Norovirus is the second leading cause of acute gastroenteritis in children worldwide after rotavirus. With the inclusion of the rotavirus vaccine in Indonesia's national immunization program, norovirus is expected to replace rotavirus as the predominant viral pathogen causing diarrhea in children. Norovirus outbreaks in the United States decreased during COVID-19 public health measures but increased again after restrictions were relaxed. Supportive care is the primary treatment for norovirus, while prevention relies on maintaining good hygiene. Ongoing norovirus surveillance is important in Indonesia given its potential to become the leading cause of pediatric gastroenteritis.

1. The Potential of Norovirus
Outbreak to Replace Rotavirus
as the Leading Pathogen of
Acute Gastroenteritis in Children
Vini Jamarin
Madya of Infection and Tropical Disease Division
December 4th 2022

2. Norovirus (NoV) and Its Potential
• The cause of acute gastroenteritis (AGE) in all ages and the
second causative pathogen after rotavirus for cases of AGE in
children under 5 years of age
• 699 million morbidities and 219,000 deaths
• NoV outbreaks in the United States have decreased significantly in
April 2020, but then increased again in January 2022
• The main cause of AGE in children in several countries have
promoted rotavirus vaccination, both in developed and
developing countries, including Indonesia
• Because the rotavirus vaccine will be included in Indonesia's
national immunization program, NoV is expected to become the
predominant pathogen in viral diarrhea replacing rotavirus
1. Safadi MA, Riera-Montes M, Bravo L, Tangsathapornpong A, Lagos R, Thisyakorn U, et al. The burden of norovirus disease in children: a multi-country study in Chile, Brazil, Thailand and the Philippines. Int J Infect Dis. 2021;109:77–84.
2. Shah MP, Hall AJ. Norovirus illnesses in children and adolescent. 2018;32:103-18.
3. Kambhampati AK, Wikswo ME, Barclay L, Jan V, Mirza SA. Notes from the field: norovirus outbreaks reported through NoroSTAT — 12 States, August 2012 – July 2022. US Department of Health and Human Services/Centers for Disease Control and
Prevention. 2022;71:1222–4.
4. Utsumi T, Lusida MI, Dinana Z, Wahyuni RM, Soegijanto S, Soetjipto, et al. Molecular epidemiology and genetic diversity of norovirus infection in children hospitalized with acute gastroenteritis in East Java, Indonesia in 2015–2019. Infect Genet Evol.
2021;88.

3. Background
• First identified in the faeces during the AGE outbreak in Norwalk,
Ohio in 1968 and became known as the Norwalk virus
• Winter vomiting disease in 1929
• In countries with rotavirus vaccination programs, NoV is the main
cause of AGE in children
• Incidence of NoV in the United States has decreased significantly
in April 2020 due to non-pharmacological interventions against
COVID-19 pandemic: closing public facilities, maintaining social
distance, and improving hand hygiene
• As the interventions have relaxed, in January 2022, NoV
outbreaks increased again, almost close to pre-pandemic levels
• To explore outbreaks of NoV disease that have the potential to
replace rotavirus as the main cause of GEA in children
1. Safadi MA, Riera-Montes M, Bravo L, Tangsathapornpong A, Lagos R, Thisyakorn U, et al. The burden of norovirus disease in children: a multi-country study in Chile, Brazil, Thailand and the Philippines. Int J Infect Dis. 2021;109:77–84.
2. Shah MP, Hall AJ. Norovirus illnesses in children and adolescent. 2018;32:103-18.
3. Robilotti E, Deresinski S, Pinsky BA. Norovirus. Clin Microbiol Rev. 2015;28:134–64.
4. Williams DJ, Edwards KM, Payne DC, Manning J, Parashar UD, Lopman BA. Decline in gastroenteritis-related triage calls after rotavirus vaccine licensure. Pediatrics. 2012;130:e872-8.

