Dias JA¹; Cordeiro M²; Afzal MA³, Freitas MG⁴; Morgado MR⁴; Silva JL⁴; Nunes LM²; Lima MG¹; Avilez F⁵

1. Division of Epidemiology and Biostatistics, Directorate-General of Health, Lisbon , Portugal.
2. Division of Mother and Child Health, Directorate-General of Health, Lisbon, Portugal.
3. Division of Virology, National Institute for Biological Standards and Control, London, UK.
4. Division of Communicable Diseases, Directorate-General of Health, Lisbon, Portugal.
5. Laboratory of Virology, National Institute of Health, Lisbon, Portugal.

Introduction

A measles, mumps, and rubella (MMR) trivalent vaccine was added to Portugal's National Immunisation Programme (NIP) in 1987. All vaccines are given at health centres, free of charge, but an epidemic of mumps began in 1995, firstly in northern Portugal and has now spread to other areas.

Initially, only one dose of MMR vaccine at the age of 15 months was recommended. In 1990 a second dose at the age of 11 to 13 years was added. Portugal was one of the first countries in Europe to advocate this policy (1). After the introduction of MMR in the NIP, the number of notified cases of mumps from 2197 in 1987 fell to 627 in 1993 (figure 1), although there was a slight rise in 1989, probably due to increased reporting during that year in association with a major epidemic of measles (2). In 1994, however, the total rose to 1445, in 1995 to 1841 cases, and during the first 8 months of 1996 7620 cases have been notified.

In the spring of 1995 (figure 2), as the number of notified cases of mumps began to rise, particular attention was given to the characteristics of cases, their living conditions and geographical distribution, associated complications, as well as vaccination status, and the conditions of vaccine storage and administration.

In addition studies were undertaken to determine the prevalent virus strains, and to assess possible vaccine failure and/or lapses in immunisation procedures.

Methods

Most of the data used to describe cases were routinely produced by the national system of compulsory notification. Local outbreak investigations were conducted and laboratory tests were used to confirm cases and to determine the prevalent strains. A revised case definition was applied to a sample of cases from health centres, hospitals, and private paediatricians, randomly selected from a telephone directory in the area around Lisboa. Specimens obtained from cases from some of the most affected areas or institutions were sent to the National Institute of Health in Lisboa (NIH) for confirmation. The National Institute for Biological Standards and Controls (NIBSC) in England determined the molecular characteristics of circulating mumps viruses. Cases diagnosed by paediatricians in the emergency facilities of three hospitals in the Lisboa area were studied. Parents were asked to bring their affected children to the Directorat-General of Health, fasted and before cleaning their teeth, for the collection of saliva and throat swabs. After parents signed consent forms specimens of blood and urine were collected. Vaccination status was determined from child immunisation records held by parents. Information about disease onset, associated symptoms, and complications was given by the parents or an accompanying person. All specimens were sent to NIBSC in England, by express mail.

Results and discussion.

The 1995/96 epidemic affected people of all ages throughout the country, but the highest rates were in children aged 1 to 4 years (table 1).

Apart from the fact that older age groups show a similar trend, which could be explained by low vaccination rates before 1990 (when the booster dose was introduced), the incidence in children aged 1 to 4 years has been rising since 1993. This was unexpected because reported vaccination coverage between 12 and 23 months of age has been over 90% since 1991 (table 2). Lower vaccination rates in adolescents, such as the 60% reported from Leiria (3), could account for the high incidence of mumps in older children.

Substantial numbers of cases occurred in kindergartens, schools and other child care and education facilities, affecting children that were known to have received at least one dose of the vaccine.

Tests performed at the NIH in Lisboa on cases from outbreaks in Viseu, Parede, and Almada confirmed that 40% to 60% of cases occurred in immunised people (4). Most cases presented with tenderness of salivary glands on one or both sides, usually parotid or submaxilary glands. Most cases were unilateral with few complications. In some cases, however, orchitis, pancreatitis or aseptic meningitis were reported. No case was known to be fatal.

Analysis of viral genetic material from 21 clinical specimens showed the epidemic to be caused by at least five distinct genotypes, which belong to two separate lineage groups. Moreover, viruses characterised from the current outbreak share extensive genetic homology with other European isolates. The results of the phylogenetic analysis show that wild type viruses currently circulating in Portugal and elsewhere in Europe belong to groups B and C, while all vaccine strains used for immunisation belong to group A (Afzal et al, in preparation).

