Survey of European programmes for the epidemiological surveillance of congenital toxoplasmosis.

The objective of this investigation was to describe systems for the epidemiological surveillance of congenital toxoplasmosis implemented in European countries. In September 2004, a questionnaire, adapted from the evaluation criteria published by the United States Centers for Disease Control and Prevention, was sent to a panel of national correspondents in 35 countries in the European geographical area with knowledge of the epidemiological surveillance systems implemented in their countries. Where necessary, we updated the information until July 2007. Responses were received from 28 countries. Some 16 countries reported routine surveillance for toxoplasmosis. In 12 countries (Bulgaria, Cyprus, Czech Republic, England and Wales, Estonia, Ireland, Latvia, Lithuania, Malta, Poland, Scotland and Slovakia), surveillance was designed to detect only symptomatic toxoplasmosis, whether congenital or not. Four countries reported surveillance of congenital toxoplasmosis, on a regional basis in Italy and on a national basis in Denmark, France and Germany. In conclusion, epidemiological surveillance of congenital toxoplasmosis needs to be improved in order to determine the true burden of disease and to assess the effectiveness of and the need for existing prevention programmes.


Introduction
Toxoplasmosis is caused by a protozoan parasite ( . While toxoplasmosis infection is often benign, congenital Toxoplasma gondii) toxoplasmosis (transmission to the foetus when a pregnant woman acquires toxoplasma infection for the first time during pregnancy) can lead to severe sequelae for the foetus and the newborn with visual or neurological impairment or death.
It is important to evaluate the burden of toxoplasma infection in the general population, as well as in pregnant women, foetuses, newborns and children, because this contributes to the rationale behind the different screening programmes currently performed (none, prenatal or postnatal) . Frequency and severity of a disease are the basic measurements used to assess its burden, and data on this can [1][2][3] be collected in specific studies or surveillance systems. The value of epidemiological surveillance is that it can be used to monitor trends over time. Public health strategies to prevent congenital toxoplasmosis differ between European countries. It is still being debated which are the best methods for controlling congenital toxoplasmosis, and the debate is not always based on accurate information.
The EUROTOXO project ( ) is a European consensus initiative aimed at defining the implications http://eurotoxo.isped.u-bordeaux2.fr of current scientific knowledge for a research agenda and for policy decisions on how best to prevent congenital toxoplasmosis and its consequences. The project has reviewed the state of the knowledge concerning the burden of toxoplasma infection in Europe. This article presents a systematic review of the systems implemented in European countries for the epidemiological surveillance of toxoplasmosis.

Source of information
We identified contacts for national surveillance programmes in 30 European countries ( ) from the following sources: Table 1 the members of the Eurosurveillance Editorial Board listed on the Eurosurveillance website at the time; 2 9 Contacts for six other European countries (Albania, Bosnia-Herzegovina, Bulgaria, Croatia, Macedonia, and Serbia-Montenegro) were identified by Google search.
We did not find correspondents for Andorra, Monaco or Northern Ireland. The list of correspondents is shown in . All contacts Table 1 were sent emails in September 2004 and those who did not respond were sent three further emails in January/February, April, and July 2005. We maintained contact with our correspondents in each participating countries until July 2007 and updated the data when a change in the surveillance systems was signalled. This was the case for France (implementation of a new surveillance system) and Denmark (surveillance system stopped).

Data collection and interpretation
We developed a comprehensive questionnaire, based on the criteria published by the United States (US) Centers for Disease Control ' and Prevention (CDC) for the evaluation of epidemiological surveillance systems . Epidemiological surveillance was defined as ongoing [4] and systematic collection, analysis, and interpretation of health data in the process of describing and monitoring a health event. The survey included questions about the objective of the surveillance system, the description of the health event under surveillance (case definition), the population under surveillance, the period of data collection, who was responsible for case reporting (sources of information) and a flow chart describing the system. We also asked how often the data were analysed and fed back to the reporting sources, and for the estimated costs of the toxoplasmosis surveillance system.
The usefulness of a given surveillance system was evaluated according to the following criteria: simplicity (ease of operation), flexibility (adaptability to changing information needs or operating conditions) and acceptability (cooperation of people on whom the system depends) based on the number and qualification of the reporting sources; sensitivity (proportion of cases detected by the system) and representativeness (the ability to describe the distribution of cases over time and in the population) based on the qualification of the reporting sources and on the figures available from the surveillance systems; timeliness (delay between steps in the system) based on the frequency of analysis and reports distribution.

