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Mumps: A year of enhanced surveillance in Catalonia, Spain
Vaccine 27 (2009) 3492–3495
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Mumps: A year of enhanced surveillance in Catalonia, Spain Angela Dominguez a,b,∗ , Manuel Oviedo b,c , Nuria Torner b,c , Gloria Carmona c , Josep Costa d , Joan Caylà e , M. Rosa Sala c , Irene Barrabeig c , Neus Camps c , Sofia Minguell c , Josep Alvarez c , Pere Godoy c,b , Josep M. Jansà c,b , the Mumps Control Working Group of Catalonia a
Department of Public Health, University of Barcelona, Casanova 143, 08036 Barcelona, Spain CIBER Epidemiología y Salud Pública (CIBERESP), Spain, Dr Aiguader 88, 08003 Barcelona, Spain Department of Health, Generalitat of Catalonia, Roc Boronat 81-95, 08005 Barcelona, Spain d Department of Microbiology, Hospital Clinic, Casanova 143, 08036 Barcelona, Spain e Public Health Agency of Barcelona, Pl Lesseps 1, 08024 Barcelona, Spain b c
a r t i c l e
i n f o
Article history: Available online 31 March 2009 Keywords: Mumps Enhanced surveillance Laboratory confirmation
a b s t r a c t Mumps is a vaccine-preventable disease candidate for elimination. Positive predictive value (PPV) of clinical case definition was assessed. During 2007, 410 suspected cases were reported in Catalonia: 348 fulfilled clinical case definition and 159 were laboratory confirmed. Incidence rate was 4.8 per 100,000 for cases that fulfilled the clinical definition, and 2.2 for laboratory confirmed cases. Global PPV was 44.5%; 38.5% in <15 years and 50% in ≥15 years (p = 0.04). Most laboratory confirmed cases (72.3%) received at least one MMR dose. With sustained high MMR coverage, laboratory confirmation is necessary to control the disease and assess vaccine failure. © 2009 Elsevier Ltd. All rights reserved.
1. Introduction Mumps is an acute infectious disease caused by a virus of the Paramyxoviridae family. Although generally considered a benign childhood disease, complications are not uncommon in adolescents and adults [1]. Mumps virus infection is asymptomatic in onethird of cases, mainly in children. The disease is characterised by enlargement of the parotid or other salivary glands, although orchitis, arthritis, pancreatitis, mastitis, oophoritis or meningitis can also occur. Humans are the only natural reservoir for the mumps virus and this, together with the availability of an effective vaccine, led the International Task Force for Disease Eradication to consider the disease potentially eradicable [2]. Post-licensure studies showed that one dose of vaccine was effective in preventing clinical mumps, but outbreaks in schools with very high vaccine coverage of one dose of vaccine suggested this was not sufficient to prevent outbreaks. In Catalonia, a region in the northeast of Spain with more than 7 million inhabitants, one dose of the measles, mumps and rubella (MMR) vaccine at 12 months of age was introduced into the routine vaccination schedule in 1980. In 1987, the first dose shifted to 15 months of age and in 1988, a second dose of MMR was added at 11 years of age to replace the rubella vaccine administered to girls. In 1998, the second dose began to be administered at 4 years of
∗ Corresponding author at: Department of Public Health, University of Barcelona, Casanova 143, 08036 Barcelona, Spain. Tel.: +34 93 4024566. E-mail address: [email protected] (A. Dominguez). 0264-410X/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2009.03.022
age. This vaccination policy resulted in mumps incidence decreasing from 457 per 100,000 inhabitants in 1983 to 1.8 per 100,000 in 2006 (Fig. 1). This dramatic decrease encouraged the implementation of a program aimed at eliminating autochthonous mumps by the end of 2010, with enhanced disease surveillance by laboratory confirmation of clinically suspected cases being a key component of the program. The objective of this study was to evaluate the results of the first year of enhanced surveillance of mumps in Catalonia and the sensitivity and positive predictive value (PPV) of the clinical case definition.
