An ongoing measles outbreak in the Federation of Bosnia and Herzegovina , 2014 to 2015

M Hukic (mirsadahukic@yahoo.com)1,2, J Ravlija3, S Karakas4, M Mulaomerovic3, A Dedeic Ljubovic5, I Salimović-Besic5, M Seremet5, S Ahmetagic6, A Comor7, E Feric2 1. Department of Medical Science, Academy of Sciences and Arts of Bosnia and Herzegovina, Sarajevo, Bosnia and Herzegovina 2. International Burch University, Sarajevo, Bosnia and Herzegovina 3. Institute of Public Health of Federation Bosnia and Herzegovina, Sarajevo, Bosnia and Herzegovina 4. Institute of Public Health of Central Bosnia Canton, Travnik, Bosnia and Herzegovina 5. Department of Clinical Microbiology, University Clinical Centre Sarajevo, Bosnia and Herzegovina 6. Clinic for Infectious Diseases, University Clinical Centre Tuzla, Tuzla, Bosnia and Herzegovina 7. Institute for Biomedical Diagnostic and Research “Nalaz”, Sarajevo, Bosnia and Herzegovina

Between January 2014 and the beginning of February 2015, the Federal Institute of Public Health in the Federation of Bosnia and Herzegovina has reported 3,804 measles cases.Notable transmission has been observed in three Central Bosnia Canton municipalities: Bugojno, Fojnica and Travnik.Most cases were unvaccinated 2,680 (70%) or of unknown vaccination status 755 (20%).Health authorities have been checking vaccination records and performing necessary prevention measures.The epidemic is still ongoing.
Since the beginning of 2014, a measles outbreak is taking place in the Federation of Bosnia and Herzegovina (FB&H), including a total of 3,804 measles cases up to the start of February 2015.
The first two cases were reported in Bugojno, Central Bosnia Canton, in siblings who were teenagers, both of whom had respectively visited the local health care centre in early February 2014, with a rash that had started three days earlier.They had recently travelled to Germany.

Description of the outbreak
For the investigation of the outbreak, the general principles of the case definition of the European Union (EU) Commission Decision of 2012 were used [1].Laboratory investigations of initial patients were conducted at the Department of Microbiology, University Clinical Centre-Sarajevo, Bosnia and Herzegovina, and were based on serological findings of the measles virus specific antibody response in serum samples.
From the first municipality affected by the outbreak, Bugojno in Central Bosnia Canton, where school-aged children and adolescents (6 to 19 years-old) with measles were reported from February 2014, the outbreak subsequently spread, in two distinct epidemic waves, to other cantons, including, consecutively, Sarajevo, Zenica-Doboj, Tuzla, Una-Sana, and Herzegovina-Neretva (Figure 1).

Figure 1
Cumulative number and geographical distribution of notified cases of the measles outbreak, Federation of Bosnia and Herzegovina, January 2014-February 2015 (n=3,804 cases) The name of the cantons of the Federation of Bosnia and Herzegovina are in white font, with the number of cases below.
In the legend, the first and second waves, refer to the two waves of the measles outbreak.
The first epidemic wave of the outbreak had a peak in week 26 of 2014 (23)(24)(25)(26)(27)(28)(29) June, n=175 cases) and the second, a peak in week 4 of 2015 (29-25 January, n=167 cases) (Figure2).During the first wave which occurred from the beginning of 2014 until July of that year, 2,201 measles cases were reported, mainly in the cantons of Central Bosnia, Zenica-Doboj and Sarajevo.
The second wave, from August 2014 to February 2015, accounted for an additional 1,603 cases, mainly in the Tuzla and Una-Sana Cantons.During the second wave, cases continued to occur in the three cantons that were previously most affected (Figure 2).

Age and sex distribution of cases
Overall, most cases 3,300 (87%) were under the age of 30 years.The highest number of cases (n=713) were in children aged between 15 and 19 years, followed by one to four year-olds (n=637 cases) and five to nine year-olds (n=578 cases) (Figure 3).
With the exception of those aged 30 years and older, for which of a total of 503 affected, 266 were female, more male individuals were reported in each age group (Figure 3).

Laboratory findings
Nasopharyngeal swabs were sent to the European Regional Reference Laboratory for Measles and Rubella in Luxembourg for genotyping.Investigations of three initial cases revealed the presence of the D8 measles virus genotype, and more samples are currently being analysed.

Control measures
Catch-up vaccinations have been conducted for schoolaged children and adolescents who had not received two doses of MMR vaccine (the minimum interval between the two doses was four weeks).In addition urgent immunisation campaigns were planned/partially conducted in municipalities where members of the Roma community were affected, as for parts of this community vaccination coverage is low in FB&H (data not shown).To prevent further spread, and to control the epidemic, persons with measles were asked to stay at home and vaccinations of unvaccinated contacts were carried out in families, kindergartens, schools, etc. according to the national regulations.In total, 1,577 first doses and 3,110 second doses of MMR vaccine were administered, however an obstacle to reaching sufficient vaccination coverage stems from parents following the anti-vaccination movement.

