we analyzed hospital episode , enhanced surveillance data , and clinical and laboratory surveillance data on mumps cases with onset or admission from april 1 , 2002 , through march 31 , 2006 , covering the period of the mumps outbreak in 20042005 . when no onset date was available , the date of the sample or report was used . hospital episode statistics ( he s ) capture all admissions to national health service ( nhs ) hospitals in england and wales . the diagnoses recorded at the time of discharge are coded by using the international classification of diseases , 10th edition ( icd-10 ) , and entered in any of 13 fields . a minimum dataset was extracted for all admissions with any of the following codes : b26 ( mumps ) , n45 ( orchitis and epididymitis ) , a87 ( viral meningitis ) , n70 ( oophoritis ) , and k85 ( acute pancreatitis ) ( 19 ) . the anonymized he s identification field , generated from the nhs number , local patient identifier , postcode , sex , and date of birth , was used to link episodes from the same person admitted over the period ( 20 ) . in england and wales , clinicians who diagnose mumps are required by statute to notify the proper officer for the local authority , usually a consultant in health protection . since 1995 , all notified cases of mumps have been monitored by offering oral fluid testing for immunoglobulin ( ig ) m at the centre for infections , health protection agency . a high proportion of cases are tested ( 50%80% ) , and thus cases confirmed by testing for igm in oral fluid provide data on the incidence of mumps ( 1 ) . vaccination history is requested on the sample - testing form for the oral fluid sample . all patients with confirmed cases were then followed up by sending an enhanced surveillance form to the general practitioner ( directly or through the local health protection unit ) requesting further information . information on complications , whether the mumps case - patient was hospitalized , and the receipt of mmr ( or other mumps virus  containing vaccines ) was confirmed . those with no record of vaccination shown on the sample request form and in the general practitioner records ( as noted on the returned enhanced surveillance forms ) complications were recorded in free text , which was searched and recoded specifically for any mention of orchitis , meningitis , pancreatitis , and oophoritis . because of the high proportion of patients with notified cases that are tested by oral fluid , results for laboratory - confirmed mumps are thought to provide fairly complete estimates of clinically diagnosed mumps incidence . in 2005 , however , during the peak of the mumps outbreak , mumps oral fluid testing was temporarily suspended in those born from 1981 through 1986 . therefore , to provide a better estimate of true incidence of clinically diagnosed mumps in 2005 , we extracted the number of patients with clinically notified cases of mumps born during 19811986 from notifications of infectious diseases . in view of the high positive predictive value of clinical diagnosis in this age group and period , the number of clinically diagnosed patients with notified cases was then used as the total estimated denominator instead of laboratory - confirmed mumps cases . logistic regression analysis was used to assess the relation between hospitalization , mumps complications , and vaccination status in the enhanced surveillance data . the model was adjusted for age and sex , except in the model with mumps orchitis in which only male patients were included , and adjustment was made only for age . the age variable was included as a continuous variable by using polynomials up to the fifth degree to allow for nonlinearity of age . this option is an alternative to using a large number of age categories ( which would give similar results ) . odds ratios ( ors ) with 95% confidence intervals ( cis ) were determined ; p<0.05 was considered significant . all statistical analysis was performed in stata version 11 ( statacorp , college station , tx , usa ) . hospital episode statistics ( he s ) capture all admissions to national health service ( nhs ) hospitals in england and wales . the diagnoses recorded at the time of discharge are coded by using the international classification of diseases , 10th edition ( icd-10 ) , and entered in any of 13 fields . a minimum dataset was extracted for all admissions with any of the following codes : b26 ( mumps ) , n45 ( orchitis and epididymitis ) , a87 ( viral meningitis ) , n70 ( oophoritis ) , and k85 ( acute pancreatitis ) ( 19 ) . the anonymized he s identification field , generated from the nhs number , local patient identifier , postcode , sex , and date of birth , was used to link episodes from the same person admitted over the period ( 20 ) . in england and wales , clinicians who diagnose mumps are required by statute to notify the proper officer for the local authority , usually a consultant in health protection . since 1995 , all notified cases of mumps have been monitored by offering oral fluid testing for immunoglobulin ( ig ) m at the centre for infections , health protection agency . a high proportion of cases are tested ( 50%80% ) , and thus cases confirmed by testing for igm in oral fluid provide data on the incidence of mumps ( 1 ) . vaccination history is requested