2. Materials and methods Data were collected from the register of clinically suspected cases of mumps reported to the epidemiological surveillance units of the Department of Health of the Generalitat of Catalonia. The study period was 1 January to 31 December 2007. A clinical case was defined as acute onset of uni- or bilateral swelling of the parotid or other salivary glands for two or more days with no other apparent cause. The laboratory criteria for confirmation were detection of the viral genome by real time reverse transcription polymerase chain reaction (RT-PCR) in oral sample [3], positive serologic test for mumps immunoglobulin M (IgM) antibody or a significant rise between acute and convalescent phase titers in serum mumps immunoglobulin G (IgG) antibody level by enzyme immunoassay. A confirmed case was a case that was laboratory confirmed or a
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each case, an epidemiological form containing the following variables: age, clinical manifestations, complications, hospitalization and vaccination history, was completed. Incidence rates were calculated using the estimated population of Catalonia for 2007. The 95% confidence intervals (CI) were calculated assuming a Poisson distribution. The CI of sensitivity and PPV were calculated by the exact binomial method. The 2 and Fisher’s exact tests were used to determine statistically significant differences between proportions. The level of statistical significance was established at ˛ = 0.05. 3. Results During the study period, 410 suspected cases of mumps were reported. Of these, 348 (84.9%) fulfilled the clinical case definition, 320 (78%) were laboratory tested, 159 (38.8%) were laboratory confirmed (74 by IgM detection, 70 by RT-PCR, 15 by RT-PCR and IgM), and 131 (32.9%) met the clinical case definition and were epidemiologically linked to another case. Complications were observed in 12 patients, including orchitis (11 cases) and meningitis (1 case), of which 10 cases of orchitis and the case of meningitis occurred in the <15 years age group. Four cases were hospitalized. No deaths occurred. The global incidence rate was 4.8 per 100,000 (4.3–5.4) in the 348 cases that fulfilled the clinical case definition, 2.2 per 100,000 (1.9–2.6) in laboratory confirmed cases, and 4 per 100,000 (3.6–4.5) in any confirmed case (laboratory or epidemiological link). Highest incidence rates corresponded to 5–14 and 15–24 years for all categories of cases and the incidence of male was higher than the incidence of females (Table 1). A total of 72.3% of laboratory confirmed cases (91.7% in the 5–14 years age group) and 76.2% of all confirmed cases (95.5% in the 5–14 years age group) had received at least one MMR dose; 56% of laboratory confirmed cases and 55.5% of all confirmed cases, respectively, had received two doses. The sensitivity and PPV of the clinical case definition are shown in Table 2. The sensitivity of laboratory confirmed cases, epidemi-
Fig. 1. Reported morbidity of mumps. Catalonia, 1983–2006.
case that met the clinical case definition and was epidemiologically linked to a laboratory confirmed or to a clinical case. Reporting of mumps by physicians has been mandatory since 1982 in Catalonia, but reporting of full demographic and epidemiological data in all suspected cases is only mandatory since 1997. In the context of the Mumps Elimination Program, since 2007 all suspected cases must be reported to the Department of Health urgently (within 24 h of the suspicion) and support for laboratory confirmation was obtained. Laboratory analyses were carried out by the microbiology laboratory of the Hospital Clinic of Barcelona. The sensitivity of the clinical case definition was calculated as the proportion of confirmed cases (by laboratory or by epidemiological link) that met the clinical definition. Positive predictive value was calculated as the proportion of clinical compatible cases that were confirmed (by laboratory or by epidemiological link). For Table 1 Incidence rates (per 100,000 population) of mumps. Catalonia, 2007. Age
Laboratory confirmed cases
All confirmed cases
Rate
Rate
95% CI
Rate
95% CI
11.1 13.3 13.5 2.9 0.3 4.0
8.0–15.0 10.8–16.4 11.0–16.3 2.0–3.9 0.5–0.7 3.6–4.5
12.9 16.1 15.3 3.9 0.3 4.8
9.6–17.0 13.2–19.5 12.7–18.3 2.9–5.1 0.6–0.9 4.3–5.4
95% CI
0–4 years 5–14 years 15–24 years 25–34 years ≥35 years All ages
3.4 7.3 7.7 2.0 0.3 2.2
1.8–5.7 5.3–9.7 5.9–9.9 1.9–2.6 0.2–0.5 1.9–2.6
Gender Male Femalec
2.7a 1.8
2.2–3.2 1.3–2.3
a b c
5.2b 2.9
Clinically compatible cases
6.0b 3.6
4.4–6.0 2.3–3.4
5.3–6.9 3.0–4.2
p = 0.013. p < 0.0001. Reference category.
Table 2 Sensitivity and positive predictive value of mumps clinical definition. Age
n
<15 years ≥15 yearsc All ages a b c
177 231 410
p = 0.04. p = 0.01. Reference category.