Discussion
Part of the World Health Organization strategic plan for the control of measles has been its elimination in Europe by 2015 [2].However, the number of notified measles outbreaks especially in central and western Europe has been increasing in the last five years, with a reported peak in 2011 (32,124 cases) [3][4][5].
Several countries reported a considerable number of cases, including: France, Bulgaria, Germany, Italy, Romania, Spain, Ukraine, and the United Kingdom [4][5][6].According to a report from the European Centre for Disease Prevention and Control, 30 EU/European Economic Area (EEA) countries conducting measles surveillance reported a total of 3,840 cases between December 2013 and November 2014 [6].The ongoing outbreak of measles in FB&H accounts for 3,804 cases, highlighting the region as a European hot spot for the disease.
In order to achieve 95% immunity in the population for measles, vaccination coverage with two doses needs to be higher than 95%.However, this was not achieved in the EU [5], and, similarly, FB&H has accumulated Reported measles cases by week of rash onset, Federation of Bosnia and Herzegovina, January 2014-February 2015 (n=3,804)  (1992)(1993)(1994)(1995) and in the post-war period (1996)(1997)(1998) left a considerable number of children susceptible to measles, as well as mumps and rubella [7,8].
The probable causes of the outbreak described here, as well as its expansion, are insufficient vaccination and implementation of proposed control measures.The majority of those affected had not received necessary vaccination (two doses of MMR) at the recommended time (up to 14 years of age).Our data demonstrate that most cases in the current outbreak either did not know their vaccination status (20%) or reported being either partially (8%) or not vaccinated at all (70%).
In 2007, the measles genotype circulating in FB&H was D4 [9], however in the current outbreak genotype D8 was found, a genotype reported in the western part of Europe (England, Germany, Italy) at the end of 2011 [10].It cannot be ruled out that the genotype D8 found in this outbreak might have been imported by individuals who travelled to such countries a short time before the beginning of the epidemic [10,11].Molecular epidemiology is an important surveillance tool for routine monitoring of movement and the spreading of different virus genotypes across Europe.
In conclusion, FB&H is currently facing a large measles outbreak with 3,804 cases by the beginning of 2015.This is probably related to disruption of routine MMR vaccination during the war and post-war periods, as well as the recent wave of vaccination controversies and the anti-vaccination movement that contribute to parental hesitance and in turn to lower immunisation coverage.Monitoring of the immunisation status and vaccine effectiveness is crucial.High vaccination coverage rates with two doses and advocacy and communication campaigns ensuring effective community involvement and public awareness are necessary to control the current epidemic and to avoid future outbreaks.

Figure 3
Age and sex distribution of reported measles cases in the For each age group the total number of cases is indicated above the chart bars.

Opportunistic testing for urogenital infection with
Chlamydia trachomatis in south-western Switzerland, 2012: a feasibility study

Introduction
Chlamydia trachomatis is a frequent cause of sexually transmitted urogenital infections [1].Carriers with asymptomatic infection are a difficult to reach reservoir promoting transmission to their sexual partners [2].Complications, although rarely life threatening, can be substantial, especially for women.They include pelvic inflammatory disease, chronic abdominal pain, ectopic pregnancy, tubal sterility [2] and possibly a higher risk for adverse pregnancy outcomes [3,4].
Rates of Chlamydia-related complications in a given population correlate with the prevalence of chlamydial infection [5].Treatment of urogenital infections caused by C. trachomatis can prevent complications, at least in the short term [6,7].The pooled risk ratio for all-cause pelvic inflammatory disease after one year of followup in women invited to have C. trachomatis screening in four randomised controlled trials was 0.64 (95% confidence interval (CI): 0.45-0.90)[2].Complications may occur despite regular screening at fixed intervals because of infection after treatment or during screening intervals [8,9].It has also been hypothesised that early treatment may impede development of immunity and favour future re-infection [10,11].
Following a decline in the late 1980s and early 1990s, laboratory notifications of infections with C. trachomatis in Switzerland have more than quadrupled since 2000 [1,12].In 2003, most infections were diagnosed by gynaecologists, hospital services and primary healthcare physicians [13].One study, published in 1989, found a positive culture rate of 18% in 600 women aged 18 to 55 years at a sexual health centre in Lausanne [14].Half of these women (49%) were symptomatic.More recent studies in Switzerland using PCR testing found lower rates: In 1998, 1% of 817 pregnant women and 2.8% of 772 other sexually active women were found to be PCR-positive for Chlamydia by their gynaecologist [15].In 2006 and 2007, 1.2% of 517 male Swiss military recruits with a mean age of 20 years were found by PCR to be infected [16], as were 7.3% of 386 healthy pregnant women in the period from 2006 to 2009 [4].
The European Centre for Disease Prevention and Control (ECDC) recommends implementation of C. trachomatis control using a strategy of four levels: primary prevention, case management, opportunistic testing and systematic screening [2,17].In Switzerland, a national programme for primary prevention of human immunodeficiency virus (HIV) infection was started in 1987, and subsequently widened in 2011 to all sexually transmitted infections (STI) [18].A national guideline for case management of STI including C. trachomatis was published in 2011 [19], but no recommendations exist for testing.A C. trachomatis test with administration fees costs CHF 119 (EUR 111), not including any medical consultation fees.These costs are reimbursed by basic insurance when the yearly medical costs exceed CHF 300 (EUR 281).The young and healthy without other health expenses therefore pay screening costs directly.
This study explores the feasibility of opportunistic testing for C. trachomatis control, the third level in the ECDC recommendations.From a public health perspective, feasibility should be examined at all stages of programme implementation, from societal to individual level.These may be conceptualised as political acceptance, provider compliance, target population acceptance, and user compliance.We report on feasibility at all of these levels.