on the sample - testing form for the oral fluid sample . all patients with confirmed cases were then followed up by sending an enhanced surveillance form to the general practitioner ( directly or through the local health protection unit ) requesting further information . information on complications , whether the mumps case - patient was hospitalized , and the receipt of mmr ( or other mumps virus  containing vaccines ) was confirmed . those with no record of vaccination shown on the sample request form and in the general practitioner records ( as noted on the returned enhanced surveillance forms ) complications were recorded in free text , which was searched and recoded specifically for any mention of orchitis , meningitis , pancreatitis , and oophoritis . because of the high proportion of patients with notified cases that are tested by oral fluid , results for laboratory - confirmed mumps are thought to provide fairly complete estimates of clinically diagnosed mumps incidence . in 2005 , however , during the peak of the mumps outbreak , mumps oral fluid testing was temporarily suspended in those born from 1981 through 1986 . therefore , to provide a better estimate of true incidence of clinically diagnosed mumps in 2005 , we extracted the number of patients with clinically notified cases of mumps born during 19811986 from notifications of infectious diseases . in view of the high positive predictive value of clinical diagnosis in this age group and period , the number of clinically diagnosed patients with notified cases was then used as the total estimated denominator instead of laboratory - confirmed mumps cases . logistic regression analysis was used to assess the relation between hospitalization , mumps complications , and vaccination status in the enhanced surveillance data . the model was adjusted for age and sex , except in the model with mumps orchitis in which only male patients were included , and adjustment was made only for age . the age variable was included as a continuous variable by using polynomials up to the fifth degree to allow for nonlinearity of age . this option is an alternative to using a large number of age categories ( which would give similar results ) . odds ratios ( ors ) with 95% confidence intervals ( cis ) were determined ; p<0.05 was considered significant . all statistical analysis was performed in stata version 11 ( statacorp , college station , tx , usa ) . the total estimated number of mumps case - patients in england and wales from april 1 , 2002 , through march 31 , 2006 , obtained by combining data from laboratory diagnosis and notifications ( for those born between 1981 and 1986 in 2005 only ) , was 43,344 ( 23,246 male ) . a total of 2,647 mumps case - patients were hospitalized from april 2002 through march 2006 ( table 1 ) . hospitalized mumps case - patients , including those with a code for orchitis ( 996 patients ) , meningitis ( 154 patients ) , pancreatitis ( 146 patients ) , or none of these complications ( 1,418 patients ) showed a clear increase during the outbreak ( figure ) . most of these mumps complications were attributable to the mumps outbreak because episodes with these codes were negligible before the start of the outbreak period . of mumps complications in hospitalized patients , most ( 81% of those with orchitis , 76% with meningitis , and 78% with pancreatitis ) arose in those born from 1980 to 1989 ( table 1 ) . * in male patients total estimated number of cases of mumps and hospital episodes coded to mumps , england and wales , april 1 , 2002march 31 , 2006 . the hospitalization rate was 4.4% ( 996/22,686 ) for mumps orchitis , 0.35% ( 154/43,344 ) for mumps meningitis and 0.33% ( 146/43,344 ) for mumps pancreatitis . when results are stratified by year of birth to those born before 1980 , those born from 1980 through 1989 , and those born from 1990 through 2006 , the estimated complication rate for hospitalized mumps orchitis is lower in younger age groups than in older age groups ( table 1 ) . although rates of mumps meningitis and mumps pancreatitis in younger cohorts are lower , the pattern is less clear because of the smaller numbers involved . the rate of hospitalized mumps not coded with any of the main complications was lowest in the 19801989 cohort . from april 2002 through march 2006 , a total of 28,280 laboratory - confirmed mumps cases occurred . for 15,524 ( 55% ) case - patients , for those born pre-1980 , the response rate was 52% ( 2,298/4,455 ) , compared with 55% ( 10,865/19,763 ) for those born from 1980 through1989 and 68% ( 2,554/3,737 ) for those born from 1990 through 2006 . for those born since 1990 , the response rate was higher for confirmed case - patients listed as vaccinated on the sample request form ( 1765/2,189 [ 81% ] ) than for those with no vaccination details ( 789/1,548 [ 51% ] ) . of 15,524 confirmed mumps case - patients whose enhanced surveillance form was returned , 7,226 ( 47% ) had a documented history of vaccination ( 6,312 with 1 dose and 914 with 2 doses ) , and 8,298 ( 53.4% ) were unvaccinated ( many of whom were born before 1988 and therefore were not eligible for mmr ) . the reported complication rate for mumps meningitis was 0.3% ( 53/15,524 ) and was 0.25% ( 38/15,524 ) for mumps pancreatitis . the most common complication was