Sensitivity % (95% CI)
Positive predictive value % (95% IC)
Laboratory confirmation
Epidemiological confirmation
Any confirmation
Laboratory confirmation
Epidemiological confirmation
Any confirmation
98.4 (91.2–100) 96.9 (91.3–100) 97.5 (93.7–100)
95.1 (88.8–100) 100 (98.8–100) 96.9 (92.3–100)
98.5 (94.6–100) 96.2 (92.0–100) 97.2 (94.6–100)
38.5 (31.1–46.4)a 50.0 (43.1–57.4) 44.5 (39.5–49.9)
44.2 (36.1–52.4)b 30.5 (23.7–37.3) 36.5 (31.6–41.7
82.7 (75.8–88.3) 80.5 (75.1–86.4) 81.0 (77.1–85.3)
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A. Dominguez et al. / Vaccine 27 (2009) 3492–3495
ologically linked cases without laboratory confirmation and all confirmed cases was 97.5%, 96.9% and 97.2%, respectively, with no significant differences between age groups. The PPV for the same categories was 44.5%, 36.5% and 81.0%, respectively, with significant differences between age being observed. The PPV increased with age in laboratory confirmed cases (p = 0.04), but was higher in children in epidemiologically linked cases without laboratory confirmation (p = 0.01). 4. Discussion The incidence of reported cases fulfilling the clinical case definition (4.8 per 100,000 in 2007 vs. 1.8 in 2006) increased in the first year of enhanced mumps surveillance of mumps Catalonia. However, it is unclear if this increase is explained by changes in the surveillance system or if we are in an epidemic cycle. The incidence rate in laboratory confirmed cases was 2.2 per 100,000, similar to the reported rate in the United States in 2006 [4], but the incidence rate in all reported clinically compatible cases was more than twice as high. The incidence rate in all confirmed cases includes some cases epidemiologically related to other clinically compatible cases without laboratory confirmation and it is probable that some false cases are included. This reinforces the idea that, when the incidence of a disease is low, it is essential confirm by laboratory means all suspected cases or, at least, to consider confirmed cases as only those that are epidemiologically linked to laboratory confirmed cases. Increased mumps incidence has been reported in the United States [4], the United Kingdom [5], the Netherlands [6] and Israel [7], suggesting that the virus is circulating widely despite high coverage of two MMR. The estimated herd-immunity threshold for mumps ranges from 90 to 92% [8]. If the effectiveness of two MMR doses is estimated at 88–95% [9,10], even a 95% coverage reduces the population level of immunity to below this threshold [4]. Therefore, coverages > 95% with two doses are needed to control, and eliminate the disease, as achieved in Finland in 1996 [1]. This is especially important in situations of high population density and contact rates that facilitate the transmission [4]. The estimated coverage of one dose of MMR in Catalonia was 98.4% in 2004. However, although immigrants are offered the same health services as the indigenous population, the coverage of the first dose was only 93.3% in immigrant children compared to 98.9% in the indigenous population [11] and the two-dose coverage was slightly lower. During 2007, the Catalan population increased by 1.06% with respect to 2006, but the immigrant population increased by 6.43%, and may have contributed to increasing the probability of exposure to the mumps virus, as suggested by other authors [7]. Dayan et al. [4] found that the highest incidence was in the 18–24 years age group, suggesting an effect of waning immunity also reported in other studies [12,13]. However, we found that incidence rates were very similar in two age groups: 5–14 and 15–24 years. The percentage of all confirmed cases who had received at least one dose of MMR (76.2%) was lower than 87% and 97% found in studies carried out in United States [4,13], but higher than the 68% obtained by Pugh et al. in England and Wales [5]. The accumulation of individuals from various cohorts who were susceptible to mumps due to primary (insufficient response to vaccine) or secondary vaccine failure (waning immunity) may be an important explanation for these results. The partial use in Catalonia of the vaccine containing the Rubini strain, purchased during 1994–1996, may also have contributed, at least in part, to the resurgence of the disease in children who received their first dose in these years or later because, although this vaccine was no longer distributed in 1996, it may have been administered by local centers which had it in stock. The high proportion of confirmed cases that had received
