Global Trends in Norovirus Genotype Distribution Among Children With Acute Gastroenteritis

Jennifer L. Cannon; Joseph Bonifacio; Filemon Bucardo; Javier Buesa; Leesa Bruggink; Martin Chi-Wai Chan; Tulio M. Fumian; Sidhartha Giri; Mark D. Gonzalez; Joanne Hewitt; Jih-Hui Lin; Janet Mans; Christian Muñoz; Chao-Yang Pan; Xiao-Li Pang; Corinna Pietsch; Mustafiz Rahman; Naomi Sakon; Rangaraj Selvarangan; Hannah Browne; Leslie Barclay; Jan Vinjé

Disclosures

Emerging Infectious Diseases. 2021;27(5):1438-1445. 

In This Article

Results

A total of 1,325 dual-typed norovirus sequences collected during September 2016–August 2020 from children <5 years of age with AGE were submitted to NoroSurv. Sequences were received from 19 sites in 16 countries in Africa (South Africa, n = 13), Asia (Bangladesh, n = 32; Hong Kong, China, n = 326; India, n = 36; Japan, n = 89; the Philippines, n = 132; and Taiwan, n = 19), Oceania (Australia, n = 71; New Zealand, n = 54), Europe (Germany, n = 111 and Spain, n = 44), North and Central America (Canada, n = 90; Nicaragua, n = 78; and the United States, n = 173), and South America (Brazil, n = 14 and Chile, n = 43) (Figure 1). Each country submitted a median of 63 sequences (range 13–326); 48% of sequences were from countries in Asia. We excluded 62 of the 1,387 NoroSurv sequences: 11 that could not be typed because of poor sequence quality or missing fasta files; 7 with sample collection dates before September 1, 2016; 31 from children ≥5 years of age; and 13 from asymptomatic children.

Figure 1.

Countries participating in NoroSurv, December 2016–August 2020. Shades of blue and size of circles indicate the number of genetic sequences included from each country.

To compare genotype distribution over time, we defined seasons as September 1–August 31; these periods reflected the seasonality reported for noroviruses, with peak cases often occurring during the cooler months: October–March in the Northern Hemisphere and April–September in the Southern Hemisphere.[35] During the pilot phase (September 1, 2016–August 31, 2018), a total of 382 sequences were submitted (144 in 2016–2017 and 238 in 2017–2018). During the first 2 official years of NoroSurv, 600 sequences were submitted in the 2018–2019 season and 343 in 2019–2020 season. The number of submissions peaked between the months of October and May (Figure 2), coinciding with cooler months in the Northern Hemisphere. However, only 15% (195/1,325) of sequences were submitted by Southern Hemisphere countries; for this reason, analyzing trends in the Southern Hemisphere was difficult. Many sample collection sites in the Philippines were equatorial and had norovirus cases year-round. The number of submitted sequences declined in 2020, coinciding with the emergence of the coronavirus disease pandemic (Figure 2).

Figure 2.

Global genotype distribution of norovirus sequences catalogued in NoroSurv during September 2016–August 2020. A) Dark blue line indicates all GII.4 Sydney viruses; light blue indicates GII.4 Sydney[P16] and pink indicates GII.4 Sydney[P31]); B) yellow indicates GII.2 viruses; C) red indicates GII.3 viruses; D) orange indicates GII.6 viruses; E) purple indicates other GII viruses; F) green indicates GI viruses. Gray lines overlay the distributions of other pictured genotypes to enable comparisons.