Methods
The study was conducted in two cantons with a combined population of

Results
Results regarding each successive level of the study flow are summarised in Figure 1.
Provider compliance, assessed by rates of screening invitations, and target population acceptance, assessed by rates of participation, could be monitored in 14 of the 15 screening centres, totalling 2,995 candidates between February and December 2012.One centre did not consistently distinguish between noninvitation and non-participation and was therefore excluded from this part of the analysis.This centre was
A mean of 149 consenting participants (125 women, 24 men) were tested per week when all centres were open.Extrapolated over 52 weeks, assuming access to testing under the same conditions and 82% of the population sexually active (personal communication: Lociciro S, Spencer B, July 2014), 3.7% (6.7% of women, 1.2% of men) of the sexually active population aged between 12 and 29 years in 2012 in the study region [22] would have been tested.
Infection rates were similar for different educational levels, districts of residence, sizes of population of  In this study, infection rates varied between 1% and 11%, depending on already known risk factors, and were not substantially different from infection rates reported in Switzerland and Europe [4,15,16].
Population-based studies in European Union Member States report infection rates between < 1% and 10% for women and between < 1% and 6% for men, depending on country and characteristics of the study population [2].The National Chlamydia Screening Programme (NCSP) in the United Kingdom (UK) reported an infection rate of 7.7% in 2012 [23] and a Dutch pilot study (2008-2011) a rate of 4.3% [23,24].Infection rates for men at similar risk are consistently lower than for women of the same age and level of risk [2,23,24].Our study did not find different infection rates in individuals born in Switzerland vs those born elsewhere.
Nearly half of the female participants were younger than 20 years and the study participants had a profile of low to medium risk, with a median of one sex partner in the six months before screening.Half of all infections were therefore diagnosed in low-risk participants with only one sexual partner in the past six months.Although the questionnaire identified factors representing a relatively higher risk, such as presence of symptoms (11% positivity rate), being female and in the peak age group (10%) or having more than three sex partners in the six months before screening (11%), the only characteristic specific to individuals with no risk of infection was having had no sex partner in the past six months (having been sexually active before).Risk-based selection algorithms aiming at improved cost effectiveness [25] may therefore miss a substantial number of infections occurring in parts of the population associated with lower risk.

Limitations and challenges
Despite C. trachomatis screening proving to be technically feasible and reliable and treatment being simple and affordable, important obstacles remain.Despite near universal insurance coverage, access to screening for C. trachomatis in Switzerland is limited owing to a mandatory minimal yearly participation of CHF 300 (EUR 280).The high cost of a C. trachomatis test needs to be reviewed in order to allow affordable access, especially for adolescents.Men proved to be more difficult to reach in this context, constituting only 23% of the sample.Male participants were older than female participants and the proportion younger than 20 years was significantly lower.In the NCSP, men were more likely to order self-applied tests on the Internet than to visit a clinic for testing, and the number of tests ordered in this way increased from <1% to 6% of all tests between 2006 and 2010 [26].A screening programme in 13 schools in New Orleans, United States, in 1995 to 2005 showed up to 49% repeated testing in male students (with parental consent) [27].Of men aged 18 to 35 years in a survey in the UK, 75% had seen their family doctor in the last year, without relevant differences between different age groups among the 18 to 35-year-olds, providing general practitioners with occasions for opportunistic STI screening [28].In the NCSP, 9% of male 15 to 24 years-olds were tested by their general practitioner.Extrapolated over one year, the centres in our study alone would have tested a small proportion, ca 4%, of the 12 to 29 years-olds in the study region [1].Such testing activity would thus have little impact on Chlamydia transmission or its prevalence on a population level.In Switzerland, gynaecologists, hospitals services and primary care physicians notified most of all notified C. trachomatis infections in 2003 [13], but those healthcare providers were not included in this study.School-initiated home testing in post-obligatory schools (age 16 years and upwards) was initially intended.The school authorities in one canton declined participation, which shows a limitation on political grounds.
Nineteen per cent of all partners of tested participants with a positive result could be notified.Most partner notifications were only documented by asking the study participants.Whether sex partners actually received treatment was not assessed.Ascertaining if all partners are treated is a difficult challenge [29] and would also have been difficult in this study.In many countries, national vaccination recommendations are developed by independent expert committees, so-called national immunisation technical advisory groups (NITAG).Since the evaluation of vaccines is complex and resource-demanding, collaboration between NITAGs that evaluate the same vaccines could be beneficial.We conducted a cross-sectional survey among 30 European countries in February 2014, to explore basic characteristics and current practices of European NITAGs and identify potential modes and barriers for collaboration.Of 28 responding countries, 26 reported to have a NITAG or an equivalent expert group.Of these, 20 apply a systematic approach in the vaccine decision-making process, e.g. by considering criteria such as country-specific disease epidemiology, vaccine efficacy/effectiveness/ safety, health economics, programme implementation/logistics or country-specific values/preferences.However, applied frameworks and extent of evidence review differ widely.The use of systematic reviews is required for 15 of 26 NITAGs, while results from transmission modelling and health economic evaluations are routinely considered by 18 and 20 of 26 NITAGs, respectively.Twenty-five countries saw potential for NITAG-collaboration, but most often named structural concerns, e.g.different NITAG structures or countries' healthcare systems.Our survey gathered information that can serve as an inventory on European NITAGs, allowing further exploration of options and structures for NITAG collaboration.

