations into the region, we analyzed genotyping results and epidemiological data on measles outbreaks reported by the member states. RESULTS Since 2007, MV genotype D6 has not been reported in the WHO European Region, suggesting that its chains of transmission have been interrupted, whereas several other MV genotypes are still circulating. Although several European countries have already interrupted indigenous MV transmission, genotyping showed that 3 endemic MV transmission chains have been reestablished in other countries. CONCLUSIONS The WHO European Region 2010 goal will not be met, as indigenous transmission of MV has not been interrupted. As the region begins to document its process of elimination verification to monitor progress toward the goal, countries will need to ensure that genotyping is performed in all measles outbreaks.

The role of older children and adults in wild poliovirus transmission

Significance The incidence of poliomyelitis has dropped precipitously over the last decade. However, persistent transmission in three countries and outbreaks elsewhere challenge the end-2014 eradication target. The Global Polio Eradication Initiative is considering expanding the age range of vaccination campaigns even in the absence of adult cases, because of concerns about imperfect, waning intestinal immunity. The success of this approach will depend on the contribution to transmission by older ages, which we estimated during two large outbreaks affecting adults. Their contribution was found to depend on the setting, but there was no evidence for imperfect immunity contributing to the transmission of infection. Even small gains in the speed of vaccination response were found to have substantially greater benefit compared with expanded age range campaigns. As polio eradication inches closer, the absence of poliovirus circulation in most of the world and imperfect vaccination coverage are resulting in immunity gaps and polio outbreaks affecting adults. Furthermore, imperfect, waning intestinal immunity among older children and adults permits reinfection and poliovirus shedding, prompting calls to extend the age range of vaccination campaigns even in the absence of cases in these age groups. The success of such a strategy depends on the contribution to poliovirus transmission by older ages, which has not previously been estimated. We fit a mathematical model of poliovirus transmission to time series data from two large outbreaks that affected adults (Tajikistan 2010, Republic of Congo 2010) using maximum-likelihood estimation based on iterated particle-filtering methods. In Tajikistan, the contribution of unvaccinated older children and adults to transmission was minimal despite a significant number of cases in these age groups [reproduction number, R = 0.46 (95% confidence interval, 0.42–0.52) for >5-y-olds compared to 2.18 (2.06–2.45) for 0- to 5-y-olds]. In contrast, in the Republic of Congo, the contribution of older children and adults was significant [R = 1.85 (1.83–4.00)], perhaps reflecting sanitary and socioeconomic variables favoring efficient virus transmission. In neither setting was there evidence for a significant role of imperfect intestinal immunity in the transmission of poliovirus. Bringing the immunization response to the Tajikistan outbreak forward by 2 wk would have prevented an additional 130 cases (21%), highlighting the importance of early outbreak detection and response.

What Will It Take to Achieve Measles Elimination in the World Health Organization European Region: Progress From 2003–2009 and Essential Accelerated Actions

BACKGROUND The Member States of the European Region (EUR) of the World Health Organization (WHO) have made great progress towards achieving the goal of measles elimination by 2010. METHODS Measles surveillance and vaccine coverage data from 2003-2009 reported to WHO were analyzed. A review of feasibility of reaching the elimination goal by the 2010 target date was conducted in 2009. RESULTS From 2003-2009, the measles incidence decreased dramatically and coverage with 2 doses of measles vaccine increased among wide age groups of susceptible persons. With the decrease of disease incidence and the reduction of outbreaks in the eastern part of EUR, the proportion of reported cases in the western part increased. In 2009, outbreaks in 5 countries accounted for 89.6% of reported cases. Challenges to reach the 2010 goal include ongoing outbreaks with reestablished endemicity in some countries, decreased demand for vaccines with an increased focus on the measles vaccine safety, and population groups with limited access to immunization services. CONCLUSIONS Measles elimination in EUR is attainable, albeit not by 2010. EUR countries should ensure political commitment and resources to protect the gains made to date and address these challenges to sustain the progress and achieve the elimination goal.

