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ARCHIVED - Statement on Mumps Vaccine

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Canada Communicable Disease Report
Volume 33 • ACS-8
1 August 2007

An Advisory Committee Statement (ACS)

National Advisory Committee on Immunization (NACI)†, ††

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Preamble

The National Advisory Committee on Immunization (NACI) provides the Public Health Agency of Canada with ongoing and timely medical, scientific and public health advice relating to immunization. The Public Health Agency of Canada acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge and is disseminating this document for information purposes. People administering the vaccine should also be aware of the contents of the relevant product monograph(s). Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) of the Canadian manufacturer(s) of the vaccine(s). Manufacturer(s) have sought approval of the vaccine(s) and provided evidence as to its safety and efficacy only when it is used in accordance with the product monographs. NACI members and liaison members conduct themselves within the context of the Public Health Agency of Canada’s Policy on Conflict of Interest, including yearly declaration of potential conflict of interest.

Introduction

Mumps is an acute infectious disease caused by the mumps virus. In about 40% of those infected acute parotitis develops, which is unilateral in about 25% of cases. Nonspecific or primarily respiratory symptoms occur in about half of those who acquire infection. Subclinical infection is common. Although complications are relatively frequent, permanent sequelae are rare. Before the widespread use of mumps vaccine, mumps was a major cause of viral meningitis. Mumps meningoencephalitis can, rarely, result in permanent neurologic sequelae, including paralysis, seizures, cranial nerve palsies and hydrocephalus. Transient but occasionally permanent deafness may occur, at an estimated rate of 0.5 to 5.0 per 100,000 reported mumps cases. Orchitis occurs in 20% to 30% of postpubertal male cases and oophoritis in 5% of postpubertal female cases. Involvement of the reproductive organs is commonly unilateral; therefore, sterility as a result of mumps is rare. Mumps infection in pregnancy has not been associated with congenital malformations, but mumps infection during the first trimester of pregnancy may increase the rate of spontaneous abortion.

Canada’s goal for mumps prevention and control was set at a national consensus conference in 1994. The goal is to maintain an active prevention program for mumps to minimize serious sequelae from the disease.1

NACI has revised its recommendations for mumps-containing vaccine as a result of Canadian and international mumps epidemiology, as well as a review of available data regarding vaccine effectiveness and waning immunity.

Epidemiology of mumps in Canada

Since the approval of a mumps vaccine in Canada in 1969, the number of reported mumps cases has decreased from an average of 34,000 cases reported per year in the early 1950s to fewer than 300 cases per year in the early 1990s. A further reduction in incidence was observed following the introduction of the routine second dose of measles-mumps-rubella (MMR) vaccine for measles control in 1996-97. During the period 2000-2006, an average of 79 cases were reported annually, ranging from 28 (in 2003) to 202 cases (2002).

In the past decade, there have been two relatively large and four smaller mumps outbreaks in Canada. A British Columbia outbreak in 1996 involved 83 cases associated with "rave " parties and affected youth aged 15-24 years.2 A Quebec outbreak in 1998-1999 involved 37 children in one school and four daycare settings.3 An Alberta outbreak in 2001-2002 resulted in nearly 200 cases. It originated with an imported case from Bolivia and involved an undervaccinated community in which coverage rates were greatly below the provincial average.4 The majority of cases (77%) were pre-school or school-aged children. The disease spread through area schools and to a lesser extent the surrounding community; the majority of cases (80%) were unimmunized. Two small outbreaks occurred in Nova Scotia in 2005. The first affected 13 high school students (13-19 years old), and the second involved 19 young adults aged 20-27 years, largely in university settings in one city.5 Four of the 13 cases in the first Nova Scotia outbreak reported having received one dose of MMR vaccine, and 9 had received two doses. All but one of the 19 cases in the second outbreak reported having received one dose of MMR vaccine. The second outbreak resulted in three secondary cases in other provinces.