Introduction
The number of vaccines available on the market has grown in recent years.At the same time, national healthcare systems have faced financial constraints and sought to maximise protection for those who benefit most in a given population.It has thus become increasingly important to assess the available evidence regarding a range of aspects before introducing a new vaccine into national immunisation programs.
The assessment usually takes into account the vaccine characteristics and expected population-level effects which can be considered as context-free aspects, e.g.vaccine efficacy/effectiveness or safety.Local disease epidemiology, cost-effectiveness and societal or cultural values and preferences, which are considered as context-specific aspects, are also factors often or always considered by responsible authorities.Assessments of vaccine recommendations should ideally be standardised, transparent and evidence-based: evidence-based being defined as 'the process of systematically finding, appraising, and using contemporaneous research findings as the basis for (…) decisions' [1].
To help appraising evidence gathered in such systematic manner, a number of tools are available for quality appraisal of single studies, e.g. the Critical Appraisal Skills Programme (CASP) [2], Assessing the Methodological Quality of Systematic Reviews (AMSTAR) [3], and the Cochrane risk of bias tool [4], as well as for entire bodies of evidence, such as the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology [5,6].
In the majority of industrialised countries, national vaccine recommendations are developed by a national immunisation technical advisory group (NITAG) [7].A NITAG is an independent expert advisory committee, providing 'evidence-based recommendations to the Ministry of Health (MoH), policy makers and program managers to guide policies and formulate strategies' [8].The World Health Organization (WHO) Global Vaccine Action Plan 2011-2020 stated as first strategic objective that all countries should as a priority commit to immunisation, e.g. by strengthening national capacity through creating or strengthening existing independent bodies such as NITAGs to formulate evidence-based policies [9].
During the '1st international workshop on procedures for the development of evidence-based vaccination recommendations' in Berlin in 2010 [10], a working group of international experts involved in vaccine decisionmaking processes discussed the need for international cooperation in the development of evidence-based vaccine recommendations and how such cooperation could be organised.Participants pointed out that, for example, systematic reviews of the same body of evidence are performed by NITAGs of several countries, thereby duplicating efforts and that this could be avoided by sharing those reviews and making them publicly available.
However, NITAG mode of operation, role and procedures in the decision-making processes can differ substantially from country to country [11,12].Therefore, it is a prerequisite for the potential establishment of an international cooperation to examine in detail similarities and differences in NITAGs' structures and modes of practice.The survey conducted by Nohynek et al. in 2013 was a first step taken to comprehensively explore key characteristics of NITAGs in the European Union (EU) and European Economic Area (EEA) countries and to explain obvious differences in immunisation policies between these countries even though decisions were based on the same or similar body of evidence [12].In 2014, as part of the Vaccine European New Integrated Collaboration Effort (VENICE) [13], an EU/EEA Member States network of experts in vaccine-preventable diseases, we conducted a follow-up survey in order to (i) systematically collect basic characteristics of EU/ EEA countries' NITAGs or immunisation expert groups, (ii) explore in detail their current practices for vaccine recommendation and, if applicable, framework characteristics, and (iii) identify potential synergies and resource sharing as well as potential barriers and limitations for collaboration in the vaccine recommendation development processes of NITAGs.

Methods
The VENICE gatekeepers in all 27 EU countries (except for the new Member State Croatia) and in the three EEA countries Iceland, Liechtenstein and Norway were contacted via email and asked to nominate and provide contact information of an expert in their respective country involved in the national vaccine recommendation decision-making process.The criterion for nomination was being a member of the NITAG (preferentially the NITAG chair) or alternatively, being a staff member of the NITAG Executive Secretariat (if existing).If the country had no NITAG, the gatekeeper was asked to nominate an expert involved in the development of national vaccine recommendations.
An For each country a two to three-page country profile was constructed with all information on the NITAG characteristics and decision-making processes, which was then supplemented with additional data regarding NITAG characteristics (year NITAG/expert group was established, voting-member composition, declaration of conflict of interest, number of meetings held, meetings opened to public, minutes published online) from the first survey of Nohynek et al. [12] and then sent back to each respondent for validation [14].
Answers provided in response to the first two sections as well as parts of the third section were analysed quantitatively to obtain aggregated results describing key parameters of NITAGs/expert groups in Europe.The remaining data from the third section (open questions on potential and barriers/limitations for collaboration), and if applicable answers from the last section were analysed qualitatively.

Results
In    is introduced in the national immunisation programme or vaccination schedule.

Characteristics of NITAG/expert groups and funding of recommended vaccinations
Funding of vaccinations that are adopted into the national vaccination schedule is in 19 countries through tax revenue, in three through social insurance, and in four based on a mixed scheme.In some countries, the funding can be restricted to mandatory vaccinations only and other recommended (but non-mandatory) vaccinations have to be paid out-of-pocket.Twenty-three of the 26 participating countries have a tender system for vaccine procurement in place, either at national (n = 20), regional (n = 4) and/or at local level (n = 2).

Frameworks/processes for evidence assessment
Of the 26 countries that participated in this survey section, 20 indicated that their NITAG/expert group applies a systematic approach (e.g.framework or standard operating procedure) and 13 stated that the approach contained a fixed list of key criteria.Elements of those systematic approaches and fixed lists of key criteria, respectively, were the consideration of country-specific disease epidemiology and burden (n = 20), vaccine efficacy/effectiveness and safety (n = 16), health economic evaluations (n = 12), vaccine implementation, logistics and availability (n = 11), country-specific values and preferences and acceptability in target groups (n = 9), alternative preventive measures (n = 4), as well as experiences of other countries or WHO guidelines (n = 4).
Despite the consideration of these common key criteria, the working process or sequences varied, from e.g. one NITAG with an assessment of the local disease epidemiology and WHO recommendations to another NITAG that uses an approach with two prerequisites that have to be fulfilled i.e. vaccine is available and vaccine should induce more than a short-term immunity, followed by the assessment of three criteria and 13 aspects set by law.Further details of the different systematic approaches by country have been made publicly available in country-specific profiles [14].
The use of systematic reviews is required in 15 of the 26 of NITAGs/expert groups, for the remaining this is optional (Table 3).Most NITAGs/expert groups (n=17) make use of self-conducted and published systematic reviews, and quality appraisal tools are used by five NITAGs/expert groups.The majority incorporates transmission modelling (n=18) and health economic evaluations (n=20) in their decision-making process.A background paper with the decision rationale is usually published by 13 NITAGs/expert groups.Of those published background papers, nine usually contain references of literature used, eight a narrative summary, six detailed results of systematic reviews including meta-analysis and six other materials (multiple answers possible); two contain all of the above.It has to be noted that background paper publications may be either peer-reviewed or non-peer reviewed online publications, e.g. on the NITAG's/expert group's own website.

