Paediatric viral gastroenteritis and regional predominant viral pathogens in the post-rotavirus vaccination year: prospective Irish regional study

Abstract

Acute gastroenteritis harbours a significant global burden. Rotavirus is the primary cause of gastroenteritis in children worldwide. We aim to determine the predominant enteric viral pathogens detected in the post-rotavirus vaccine period (2016-2017) in our region in county Mayo (west of Ireland), United Kingdom. All children up to 3 years old, who presented to Mayo University Hospital with vomiting and diarrhoea, from November 18th, 2016, to November 18th, 2017, had their stools tested by real-time reverse transcription polymerase chain reaction for viral pathogens. A total of 150 stool samples were tested, and 90 (60%) tested positive for a single viral pathogen. Rotavirus was the leading cause of gastroenteritis (37 patients, 24.6%; including 6 rotavirus vaccinated infants), followed by human adenovirus F (19 patients, 13%), norovirus (18 patients, 12%), sapovirus (9 patients, 6%) and astrovirus (7 patients, 5%). Rotavirus remained the predominant cause of gastroenteritis in the first year post-rotavirus vaccination, similar to the national Irish data from the pre vaccination years (July 2014-June 2015).

INTRODUCTION

Acute viral gastroenteritis occurs throughout the year, with an autumn and winter predominance, with a significant burden globally, including Ireland [1-4]. Rotavirus (RV) gastroenteritis (GE) usually occurs in children between 6 months and 2 years of age. It occurs during autumn and winter, in temperate climates and throughout the year in tropical climates [5-6].

Norovirus (NoV) GE occurs in people of all ages, all year round, with a peak in fall and winter, is highly contagious and is the leading cause of outbreaks of GE [7-10]. It also causes sporadic GE, which occurs primarily in young children [11], and constitutes, or is becoming, the leading cause of medically attended GE in children in countries that immunize infants against RV GE [7,12-15].

Sapovirus (SaV) GE mainly affects infants and toddlers [9]. Astrovirus (AsV) occurs in people of all ages and may cause outbreaks in closed populations [9]. Sporadic AsV GE occurs primarily in children younger than 4 years, and usually occurs during the winter months.

Enteric adenovirus (AdV) GE predominantly affects children younger than 4 years [9] and occurs throughout the year, with a peak during summer [1,9,10]. Rotavirus vaccine (Rotarix^TM) was added to the primary immunisation schedule in Ireland in 2016.

Specifically, the objectives of this study were to determine the frequency of enteric viral pathogens in the post-RV vaccination year (2016/17) in one region of Ireland (Mayo, west of Ireland). Recent figures of RV vaccine uptake from the Co. Mayo Immunisation Office revealed that 2,410 infants in this region were administered the RV vaccine during the study period, with a high uptake rate of the vaccine’s first dose (94.2%) and second dose (92.8%). Those figures are based on the vaccination claim forms submitted for payment by general practitioners; therefore, we assume that the figures of the RV vaccine uptake rates will increase.

MATERIALS AND METHODS

From November 18th 2016 to November 18th 2017, recruited in this study were all children up to 3 years of age who presented to Mayo University Hospital (MUH), County Mayo, west of Ireland, with vomiting and diarrhoea (loose stool) or diarrhoeal symptoms as per case definition [16], and admitted children who developed diarrhoea 3 days (72 hours) following their admission to the paediatric ward [possible nosocomial gastroenteritis (NGE)]. Children not presenting with GE symptoms when hospitalised who were readmitted within 48 hours with diarrhoea or diarrhoea and vomiting following recent discharge (possible NGE) were also included.

Children presenting with chronic diarrhoea due to other diseases, e.g., immunodeficiency or inflammatory bowel disease were excluded as per case definition [16]. Children presenting with the same diagnosis within a 48-hour period were also excluded. In total, four children were excluded.

Information leaflets were given to parents of the children contributing to the research, explaining the purpose of the research study. Consent was obtained and parents were given the right to choose to withdraw or opt out of the research at any time. A certificate of ethical approval for the research study was obtained from the Clinical Research Ethical Committee at Mayo University Hospital in Ireland, before the study’s commencement.

Stool samples were collected and kept frozen at MUH laboratory and were sent in quarterly batches to the National Virus Reference Laboratory (NVRL) in Ireland to be tested for RV and other viruses (NoV, SaV and AsV) by reverse transcription (RT) polymerase chain reaction (PCR) of viral RNA genome and by PCR of DNA genome of adenovirus F (AdVF). Samples were extracted on the Roche MagNA Pure 96 as per the manufacturer’s protocol [17-21], and analysed on the Applied Biosystems ABI 7500 Fast (NoV) or ABI Viia7 (RV, AdVF, SaV and AsV) instrument using the ABI software version 2.3 (NoV) or version 2.1.1 (RV, AdVF, SaV and AsV), respectively.

Data related to the hospital outcome of the disease were collected confidentially using the hospital’s electronic laboratory system. Data were verified on a case-to-case basis against the following: patient name, age, date of birth, hospital number, date of hospital admission, date of hospital discharge, duration of hospital stay, date of stool sample and result of testing, including nosocomial acquisition of GE infection where applicable, onset of diarrhoea after 72 hours following hospital admission and date of hospital readmission with diarrhoea within 48 hours following hospital discharge.

Data were collected prospectively for 12 months from November 18th 2016 to November 18th 2017. The date of introduction of the RV vaccine was recorded. The RV vaccine (Rotarix^TM), introduced in Ireland on the 1st of October 2016, was scheduled to be given to all babies born in Ireland from the 1st of October 2016. Two doses were to be given to babies at 2 and 4 months of age.

