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Evaluation of live attenuated S79 mumps vaccine effectiveness in mumps outbreaks: a matched case-control study

FU, Chuan-xi; NIE, Jun; LIANG, Jian-hua; WANG, Ming

Section Editor(s): SUN, Jing

doi: 10.3760/cma.j.issn.0366-6999.2009.03.013
Original article

Background Mumps virus infection is a potentially serious viral infection of childhood and early adulthood. In China, live attenuated S79 mumps vaccine has been licensed for pediatric use since 1990. The objective of this study was to determine the effectiveness of live attenuated S79 mumps vaccine against clinical mumps in outbreaks.

Methods Cases were selected from mumps outbreaks in schools in Guangzhou between 2004 and 2005. Each case was matched by gender, age and classroom. Vaccination information was obtained from Children's EPI Administrative Computerized System. Vaccine effectiveness (VE) was calculated for 1 or 2 doses of S79 vaccine with 95% confidence intervals (CI).

Results One hundred and ninety-four cases and 194 controls were enrolled into the study. VE of the S79 mumps vaccine for 1 dose versus 0 confer protection 80.4% (95% CI, 60.0%-90.4%) and VEs against mumps in outbreaks for 1 dose of mumps vaccine are similar among those children aged 4–9 years and aged over 10 years old.

Conclusion The live attenuated S79 mumps vaccine can be effective in preventing clinical mumps outbreaks.

Edited by

Guangzhou Center of Disease Control and Prevention, Guangzhou, Guangdong 510080, China (Fu CX, Nie J, Liang JH and Wang M)

Correspondence to: Dr. WANG Ming, Guangzhou Center of Disease Control and Prevention, Guangzhou, Guangdong 510080, China (Tel: 86–20–83878986. Fax: 86–20–83815255. Email:

(Received June 19, 2008)

Mumps virus infection, a potentially serious viral infection of childhood and early adulthood, may lead to meningitis (15% of all mumps patients), sensorineural deafness (5 per 100 000), pancreatitis (4%), orchitis (20%-30% of postpubertal men with mumps), and spontaneous abortion (25%, usually in the first trimester of pregnancy).1–8 There is still no effective treatment specifically for mumps.

The burden of disease and cost of mumps virus infection led to the development of a specific vaccine in China. This live attenuated S79 mumps vaccine was derived from the Jeryl-Lynn strain (isolated in 1979) after 3 successive passages in primary chick embryo cell culture. Since 1990, several large domestic manufacturers of biological products (Shanghai, Beijing, and Lanzhou Institute of Biological Products, China) have been licensed to produce S79 strain mumps vaccine, and Chinese children have been immunized with over 109 doses. However, little data is available on the vaccine's safety and efficacy.

An assessment of the public health role of the S79 vaccine under real-world conditions of clinical practice is now needed. In China, 1 dose of S79 live vaccine is recommended in some localities for children aged over 8 months. Mumps is a great threat to children in Guangzhou, one of the largest and most prosperous cities in China, where 5171 and 7934 mumps cases (incidence rate, 70.36/100 000 and 105.53/100 000, respectively) were reported in 2004 and 2005. The S79 vaccine has been used in children since 1995 in Guangzhou and vaccination has been voluntary. Thus data were available for us to assess the vaccine effectiveness (VE) of this vaccine, and we carried out a study among mumps outbreaks cases.

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Study population

Our case definition included acute onset of unilateral or bilateral tender swelling of the parotid or salivary gland lasting 2 or more days without any other apparent cause from mumps outbreaks in schools in Guangzhou between 2004 and 2005, with outbreak defined as at least onset of three cases within one week in one school. In Guangzhou all mumps outbreaks are required to report to the Guangzhou Center for Disease Control and Prevention (Guangzhou CDC).

Only children (8 months to 12 years old) whose information was found in the Children's Expanded Programmed Immunization (EPI) Administrative Computerized System were enrolled. The Children's EPI Administrative Computerized System established in Guangzhou in 1997 was designed to manage vaccination information. The system allows healthcare workers to easily record, store, retrieve, and analyze all children's vaccination information. The demographic and vaccination information of all registered vaccinees could be found in the system. Demographic information included name, parents’ names, gender, birth date, place of residence, home telephone number, health condition, etc. Detailed vaccination information included the number and dates of vaccination, vaccine brand name, and batch number.