Throughout the study period, GII.4 Sydney was the most common genotype on all 6 continents and was detected in 52% (687/1,325) of sequences, peaking at 62% (213/343) in 2019–2020 (Figure 2; Appendix Table 1, https://wwwnc.cdc.gov/EID/article/27/5/20-4756-App1.pdf). The GII.3 (190; 14%), GII.2 (149; 11%), and GII.6 (64; 5%) genotypes comprised 30% of sequences (Figure 2; Appendix Table 1). GI.3 was the most frequently detected GI genotype, accounting for 55% (50/91) of all GI viruses and 4% of all NoroSurv sequences. The remaining 14% (185/1,325) of sequences were composed of 17 other genotypes: GI.1, GI.2, GI.4, GI.5, GI.6, GI.7, GI.9, GII.1, GII.4 Hong Kong, GII.4 untypable, GII.7, GII.8, GII.12, GII.13, GII.14, GII.17, and GII.20 (Appendix Table 1). We detected 687 GII.4 Sydney viruses associated with 3 P-types: P16 (399; 58%), P31 (280; 41%), and P4 (8; 1%). The proportions of each genotype varied by year (Figure 2; Appendix Table 1) and country (Appendix Tables 2–17). The most common P-type among the 190 detected GII.3 viruses was P12 (146; 77%) (Figure 3; Appendix Table 1). We detected 149 GII.2 viruses, most (148; 99%) of which were P16. All 64 GII.6 viruses were P7 (Figure 3; Appendix Table 1).

Figure 3.

Distribution of dual typed sequences in NoroSurv, 2016–2020. Numbers to the right of bars indicate the number of sequences detected for each dual type.

The 5 most frequently detected dual types were GII.4 Sydney[P16], GII.4 Sydney[P31], GII.2[P16], GII.3[P12], and GII.6[P7]. In total, 22% (288/1,325) of sequences were composed of 31 other dual types, each accounting for <5% of all sequences (Figure 3; Appendix Table 1). The 10 most frequently detected dual types included GII.12[P16], GII.4 untypeable[P4], GI.[P3], GII.3[P21], and GII.3[P16] (Figure 3). We found that the 23 GII.4 untypeable[P4] viruses detected in Chile, 4 in the United States, 3 in Australia, 1 in Germany, 1 in New Zealand, and 4 in Spain (1 P4 and 3 P31) formed a GII.4 Sydney subclade. This subclade exceeded the >2% designated cutoff for percent nucleotide differences between these strains and the closest GII.4 Sydney reference sequence (GenBank accession no. KX354134, mean nucleotide percent difference = 2.2%, SD = 0.3%). Several genotypes were associated with ≥2 P-types. For example, GII.3 viruses were associated with P12, P21, P16, P30, and PNA3; GI.3 viruses were associated with P3, P13, and P10; and GII.13 viruses were associated with P16 and P21 (Figure 3; Appendix Table 1). We also detected dual types rarely reported in literature, including GII.3[PNA3] in South Africa; GII.20[P20] and GII.20[P7] in New Zealand; and GII.3[P30] in Hong Kong, Canada, and Spain (Appendix Tables 5, 8, 11, 14, 15).

During the 2019–2020 season, 65% (138/213) of GII.4 Sydney viruses had a P31 polymerase, compared with only 28% (89/314) in the previous season (Figure 2; Appendix Table 1). This dual type was most common (115; 81%) in Hong Kong (Appendix Table 8). In total, sites in Hong Kong submitted 25% (326/1,325) of all NoroSurv sequences, including 46% (159/343) in 2019–2020. In Japan, South Africa, and Taiwan, GII.4 Sydney[P31] viruses were also more common than GII.4 Sydney[P16] viruses (Appendix Tables 10, 14, 16). In the 12 remaining countries, GII.4 Sydney[P16] viruses were either more than or as common as GII.4 Sydney[P31] viruses (Appendix Tables 2–7, 9, 11–13, 15, 17).

GII.4 Sydney viruses were the most common virus in all but 3 countries: GII.3[P12] viruses were most common in New Zealand (26/54; 48%) and Taiwan (7/19; 37%) and GII.4 untypeable[P4] viruses were most common in Chile (23/43; 53%) (Figure 3; Appendix Tables 6, 11, 16). Norovirus strain diversity was high in many countries, with >10 strains detected in 7 countries: 18 each in the Philippines and the United States, 16 in Spain, 15 in Germany, 13 in Hong Kong, and 12 each in Australia and New Zealand (Appendix Tables 2, 7, 8, 11, 13, 15, 17).

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