4. Epidemiology and Outbreak
• 699 million illnesses and 219,000 deaths globally every year
• 453 million illnesses and 95,000 deaths occur in children under 5
years of age
• The leading cause of severe childhood AGE in countries with
rotavirus vaccination, like Finland, the United States, and Brazil;
also low-resource-settings
• Indonesia: sporadically, prevalence of 15 – 61%
• A higher prevalence in the government-owned hospital compared
to the private hospital—different hygiene statuses
• Very limited studies—only 5 hospital-based surveillances (Jakarta,
Yogyakarta, Mataram, Surabaya, and Jambi)
• In these five studies, norovirus prevalence was about 15–30%, with
19.3% were co-infected with rotavirus
1. Hakim MS, Nirwati H, Aman AT, Soenarto Y, Pan Q. Significance of continuous rotavirus and norovirus surveillance in Indonesia. World J Pediatr. 2018;14:4–12.
2. Nirwati H, Donato CM, Mawarti Y, Mulyani NS, Ikram A, Aman AT, et al. Norovirus and rotavirus infections in children less than five years of age hospitalized with acute gastroenteritis in Indonesia. Arch Virol. 2019;164:1515–25.
3. Subekti D, Lesmana M, Tjaniadi P, Safari N, Frazier E, Simanjuntak C, et al. Incidence of Norwalk-like viruses, rotavirus and adenovirus infection in patients with acute gastroenteritis in Jakarta, Indonesia. FEMS Immunol Med Microbiol.
2002;33:27–33.
4. Wulandari PS, Juniastuti, Wahyuni RM, Amin M, Yamani LN, Matondang MQY, et al. Predominance of norovirus GI.4 from children with acute gastroenteritis in Jambi, Indonesia, 2019. J Med Virol. 2020;92:3165–72.
5. Sudarmo SM, Shigemura K, Athiyyah AF, Osawa K, Wardana OP, Darma A, et al. Genotyping and clinical factors in pediatric diarrhea caused by rotaviruses: One-year surveillance in Surabaya, Indonesia. Gut Pathog. 2015;7:1–10.

5. Epidemiology and Outbreak
• In 2012 CDC established the Norovirus Sentinel Testing and
Tracking Network (NoroSTAT)
• The number of NoV outbreaks in 2021 – 2022 surveillance was
almost three times the number of 2020 – 2021 surveillance
reports.
• Nonpharmacological interventions applied during the early days
of the COVID-19 pandemic  effective for other infectious
diseases, including NoV.
• As interventions have relaxed, NoV outbreaks have returned to
nearly the same size as pre-pandemic surveillance
1. Safadi MA, Riera-Montes M, Bravo L, Tangsathapornpong A, Lagos R, Thisyakorn U, et al. The burden of norovirus disease in children: a multi-country study in Chile, Brazil, Thailand and the Philippines. Int J Infect Dis. 2021;109:77–84.
2. Kambhampati AK, Wikswo ME, Barclay L, Jan V, Mirza SA. Notes from the field: norovirus outbreaks reported through NoroSTAT — 12 States, August 2012 – July 2022. US Department of Health and Human Services/Centers for Disease Control and
Prevention. 2022;71:1222–4.
3. Utsumi T, Lusida MI, Dinana Z, Wahyuni RM, Soegijanto S, Soetjipto, et al. Molecular epidemiology and genetic diversity of norovirus infection in children hospitalized with acute gastroenteritis in East Java, Indonesia in 2015–2019. Infect Genet Evol
2021;88.
4. Nirwati H, Donato CM, Mawarti Y, Mulyani NS, Ikram A, Aman AT, et al. Norovirus and rotavirus infections in children less than five years of age hospitalized with acute gastroenteritis in Indonesia. Arch Virol. 2019;164:1515–25.

6. Outbreaks of Norovirus in the US
Figure 1. Norovirus outbreak report by NoroSTAT for the period 2012 – 2022
Kambhampati AK, Wikswo ME, Barclay L, Jan V, Mirza SA. Notes from the field: norovirus outbreaks reported through NoroSTAT — 12 States, August 2012 – July 2022. US Department of Health and Human Services/Centers for Disease Control and
Prevention. 2022;71:1222–4.

7. Outbreaks of Norovirus in Indonesia
Figure 2. Norovirus infection in East Java. In Indonesia there are only two seasons:
the rainy season (November – April) and the dry season (May – October)
Utsumi T, Lusida MI, Dinana Z, Wahyuni RM, Soegijanto S, Soetjipto, et al. Molecular epidemiology and genetic diversity of norovirus infection in children hospitalized with acute gastroenteritis in East Java, Indonesia in 2015–2019. Infect Genet Evol.
2021;88.

8. Outbreaks of Norovirus in Indonesia
Figure 3. Distribution of cases of NoV and rotavirus infections
in Mataram and Yogyakarta, Indonesia based on time of occurrence
Nirwati H, Donato CM, Mawarti Y, Mulyani NS, Ikram A, Aman AT, et al. Norovirus and rotavirus infections in children less than five years of age hospitalized with acute gastroenteritis in Indonesia. Arch Virol. 2019;164:1515–25.