at least one dose of vaccine in the 5–14 years age group supports this hypothesis. In contrast to the results obtained by other authors [4,5,13], we have found higher incidence rates in male than in female. Behavioral patterns have been suggested as a possible explanation of differences between genders, but more research is needed [4,13]. Only four cases were hospitalized, but complications, especially orchitis, were not uncommon, confirming other reports [1,4,12]. In laboratory confirmed cases, the sensitivity of the clinical case definition was 97.5%, slightly higher than that reported by Guy et al. [14] and similar to that obtained by Vandermeulen et al. [12]. However, the PPV of 44.5% in the same laboratory confirmed cases was clearly higher than the 10% obtained in the study by Guy et al. [14]. In conclusion, our results show the importance of laboratory confirmation of suspected cases of mumps because, when a disease has a low incidence, as is the case of some vaccine-preventable diseases in countries with high vaccine coverages, the PPV of clinical diagnoses decreases. The availability of RT-PCR techniques for oral samples has been very useful during this first year of enhanced surveillance in Catalonia. All confirmed cases should be laboratory confirmed or, at least, be linked to a laboratory confirmed case. Achieving elimination of mumps requires assessment of the number and nature of vaccine failures and adjustment of vaccination policies according to the new information obtained. Acknowledgements The other members of the Mumps Control Working Group of ˜ J.P., Batalla J., Catalonia are: Alsedà M., Arias C., Artigues A., Balana ˜ Cardenosa N., Ciruela P., Companys M., Follia N., Parrón I., Plasencia E., Rovira A., Torres J., Urbiztondo L. (Department of Health, Generalitat of Catalonia, Spain) and Rius C. (Public Health Agency of Barcelona, Spain). We thank the reporting physicians and technicians of the Epidemiological Surveillance Units of the Department of Health of the Generalitat of Catalonia and the Public Health Agency of Barcelona for their collaboration. This work was partially funded by CIBER Epidemiología y Salud Pública (CIBERESP), Spain. References [1] Galazka AM, Robertson SE, Kraigher A. Mumps and mumps vaccine: a global review. Bull World Health Organ 1999;77:3–14. [2] Centers for Disease Control Prevention. Recommendations of the international task force for disease eradication. MMWR 1993;42. RR-16. [3] Krause CH, Eastick K, Ogilvie MM. Real-time PCR for mumps diagnosis on clinical specimens—comparison with results of conventional methods of virus detection and nested PCR. J Clin Virol 2006;37:184–9. [4] Dayan GH, Qinlisk MP, Parker AA, Barskey AE, Harris ML, Schwartz JMH, et al. Recent resurgence of mumps in the United States. N Engl J Med 2008;358:1580–9. [5] Pugh RN, Akinosi B, Poorannsingh S, Kumar J, Grant S, Livesley E, et al. An outbreak of mumps in the metropolitan area of Walsall, UK. Int J Infect Dis 2002;6:283–7. [6] Kaajik P, van der Zeijstst BA, Boog M, Hoitink CW. Increased mumps incidence in the Netherlands: review of the possible role of vaccine strain and genotype. Euro Surveill 2008;13(26):pii=18914. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?Articled=18914. Accessed September 15 2008. [7] Huerta M, Davidovitch N, Aboudy Y, Ankol OE, Balicer RD, Zarka S, et al. Declining population immunity to mumps among Israeli military recruits. Vaccine 2006;24:6300–3. [8] Anderson RM, May RM. Immunisation and herd immunity. Lancet 1990;335: 641–5. [9] Harling R, White JM, Ramsay ME, Macsween KF, van den Bosch C. The effectiveness of the mumps component of the MMR vaccine: a case control study. Vaccine 2004;23:4070–4. [10] Cohen C, White JM, Sevage EJ, Glynn JR, Choi Y, Andrews N, et al. Vaccine effectiveness estimates 2004–2005 mumps outbreak, England. Emerg Infect Dis 2007;13:12–7.
A. Dominguez et al. / Vaccine 27 (2009) 3492–3495 ˜ [11] Borrás E, Domínguez A, Batalla J, Torner N, Cardenosa N, Nebot M, et al. Vaccination coverage in indigenous and immigrant children under 3 years of age in Catalonia (Spain). Vaccine 2007;25:3240–3. [12] Vandermeulen C, Roelants M, Vermoere M, Roseeuw K, Goubau P, Hoppenbrouwers K. Outbreak of mumps in a vaccinated child population: a question of vaccine failure? Vaccine 2004;22:2713–6.
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[13] Cortese MM, Jordan HT, Curns AT, Quinlan PA, Ens KA, Denning PM, et al. Mumps vaccine performance among university students during an outbreak. Clin Infect Dis 2008;46:1172–80. [14] Guy RJ, Andrews RM, Kelly HA, Leydon JA, Riddell MA, Lambert SB, et al. Mumps and rubella: a year of enhanced surveillance and laboratory testing. Epidemiol Infect 2004;132:391–8.
