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Eurosurveillance, Volume 7, Issue 4, 01 April 2002
Scientific review
Measles in France: the epidemiological impact of suboptimal immunisation coverage

Citation style for this article: Bonmarin I, Lévy-Bruhl D. Measles in France: the epidemiological impact of suboptimal immunisation coverage. Euro Surveill. 2002;7(4):pii=322. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=322

I. Bonmarin, D. Levy-Bruhl

Institut de Veille Sanitaire, Saint-Maurice, France


The promotion of immunisation in France since 1983 has resulted in a 97% reduction in morbidity and a reduction of 60% of mortality. However, the stable and sub-optimal coverage around 84% leads to a shift in higher age groups, where complications are more frequent and serious. The proportion of those aged over 10 years was 13% in 1985 and reached 48% in 1997, the transmission of measles being maintained in France. To eliminate the disease, vaccine coverage with 2 doses and over 95% would be necessary.

 

The incidence of measles has decreased in many countries around the world since the introduction of immunisation.

In 1994, a policy was initiated in the Americas to eliminate the disease. This has resulted in the interruption of the virus’ autochthonous transmission in North America, and a substantial decrease of its incidence in the rest of the Americas (1,2). European countries, including France, have set themselves the goal of eradicating measles by 2007 (3). In Finland, no autochthonous cases of measles have been recorded since 1996 (4).

Is France on the way to achieving this goal? To answer this question, this article presents an overview of the epidemiology of measles in France.

Evolution of the immunisation policy

The vaccine came on the market in 1966 in France and was introduced into the vaccination schedule in 1983, for children between the ages of 12-15 months. Three years later, mumps and rubella vaccination was added to the measles vaccine.

In 1996, a second dose, justified by the elimination prospect of the disease was introduced for children aged 11-13 years. This second dose enables us to protect children who have missed vaccination, and also those for whom it was not effective (there are failure rates of between 5 and 10% after the first dose). This prevents the accumulation of non-protected subjects, thereby hampering the emergence of clusters. Modelling studies (5) have shown that the disease could be eliminated faster if the second dose were given to children at a younger age, and recommendations are now to give it to children between 3 and 6 years of age (6).

Up to the age of 6, two doses are administered. After 6 and until 13, only one dose is offered to those who have never been vaccinated. Vaccination is carried out mostly by doctors in private practice. Campaigns are carried out each year to promote the triple vaccine for measles, mumps and rubella (MMR). The focus of the 1999 campaign was that the vaccine was available free of charge. This action gave the vaccine a priority status by making it more accessible.

Vaccination coverage surveillance

Since 1985, data on vaccination coverage have been collected and managed by the Direction de la Recherche des Etudes de l’Evaluation et des Statistiques (DREES) at the Ministry of Health.

National and departmental evaluations rely on the yearly analyses of health certificates filled by the doctors at a child’s twenty fourth month. Although these are mandatory, the certificates of only 60% of children aged 24 months are sent and analysed by the DREES. Coverage for the first dose alone is evaluated. Moreover, twice-yearly transversal surveys are carried out in schools using a representative sample of the French population aged 6 years.

National coverage of 24 month old children was 32% in 1985 and reached 80% in 1994. It has been stable since then (figure 1). It was 82.7% in 1999 and varied from 60.5% and 92.3% depending on the departments. Northern France attained the highest coverage rates (7) (figure 2). Provisional data for 2000 showed an 84.2% coverage rate.

During the last survey conducted in 2000-01, coverage for six year olds was 90%. This shows that catch up vaccination was incomplete for children over the age of 2 years (8).

Surveillance of morbidity

In 1945, measles was made a notifiable disease, but this notifiable status was suspended in 1986 because of the low level of notifications being made by doctors.

The Sentinel network, created by the INSERM U444 has been monitoring measles since 1985 (9). It is composed of around 300 volunteer general practitioners, who report electronically the number of measles cases observed during their consultations each week. The case definition, comparable to the one used by the Centers for Disease Control and Prevention (CDC) (10) includes generalised rash of more than three days, and a fever above 38.5 °C, associated with coughing, coryza or conjunctivitis.

Since its creation, the network doctors have reported more than 8000 cases of measles. National incidence, extrapolated from this data, has decreased considerably, from nearly 300 000 cases per year in 1985 to around 10 000 cases in 2000 (figure 3).

At the same time, the Sentinel network observed an increase in the age of the cases. The proportion of patients over 10 years old rose from 13% in 1985 to 48% in 1997. The proportion of vaccinated cases also increased from 3% to 58% over the same period. This increase primarily reveals the improvement of vaccination coverage. Until 1998, these rates were calculated from more than 200 cases described by the network doctors. In 1998, this number was reduced to around fifty cases, which has made data interpretation very difficult.

Surveillance relies on clinical data alone, and presently no laboratory confirmation of cases or procedure for the typing of strains exist.