Supplementary Immunization Activities to Achieve Measles Elimination: Experience of the European Region

BACKGROUND Supplementary immunization activities (SIAs) using measles-containing vaccine (MCV) have had a substantial impact on reducing mortality associated with measles worldwide. METHODS To assess impact of SIAs on measles incidence in the World Health Organization European Region and their role at the final stages of measles elimination efforts in Europe, we reviewed information on SIAs, measles surveillance, and routine vaccination coverage during 2000-2009. RESULTS During 2000-2009, >57 million persons received MCV through SIAs in 16 countries. The Region primarily focused on catch-up campaigns with wider target age groups than in other regions and subsequently relied on routine vaccination rather than periodic follow-up SIAs for the second MCV dose. In addition, the concept of SIAs has been expanded from short-term (<30 days) mass campaigns implemented in other regions to incorporate vaccination efforts over longer periods and outbreak response vaccination. In 2009, 14 of 16 countries that conducted SIAs reported no measles cases or <1 case per 1,000,000 population, reflecting the post-SIA decrease in incidence. CONCLUSIONS SIAs have made a substantial contribution to the success of measles elimination efforts and will likely remain an important strategy for interrupting measles virus transmission in the European Region, although specific approaches will vary by country.

World Health Organization regional assessments of the risks of poliovirus outbreaks.

While global polio eradication requires tremendous efforts in countries where wild polioviruses (WPVs) circulate, numerous outbreaks have occurred following WPV importation into previously polio-free countries. Countries that have interrupted endemic WPV transmission should continue to conduct routine risk assessments and implement mitigation activities to maintain their polio-free status as long as wild poliovirus circulates anywhere in the world. This article reviews the methods used by World Health Organization (WHO) regional offices to qualitatively assess risk of WPV outbreaks following an importation. We describe the strengths and weaknesses of various risk assessment approaches, and opportunities to harmonize approaches. These qualitative assessments broadly categorize risk as high, medium, or low using available national information related to susceptibility, the ability to rapidly detect WPV, and other population or program factors that influence transmission, which the regions characterize using polio vaccination coverage, surveillance data, and other indicators (e.g., sanitation), respectively. Data quality and adequacy represent a challenge in all regions. WHO regions differ with respect to the methods, processes, cut-off values, and weighting used, which limits comparisons of risk assessment results among regions. Ongoing evaluation of indicators within regions and further harmonization of methods between regions are needed to effectively plan risk mitigation activities in a setting of finite resources for funding and continued WPV circulation.

Status of Rubella and Congenital Rubella Syndrome Surveillance, 2005–2009, the World Health Organization European Region

BACKGROUND The World Health Organization European Region has a goal for rubella elimination and congenital rubella syndrome (CRS) prevention. Although all Member States recommend a rubella-containing vaccine in their national immunization programs, rubella and CRS continue to occur, and surveillance quality varies throughout the region. METHODS To describe the status of regional rubella and CRS surveillance and assess progress toward elimination, we reviewed surveillance practices by surveying all 53 Member States and analyzed rubella and CRS surveillance data during 2005-2009. RESULTS Overall, 41 (91%) of 45 responding Member States have nationwide rubella surveillance, and 39 (87%) have nationwide CRS surveillance. During 2005-2009, rubella cases reported in the region decreased by 94% from 206,359 cases to 11,623 cases. The greatest decrease (99%) was observed in newly independent states of the former Soviet Union. In the rest of the region, high rubella incidence was observed in Poland, Romania, Italy, and San Marino during 2005-2008 and in Poland, Bosnia and Herzegovina, and Austria in 2009. A total of 68 CRS cases were reported during 2005-2009. CONCLUSIONS As the foundation to achieving and verifying rubella elimination, high-quality rubella and CRS surveillance needs to be implemented and sustained in all Member States.

Population immunity to polioviruses in the context of a large-scale wild poliovirus type 1 outbreak in Tajikistan, 2010.