RESULTS

Number of viral gastroenteritis cases, age and gender distribution (2016-2017)

A total of 157 patients were diagnosed with viral GE, after excluding two females who presented twice during the study period with GE. Of these (Figure 1), 87 were male (55%); 85 patients were between 1 and 3 years of age (54%), of whom 49 were male (56% of the total male number) and 36 were female (51%); 72 were aged ≤1 year (46%), of whom 38 patients were male (44% of the total male number) and 34 patients were female (49%). The median age at presentation was 15 months. The two female patients who presented twice with GE did not contract the same viral pathogen more than once. Nine samples were not tested in the NVRL as the samples were either missing or mislabelled. They were excluded from RV and other viruses testing.

Figure 1.

Number of viral gastroenteritis (GE) cases (age and gender distribution) (2016-2017). Y, year.

The total number of stool samples tested for RV and other viruses was 150. The total number of stool samples (patients) which tested positive for a single infection with one of the viruses causing GE was 90 (60%). Nineteen infants received the first and/or second dose of the RV vaccine (13%); 10 were male; 17 were tested.

Viral pathogens

Rotavirus was the leading cause of GE (37 patients, 24.6%), followed by human AdV F (19 patients, 13%), NoV (18 patients, 12%), SaV (9 patients, 6%) and AsV (7 patients, 5%); Figures 2 and 3 show the distribution by age and gender. Rotavirus positive GE was detected in six RV vaccinated infants (35%); five were still eligible for the second dose of the RV vaccine and four were male (67%).

Figure 2.

Specific types of viral gastroenteritis. AdenoV, adenovirus; AstroV, astrovirus; NoroV, norovirus; RV, rotavirus; SapoV, Sapovirus.

Figure 3.

Specific types of viral gastroenteritis (gender and age). AdenoV, adenovirus; AstroV, astrovirus; NoroV, norovirus; RV, rotavirus; SapoV, Sapovirus; Y, year.

DISCUSSION

According to the unpublished national data from the NVRL annual report during 2014/2015, 11,510 faecal specimens from all age groups across Ireland were tested at the NVRL for the five primary viral agents associated with GE. Of these, 27.8% (n = 3,206) tested positive for at least one viral pathogen. As expected, the predominant virus detected was NoV (n = 1,479) of which 89% were genogroup II (GII), followed by RV (n = 870), SaV (n = 390), AsV (n = 291) and group F adenoviruses (n = 176). RV was the principal pathogen identified in paediatric patients, detected in 15.8% of the specimens tested from patients aged ≤5 years; followed by NoV (13.2%), SaV (5.9%), AsV (5.2%) and group F adenoviruses (3.5%).

The data in this study represent one region of our country, in the year following the introduction of the RV vaccine (2016/2017) and shows that RV remained the predominant cause of GE in the first year following the RV vaccine. The frequency of different viruses detected for 2016-2017 was similar to the data acquired from the NVRL (July 2014-June 2015). However, the NVRL data were from children up to the age of 5 years, with more NoV GE cases and less AdVF GE cases detected compared with our study. More or less similar percentages of SaV GE and AsV GE cases were noted in both our studies and the data from the NVRL (6% and 5%, respectively). The high levels of NoV infection in paediatric patients have previously been reported by the NVRL and others, and are a reminder that NoV should always be considered in paediatric diarrhoeal illness. In fact, should the RV vaccine be introduced, the likelihood is that NoV would quickly become the predominant virus associated with paediatric GE [7,12-15].

Other viruses, such as NoV and AdV, are expected to become predominant causes of GE in the years to come due to the anticipated protective effect of RV vaccine in reducing the number of RV GE, not only in infants eligible for the RV vaccine but also in older children due to the possible herd protection effect of the RV vaccine and this will require additional research and monitoring over the coming years in Ireland. Norovirus is becoming the leading cause of GE in children in countries that immunize infants against RV GE [7,12-15].

It was not applicable to compare results statistically with the national unpublished data from the NVRL (July 2014-June 2015). The sample size in this study was small (150 stool samples) from one geographical location in Ireland and was conducted for only 1 year in the post-vaccination era; therefore, no formal statistical approach was applicable. Additionally, stool samples were not tested for all enteric viral pathogens prior to our study; the study was the first study to evaluate all viral pathogens in a regional context, a limitation that makes comparative analysis in our region difficult. Additional research for many years in the post-RV vaccination era in larger geographical locations with a larger sample size is required to better evaluate the frequency of enteric viral pathogens and whether other viruses, such as noroviruses, will become the predominant cause of viral gastroenteritis in Irish children in the post-vaccination era. We hope this study will serve as a baseline novel epidemiological analysis for future researchers in this field in Ireland.

CONCLUSION

We have shown for the first time in an Irish context the frequency of viral pathogens in the year following the RV vaccine introduction in Ireland. Rotavirus remains a leading cause of paediatric GE in the post-vaccination year. Additional research is required in larger geographical locations for many years in Ireland to determine any possible switch of this trend in favour of other viruses, such as noroviruses.

CONFLICT OF INTEREST

The author declares that he has no conflicts of interest.

FUNDING

None.

ETHICAL APPROVAL

A certificate of ethical approval for the research study was obtained from the Clinical Research Ethical Committee at Mayo University Hospital in Ireland, before the study’s commencement. Informed consent was obtained from the parents of participants included in the study.