The largest and most recent outbreak started in 2007 and is ongoing. As of 13 July, 2007, activity remains centred in Nova Scotia and New Brunswick (555 confirmed cases) with sporadic exportations (30 cases) to six other provinces. The majority of cases (64%) have occurred in persons aged 17-37 years, many of whom are college or university students. Data regarding mumps hospitalizations and complications are incomplete, although complications have been reported in approximately 9% of cases (51 reports): orchitis (41 reports), oophoritis (5 reports), hearing loss (4 reports) and encephalitis (1 report). Six mumps hospitalizations and no deaths have been reported. Immunization status is known for 284 cases: 16% were unimmunized, 75% received one dose, and 9% received two doses of mumps-containing vaccine.

Viruses from the three Nova Scotia outbreaks were nearly identical to each other and related to the genotype G identified in recent outbreaks in the United Kingdom and the United States, described below.

The age distribution of mumps in Canada has changed over time. The proportion of reported cases aged 20 years and older increased from 14% in 1988-1990 to 64% in 2003-2005. Conversely, the proportion of cases aged 1-9 years fell from 49% to 17% during the same period.

It is assumed that the majority of Canadians over the age of approximately 40 years have natural immunity to mumps. The age for the natural immunity assumption is based upon the year that mumps vaccine was licensed in Canada (1969) and subsequent introduction of mumps-containing vaccine programs throughout the country. Therefore, there would likely have been natural exposure to mumps until at least 1969 as a result of naturally circulating disease. However, it is important to recognize that some individuals born before 1970 may still be susceptible to mumps. Depending on the province or territory of residence, older children/youth currently up to either 12 or 17 years of age have been offered two doses of mumps vaccine with the introduction of a routine second dose of MMR vaccine for measles control, which began in 1996-97 at either 18 months or 4-6 years of age. This leaves a cohort of people between the approximate ages of either 12 or 17 (depending on the province or territory) and 40 years who were eligible for only one dose of MMR vaccine and who are not assumed to have natural immunity.

Mumps outbreaks in the United Kingdom and the United States

There was a very large mumps outbreak in the United Kingdom from 2004 to 2006 with more than 70,000 cases reported. The peak occurred in 2005, when over 56,000 notifications were made in England and Wales.6 The majority of the confirmed cases were 15-24 years of age, most of whom had not been eligible for routine two-dose mumps immunization. The Health Protection Agency has attributed the outbreak to gaps in the immunity of certain cohorts.7 Among all mumps patients in the UK in 2004, about 3.3% were reported as having received two doses of MMR vaccine, and 30.1% had received one dose. In 2004, attack rates per 100,000 population were lowest in those born before 1979, who are presumed immune, and those born between 1993 and 2002, who routinely were given two doses of MMR (attack rate under 10/100,000 population); rates were highest in those born between 1981 and 1987, who were not eligible for routine MMR immunization (140-165/100,000 population). Those born between 1988 and 1989 routinely received one dose of MMR and had an intermediate attack rate (40-60/100,000 population).8

Scotland also had a mumps outbreak (2003-2004), with over 500 cases reported in 7 months, affecting 12 of 15 health regions.9 As in England and Wales, the age groups affected were adolescents and young adults 13-25 years of age. The circulating strain has been identified as genotype G. The G genotype is not unusual or rare and, like the rest of known genotypes of mumps, it has been circulating globally for decades or longer.

There have also been mumps outbreaks in the United States. Most notably, from January to June 2006, at least 11 states were affected by a large outbreak with activity centred in Iowa.10 Preliminary results suggest that there were over 2,500 cases with a median age of 21 years and that approximately 1 in 4 were college/university students. At least one Canadian case, reported in Ontario, was epidemiologically linked to this multi-state outbreak. Complications included 27 reports of orchitis, 11 of meningitis, four of encephalitis, four of deafness, and one each of oophoritis, mastitis, pancreatitis and unspecified complications; no deaths were reported.10 Data from the Iowa outbreak have not been fully analyzed or published. However, of 1,192 patients, 6% were unvaccinated, 12% had had one dose of MMR, 51% had had two doses of MMR, and 31% had no vaccine records. Preliminary data from two college campuses identified attack rates of 2% in a college where 97% of students were documented as having had two doses of MMR, versus 3.8% in a college where 77% had had two documented doses. This outbreak has also been identified as associated with genotype G.