Alongside this surveillance system, data on morbidity has been reported during the investigation of clusters or small outbreaks. From 1995 to 2000, seven investigations were led by or reported to the Institut de Veille Sanitaire. Vaccine efficacy, calculated in two primary schools and a high school on clinical and biologically confirmed cases has always been over 92% (11,12).

Surveillance of mortality

Data on mortality is collected by the epidemiological centre for the medical causes of deaths (Centre d’Epidémiologie sur les causes médicales de décès, CépiDc). This data has been available since 1979.

Only information regarding the main causes of death has been analysed. A detailed study including all the recorded causes of deaths (principal, associated and immediate) showed that only two deaths were not included in the 35 main causes registered from 1995 and 1998. This represents a 5% underestimation of the number of deaths reported.

Mortality has decreased steadily, from around 30 deaths per year in the 1980s to less than 10 per year at the present time. The proportion of deaths in children under five years of age decreased from over 50% in 1979 to less than 5% in recent years (figure 4).

In the same period, the main causes of death also changed. From 1979 to 1987, causes other than encephalitic ones represented the majority of deaths, bronchopneumonias being responsible for 34% of the other causes. Since 1987, encephalitis is the first reported cause of deaths, whether it is late encephalitis occurring a few years after measles (subacute sclero-sing panencephalitis) or acute immediate or delayed post-measles encephalitis occurring a few days or months after measles.

Serological survey

A European seroepidemiological survey (13) (ESEN) was carried out in seven countries. Immuno-globulins G of nearly 29 000 serum samples were analysed with standardised titration methods (14).

In metropolitan France, serum samples came from subjects whose blood samples were drawn in medical laboratories. The choice of serum samples was made according to predefined quotas by age group, sex, and location to ensure a satisfactory representativeness without random sampling (15).

In France, about 3500 serum sampled mainly in 1998 were analysed (13) (figure 5). Results for measles showed an important rate of seronegative children (7% in those aged between 5 and 19 years). Rates of seronegatives observed in all age groups under 20 are higher than seronegativity thresholds proposed by the WHO European region to reach the objective of measles elimination. Serological data have also confirmed that the half southern metropolitan France, as defined in figure 2 was less protected than the northern half.

Other data

Only the data from the Permanent Medical Prescription Survey (16) currently allows us to appreciate the implementation of catch up doses for children up to the ages of 11-13, and the introduction of the second dose in 1998, through the analysis of prescriptions made by private practitioners.

This survey is carried out by a list of GPs and specialists, from which is selected a representative sample stratified according to the doctors’ region and activity level. During a period of seven days, the doctor reports a set of information on all his or her patients, as well as copies of all prescriptions. The results are then extrapolated to all French practitioners, yielding national incidence estimates.

In children under the age of two and a half years, the rate of prescription of the triple vaccine has remained stable since 1996, data confirmed by the stagnation of vaccine coverage at 24 months. The rate of prescription has increased in children aged between two and a half and seven years of age since 1997, when the age for the second dose was lowered, yielding a coverage for the second dose of about 50%. Finally, in children over seven years of age, prescriptions have increased widely, although it has been impossible to dissociate vaccines administered as late second doses from those corresponding to first doses in non-vaccinated children. The decrease of cases registered by the Sentinel network in recent years favours the second hypothesis (figure 6).

Discussion

Since 1983, promotion of measles vaccination has been accompanied by a 97% reduction in morbidity and a 60% reduction in mortality. These encouraging results are not equivalent to elimination. Stable and suboptimal coverage around 84% causes a shift in the age of patient, and the continuation of disease transmission within the country.

Because of the reduced circulation of the virus, measles cases now occur in older patients. But complications are more frequent and case fatality ratio is higher in adults, with acute encephalitis being the major cause of death (17). This age shift in cases could therefore partly explain the slower decrease of mortality compared to morbidity, a stable number of deaths caused by post-measles encephalitis since 1988, and the increase in the age of the deceased patients. Deaths caused by subacute sclerosing panencephalitis occur about ten years after infection by the measles virus, and do not reflect the current incidence of the disease, although they illustrate the severe potential of a disease that is too often considered to be totally benign.

These paradoxical effects of vaccination linked to the age shift can be fought only by eliminating the disease, and this requires a vaccine coverage of more than 95% and the administration of two doses of an efficient vaccine.

The vaccine used in France is of good quality considering that the measures of vaccine efficacy carried out in investigations of clustered cases have always been over 90%. However, the coverage reached is not high enough to avoid the accumulation of susceptible subjects, as confirmed by serological surveys and the occurrence of epidemic clusters. France is still in the ‘honeymoon’ period, the name given when the decrease of cases suggests that a disease is disappearing, yet without any sign, groups of unprotected individuals are forming the source of future outbreaks. Vaccination efforts have allowed an important decrease of incidence without preventing the silent formation of these groups. Important catch up activities in recent years have probably reduced these groups of susceptible subjects without causing them to disappear. Geographical differences are important, and alongside national promotional campaigns, each department must strive to identify the populations with the lowest vaccination coverage in order to find solutions. This search is made possible by the measurement of local vaccine coverage, the identification of clusters, and notification of all cases.