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Mumps: A year of enhanced surveillance in Catalonia, Spain Angela Dominguez a,b,∗ , Manuel Oviedo b,c , Nuria Torner b,c , Gloria Carmona c , Josep Costa d , Joan Caylà e , M. Rosa Sala c , Irene Barrabeig c , Neus Camps c , Sofia Minguell c , Josep Alvarez c , Pere Godoy c,b , Josep M. Jansà c,b , the Mumps Control Working Group of Catalonia a
Department of Public Health, University of Barcelona, Casanova 143, 08036 Barcelona, Spain CIBER Epidemiología y Salud Pública (CIBERESP), Spain, Dr Aiguader 88, 08003 Barcelona, Spain Department of Health, Generalitat of Catalonia, Roc Boronat 81-95, 08005 Barcelona, Spain d Department of Microbiology, Hospital Clinic, Casanova 143, 08036 Barcelona, Spain e Public Health Agency of Barcelona, Pl Lesseps 1, 08024 Barcelona, Spain b c
a r t i c l e
i n f o
Article history: Available online 31 March 2009 Keywords: Mumps Enhanced surveillance Laboratory confirmation
a b s t r a c t Mumps is a vaccine-preventable disease candidate for elimination. Positive predictive value (PPV) of clinical case definition was assessed. During 2007, 410 suspected cases were reported in Catalonia: 348 fulfilled clinical case definition and 159 were laboratory confirmed. Incidence rate was 4.8 per 100,000 for cases that fulfilled the clinical definition, and 2.2 for laboratory confirmed cases. Global PPV was 44.5%; 38.5% in <15 years and 50% in ≥15 years (p = 0.04). Most laboratory confirmed cases (72.3%) received at least one MMR dose. With sustained high MMR coverage, laboratory confirmation is necessary to control the disease and assess vaccine failure. © 2009 Elsevier Ltd. All rights reserved.
1. Introduction Mumps is an acute infectious disease caused by a virus of the Paramyxoviridae family. Although generally considered a benign childhood disease, complications are not uncommon in adolescents and adults [1]. Mumps virus infection is asymptomatic in onethird of cases, mainly in children. The disease is characterised by enlargement of the parotid or other salivary glands, although orchitis, arthritis, pancreatitis, mastitis, oophoritis or meningitis can also occur. Humans are the only natural reservoir for the mumps virus and this, together with the availability of an effective vaccine, led the International Task Force for Disease Eradication to consider the disease potentially eradicable [2]. Post-licensure studies showed that one dose of vaccine was effective in preventing clinical mumps, but outbreaks in schools with very high vaccine coverage of one dose of vaccine suggested this was not sufficient to prevent outbreaks. In Catalonia, a region in the northeast of Spain with more than 7 million inhabitants, one dose of the measles, mumps and rubella (MMR) vaccine at 12 months of age was introduced into the routine vaccination schedule in 1980. In 1987, the first dose shifted to 15 months of age and in 1988, a second dose of MMR was added at 11 years of age to replace the rubella vaccine administered to girls. In 1998, the second dose began to be administered at 4 years of
∗ Corresponding author at: Department of Public Health, University of Barcelona, Casanova 143, 08036 Barcelona, Spain. Tel.: +34 93 4024566. E-mail address: [email protected] (A. Dominguez). 0264-410X/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2009.03.022
age. This vaccination policy resulted in mumps incidence decreasing from 457 per 100,000 inhabitants in 1983 to 1.8 per 100,000 in 2006 (Fig. 1). This dramatic decrease encouraged the implementation of a program aimed at eliminating autochthonous mumps by the end of 2010, with enhanced disease surveillance by laboratory confirmation of clinically suspected cases being a key component of the program. The objective of this study was to evaluate the results of the first year of enhanced surveillance of mumps in Catalonia and the sensitivity and positive predictive value (PPV) of the clinical case definition.