BACKGROUND A serosurvey to evaluate population immunity to polioviruses (PVs) in the context of the importation-related wild PV1 outbreak in Tajikistan in 2010 (461 confirmed cases among children and young adults) was conducted. METHODS Serum specimens from a nationwide sample of 1-24 year-old persons selected through stratified cluster sampling (n=2447) were tested for neutralizing antibodies to all three PV types. Samples with titers<1:8 were considered seronegative. The serosurvey was conducted during the interval after mOPV1 supplementary immunization activities (SIAs) and before tOPV SIAs (targeting ages ≤ 15 years) implemented to control the outbreak. In the absence of pre-outbreak specimens, results for PV3 were used as a proxy for pre-outbreak PV1 immunity patterns. RESULTS Overall, PV1 seroprevalence was 98.9%, PV2 seroprevalence was 98.8%, and PV3 seroprevalence was 86.9%. PV1 and PV2 seroprevalence exceeded 95% in all age groups and regions. PV3 seroprevalence was <90% in all age groups and regions, except 15-19 year-olds (91.7%) and Dushanbe (90.0%). PV3 seroprevalence was lowest among 1-4 (82.7%) and 5-9 (84.4%) year-olds, particularly among 1-4 year-olds in Kurgan-Tube (76.3%) and RRS (80.0%) regions. Birth cohorts immunized only through routine services (ages, 1-7 years) had lower PV3 seroprevalence than birth cohorts targeted by the SIAs during 1995-2002 (8-19 years): 82.5% versus 89.3%, p<0.001. CONCLUSIONS Suboptimal (<90%) PV3 seroprevalence across wide age range suggests the outbreak resulted from accumulation of susceptibles due to suboptimal coverage over a long time period, particularly in the birth cohorts immunized only through routine services and in areas where the outbreak began (Kurgan-Tube and RRS). High PV1 seroprevalence indicates that mOPV1 SIAs with expanded target age (≤ 15 years) succeeded in closing the immunity gap and ongoing WPV1 transmission is unlikely. To accelerate outbreak control in areas which have been polio-free for long time, expanding SIA target age should be considered.

Control of Japanese encephalitis in Asia: the time is now.

Japanese encephalitis (JE) virus is the most common vaccine-preventable cause of encephalitis in Asia. Recent progress in the development and availability of improved JE vaccines has revitalized the prospects for JE control. There now are a number of safe and effective vaccines, two WHO prequalified vaccines available for pediatric use, at least one vaccine considered affordable for use in lower income countries, and a GAVI Alliance commitment to provide financial support to eligible countries for campaigns for children aged 9 months through 14 years. While challenges remain, this tremendous progress means there is a better opportunity than at any time in the past to prevent the substantial morbidity and mortality from this disease.

Seroepidemiology of diphtheria and tetanus among children and young adults in Tajikistan: nationwide population-based survey, 2010.

BACKGROUND Tajikistan had a major diphtheria outbreak (≈ 10,000 cases) in the 1990 s, which was controlled after nationwide immunization campaigns with diphtheria-tetanus toxoid in 1995 and 1996. Since 2000, only 52 diphtheria cases have been reported. However, in coverage surveys conducted in 2000 and 2005, diphtheria-tetanus-pertussis vaccine coverage was lower than administratively reported estimates raising concerns about potential immunity gaps. To further assess population immunity to diphtheria in Tajikistan, diphtheria antibody testing was included in a large-scale nationwide serosurvey for vaccine-preventable diseases conducted in connection with a poliomyelitis outbreak in 2010. In addition, the serosurvey provided an opportunity to assess population immunity to tetanus. METHODS Residents of all regions of Tajikistan aged 1-24 years were included in the serosurvey implemented during September-October 2010. Participants were selected through stratified cluster sampling. Specimens were tested for diphtheria antibodies using a Vero cell neutralization assay and for tetanus antibodies using an anti-tetanus IgG ELISA. Antibody concentrations ≥ 0.1 IU/mL were considered seropositive. RESULTS Overall, 51.4% (95% CI, 47.1%-55.6%) of participants were seropositive for diphtheria and 78.9% (95% CI, 74.7%-82.5%) were seropositive for tetanus. The lowest percentages of seropositivity for both diseases were observed among persons aged 10-19 years: diphtheria seropositivity was 37.1% (95% CI, 31.0%-43.7%) among 10-14 year-olds, and 35.3% (95% CI, 29.9%-41.1%) among 15-19 year-olds; tetanus seropositivity in respective age groups was 65.3% (95% CI, 58.4%-71.6%) and 70.1% (95% CI, 64.5%-75.2%). CONCLUSIONS Population immunity for diphtheria in Tajikistan is low, particularly among 10-19 year-olds. Population immunity to tetanus is generally higher than for diphtheria, but is suboptimal among 10-19 year-olds. These findings highlight the need to improve routine immunization service delivery, and support a one-time supplementary immunization campaign with diphtheria-tetanus toxoid among birth cohorts aged 1-19 years in 2010 (3-21 years in 2012) to close immunity gaps and prevent diphtheria outbreaks.