Attitudes towards and potential modes and barriers for collaboration
Of the 27 countries that responded, 25 thought that there is 'potential for a collaboration/resource-sharing between NITAGs to support the individual country's process of developing vaccination recommendations'.Regarding areas or aspects for collaboration, five of them named systematic literature reviews in general.Fourteen of the 25 countries explicitly mentioned collaborating in the evidence review of context-free aspects like vaccine efficacy/effectiveness or safety, and 19 of context-specific aspects (e.g.local disease burden or local cost-effectiveness).
Regarding the latter, one country stated that 'there is always a value to also share the context-specific aspects', another that 'context-specific material may be illustrative of possible interpretations, assessments and recommendations'.Cost-effectiveness and/ or transmission modelling were explicitly named by 15 countries and disease burden assessment by 11 countries.It was suggested that 'mathematical models and cost-effectiveness models could be shared in order to be adapted to every specific country' and that '(…) burden assessment templates and mathematical modelling templates [should be shared] in which specific assumptions and country data could be introduced'.
When asked about minimum requirements for conducting joint systematic reviews, transmission modelling and/or economic evaluations, 18 of 25 countries favoured agreed methodologies and written guidelines.However, while most only mentioned that there should be such agreed methodologies, some countries voiced more detailed ideas about the optimal content of those agreements: 'Collaborating NITAGs should have the possibility to give input in the beginning of the process, e.g. which outcomes should be considered in the review or inclusion/exclusion criteria of studies', and a common methodology should include 'e.g. a search strategy, paper selection, and exclusion criteria of publications', make '(…) use of the same tools, e.g.GRADE, AMSTAR etc.' and should '(…) guarantee high quality of the work, for better comparability and to make the review process more transparent'.Finally, one country mentioned that there should also be 'a plan for peer review/publication' of those collaborative/shared systematic reviews to make transparent what is currently being worked on.
Regarding barriers and limitations for collaboration, responses could be grouped into the different categories (i) structural concerns, (ii) lack of funding and/ or lack of (human) resources and/or lack of available expertise, and (iii) possible language barriers and cultural differences, mentioned by 16, 10 and two countries, respectively.
In terms of structural concerns the countries highlighted either limiting differences in the countries' healthcare systems/vaccine delivery structures or differences among countries regarding the respective role of the NITAG and NITAG (working) structures.

Discussion
This survey gathered information from 28 of 30 EU/ EEA countries, thereby allowing for a detailed and representative inventory of NITAGs and equivalent expert groups involved in the process of developing national vaccination recommendations in the EU/EEA.In our survey, 26 of the participating countries reported having a NITAG or equivalent expert group, and the number will rise further once Cyprus has finished the process of re-establishing its NITAG.Liechtenstein relies on the evidence-based recommendations of the Swiss NITAG [26], an alternative approach for very small countries also proposed by the WHO [8].
Twenty of the surveyed countries indicated that they apply a systematic approach when developing a vaccination recommendation.The approaches reported by all/most of countries include an assessment of country-specific disease epidemiology/burden and vaccine efficacy/effectiveness and safety.About half also assess context-specific questions regarding programme implementation and vaccine logistics as well as potential acceptability in the target population.However, some countries have, as part of their specific formal requirements, a comprehensive set of questions or topics that need to be addressed in a predefined sequence.Furthermore, five countries use quality of evidence assessment tools.The extent and specifics that NITAGs/expert groups apply such systematic approaches, rely on systematic reviews, and consider results from transmission modelling and health economic evaluations differ between countries.Reasons for these differences are diverse and may be rooted in the role of the NITAG/expert group decision-making process.For example, if the NITAG is the final decisionmaker for inclusion of a vaccine in the national programme, the NITAG might feel a stronger responsibility to apply rigorous methodologies and to be as transparent as possible.Other reasons for these diversities might be cultural variations among countries regarding societal or governmental value/demand of transparency and evidence-based approaches vs trust in expert opinion as well as different resources for the NITAGs (e.g. the existence of an executive secretariat, own budget, or other contributing institution) or historical developments.
Less than half of the countries with a framework had it published, which makes it difficult to assess their differences in detail.Of those countries with a published framework, only Finland and the Netherlands [16,23] published it in English in peer-reviewed journals, thereby making it accessible for a wider audience.The remaining frameworks were published on websites associated with the NITAG/expert group or government, making it necessary to know specifically what and where to look for.Furthermore, four of those remaining seven frameworks are only available in the country's language.In comparison, NITAG frameworks of Canada, Switzerland and the United States [26][27][28][29][30] and WHO SAGE [31] can easily be found in English in peer-reviewed journals.
Despite those framework differences and respondents' concerns especially about structural differences among NITAGs or country systems posing essential barriers for collaboration, all but two saw potential for collaboration or resource-sharing to support the individual countries' processes of developing evidence-based vaccination recommendations.The great majority would favour to collaborate in systematic reviews regarding context-free and context-specific aspects.Fundamental for such collaboration is to recognise, that -as suggested by the GRADE working group -two steps can be separated when developing a recommendation: The assessment of the body of evidence and the process when moving from evidence to recommendation [5,6].Collaboration between NITAGs should focus on the first step.The strength of such an effort would be that it does not aim to harmonise vaccination recommendations across Europe and that it acknowledges that final decisions lie in the mandate of each country, with country-specific particularities being considered in their decision-making process.
Fifteen of the NITAGs/expert groups are required and ten optionally use systematic reviews in the recommendation process.Thus it is not surprising that countries saw potential for collaboration in conducting systematic reviews, a time and resource consuming undertaking, often requiring at least 12 months per review [32].Though the majority favoured agreed methodologies and written guidelines as a minimum requirement, only a small number of countries suggested possible concrete requirements, most likely to make the review process more transparent or applicable to their own framework requirements.Furthermore, so far the use of quality appraisal tools is not yet common among NITAGs/expert groups and is currently only performed by five countries.By definition, cooperation regarding context-free aspects will be less of a challenge as results are usually easily transferrable across countries.Regarding context-specific aspects, respondents found it valuable to share tools or generic models, rather than results, so countries could then apply their own country-specific assumptions or epidemiological data to these models.However, such adaptations of existing models could require special skills -so far seven countries have experiences of adopting existing models to their own local setting.Nevertheless, as one respondent stated, sharing context-specific information could still be helpful in the decision-making process, as it can provide an illustration of other countries' assessments and interpretations.
Our survey has two main limitations.Though answers in the questionnaire were followed up by a telephone interview or email, language barriers or differences in cultural perception may have led to misunderstandings of interview questions or responses.For example, the fact that in two countries transmission modelling was not named as part of the recommendation process but health economic assessments was (though transmission modelling is usually necessary to conduct cost-effectiveness analyses) might indicate that respondents could have interpreted the two terms and what they comprise in different ways.However, to avoid misunderstanding, summarised answers by country were given to the respondent for final validation to minimize interview misunderstandings.Second, the views and attitudes towards collaboration were retrieved usually only from one expert per country and might not necessarily represent the view of the entire NITAG or other stakeholders involved in NITAG work.However, we believe that these views and information constitute an important starting point for further discussions and stakeholder involvement with the aim to develop a draft roadmap for NITAG collaboration and resource-sharing in the EU/EEA as currently envisioned by ECDC and the VENICE project partners.
In 2008, the Supporting National Independent Immunization and Vaccine Advisory Committees (SIVAC) initiative has founded a platform to support the establishment of NITAGs in low-and middle income countries by providing information, tools and short-learning modules [33]