Improving vaccine coverage must be accompanied by a change in the surveillance system. The decrease of incidence makes the estimates from the Sentinel network very imprecise. In 2001, incidence was extrapolated from 22 reported cases; the 95% confidence interval was 2870-14050 (18). The decrease in the number of cases also ‰

‰ decreases the positive predictive value of the clinical definition. In England and Wales, 2466 cases of measles were reported from the clinical definition in 2000, 1751 (71%) had a saliva sample, of which 74 (4 %) only were positive (19).

In the long term, surveillance tools should be those used by the countries which are most advanced in the elimination process (20), namely: exhaustive notification; wide clinical definition for high sensitivity allowing detection of all suspect cases; biological confirmation to improve specificity and to take into account real cases only; typing of strains to trace their origin; measure of vaccine coverage for each dose; and evaluation of the rate of susceptible population by modelling or serological survey.

As clusters affect communities, school doctors should be involved in the surveillance of the disease. Protocols for procedures to be followed when one or several cases occur will be developed to encourage case notification and investigation.

Research projects are led by the Sentinel network, in collaboration with the Public Health Laboratory Service (PHLS) in London and are related to the evaluation of the saliva diagnosis by IgM detection and virological typing of strains. The results will contribute to setting up the biological support to eliminate the disease.

In conclusion, France has improved its vaccine coverage, but the rate reached still permits transmission of the disease, and shifts the age of the cases to an age where complications and case fatality ratio are higher. To eliminate the disease, vaccine coverage over 95% with two doses will have to be reached.

All the tools can gradually be implemented to reach this objective. The main obstacle, however, is to convince the policy decision makers, the health professionals, and the public of the need to eliminate the disease.


 

Références

1. de Quadros CA, Olive JM, Hersh BS, Strassburg MA, Henderson DA, Brandling-Bennett D, Alleyne GA.
Measles elimination in the Americas. Evolving strategies.JAMA. 1996 Jan 17;275(3):224-9.

2. Vitek CR, Redd SC, Redd SB, Hadler SC. Trends in importation of measles to the United States, 1986-1994. JAMA. 1997 Jun 25;277(24):1952-6.

3. Progress towards measles elimination, WHO Eastern Mediterranean Region, 1980-1998. Wkly Epidemiol Rec. 1999 Dec 17;74(50):434-9.

4. Heinonen OP, Paunio M, Peltola H. Total elimination of measles in Finland. Ann Med. 1998 Apr;30(2):131-3.

5. Levy-Bruhl D, Maccario J, Richardson S, Guérin N. Modélisation de la rougeole en France et conséquences pour l'âge d'administration de la seconde vaccination Rougeole-Oreillons-Rubéole. Bull Epidemiol Hebd 1997 ; 29 : 133-5

6. BEH 27/2000 : Calendrier vaccinal 2000. Maladie inexpliqué et décès chez les usagers de drogues par injection en Grande-Bretagne et en Irlande

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11. Antona D et al. Mise en place d'une surveillance exhaustive des cas résiduels de rougeole en France. Étude pilote dans trois départements français à couverture vaccinale élevée (Cher, Paris, Val-d'Oise). BEH 1996;37:163-4.

12. S. Baron et al. Investigation d'une épidémie de rougeole en Indre-et-Loire. BEH 1995 ;34 :153-55

13. de Melker H et al. The seroepidemiology of measles in Western Europe. Epidemiol Infect. 2001 Apr;126(2):249-59.

14. Andrews N et al. The European Sero-Epidemiology Network: standardizing the enzyme immunoassay results for measles, mumps and rubella. Epidemiol Infect. 2000 Aug;125(1):127-41.

15. Edmunds WJ et al. The sero-epidemiology of diphtheria in Western Europe. ESEN Project. European Sero-Epidemiology Network. Epidemiol Infect. 2000 Aug;125(1):113-25.

16. Analyse des volumes de prescriptions de vaccins associés - à partir des données extraites de l'EPPM. IMS-Health - Novembre 2002, Département services Clients

17. Epidemiology and Prevention of Vaccine-Preventable Diseases, The Pink Book, Course Textbook, 6th Edition, (2nd Printing, January 2001), http://www.cdc.gov/nip/publications/pink/

18. Sentinelles. Surveillance épidémiologique du réseau Sentinelles. Bilan annuel Janvier-Décembre 2001

19. Measles notification - confirmed cases, England and Wales, 1995-2000 by Quarter : http://www.phls.co.uk/facts/Immunisation/Measles/meas-t03.htm

20. EPI - WHO Europe. Measles : a strategic framework for the elimination of measles in the European region, Copenhague 1999

 



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