Controls were confirmed to be children without symptoms of mumps (i.e., no acute onset of unilateral or bilateral tender swelling of the parotid or salivary gland). Confirmation was obtained by telephone or face-to-face interview with the children's parents or guardians.

For each case subject, three potential controls were randomly selected by gender, age and classroom. The closer the date of birth, the sooner to be approached; for example, born in the same month. Finally we selected one control for every case.

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Data collection

The information needed to enroll cases and controls was obtained by trained staff using a questionnaire. The questionnaire was designed by researchers and revised after a pilot investigation in two primary schools.

Basic information (name, gender, birth date, home telephone number, address, grade and class) and S79 mumps vaccine vaccination information (total number doses, dates of vaccination, and vaccine batch numbers) were obtained for both cases and controls.

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Statistical analysis

Data were collected and processed at Guangzhou CDC. Exclusion criteria for cases and controls were the absence of patient records in the Children's EPI Administrative Computerized System. For cases, only those vaccinated at least 4 weeks before onset of disease were considered valid. For controls with valid vaccination, days from birth to vaccination had to be at least 4 weeks earlier than the days from birth to onset for the matched case. Analysis was performed using SPSS 13.0. Simple descriptive statistics such as means, standard deviations, and proportions were used when appropriate. Student's t test and X2 tests were used to analyze group differences. VE was analyzed separately for receipt of 1 dose only and receipt of 2 doses of the S79 vaccine. VE was calculated as one minus the adjusted matched odds ratio (OR) × 100%, where the OR was the odds of cases developing in the vaccinated group compared with the odds of cases developing in the unvaccinated group.

Cox survival regression was used to calculate the ORs and 95% confidence intervals (CI).9,10 Records (case or control) in the database were stratified according to ID number: 1 was assigned to cases and 0 to controls. Pairs that were discordant for vaccine receipt (e.g., case received vaccination and control received no vaccination) were also included. For all analysis, P values not more than 0.05 were regarded as significant.

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One hundred and ninety-four mumps cases in 37 outbreaks between grade 1 and grade 5 from March 2004 to July 2005 were finally enrolled in our study. For enrolees, age varied from 6.4 years old to 12.0 years old, with a median age of 10.0 years old, residing in 9 administrative areas in Guangzhou. Most of cases were 8–11 years of age (89.7%, n=174).

Occurring almost in every month, the peak onset periods were from March to June (88 cases, 45.4% of all cases) and from October to December (76 cases, 39.2% of all cases). The least number was found in August, 2004 (0 case) (Figure).



We identified 582 children (for 194 cases) as potential controls and included 194 controls in the analysis. Age, gender and classroom were identical for each pair.

Among 388 study participants, 201 had been vaccinated with valid S79 mumps vaccine, whereas 179 had received 1 dose of the vaccine, 22 were vaccinated with 2 doses. The percent of children vaccinated among the controls was much higher than that of cases (66.0% vs 37.6%, X2=31.226, P =0.000, Table 1). For those vaccinated, the median age receiving the first dose of vaccine is 1.22 years old (range from 8 months to 9.0 years old) with the second dose median age 5.23 years old (range from 4.0 to 6.0 years old). For cases, 73 of 194 had received 1 or 2 dose of S79 mumps vaccine, at median onset age 9.06 years and average time 7.56 years from first vaccination to onset.

Table 1

Table 1

Overall VE of S79 mumps vaccine against clinical mumps in outbreaks in children was 83.3% (95% CI, 68.4% to 91.2%). For one dose, VE of S79 mumps vaccine was a bit lower (80.4%). No difference was found between VEs in the 0–9 years old and those aged over 10 years old age groups (Table 2). VE of 2 doses (90.0%) was not found to be statistically effective because of a small sample size (95% CI, -123.7% to 97.2%).