9. Virology and Virulence
• Single-stranded RNA viruses from the Caliciviridae family
• First discovered by electron microscopy from patient faeces during
the 1968 outbreak and became the first pathogen to cause AGE
• Gene groups of GI to GX based on the identity of the amino acids in
the major proteins
• GI, GII, and GIV groups are known to cause disease in humans.
• GII.4 genotype is the main cause of NoV disease  more severe
case and worse health burden
• Highly contagious, faecal-oral route, ingestion of aerosol
vomitus, or indirect exposure to contaminated vomit or surfaces
• Major cause of sporadic cases and outbreaks of foodborne illness
• Peak virulence on the second to fifth day after infection and is
found primarily in the feces, but may also occur in vomitus.
1. Shah MP, Hall AJ. Norovirus illnesses in children and adolescent. 2018;32:103-18.
2. Utsumi T, Lusida MI, Dinana Z, Wahyuni RM, Soegijanto S, Soetjipto, et al. Molecular epidemiology and genetic diversity of norovirus infection in children hospitalized with acute gastroenteritis in East Java, Indonesia in 2015–2019. Infect Genet
Evol. 2021;88.
3. Centers for Disease Control and Prevention. Updated norovirus outbreak management and disease prevention guidelines. MMWR. 2011;60:1–18.

10. Diagnosis
• The gold standard examination for NoV infection is by molecular
testing of stool specimens: enzyme immunoassays, rapid
immunochromatographic assays, or reverse transcription
polymerase chain reaction (RT-PCR)
• Samples must be taken and stored in a closed container within 48-
72 hours from onset of symptoms, although may still be detectable
up to 7–10 days from onset
• Stored at 40C prior to evaluation or frozen for long term storage
• Alternative specimen: vomitus
1. Shah MP, Hall AJ. Norovirus illnesses in children and adolescent. 2018;32:103-18.
2. Robilotti E, Deresinski S, Pinsky BA. Norovirus. Clin Microbiol Rev. 2015;28:134–64.

11. Diagnosis
• Kaplan clinical and epidemiological criteria with all criteria to be met
Table 1. Kaplan Criteria
Criterion Description
1 Vomiting in more than half of symptomatic cases
2 Mean (or median) incubation period of24 to 48 h
3 Mean (or median) duration of illness of12 to 60 h
4 No bacterial pathogen isolated in stool culture
Robilotti E, Deresinski S, Pinsky BA. Norovirus. Clin Microbiol Rev. 2015;28:134–64.

12. Therapy and Prevention
• Supportive management: improving hydration status and
electrolyte balance, also antiemetics or antimotility
• Prevention: washing hands with soap and water, avoiding food
preparation until more than 48 hours after symptoms disappear,
and disinfecting surfaces contaminated with faeces or vomitus
• Administration of probiotics or bovine lactoferrin has not been
proven to prevent NoV in children
• Currently, an NoV vaccine is being developed using VLP (virus-like
particles) as immunogens, especially GI genotype
1. Kambhampati AK, Wikswo ME, Barclay L, Jan V, Mirza SA. Notes from the field: norovirus outbreaks reported through NoroSTAT — 12 States, August 2012 – July 2022. US Department of Health and Human Services/Centers for Disease Control
and Prevention. 2022;71:1222–4.
2. Utsumi T, Lusida MI, Dinana Z, Wahyuni RM, Soegijanto S, Soetjipto, et al. Molecular epidemiology and genetic diversity of norovirus infection in children hospitalized with acute gastroenteritis in East Java, Indonesia in 2015–2019. Infect Genet
Evol. 2021;88.
3. Robilotti E, Deresinski S, Pinsky BA. Norovirus. Clin Microbiol Rev. 2015;28:134–64.

13. Conclusion
• Norovirus is the second cause of AGE in children worldwide after
rotavirus
• Symptoms may vary from mild to severe, with a fairly high
transmission rate
• Treatment is the same as management of acute diarrhea due to
rotavirus: supportive and symptomatic
• Prevention: maintaining hygiene
• Since the rotavirus vaccine will be included in Indonesia's national
immunization program, NoV is expected to become the
predominant pathogen in viral diarrhea replacing rotavirus
• Surveillance of NoV infection in Indonesia needs to be of concern

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