On 17 May, 2006, the Advisory Committee on Immunization Practices (ACIP) in the United States updated the mumps vaccination recommendations. Documentation of adequate vaccination was changed to two doses of a live mumps-containing vaccine (instead of one dose) for school-aged children (i.e., grades K-12) and adults at high risk (e.g., persons who work in health care facilities, international travelers and students at post-high school educational institutions).11

Mumps remains endemic in many countries throughout the world, and mumps vaccine is used in only 57% of World Health Organization member countries, predominantly in countries with more developed economies.

Mumps vaccine effectiveness and waning immunity

It is unknown whether primary vaccine failure or waning immunity is the major risk factor for mumps in vaccinated individuals. In controlled clinical trials, one dose of mumps vaccine was 95% efficacious in preventing mumps disease12. However, observational studies conducted during mumps outbreaks have demonstrated lower estimates of vaccine effectiveness, usually around 70%-80% with single-dose regimens.13-18 Mumps outbreaks have been reported in school populations in the United States with very high (> 95%) coverage with single-dose mumps-containing vaccine, suggesting that one dose of mumps-containing vaccine is not sufficient to prevent mumps outbreaks in the school setting.18,19

A number of observational studies have evaluated vaccine effectiveness of one and two doses of mumps-containing vaccine.13,14,18,20 A case control study in the UK demonstrated a vaccine effectiveness against mumps of 64% (95% confidence interval [CI]: 40%-78%) with single dose MMR compared with 88% (95% CI: 62%-96%) with two doses of MMR vaccine during a 1998-99 outbreak in London.13 In a small outbreak in Sweden in 2004, vaccine effectiveness of 65% was found in those with a history of one dose of a mumps-containing vaccine and 91% in those with two doses.20 A study from the recent UK outbreak demonstrated a vaccine effectiveness of 87.8% (95% CI: 83%-91%) for one dose of MMR vaccine and 94.6% (95% CI: 93%-96%) for two doses.14 A two-dose MMR immunization schedule used in Finland since 1982 has resulted in higher mumps-specific antibody levels, a higher seropositivity rate, slower decay of antibody levels and the elimination of indigenous mumps after 12 years of the two-dose program.21

The duration of vaccine-induced immunity is unknown. There are many studies demonstrating a drop in antibody levels over time (i.e., waning immunity).15,18,19,22-24 The length of antibody persistence is unknown in settings with high vaccine coverage but low or no circulating wild virus, and no data are currently available correlating specific antibody titres with susceptibility to mumps. Students vaccinated > 3 years before a Tennessee outbreak in 1991 had a moderately greater risk of mumps than those vaccinated more recently (relative risk [RR] 2.9, 95% CI: 0.7-11.6).19 Those vaccinated 4 years before an outbreak in Kansas in 1988-89 appeared to have a higher attack rate (RR 4.3, 95 % CI: 0.6-30.0), but this association was not significant when risk was evaluated on the basis of the number of vaccine doses received.18 Students who had received only one dose of vaccine were at greater risk than those who had received two doses (RR 5.2; 95% CI: 1.0-206.2). During a 1995-96 outbreak in Bruges, Belgium, the proportion of vaccinated children with mumps increased progressively with increasing time interval since the last dose of mumps-containing vaccine was administered. The contribution of waning immunity was estimated using a logistic regression model. In this model, the odds of developing mumps increased rapidly with increasing time interval between the last vaccination and the outbreak.15 A study during the recent UK outbreak estimated that the effectiveness of one dose of mumps-containing vaccine was 95.9% (95% CI: 81.1%-99.1%) in 2-year-olds decreasing to 65.9% (95% CI: 30.3%-83.3%) in those aged 11-12; the effectiveness of two doses was 98.8% (95% CI: 97.0%-99.5%) in children 5-6 years old and decreased to 86.4% (95% CI: 74.1%-92.9%) in children 11-12 years olds.14 This statistically significant relationship of vaccine effectiveness decreasing with increasing age for those who received either one or two doses (p < 0.001) also suggests that there is waning immunity.

Recommended use

There is currently no single-component mumps-containing vaccine available in Canada. Combined measles, mumps, rubella (MMR) vaccine is the only mumps vaccine available. The Canadian Immunization Guide25 contains information on the MMR vaccine, including vaccine safety and dosing intervals. If indicated, the second dose of MMR vaccine should be given ≥ 1 month after the first dose.