2. Materials and methods Data were collected from the register of clinically suspected cases of mumps reported to the epidemiological surveillance units of the Department of Health of the Generalitat of Catalonia. The study period was 1 January to 31 December 2007. A clinical case was defined as acute onset of uni- or bilateral swelling of the parotid or other salivary glands for two or more days with no other apparent cause. The laboratory criteria for confirmation were detection of the viral genome by real time reverse transcription polymerase chain reaction (RT-PCR) in oral sample [3], positive serologic test for mumps immunoglobulin M (IgM) antibody or a significant rise between acute and convalescent phase titers in serum mumps immunoglobulin G (IgG) antibody level by enzyme immunoassay. A confirmed case was a case that was laboratory confirmed or a
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each case, an epidemiological form containing the following variables: age, clinical manifestations, complications, hospitalization and vaccination history, was completed. Incidence rates were calculated using the estimated population of Catalonia for 2007. The 95% confidence intervals (CI) were calculated assuming a Poisson distribution. The CI of sensitivity and PPV were calculated by the exact binomial method. The 2 and Fisher’s exact tests were used to determine statistically significant differences between proportions. The level of statistical significance was established at ˛ = 0.05. 3. Results During the study period, 410 suspected cases of mumps were reported. Of these, 348 (84.9%) fulfilled the clinical case definition, 320 (78%) were laboratory tested, 159 (38.8%) were laboratory confirmed (74 by IgM detection, 70 by RT-PCR, 15 by RT-PCR and IgM), and 131 (32.9%) met the clinical case definition and were epidemiologically linked to another case. Complications were observed in 12 patients, including orchitis (11 cases) and meningitis (1 case), of which 10 cases of orchitis and the case of meningitis occurred in the <15 years age group. Four cases were hospitalized. No deaths occurred. The global incidence rate was 4.8 per 100,000 (4.3–5.4) in the 348 cases that fulfilled the clinical case definition, 2.2 per 100,000 (1.9–2.6) in laboratory confirmed cases, and 4 per 100,000 (3.6–4.5) in any confirmed case (laboratory or epidemiological link). Highest incidence rates corresponded to 5–14 and 15–24 years for all categories of cases and the incidence of male was higher than the incidence of females (Table 1). A total of 72.3% of laboratory confirmed cases (91.7% in the 5–14 years age group) and 76.2% of all confirmed cases (95.5% in the 5–14 years age group) had received at least one MMR dose; 56% of laboratory confirmed cases and 55.5% of all confirmed cases, respectively, had received two doses. The sensitivity and PPV of the clinical case definition are shown in Table 2. The sensitivity of laboratory confirmed cases, epidemi-
Fig. 1. Reported morbidity of mumps. Catalonia, 1983–2006.
case that met the clinical case definition and was epidemiologically linked to a laboratory confirmed or to a clinical case. Reporting of mumps by physicians has been mandatory since 1982 in Catalonia, but reporting of full demographic and epidemiological data in all suspected cases is only mandatory since 1997. In the context of the Mumps Elimination Program, since 2007 all suspected cases must be reported to the Department of Health urgently (within 24 h of the suspicion) and support for laboratory confirmation was obtained. Laboratory analyses were carried out by the microbiology laboratory of the Hospital Clinic of Barcelona. The sensitivity of the clinical case definition was calculated as the proportion of confirmed cases (by laboratory or by epidemiological link) that met the clinical definition. Positive predictive value was calculated as the proportion of clinical compatible cases that were confirmed (by laboratory or by epidemiological link). For Table 1 Incidence rates (per 100,000 population) of mumps. Catalonia, 2007. Age
Laboratory confirmed cases
All confirmed cases
Rate
Rate
95% CI
Rate
95% CI
11.1 13.3 13.5 2.9 0.3 4.0
8.0–15.0 10.8–16.4 11.0–16.3 2.0–3.9 0.5–0.7 3.6–4.5
12.9 16.1 15.3 3.9 0.3 4.8
9.6–17.0 13.2–19.5 12.7–18.3 2.9–5.1 0.6–0.9 4.3–5.4
95% CI
0–4 years 5–14 years 15–24 years 25–34 years ≥35 years All ages
3.4 7.3 7.7 2.0 0.3 2.2
1.8–5.7 5.3–9.7 5.9–9.9 1.9–2.6 0.2–0.5 1.9–2.6
Gender Male Femalec
2.7a 1.8
2.2–3.2 1.3–2.3
a b c
5.2b 2.9
Clinically compatible cases
6.0b 3.6
4.4–6.0 2.3–3.4
5.3–6.9 3.0–4.2
p = 0.013. p < 0.0001. Reference category.
Table 2 Sensitivity and positive predictive value of mumps clinical definition. Age
n
<15 years ≥15 yearsc All ages a b c
177 231 410
p = 0.04. p = 0.01. Reference category.