orchitis , reported for 6.1% ( 486/7,917 ) of male case - patients the proportion of case - patients with each complication ( excluding those with > 1 ) that were hospitalized was lowest for mumps orchitis at 35.3% ( 166/470 ) , followed by the proportion for mumps meningitis , 78.3% ( 36/46 ) , and for mumps pancreatitis , 81.5% ( 22/27 ) . the remaining 228 case - patients were hospitalized for varied reasons , ranging from airway concerns to anxious parents . the rate of hospitalization and rate of each main mumps complication were lower in those that were vaccinated than in the unvaccinated ; rates were particularly low among those who had received 2 doses of vaccine ( table 2 ) . * or , odds ratio ; ci , confidence interval ;  , not estimable . the ors of reported hospitalization , orchitis , and meningitis were significantly lower in the vaccinated ( 1- or 2-dose mmr ) than in the unvaccinated patients ( table 2 ) . the polynomials for the age variable in the final logistic regression model for hospitalization , orchitis , meningitis . and pancreatitis are second , fourth , first , and second , respectively . adjusting for age and sex had very little effect on the protective effect of vaccination in reducing the risk for hospitalization . the or of having mumps meningitis was also found to be higher in male patients at 1.93 ( 95% ci 1.073.48 ) after vaccination status and age were controlled for . the mumps outbreak in england and wales led to a clear increase in hospitalizations caused by mumps complications , which mirrored the outbreak curve . from april 1 , 2002 , through march 31 , 2006 , the estimated hospitalization rate from he s data was 6.1% overall . a much lower rate of hospitalization ( 2.9% ) was derived from the enhanced surveillance forms . in contrast , the rate of mumps orchitis estimated from he s data was lower than that found by enhanced surveillance . this may be explained by the fact that most mumps orchitis cases were managed in primary care . most reported case - patients with mumps meningitis and pancreatitis were admitted to the hospital , but the estimated rate of these complications was low ( < 0.5% ) by using either method . on the basis of the rate of hospital episodes and data from enhanced surveillance , the complication rates observed here are low in comparison to results of studies from the prevaccine era . previously published complication rates for mumps suggest that orchitis is the most common complication in 15%30% of adult men with mumps ( 2124 ) . mumps meningitis has been reported in 1%10% , mumps pancreatitis in 4% , and mumps oophoritis in 5% of persons with mumps ( 3,25,26 ) . the much lower rates observed in our study likely reflect the fact that the denominator is derived from population - based surveillance which aims to capture all cases of diagnosed mumps . because the united kingdom provides free universal access to primary care , we were able to ascertain milder cases that may not have been included in studies that use secondary care data or in studies conducted in other countries . the estimated complication rates were lower in younger persons , particularly in the cohorts eligible for mumps vaccination . the outbreak in england and wales during 20042005 affected mainly those born from 1980 through 1989 ( 1,8 ) . only those born in the second half of the 1980s could have been offered mmr ; either routinely in the second year of life ( those born from 1987 onwards ) or as a catch - up at school entry for those who had not received measles vaccine . those born after 1989 were eligible for routine mmr at 13 months and for a second dose of mmr at school age when it was introduced in 1996 . the lower estimated hospitalization rate for mumps orchititis in younger cohorts could be attributed to less severe disease in younger persons or to the effect of mumps vaccination . the latter explanation was supported by the finding that a history of mumps vaccination was also associated with a lower risk for mumps hospitalization , mumps orchitis , and mumps meningitis in the enhanced surveillance data , even after age and sex were controlled for . our analysis suggests that the adjusted odds of being hospitalized with mumps are reduced 50% in those with a history of at least 1 mumps vaccination . we observed an even lower rate of hospitalization in those who had received 2 doses than in those who had received 1 dose of vaccine , although this difference was not significant . male patients had a higher risk for mumps meningitis , even after vaccination status was adjusted for . results of vaccine effectiveness studies and the long - term persistence of mumps antibody have not shown differences on the basis of sex ( 7,12,26 ) . however , mumps meningitis has been shown to affect male patients more often than female patients ( 25 ) . most published complication rates derive from the prevaccine era ; however , almost half of the case - patients included in our enhanced surveillance had been vaccinated . our findings are more consistent with those of other studies in the mmr era in which rates of orchitis in postpubertal male patients were 10%12% , and the rate of mumps meningitis was 0.9% ( 11,12 ) . to our knowledge , information on the association between mumps vaccination and mumps complications is limited . a study of outbreaks of mumps in us colleges in 2006 showed no significant association between vaccination status and complications in a highly vaccinated population ( 11 ) . the larger sample size in our analysis allowed us to detect differences in complication rates by vaccination status , which may be undetectable in smaller studies or when the number of unvaccinated persons is low . a limitation of the enhanced surveillance database is the possible bias from nonresponses . the higher response rates in younger however , we observed lower complication rates in the young and vaccinated , which suggests that our observations are not due to response bias . we believe it is plausible that vaccination against mumps can lead to a shift toward milder forms of the disease in a similar way as has been observed with varicella vaccine ( 27 ) . natural mumps in unvaccinated persons is known to be manifested as a minimally symptomatic infection with viral shedding ( 28 ) . studies have also reported a high proportion of asymptomatic or minimally symptomatic infections among vaccinated persons ; more than half of case - patients did not have classical parotitis ( 12 ) . the possibility of reduced severity of infections in vaccinated case - patients is also supported by findings of a lower virus isolation rate and shorter duration of viral detection in studies that compare vaccinated to unvaccinated patients ( 29,30 ) . the lower rates of complications in vaccinated teenagers and young adults are consistent with secondary vaccine failure , which suggests that the primed person is able to mount an immune response to prevent more serious complications . a large number of cases with secondary vaccine failure is also consistent with declining protection with time since vaccination ( 7,31 ) . by using he s data , however , we could have underestimated the rates of complications because a substantial number of hospitalizations were coded for mumps alone . the overall rate based on hospital episodes is probably a high estimate because the numerator derives from an exhaustive database , whereas the denominator was derived from number of confirmed cases , a category that is prone to some underreporting . to minimize this underreporting effect , we combined clinical notifications during a period of high positive predictive value with laboratory - confirmed mumps cases derived from population - based surveillance by using noninvasive oral fluid testing . the use of laboratory - confirmed mumps cases based on serologic testing alone in the denominator is likely to overrepresent hospitalized case - patients and therefore to overestimate complication rates . the rate from enhanced surveillance is more likely to be a true reflection of absolute rate because both numerator and denominator are derived from the same source . in addition , although both estimates are dependent on patients seeking care for the complication , clinical details in the enhanced surveillance were supplied directly from primary care physicians who had diagnosed mumps . therefore , complications exhibited some time after infection were less likely to be attributed to mumps . the effects of long - term complications , such as sensorineural deafness and the possible link between mumps orchitis and infertility , were not included in our analysis ( 3,3235 ) . with the current outbreaks in colleges as well as in other congregate settings , mumps orchitis in postpubertal young men may require further research . a concern exists that mumps epididymitis ( which carries a risk for testicular damage with subsequent infertility ) is easily misdiagnosed as orchitis ( 36 ) . as reports of mumps outbreaks in highly immunized populations of older teenagers and young adults continue to occur , the long - term effects of mumps complications may be substantial . our analysis , however , suggests that vaccination provides higher levels of protection against hospitalization and risk for orchitis and meningitis in those diagnosed with mumps . the effect of vaccination on mumps complications will therefore be increasingly critical in assessing the outcome of current and future mumps control strategies .
we analyzed data from hospital admissions and enhanced mumps surveillance to assess mumps complications during the largest mumps outbreak in england and wales , 20042005 , and their association with mumps vaccination . when compared with nonoutbreak periods , 
 the outbreak was associated with a clear increase in hospitalized patients with orchitis , meningitis , and pancreatitis . 
 routine mumps surveillance and hospital data showed that 6.1% of estimated mumps patients were hospitalized , 4.4% had orchitis , 0.35% meningitis , and 0.33% pancreatitis . 
 enhanced surveillance data showed 2.9% of mumps patients were hospitalized , 6.1% had orchitis , 0.3% had meningitis , and 0.25% had pancreatitis . 
 risk was reduced for hospitalization ( odds ratio [ or ] 0.54 , 95% confidence interval [ ci ] 0.430.68 ) , mumps orchitis ( or 0.72 , 95% ci 0.560.93 ) and mumps meningitis ( or 0.28 , 95% ci 0.140.56 ) when patient had received 1 dose of measles , mumps , and rubella vaccine . 
 the protective effect of vaccination on disease severity is critical in assessing the total effects of current and future mumps control strategies .