Letters
Letter to the editor: Measles outbreak linked to an international dog show in Slovenia -primary cases and chains of transmission identified in Italy, November to December 2014 A Filia (antonietta.filia@iss.it) 1 , F Riccardo

To the editor:
Recently, Grgič-Vitek et al. reported a measles outbreak in Slovenia linked to an international dog show held in Vrtjoba/Šempeter from 8 to 9 November 2014, involving 44 cases [1].Genotype D8 was identified in seven cases and viral sequences were deposited in the World Health Organization (WHO) MeaNS database [1].
In December 2014, the European Centre for Disease Prevention and Control (ECDC) conducted a Rapid Risk Assessment of the outbreak and recommended that, since the dog show had exhibitors from 27 European countries, national public health authorities from these countries should consider contacting the exhibitors to verify their measles vaccination status and illness histories, and perform contact tracing for identified cases [2].
The dog show was held near the Italian border and over 350 of the 670 registered exhibitors had reported an Italian address.The Infectious Diseases Epidemiology Unit of the Istituto Superiore di Sanità (ISS), in collaboration with regional and local health authorities in Italy contacted the Italian exhibitors, as recommended.
We obtained the names of registered exhibitors from the Slovenian authorities through the Early Warning and Response System (EWRS), listed these by region of residence and sent them to the regional health authorities (RHA) of 16 regions.We asked RHAs to (i) verify

Figure
Number of measles cases linked to an international dog show in Slovenia, by date of rash onset, Italy, November-December 2014 (n=18) Eighteen measles cases [3] were identified and reported to the national measles surveillance system: 11 primary cases, three secondary cases and four tertiary cases (Figure ).
The median age of the cases was 31 years (range 5-52 years); 16/18 cases were female.Vaccination status is known for 17/18 cases of whom 15 were unvaccinated and two had received one dose.Seventeen cases tested IgM/PCR positive against measles.Genotype D8 was isolated in three primary cases and phylogenetic analysis showed that viral sequences were identical to each other and to those identified in Slovenia [1].Sequencing and genotyping results for additional cases are pending.
The epidemiological, serological and molecular characterisation of cases linked to international mass gatherings is helpful in tracing international measles virus transmission pathways and identifying susceptible population groups, and will become increasingly important as Europe approaches measles elimination.
Although it is possible that additional cases will be identified in Italy, local transmission appears limited to date, suggesting that the public health response to the outbreak was timely in the regions involved.Measles vaccination coverage is suboptimal in Italy (88% for the first dose at two years of age, in 2013), ranging from 85.8% to 93.1% in the regions of residence of the participants at this event, and pockets of susceptible persons are known to exist, especially among adolescents and young adults [4].The fact that most Italian cases linked to the dog show were also young adults, further underlines the importance of closing immunisation gaps against measles in this population group.It is well known that the risk of measles transmission can be high at mass gatherings because of the large number of participants from many different countries (with varying vaccination and incidence rates) in a crowded setting [5].National public health authorities should raise awareness among the population of the risk of measles transmission during travel and mass gatherings, and of the importance of verifying one's immunity before departure.Governments hosting mass gatherings should work with event organisers to include measles immunisation advice for participants and visitors in the event information packages [6].
To the editor: We would like to thank Drs Goris and Hartskeerl for their interest in our paper.In Denmark, Patoc has traditionally been used as a functional classification group, exhibiting cross-reactivity to a large number of Leptospira serogroups.Therefore, while we are aware of the nomenclature of Leptospira, we chose nevertheless to use the term Patoc for this overview of more than 30 years of leptospirosis cases.It would have been relevant to underline in the abstract that reactivity with a titre ≥ 100 towards serovar Patoc should be seen as a 'probable infecting serogroup that could not be determined'.
Indeed, leptospirosis is a neglected disease in Europe and deserves attention.We agree that persistent complaints after acute leptospirosis must not be ignored.Yet, the true burden of both acute and chronic leptospirosis and the pathogenesis of persistent complains is not yet clear and chronicity has largely been described through individual case studies.The disease needs more attention, in order to improve our knowledge on this issue.While it is well established that the causative organism Leptospira spp. is endemic in the animal reservoirs in Europe, the number of diagnosed human cases is very low.This can partly be explained by the unspecific symptoms of the disease and the fact that the diagnosis may often not be considered as shown for leptospirosis among travellers returning from the tropics [1].
An example of a probably cause of climate changeassociated cases also in Denmark is an unusually heavy rainstorm that occurred over Copenhagen in July 2011.Sewer overflow led to severe flooding in the city and within buildings, which resulted in an increased number of acute leptospirosis cases.Five persons with leptospirosis were notified; two were admitted to hospital and one patient died [2].This event underlines the potential for prevention, stated in our paper, that can be achieved by raising awareness about the infection both among doctors and those at risk of infection.

