Epidemiological analysis
Between 1 October 2019 and 31 March 2020, 102 mumps cases were notified with a date of onset within this period. Of these, 92 (90%) were laboratory-confirmed, and 10 (10%) were epidemiologically-linked. The median age of all cases was 26 years (range: 3–71 years). Of all cases, 57 (56%) were male and 31 (31%) were students. For 97 out of 102 (95%) cases, the vaccination status was known. Of those, 58 (60%) cases had received two or more MMR doses, 14 (15%) one dose, 4 (4%) were vaccinated with number of doses unknown, and 21 (21%) were unvaccinated. Of the 21 unvaccinated cases, the median age was 35 years old (range 3-71). Two patients, aged 21 and 44 years, and vaccinated with two doses, were hospitalised; both reported orchitis. Among the cases not hospitalised, 5 cases reported orchitis, and 1 case reported an eye infection. Nineteen cases (19%) acquired the infection abroad and country of infection was unknown for 7 cases (7%).
Forty-six of the 102 mumps cases were identified to be part of 14 epidemiological clusters (Table 1, Figure 1). All 14 epidemiological clusters were identified using epidemiological information alone. The median age among epidemiological cluster-associated cases was 25.5 years (range 3-71 years). Of all cases, 30 (65%) were male. All of the identified epidemiological clusters contained some close-contact involvement and settings included contact at a party, secondary schools, football match, hotels, and sharing the same household (Table 1).
Two of 14 epidemiological clusters had 2 co-primary cases in each with the same earliest date of symptom onset as the initial source case of their cluster was not identified. The median age of the 16 source cases of each cluster was 22.5 years (range 5–42 years), 15 cases were vaccinated, and 6 acquired the infection abroad. The place of infection of the source case or co-primary case of the cluster infected abroad was in either Western Europe, Central Europe, or North America (Table 1).
The first identified and largest epidemiological cluster (2019-7) occurred in the provinces South Holland and North Holland, including 12 cases (Table 1, Figure 1A). The index case had attended a party and was also working at a secondary school. Thereafter, secondary and tertiary cases occurred among attendees of the party and their partners as well as among 4 staff and 1 student at the secondary school. The second epidemiological cluster (2019-8) occurred among attendees of a football match in South Holland and Gelderland. Four additional epidemiological clusters occurred in South Holland (2019-9, 2019-10, 2019-11, and 2019-12). Two of these clusters occurred in school settings, and the other 2 occurred among family members.
For the remaining 8 epidemiological clusters, all contained transmission in close-contact settings among family, friends, or partners (Table 1). Geographically, 4 of these epidemiological clusters (2020-1, 2020-5, 2020-6, and 2020-7) contained cases reporting onset of symptoms in North Holland. One of the clusters (2020-5) contained cases reporting onset of symptoms in North Holland and Utrecht provinces as they attended a winter sports trip together in another location and returned to their respective provinces of residence. One epidemiological cluster (2020-3) occurred among partners in Zeeland who had travelled abroad. Two epidemiological clusters occurred in Groningen (2020-2 and 2020-4); the first occurring among attendees of a swimming club and their family and the second occurring among 2 persons travelling on holiday together. The final epidemiological cluster (2020-8) occurred in Gelderland province among family members.
Molecular surveillance
Using sequence data from the SH gene, a genotype could be obtained from 59 out of 60 mumps cases from which one or more clinical materials were submitted to the RIVM. In 58 cases, a mumps genotype G virus was detected, while in 1 case a mumps genotype C virus was detected. Complete NCRs sequence data could be obtained from 50 mumps genotype G viruses (Genbank accession numbers MW006669-MW006820). Sequence analysis of these mumps genotype G viruses revealed that at 30 nucleotide positions within the SH+NCRs sequences nucleotide variation was present, which resulted in 19 different molecular variants (A to S) with one or more viruses that had at least one nucleotide difference compared to other mumps viruses (Figure 1C, Supplementary Figure S1). From reviewing the 19 molecular variants, 12 of these contained 2 or more cases. Therefore, 12 molecular groups were identified according to the definition including 43 mumps viruses in total.
Comparison of results of epidemiological analysis and molecular surveillance
Molecular group A contained the highest number of mumps cases (13); ten from 4 different epidemiological clusters and 3 individual cases (Figure 1C). Combined information redefined 4 epidemiological clusters into 1 distinct molecular group. All 13 cases were shown to be dispersed over time with dates of symptom onset occurring over 14 weeks in total, as well as geographically with the majority from South Holland (12/13), and Gelderland provinces (1/13). Three of the 13 cases were not identified as part of an epidemiological cluster.
The second biggest molecular group E contained 6 cases; four from 3 different epidemiological clusters and 2 individual cases (Figure 1C). Combined information redefined 3 epidemiological clusters into 1 distinct molecular group. Cases had dates of symptom onset over a duration of 6 weeks in total, and cases occurred in 4 different provinces, Gelderland, North and South Holland, and Utrecht.
Four molecular groups (D, M, R, and S) each contained 3 mumps viruses with sequence data. Molecular group R contained cases linked by geography and time but without an epidemiological-link. Molecular group S contained 3 cases from the same epidemiological cluster and cases had dates of symptom onset over a duration of 2 weeks. Molecular group M contained 2 cases from the same epidemiological cluster and 1 individual case. Molecular cluster D contained 1 case from an epidemiological cluster and 2 individual cases.
The remaining 6 molecular groups each contained mumps viruses detected in 2 cases. Only 1 of these molecular groups contained 2 cases from the same epidemiological cluster (J), while the rest only included individual cases.
Table 1. Characteristics of epidemiological clusters, the Netherlands, 1 October 2019–31 March 2020 (n = 46 cases)
Epidemiological cluster
|
Cases
|
Province of symptom onset
|
Description of setting
|
Place of infection of source or co-primary case (if abroad)
|
2019-7
|
12
|
South Holland, North Holland
|
Party, secondary school
|
|
2019-8
|
4
|
South Holland, Gelderland
|
Football match
|
|
2019-9
|
2
|
South Holland
|
Secondary school
|
|
2019-10
|
3
|
South Holland
|
Hotel, family
|
|
2019-11
|
2
|
South Holland
|
School
|
|
2019-12
|
2
|
South Holland
|
Family
|
|
2020-1
|
2
|
North Holland
|
Friends
|
Western Europe
|
2020-2
|
4
|
Groningen
|
Swimming club, family
|
|
2020-3
|
2
|
Zeeland
|
Partners
|
Western Europe
|
2020-4
|
2
|
Groningen
|
Holiday abroad
|
Central Europe
|
2020-5
|
2
|
North Holland, Utrecht
|
Winter sport trip abroad
|
Western Europe
|
2020-6
|
3
|
North Holland
|
Family
|
|
2020-7
|
3
|
North Holland
|
Partners and friend
|
North America
|
2020-8
|
3
|
Gelderland
|
Family
|
|