Table 2

Table 2

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We matched vaccination information for 194 clinical cases in mumps outbreaks and 194 matched controls (collected from March, 2004 to July, 2005) to discover that 1 dose of live attenuated S79 mumps vaccine is effective in preventing mumps outbreaks. This post-licensing study of VE found VE of S79 mumps vaccine for 1 dose versus 0 confers protection in 80.4% (95% CI, 60.0%-90.4%) of recipients during a mumps outbreak.

The serological response to the S79 mumps vaccine conferred only moderate protection against mumps (74.07%-83.50%), but no further information is available.

Our study showed that our VE of 80.4% was lower than the result of efficacy trials (89.04%). However, detailed information on this efficacy trial is not available. The protection afforded by vaccination can be overestimated by those efficacy studies with poor methodology. S79 vaccine may also be less effective under field conditions due to problems with storage (for example, a failure to correctly maintain the cold chain for this attenuated vaccine).

Pre-licensing studies normally evaluate protection under the optimal conditions of clinical trials. However, vaccine protection is better estimated under field conditions. Efficacy figures from clinical trials can not easily be converted to VE because, during routine practice, not all susceptible children will be immunized before exposure or receive the full immunization series. In addition, the spectrum of vaccine recipients in practice is typically wider than the healthy, highly responsive vaccine recipients usually selected for efficacy trials. So, from a public health perspective, the impact of vaccination on outcome in the field should be analyzed.11–14

In the past ten years since the vaccine has been in use in China, VE has not been reported, although the VE of other mumps vaccines have been evaluated. VEs of Jery1 Lynn and RIT4385 mumps vaccines were reported to be 75%—91% in mumps outbreaks.15–19

The small hydrophobic (SH) protein gene is the most variable part of the mumps virus genome. The distribution of mumps virus genotypes varies extensively both temporally and geographically. Xu et al20 reported in China that the nucleotide sequences of the 1995 wild-type mumps virus were clearly different from those of the vaccine S79 strain.

We find that the S79 strain vaccine is still effective in preventing mumps, partly because the key gene in the wild-type mumps virus has remained almost unchanged. The VEs for 1 dose of S79 mumps vaccine are similar among those children aged 4–9 years and aged over 10 years old, which is not described in efficacy trials. This result may be explained by the long protective period of 1 dose of S79 mumps vaccine among those vaccinated.

In China the mumps vaccine is not included in the national immunization systems. The low coverage of this vaccine leaves most pupils vulnerable to mumps virus infection. Since the vast majority of mumps cases occur in children and 1 dose of is not 100% effective, in developing countries, at a minimum, 1 dose administrated as early as possible in the first year is greatly needed and the second dose of mumps vaccine is recommended to get full protection from mumps as other mumps vaccine.21

In our study, cases and their matched controls were selected at the same time and classroom to control for seasonal effects and the effects of other risk factors for mumps virus infection.

Our study might have many limitations. The cases may not be representative of all mumps patients. Nearly one third of mumps infections are subclinical, and the cases in our sample were severe. Cases were not laboratoryconfirmed and some of our controls may have been latent or subclinical cases. The VE referred to in our study was against clinical cases or against cases with severe symptoms.

The observational nature of case-control studies can result in bias and confounding. We tried to avoid selection bias in controls by using standardized computer methods to locate and enroll them. We also controlled for several possible confounders such as gender and age. Because of its large size, our study could assess the VE of 1 dose of S79 mumps vaccine. Memory bias was eliminated by using the Children's EPI Administrative Computerized System. Vaccination history was based on computer records rather than parents’ or guardians’ recall, so the order of onset and vaccination date is explicitly known and valid vaccination is confirmed.

This post-licensing study of the VE of the live attenuated S79 mumps vaccine found that 1 (versus 0) dose was effective in preventing mumps outbreaks. The next challenge is to evaluate the VE of 2 doses of S79 mumps vaccine.

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The authors thank the healthcare workers and staff who devoted themselves to the study. We are indebted to all children and their families who participated in the survey.

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mumps; outbreaks; case-control studies

© 2009 Chinese Medical Association