Figure 4
Figure 4Chlamydia trachomatis infection rate by number of sex partners in the six months before screening, Switzerland, 2012 (n = 2,438; 17 missing answers)

Figure
FigureRole of National Immunisation Technical Advisory Groups and equivalent expert groups in the decision making process of a national vaccination introduction, European Union and European Economic Area countries, April 2014 (n = 26) One of 15 centres did not consistently distinguish between non-invitation and non-participation and was excluded from the inclusion part of analysis.This centre provided an additional 314 consenting participants included in screening and follow up.b Control test by PCR at 6 months after treatment.c Negative control test by PCR at six months after treatment. a

Table 1
Reasons given for declining Chlamydia trachomatis screening by 269 of 384 persons invited in 14 of 15 screening centres, Switzerland, 2012 (n = 269)

Table 2
Characteristics of tested participants and questionnaire answers, Chlamydia trachomatis screening, Switzerland, 2012 (n = 2,455) Valais: mostly patients treated for other infectious diseases such as HIV and hepatitis C (infectious disease clinic in Sion).
NA: not applicable; STI: sexually transmitted infection.Statistic tests (comparisons between the two cantons): for proportions (2x2): Fisher's exact test; for continuous data: Kruskal-Wallis.p values are not corrected for multiple testing.Totals can be lower than those in the column header because of missing answers or counts in subpopulations.a Valais: travellers coming for vaccination (infectious disease clinic in Sion).b

de) 1 , O Wichmann 1 , P Carrillo-Santisteve 2 , S Cotter 3 , D Lévy-Bruhl 4 , I Paradowska-Stankiewicz 5 , P Valentiner-Branth 6 , F D'Ancona 7 , the VENICE III NITAG Survey Group 8
this trend corresponds to an increasing incidence or other factors such as increased screening or an increased notification rate.Based on our results four main statements can be made to inform the public health authorities of Valais and Vaud regarding preventive measures for urogenital C. trachomatis infection and its complications.Firstly, C. trachomatis is present in the study region and therefore screening and efficient treatment would be desirable to prevent complications, no less than in other countries with similar infection rates.Secondly, as this study shows that C. trachomatis screening in existing sexual health centres in south-western Switzerland is technically feasible, these screening services can also be used for epidemiological investigation.Thirdly, C. trachomatis testing at low and affordable cost could promote use by those at risk.Finally, more screening opportunities need to be created, especially for difficult to reach populations such as men or people living in regions with difficult access for geographical reasons, and drop-outs during the screening and follow-up process need to be decreased.Georges Dupuis, former Head of public health in Valais, initiated the planning of this study.We are very grateful to the staff all screening centres for their enthusiastic participation in this study.We thank Mark Chung from the Melbourne Sexual Health Centre for providing us with illustrated instructions on how to take samples which could be adapted to local needs.Thanks go to Helen Di Lallo for proof-reading the manuscript.Funding: The study received two grants from public health services, one for each canton.The Institut de Microbiologie Universitaire in Lausanne executed the Chlamydia tests at a lower than usual rate for Vaud and Roche Diagnostics, Switzerland, provided commercial Chlamydia PCR kits at a preferred price for Valais.Study organisation: Mandate Valais: the Service des maladies infectieuses, Institut Central (Hôpital du Valais -ICHV), was mandated by the Service de la santé publique de l'Etat du Valais.Vaud: the Fondation Profa, Consultations de santé sexuelle, was mandated by the Service de la santé publique de l'Etat de Vaud. 1. Robert Koch Institute, Berlin, Germany 2. European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden 3. Health Protection Surveillance Centre, Dublin, Ireland 4. Institut de Veille Sanitare, Saint-Maurice, France 5. National Institute of Public Health -National Institute of Hygiene, Warsaw, Poland 6. Statens Serum Institut, Copenhagen, Denmark 7. Istituto Superiore di Sanitá, Rome, Italy 8. Members of the VENICE III NITAG Survey Group are listed at the end of the article Takla A, Wichmann O, Carrillo-Santisteve P, Cotter S, Lévy-Bruhl D, Paradowska-Stankiewicz I, Valentiner-Branth P, D'Ancona F, the VENICE III NITAG Survey Group.Characteristics and practices of National Immunisation Technical Advisory Groups in Europe and potential for collaboration, April 2014.Euro Surveill.2015;20(9):pii=21049. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=21049 Article submitted on 20 October 2014 / published on 05 March 2015 C. trachomatis notifications inSwitzerland have increased from 2,123 in 1999 to 9,701 in 2014.It remains unknown if The study was supported by grants from the Public Health Authorities in Vaud and Valais, allowing 1,200 screening tests in each canton.Roche Diagnostics provided Valais with C. trachomatis PCR kits at a reduced price.IMUL offered testing by C. trachomatis PCR at a preferential rate.ICHV provided study and data administration services and the study analysis.We thank the public health services of both cantons, Valais and Vaud, for sponsoring this study.santé sexuelle et reproductive, centre SIPE de Sion, Sion).Vaud: Gilbert Greub, Prof., MD PhD (Institute of Microbiology, University Hospital of Lausanne, Lausanne).Katia Jaton, PhD (Institute of Microbiology, University Hospital of Lausanne, Lausanne).Eric Masserey, MD (Médecin cantonal adjoint pour les maladies transmissibles, Service de la santé publique, Lausanne).Christiane Petignat, MD (Médecin associée, responsable Unité HPCI, CHUV et Service de la santé A Takla (taklaa@rki.