Results
We received responses from 28 of 35 countries. Seven countries (Albania, Luxembourg, Croatia, Hungary, the Former Yugoslav Republic of Macedonia, Serbia-Montenegro and Spain) did not send a response at all. Information on Denmark and France was updated in July 2007.
Of the 28 countries that responded, 12 did not have a surveillance system for toxoplasmosis (congenital or not). The 16 countries that did report to have a system for the epidemiological surveillance of toxoplasmosis in place, are almost all situated in central or eastern Europe ( ) ( ). Poland has the oldest surveillance system (dating from 1966), while the most recent systems are in Cyprus, Figure Table 2 Ireland and Malta (dating from 2004).
Only four countries operate surveillance specifically for congenital toxoplasmosis: Denmark, France, Italy and Germany.

In
, a nationwide neonatal screening programme based on neonatal Guthrie card testing for toxoplasma-specific IgM was Denmark implemented in 1999 but discontinued on 31 July, 2007 (Petersen E; personal communication). The Danish National Health Board found insufficient evidence that treatment for toxoplasmosis was effective, neither in preventing later attacks of ocular toxoplasmosis in children born without ocular lesions nor in preventing further attacks in children born with ocular lesions . In case of a positive Guthrie result, [6] peripheral blood samples were taken from the newborn and the mother and analysed for IgM, IgA and IgG profiles. The epidemiological surveillance system was based on this screening programme and therefore included all infants with congenital toxoplasmosis, whether or not they had clinical manifestations. Surveillance and all laboratory analyses were coordinated by Statens Serum Institut in Copenhagen. Detection of specific IgM or IgA antibodies; 3 9 Neosynthesis of specific IgG, IgM or IgA antibodies; Stable specific IgG titres until after the age of one month; Persistently stable specific IgG titres until the age of one year.
Cases are notified by laboratories qualified for antenatal or postnatal diagnosis.

In
, congenital toxoplasmosis cases have been notifiable since 2001, when a nationwide surveillance system was Germany implemented under the Protection Against Infection Act. The case definition of congenital toxoplasmosis is based on at least one of the following criteria: Demonstration of in body tissues or fluids; Toxoplasma gondii Detection of specific IgM or IgA antibodies; Persistently stable specific IgG titres or a single elevated specific IgG-titre.
Laboratories report anonymised cases to the Robert Koch institute in Berlin. Part of the data can be accessed at . Quarterly summaries and yearly reports are also published . http://www3.rki.de/SurvStat/QueryForm.aspx [7] In , surveillance is confined to a regional programme in the Campania region, which has been running since 1997. The population Italy under surveillance are living newborn babies. A case of congenital toxoplasmosis in defined as the persistence of specific IgG antibodies until the age of one year. Cases are reported by social workers, paediatricians and neonatalogists. Information about toxoplasmosis primary infection among pregnant women is collected retrospectively on medical records, and information about congenital toxoplasmosis and complications among congenitally infected children are collected prospectively. The creation of a nationwide surveillance system is still being debated.
In the 12 other countries (Bulgaria, Cyprus, Czech Republic, England and Wales, Estonia, Ireland, Latvia, Lithuania, Malta, Poland, Scotland, and Slovakia, see ), the health event under surveillance is toxoplasmosis (congenital or not), as defined by the European Table 2 Union (symptomatic toxoplasmosis cases serologically confirmed) . It is considered a notifiable disease and subject to continuous data [8] collection ( ). Cases are reported by physicians, epidemiologists, or laboratories. Several sources of reporting contribute to the Table 2 systems, except in Cyprus, Lithuania, Poland and Slovakia, where the physicians are the only health professionals to report cases, and in the Czech Republic and Scotland, where cases are declared only by epidemiologists and laboratories, respectively.
All 16 surveillance systems analyse the data regularly (from daily to annually). The reports are sent to the health authorities weekly to annually.
Only two countries were able to provide data about the costs of the system. In Italy, the global cost of the regional pilot programme is estimated to be 68,000 Euros a year for 67,000 to 70,000 live births. In Denmark, the cost of the nationwide surveillance system was estimated to be 600,000 Euros a year.