Sensitivity % (95% CI)
Positive predictive value % (95% IC)
Laboratory confirmation
Epidemiological confirmation
Any confirmation
Laboratory confirmation
Epidemiological confirmation
Any confirmation
98.4 (91.2–100) 96.9 (91.3–100) 97.5 (93.7–100)
95.1 (88.8–100) 100 (98.8–100) 96.9 (92.3–100)
98.5 (94.6–100) 96.2 (92.0–100) 97.2 (94.6–100)
38.5 (31.1–46.4)a 50.0 (43.1–57.4) 44.5 (39.5–49.9)
44.2 (36.1–52.4)b 30.5 (23.7–37.3) 36.5 (31.6–41.7
82.7 (75.8–88.3) 80.5 (75.1–86.4) 81.0 (77.1–85.3)
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ologically linked cases without laboratory confirmation and all confirmed cases was 97.5%, 96.9% and 97.2%, respectively, with no significant differences between age groups. The PPV for the same categories was 44.5%, 36.5% and 81.0%, respectively, with significant differences between age being observed. The PPV increased with age in laboratory confirmed cases (p = 0.04), but was higher in children in epidemiologically linked cases without laboratory confirmation (p = 0.01). 4. Discussion The incidence of reported cases fulfilling the clinical case definition (4.8 per 100,000 in 2007 vs. 1.8 in 2006) increased in the first year of enhanced mumps surveillance of mumps Catalonia. However, it is unclear if this increase is explained by changes in the surveillance system or if we are in an epidemic cycle. The incidence rate in laboratory confirmed cases was 2.2 per 100,000, similar to the reported rate in the United States in 2006 [4], but the incidence rate in all reported clinically compatible cases was more than twice as high. The incidence rate in all confirmed cases includes some cases epidemiologically related to other clinically compatible cases without laboratory confirmation and it is probable that some false cases are included. This reinforces the idea that, when the incidence of a disease is low, it is essential confirm by laboratory means all suspected cases or, at least, to consider confirmed cases as only those that are epidemiologically linked to laboratory confirmed cases. Increased mumps incidence has been reported in the United States [4], the United Kingdom [5], the Netherlands [6] and Israel [7], suggesting that the virus is circulating widely despite high coverage of two MMR. The estimated herd-immunity threshold for mumps ranges from 90 to 92% [8]. If the effectiveness of two MMR doses is estimated at 88–95% [9,10], even a 95% coverage reduces the population level of immunity to below this threshold [4]. Therefore, coverages > 95% with two doses are needed to control, and eliminate the disease, as achieved in Finland in 1996 [1]. This is especially important in situations of high population density and contact rates that facilitate the transmission [4]. The estimated coverage of one dose of MMR in Catalonia was 98.4% in 2004. However, although immigrants are offered the same health services as the indigenous population, the coverage of the first dose was only 93.3% in immigrant children compared to 98.9% in the indigenous population [11] and the two-dose coverage was slightly lower. During 2007, the Catalan population increased by 1.06% with respect to 2006, but the immigrant population increased by 6.43%, and may have contributed to increasing the probability of exposure to the mumps virus, as suggested by other authors [7]. Dayan et al. [4] found that the highest incidence was in the 18–24 years age group, suggesting an effect of waning immunity also reported in other studies [12,13]. However, we found that incidence rates were very similar in two age groups: 5–14 and 15–24 years. The percentage of all confirmed cases who had received at least one dose of MMR (76.2%) was lower than 87% and 97% found in studies carried out in United States [4,13], but higher than the 68% obtained by Pugh et al. in England and Wales [5]. The accumulation of individuals from various cohorts who were susceptible to mumps due to primary (insufficient response to vaccine) or secondary vaccine failure (waning immunity) may be an important explanation for these results. The partial use in Catalonia of the vaccine containing the Rubini strain, purchased during 1994–1996, may also have contributed, at least in part, to the resurgence of the disease in children who received their first dose in these years or later because, although this vaccine was no longer distributed in 1996, it may have been administered by local centers which had it in stock. The high proportion of confirmed cases that had received