In 1987 MMR trivalent vaccines available commercially contained either of the following three mumps virus strains: Urabe Am9 (Japanese strain), Rubini (Swiss strain), and Jeryl Lynn (American strain). Following post-vaccination meningitis problems in the UK, Canada, and Japan that were possibly related to the Urabe Am 9 strain, the sale of this vaccine in Portugal was suspended in October 1992 (5). Since then the MMR vaccine produced by Triviraten Berna and containing the Rubini strain as its mumps component has been used exclusively. Vaccine is obtained for the NIP through an annual public contract.

Data from WHO showed that the incidence of mumps in recent years has been similar in Portugal and Spain, lower than in Italy, but higher than in the UK (table 3) (6). The Rubini strain has been used in all these countries, except the UK where since 1992 only the Jeryl Lynn strain has been used.

When cases notified either in 1995 or 1996 are plotted according to their probable month and year of vaccination, assuming that all cases born since 1986 were immunised at 15 months (figure 3), a large increase is seen in the incidence of mumps in children vaccinated after October 1992 - when the Urabe Am9 vaccine was suspended. This may be due to low vaccine efficacy of the Rubini strain, which will require further studies. The Sentinel Network of General Practitioners in Switzerland has reported the Rubini strain of mumps vaccine to be less efficacious than vaccines using either the Jeryl Lynn or Urabe Am9 strains (7,8) .

Public health measures and further studies

Because primary vaccine failure may have caused the current measles epidemic several measures were taken or are being implemented, such as:

* Maintain the current vaccination scheme, until more conclusive information can be obtained, since the disease is mild in vaccinees;

* Improve vaccine coverage in adolescents to at least 95%;

* Reduce undernotification in some areas, as well as notification in error, influenced by the occurrence of the epidemic;

* Keep WHO and other public health authorities abroad informed, providing the opportunity for international scientific collaboration.

Studies underway:

* Characterisation of more circulating strains

* Nationwide retrospective study to determine MMR vaccine coverage and relate the occurrence of the disease to vaccine status, vaccine strain, and batch, before and after 1992

* Prospective studies to determine the serological response and field efficacy of the Rubini strain vaccine.

The authors gratefully acknowledge the generous collaboration of the National Institute for Biological Standards and Control; the assistance of Drs Ana Santos Silva, Helena Andrade, Teresa Paixão; nurses: Barbara Menezes, Ana Batista, Margarida Valente and laboratory technician Guilhermina Simões during the investigation and to Dr João Feliciano for their helpful contribution of data processing.

References

1. Circular Normativa 10/DTP - “Normas de vacinação do Programa Nacional de Vacinação”; Direcção-Geral da Saúde; 4/09/1990;

2. Miranda AM, Falcão JM, Dias JA, Nóbrega SD, Rebelo MJ, Pimenta ZP et al. Measles transmission in health facilities during outbreaks. International Journal of Epidemiology 1994; 23 (4): 843-8

3. Passadouro R, Silva A, Mendes O, Lopes C. Investigação Epidemiológica de um surto de parotidite no Concelho de Leiria. Saúde em Números 1995; 10 (4): 26-27 [October]

4. Andrade, HR - Relatórios do Laboratório de Virulogia do INSA, sobre a positividade dos casos nalguns surtos seleccionados; 1995;

5. Nota Informativa sobre a suspensão da vacina Pluserix pela DGAF; Direcção-Geral da Saúde; 28/10/1992;

6. World Health Organisation - “Health for All” statistical database; Regional Office for Europe; Copenhagen, May 1996;

7. Swiss Federal Office of Public Health. ”Perspectives dans le domaine de la vaccination”; Information from the OFOPH expertee group for questions related with vaccination. Bulletin de l'Office Fédéral de La Santé Publique 1994; 38 (3, 10) : 650-651

8. Zimmerman H, Matter HC, Kiener T et al - “Mumps - Epidemiologie in der Schweiz”; Ergbnisse der Sentinella-Uberwachung 1986-1993; Soz Praventivmed 1995; 40: 80-92

This report is based on one published in Saúde em Números 1996; 11:17-20 but includes more recent data.