Discussion
Our study provides detailed, up-to-date information on systems implemented for the surveillance of toxoplasmosis (congenital or not) in 28 European countries. We have identified a high degree of heterogeneity.
12 countries do not have any surveillance system for toxoplasmosis in place. In 12 countries, the event under surveillance was symptomatic toxoplasmosis. Five of those countries did not provide details about the qualification of the physicians who reported the information. In the field of toxoplasmosis, gynaecologists, ophthalmologists, paediatricians or neurologists are able to diagnose toxoplasmosis at different stages of the disease. Therefore, it is important that all those specialists take part in the surveillance process.
However, toxoplasmosis is a notifiable disease in all those countries, and we assume that all registered medical practitioners are involved in the surveillance system.
Denmark, France, Germany, and Italy (the latter only at regional level), are the only participating European countries who have implemented a surveillance system that is specifically dedicated to congenital toxoplasmosis and that is able to detect symptomatic as well as asymptomatic cases. Systems which survey symptomatic toxoplamosis in the general population are of least interest because it is impossible to distinguish congenital from acquired toxoplasmosis without data on the serological status during pregnancy or at birth . [9] Furthermore, the vast majority of acquired toxoplasmosis infections in healthy individuals are benign and the proportion of asymptomatic cases is estimated to be 70 . Differences in the structure of these four specific surveillance systems may be responsible for differences in their usefulness. We consider the surveillance system in Denmark to be simpler than those in Italy, Germany, and France.
Centralised analysis like in Denmark and France also increases the acceptability as the system relies on professionals specifically dedicated to the system, contrary to the systems in Italy and Germany where the tasks are divided between health professionals and laboratories. The Danish surveillance system could also be considered the most flexible, because of its centralised approach, which allows for changes to be implemented in only one place, should they become necessary.
In Denmark, the surveillance system was linked to a nationwide systematic neonatal screening . The sensitivity and the [14] representativeness of this system could thus be considered higher than in Germany where the surveillance system is suffering . According to these data, the estimated frequency of congenital toxoplasmosis is ten-fold lower [14] in Germany than in Denmark. Based on what is known about the geographical variation of the burden of congenital toxoplasmosis, this is unlikely.
In Italy, congenital toxoplasmosis cases are declared by social workers, paediatricians and neonatalogists. It is well known that passive reporting by physicians only captures a fraction of cases, most often only the most serious ones , . [15 16] Overall, we consider the epidemiological surveillance system that was implemented in Denmark be the most useful. However, it was discontinued in July 2007.
A European survey was conducted within the EUROTOXO initiative to describe the national public health policies and routine programmes to prevent congenital Toxoplasmosis . One of the fundamental criteria to evaluate the efficiency of such programmes is [17] the frequency of the disease in question. Some countries did not define congenital toxoplasmosis as a public health issue and consequently have not implemented a prevention programme or surveillance system.
Several countries that do not have a congenital toxoplasmosis prevention policy have nevertheless defined congenital toxoplasmosis as a public health issue and implemented a surveillance system. But of these countries only Germany has implemented a system specifically dedicated to congenital toxoplasmosis.
Austria, Denmark, France, Italy, Lithuania and Slovenia have defined congenital toxoplasmosis as a public health issue and implemented a national systematic prevention programme . Among these six countries, Denmark and France are the only countries [17] where a specific and exhaustive surveillance system of congenital toxoplasmosis was implemented. However, screening and surveillance in Denmark were stopped in July 2007 and in France has only existed since May 2007, 29 years after the implementation of the national screening programme.
In the absence of a dedicated surveillance system, data on the burden of a disease can be obtained only through epidemiological ad hoc surveys. A systematic review of the published data on the burden of congenital toxoplasmosis was conducted by the EUROTOXO study group in 2005 . The main results of this review were the following: Firstly, the prevalence of toxoplasmosis among pregnant women [18] (the reservoir of congenital toxoplasmosis) decreases over the years, as previously reported. Due to limited available data, other epidemiological parameters such as incidence of seroconversion in susceptible pregnant women or incidence of complications among congenitally infected children cannot be analysed in detail. Such accurate data on the trends of diseases can only be obtained through continuous data collection such as surveillance systems.
Secondly, published data on the burden of congenital toxoplasmosis in Europe are limited, in terms of both quantity and quality. In fact, the vast majority of surveys evaluated by the group were not representative, in particular with respect to rare events such as the incidence of complications among congenitally infected children. For these estimates to be sufficiently precise, children were recruited in specialised centres. Such representative estimates could be improved by systematic data collection, for example as part of a surveillance system.
Nevertheless, periodic snapshot surveys based on consistent reporting definitions can also be an effective way of determining the burden of congenital toxoplasmosis. This is the approach used in the United Kingdom for symptomatic toxoplasmosis in children through the British Paediatric Surveillance Unit and the British Ophthalmic Surveillance Unit . [9] Few countries in Europe have implemented specific surveillance systems in accordance with their prevention policies regarding congenital toxoplasmosis. The epidemiological surveillance of congenital toxoplasmosis needs to be improved in order to determine the true burden of disease and assess the need for and effectiveness of existing prevention programmes.

Ackowledgements:
The authors would like to thank Alain Moren (EPIET training programme coordinator) and H l ne Therre (Eurosurveillance Monthly editor)  Distinction between acquired and congential toxoplasmosis since 1999 ◆ Distinction between acquired and congential toxoplasmosis since 1997.