at least one dose of vaccine in the 5–14 years age group supports this hypothesis. In contrast to the results obtained by other authors [4,5,13], we have found higher incidence rates in male than in female. Behavioral patterns have been suggested as a possible explanation of differences between genders, but more research is needed [4,13]. Only four cases were hospitalized, but complications, especially orchitis, were not uncommon, confirming other reports [1,4,12]. In laboratory confirmed cases, the sensitivity of the clinical case definition was 97.5%, slightly higher than that reported by Guy et al. [14] and similar to that obtained by Vandermeulen et al. [12]. However, the PPV of 44.5% in the same laboratory confirmed cases was clearly higher than the 10% obtained in the study by Guy et al. [14]. In conclusion, our results show the importance of laboratory confirmation of suspected cases of mumps because, when a disease has a low incidence, as is the case of some vaccine-preventable diseases in countries with high vaccine coverages, the PPV of clinical diagnoses decreases. The availability of RT-PCR techniques for oral samples has been very useful during this first year of enhanced surveillance in Catalonia. All confirmed cases should be laboratory confirmed or, at least, be linked to a laboratory confirmed case. Achieving elimination of mumps requires assessment of the number and nature of vaccine failures and adjustment of vaccination policies according to the new information obtained. Acknowledgements The other members of the Mumps Control Working Group of ˜ J.P., Batalla J., Catalonia are: Alsedà M., Arias C., Artigues A., Balana ˜ Cardenosa N., Ciruela P., Companys M., Follia N., Parrón I., Plasencia E., Rovira A., Torres J., Urbiztondo L. (Department of Health, Generalitat of Catalonia, Spain) and Rius C. (Public Health Agency of Barcelona, Spain). We thank the reporting physicians and technicians of the Epidemiological Surveillance Units of the Department of Health of the Generalitat of Catalonia and the Public Health Agency of Barcelona for their collaboration. This work was partially funded by CIBER Epidemiología y Salud Pública (CIBERESP), Spain. References [1] Galazka AM, Robertson SE, Kraigher A. Mumps and mumps vaccine: a global review. Bull World Health Organ 1999;77:3–14. [2] Centers for Disease Control Prevention. Recommendations of the international task force for disease eradication. MMWR 1993;42. RR-16. [3] Krause CH, Eastick K, Ogilvie MM. Real-time PCR for mumps diagnosis on clinical specimens—comparison with results of conventional methods of virus detection and nested PCR. J Clin Virol 2006;37:184–9. [4] Dayan GH, Qinlisk MP, Parker AA, Barskey AE, Harris ML, Schwartz JMH, et al. Recent resurgence of mumps in the United States. N Engl J Med 2008;358:1580–9. [5] Pugh RN, Akinosi B, Poorannsingh S, Kumar J, Grant S, Livesley E, et al. An outbreak of mumps in the metropolitan area of Walsall, UK. Int J Infect Dis 2002;6:283–7. [6] Kaajik P, van der Zeijstst BA, Boog M, Hoitink CW. Increased mumps incidence in the Netherlands: review of the possible role of vaccine strain and genotype. Euro Surveill 2008;13(26):pii=18914. Available online: http://www.eurosurveillance.org/ViewArticle.aspx?Articled=18914. Accessed September 15 2008. [7] Huerta M, Davidovitch N, Aboudy Y, Ankol OE, Balicer RD, Zarka S, et al. Declining population immunity to mumps among Israeli military recruits. Vaccine 2006;24:6300–3. [8] Anderson RM, May RM. Immunisation and herd immunity. Lancet 1990;335: 641–5. [9] Harling R, White JM, Ramsay ME, Macsween KF, van den Bosch C. The effectiveness of the mumps component of the MMR vaccine: a case control study. Vaccine 2004;23:4070–4. [10] Cohen C, White JM, Sevage EJ, Glynn JR, Choi Y, Andrews N, et al. Vaccine effectiveness estimates 2004–2005 mumps outbreak, England. Emerg Infect Dis 2007;13:12–7.
A. Dominguez et al. / Vaccine 27 (2009) 3492–3495 ˜ [11] Borrás E, Domínguez A, Batalla J, Torner N, Cardenosa N, Nebot M, et al. Vaccination coverage in indigenous and immigrant children under 3 years of age in Catalonia (Spain). Vaccine 2007;25:3240–3. [12] Vandermeulen C, Roelants M, Vermoere M, Roseeuw K, Goubau P, Hoppenbrouwers K. Outbreak of mumps in a vaccinated child population: a question of vaccine failure? Vaccine 2004;22:2713–6.
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[13] Cortese MM, Jordan HT, Curns AT, Quinlan PA, Ens KA, Denning PM, et al. Mumps vaccine performance among university students during an outbreak. Clin Infect Dis 2008;46:1172–80. [14] Guy RJ, Andrews RM, Kelly HA, Leydon JA, Riddell MA, Lambert SB, et al. Mumps and rubella: a year of enhanced surveillance and laboratory testing. Epidemiol Infect 2004;132:391–8.