Table 1
General characteristics of National Immunisation Technical Advisory Groups and equivalent expert groups, European Union and European Economic Area countries, April 2014 (n=26) Neither Ministry of Health nor national public health institute (or equivalent) 5NITAGs/expert groups with Executive Secretariat or administrative office 17NITAGs/expert groups with additional persons/institutes scientifically supporting their work 20NITAGs/expert groups with official website 11Providing English translations of NITAG/expert group information or materials (only non-English speaking countries) 2 NITAG: National Immunisation Technical Advisory Groups.aClassification as NITAG or expert group by respondent.b Might not include additional, ad hoc meetings.c Multiple answers possible.

Table 2
Professional expertise represented among National Immunisation Technical Advisory Groups and equivalent expert groups, European Union and European Economic Area countries, April 2014 (n = 26) a Multiple answers possible.b Representative from the Association of Pharmaceutical Companies

Table 1
depicts general characteristics of the 26 NITAGs/ expert groups such as number of years since its establishment, whether members have to declare potential conflicts of interest, or if the NITAG is supported by an executive secretariat.A large range of professional expertise is usually represented among NITAGs/expert groups (Table2).In 15 countries staff from the National Public Health Institute or an equivalent institution is also represented as a voting member in the committee (Table1).The role of NITAGs/expert groups can be different during the decision-making process of a national vaccine introduction in EU/EEA countries(Figure).Most commonly, NITAGs/experts groups provide advice to the National Public Health Institute or the MoH.The latter, often together with other stakeholders, usually makes the final decision whether or not a new vaccine

Table 3
Elements of the vaccine recommendation development processes in National Immunisation Technical Advisory Groups and equivalent expert groups, European Union and European Economic Area countries, April 2014 (n=26) AMSTAR: Assessing the Methodological Quality of Systematic Reviews; CASP: Critical Appraisal Skills Programme; GRADE: Grading of Recommendations Assessment, Development and Evaluation; NITAG: National Immunisation Technical Advisory Groups; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses. a Usually or often conducted or if resources permit.
NITAG/expert group is allowed to outsource reviews to a third party (e.g.institution, private company) 8Quality of evidence appraisal is performed 5Contract allows to share results with other parties (e.g.foreign NITAGs or national public health institutes) 5

1,2 , M Del Manso 1 , P D'Agaro 3 , F Magurano 4 , A Bella 1 , Regional contact points for measles surveillance 5
1. Infectious Diseases Epidemiology Unit, National Centre for Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Rome, Italy 2. European Programme for Intervention Epidemiology Training (EPIET), European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden 3. Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy 4. Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy 5.The regional contact points for measles surveillance are listed at the end of the article

Citation style for this article:
Filia A, Riccardo F, Del Manso M, D'Agaro P, Magurano F, Bella A, Regional contact points for measles surveillance.Letter to the editor: Measles outbreak linked to an international dog show in Slovenia -primary cases and chains of transmission identified in Italy, November to December 2014.Euro Surveill.2015;20(9):pii=21050.Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=21050 Article submitted on 23 February 2015 / published on 05 March 2015 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 222324 25Cases were classified according to the European Commission case definitions of 8 August 2012[3].whetheranymeasles cases had been reported since 1 November 2014 among the persons listed; (ii) contact exhibitors by telephone and conduct an interview, based on a standard questionnaire prepared by ISS, to collect demographic information and enquire about vaccination status, measles symptoms since 1 November 2014 and other known non-registered participants; (iii) contact additional participants identified; (iv) report identified measles cases to the national surveillance system, including laboratory testing and genotyping results and (v) perform contact tracing of cases.The above-mentioned activities were performed by local health authorities (LHA) who were in contact with 276 of 374 (73.8%) registered exhibitors, of whom 226 confirmed their attendance to the dog show and agreed to be interviewed.Additionally, 164 non-registered participants were identified, of whom 78 have been interviewed to date.Overall, 304/538 (56.5%) participants or their guardians were interviewed, 281 (92%) of whom residing in six regions, mostly located in northern Italy.The median age of participants was 45 years (range 2 months-74 years); 144 (47.4%) were male.Measles vaccination status was reported by 245 participants (80.6%), of whom 189 (77.1%) were unvaccinated.Information on prior measles infection was available for 169 unvaccinated participants, of whom 25 (15.2%) reported no history of illness.