  1. Infants and children. For routine immunization of all children, two doses of mumps-containing vaccine should be given. Infants should receive a first dose combined with measles and rubella vaccine (MMR vaccine) on or shortly after their first birthday; the second dose should be given after 15 months of age or older but before school entry.

  2. Students at educational institutions. Students attending educational institutes (i.e., secondary and post-secondary) should have documented receipt of two doses of a mumps-containing vaccine or have laboratory evidence of immunity or a history of laboratory-confirmed mumps disease or have been born before 1970.

  3. Health care workers (HCWs). HCWs should have documented receipt of two doses of a mumps-containing vaccine or have laboratory evidence of immunity or a history of laboratory-confirmed mumps disease or have been born before 1970. Among those born before 1970, a single dose of MMR vaccine could be considered.

  4. Military. Military personnel should have documented receipt of two doses of a mumps-containing vaccine or have laboratory evidence of immunity or a history of laboratory-confirmed mumps disease or have been born before 1970. Among those born before 1970, a single dose of MMR vaccine could be considered.

  5. Outbreak control. A full discussion of mumps outbreak control is beyond the scope of this statement. With the implementation of a two-dose schedule for mumps vaccine, it is expected that large outbreaks of mumps will occur much less frequently.;However, cases that do occur may result in transmission of mumps, usually among unvaccinated children and young adults who have not received two doses of vaccine and who were born after wide circulation of natural mumps disease was common. A dose of mumps-containing vaccine should be given to susceptible (which includes those born in or after 1970 who received only one dose of a mumps-containing vaccine), at-risk populations during outbreaks. At-risk populations will need to be defined by the specifics of the outbreak. No more than two doses of MMR vaccine are currently recommended.

People born before 1970 are assumed to have natural immunity to mumps. However, some of these individuals may be susceptible. A dose of MMR vaccine could be considered among high-risk adults (HCWs or military personnel) born before 1970 who do not have laboratory evidence of immunity or a history of laboratory-confirmed mumps disease.

NACI will revise and reconsider this statement as new information becomes available. Important, but as yet unknown, issues include the following:

  1. The effect of one dose versus two doses of mumps-containing vaccine on the prevention of complications and sequelae.

  2. A more thorough understanding of the duration of immunity and waning of immunity and how this is impacted by the administration of a second dose of mumps-containing vaccine

  3. The immunologic correlates of protection from disease and the impact of a second dose of mumps - containing vaccine on the immunologic response.

  4. The optimal timing of the second dose of the two dose schedule.

References

  1. Health Canada. Mumps and rubella consensus conference. CCDR 1994;20(19):165-76.

  2. Bell A, Fyfe M, Bigham M et al. Outbreak of mumps among young adults: Vancouver, British Columbia. CCDR 1997;23(22):F1-F3

  3. Sciberras J. Outbreak of mumps, Montreal, October 1998 to March 1999, with a particular focus on a school. CCDR 2000;26(8):69-71.

  4. Alberta Health and Wellness. Public health notifiable disease management guidelines. June 2005. URL: <http://www.health.gov.ab.ca/professionals/NotifiableDiseases.html>. Accessed 2 Feb, 2007.

  5. Watson-Creed G, Saunders A, Scott J et al. Two successive outbreaks of mumps in Nova Scotia among vaccinated adolescents and young adults. CMAJ 2006;175(5):483-8.

  6. Savage E, Brown D, Ramsay M et al. Mumps epidemic: United Kingdom, 2004-2005. MMWR 2006;55(7):173-5.

  7. Bloom S. Mumps outbreak among young adults in UK [editorial]. BMJ 2005;5:260-1.

  8. Savage E, Ramsay M, White J et al. Mumps outbreak across England and Wales in 2004: observational study. BMJ 2005;330:1119-20.

  9. Donaghy M, Cameron J, Friederichs V. Increasing incidence of mumps in Scotland: options for reducing transmission. J Clin Virol 2006;35(2):121-9.

  10. Centers for Disease Control and Prevention. Update: multi-state outbreak of mumps, United States, January 1- May 2, 2006. MMWR 2006;55(20):559-63.

  11. Centers for Disease Control and Prevention. Notice to readers: updated recommendations of the Advisory Committee on Immunization Practices (ACIP) for the control and elimination of mumps. MMWR 2006;55(22):629-30.

  12. Plotkin S, Mumps vaccine. In: Plotkin S, Orenstien W & Offit P, editors. Vaccines (4th edition). WB Saunders Company; 2003: 441-60

  13. Harling R, White J, Ramsay M et al. The effectiveness of the mumps component of the MMR vaccine: a case-control study. Vaccine 2005;23:4070-4.

  14. Cohen C, White JM, Savage EJ et al. Vaccine effectiveness estimated, 2004-2005 mumps outbreak, England. Emerg Infect Dis 2007;13(1):12-17.

  15. Vandermeulen C, Roelants M, Vermoere M et al. Outbreak of mumps in a vaccinated child population: a question of vaccine failure? Vaccine 2004;22:2713-6.

  16. Gay N, Miller, Hesketh L et al. Mumps surveillance in England and Wales supports introduction of two-dose vaccination schedule. Commun Dis Rep CDR Rev 1997;7:R21-6.

  17. Wharton M, Cochi S, Hutcheson R et al. A large outbreak of mumps in the postvaccine era. J Infect Dis 1988;158(6):1253-60.

  18. Hersh B, Fine P, Kent W et al. Mumps outbreak in a highly vaccinated population. J Pediatr 1991;119:187-93.

  19. Briss P, Fehrs L, Parker R et al. Sustained transmission of mumps in a highly vaccinated population: assessment of primary vaccine failure and waning vaccine-induced immunity. J Infect Dis 1994;169:77-82.

  20. Sartorius B, Penttinen P, Nilsson J et al. An outbreak of mumps in Sweden, February-April 2004. Euro Surveill 2005;10(9):191-3.

  21. Peltola H, Heinonen O, Valle M et al. The elimination of indigenous measles, mumps and rubella from Finland by a 12 year, two-dose vaccination program. N Engl J Med 1994;331:1397-1402.

  22. Pebody R, Gay N, Hesketh L et al. Immunogenicity of second dose measles-mumps-rubella (MMR) vaccine and implications for serosurveillance. Vaccine 2002;20:1134‑40.

  23. Davidkin I, Malle M, Julkunen I. Persistence of anti-mumps virus antibodies after a two-dose MMR vaccination: a nine-year follow-up. Vaccine 1995;13(16):1617-22.

  24. Park DW, Nam MH, Kim JY et al Mumps outbreak in a highly vaccinated school population: assessment of secondary vaccine failure using IgG avidity measurements. Vaccine 2007;25(24):4665-70.

  25. The National Advisory Committee on Immunization. Canadian immunization guide, 7th ed. Ottawa: PHAC, 2006. Cat. no. HP40-3/2006E. (http://www.phac-aspc.gc.ca/publicat/cig-gci/index.html)

† Members: Dr. J. Langley (Chairperson), Dr. S. Deeks (Executive Secretary), Dr. K. Laupland, Dr. S. Dobson, Dr. B. Duval, Dr. J. Embree, Ms. A. Hanrahan, Dr. A. McGeer, Dr. S. McNeil, Dr. M-N Primeau, Dr. B. Seifert, Dr. B. Tan, Dr. B. Warshawsky.

Liaison Representatives: Ms. S. Callery (CHICA), Dr. P. Hudson (CPHA), Dr. B Bell (CDC), Dr. D. Money (SOGC), Ms. E. Holmes (CNCI), Dr. B. Larke (CCMOH), Dr. M. Salvadori (CPS), Dr. S. Rechner (CFPC), Dr. J. Salzman (CATMAT), Dr. D. Scheifele (CAIRE), Dr. P. Orr (AMMI Canada)

Ex-Officio Representatives: Dr. H. Rode (BGTD), Dr. M. Lem (FNIHB), Dr. J. Anderson (DND). Dr. B. Law (IRID)

† † This statement was prepared by Dr. Shelley Deeks, Dr. Marina Salvadori, Ms. Tammy Lipskie and approved by NACI and the Public Health Agency of Canada.


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