Abstract
Background:
Swaziland introduced rotavirus vaccine in the National Immunization Program, in May 2015, with the objective of reducing the burden of rotavirus diarrheal disease. We monitored the early impact of the vaccine in reducing rotavirus diarrhea.
Methods:
We conducted sentinel rotavirus surveillance from January 2013 – December 2016 in children under five years of age admitted with acute gastroenteritis attending Mbabane Government Referral Hospital in the Hhohho Region and Raleigh Fitkin Memorial Hospital in the Manzini Region. All cases had stool samples collected and tested for rotavirus antigen by enzyme immunoassay.
Results:
Between 2013 and 2016, 596 samples were collected and tested. Rotavirus positivity reduced from average of 50.8% (172/338) (in 2013 – 2014 (pre vaccine period)) to 29% (24/82) in 2016, post-vaccine introduction. The median age of children with rotavirus infection increased from average of 10 months in 2013 – 2014 to 13.7 months in 2016. The peak season for all-cause diarrhea and rotavirus-specific hospitalizations among children under five years of age was June – August in all years with a blunting of the peak season in 2016. Rotavirus positivity among children 0 – 11 months reduced from an average of 49% in 2013 – 2014 (116/236) to 33% (15/45) in 2016, a 33% reduction following rotavirus vaccine introduction.
Conclusion:
There has been a rapid reduction of all-cause diarrhea and rotavirus hospitalizations in Swaziland, particularly in young children and during the rotavirus season, after the introduction rotavirus vaccine. Continued surveillance is needed to monitor the long-term impact of rotavirus vaccine introduction.
Keywords: Diarrhoea, Rotavirus, vaccine impact, Swaziland
1. INTRODUCTION
Rotavirus is the most common cause of severe diarrhea among children under 5 years old globally [1]. In 2013, an estimated 215,000 deaths in children <5 years of age worldwide were attributed to rotavirus and over half of these deaths (n=121,000) occurred in sub-Saharan African children [1]. Rotavirus is also a major cause of hospitalizations due to diarrhea. In sub-Saharan Africa, rotavirus is responsible for 21%–56% of acute diarrhoeal hospitalizations among children <5 years of age based on data from sentinel hospital-based surveillance in many countries [2–11].
Rotavirus vaccines are an effective intervention to reduce severe rotavirus disease [12]. In 2006, clinical trials of two live oral rotavirus vaccines – a 3-dose pentavalent bovine-human reassortant vaccine (RV5; RotaTeq, Merck &Co) and a 2-dose monovalent human vaccine (RV1; Rotarix, GSK Biologicals) - found high efficacy (85%–98%) in preventing severe rotavirus gastroenteritis in high and middle income countries [13][14]. These vaccines had more modest efficacy (59%–64%) in subsequent trials in Africa but given the large disease burden in the region, the vaccine prevented more disease in higher burden settings despite lower efficacy than in low burden settings [15.16]. In 2009, WHO expanded its recommendation for use of rotavirus vaccine in all countries globally and particularly those countries with high diarrhoeal mortality [17].
During the first week of July 2014, two hospitals (Raleigh Fitkin Memorial Hospital (RFM) and Good Shepherd Hospital) in the Kingdom of Swaziland reported an unusually increased number of diarrhoea cases occurring mainly in children < 2 years. During the period 1st – 19th July 2014, a total of 1265 cases with a case fatality of 2.2% were reported. Subsequent laboratory testing conducted at the national laboratory found that 64.3% of stool specimens from RFM and 79.3% of stool specimen from Mbabane Government Hospital were confirmed positive for rotavirus. Additionally, 67% samples from Women and Children’s clinic were positive for rotavirus.
This outbreak further highlighted the need for rotavirus vaccination and in May 2015, the Government of Swaziland made a decision to introduce rotavirus vaccine (Rotarix, GSK Biologicals) into its National Immunization Program. This paper describes the early impact of rotavirus vaccine introduction on all-cause diarrhea and rotavirus hospitalizations among children <5 years of age in Swaziland.
2. MATERIALS AND METHODS
Swaziland has conducted active, hospital-based rotavirus sentinel surveillance since 2013 at two sentinel hospital sites (Mbabane Government Referral Hospital and Raleigh Fitkin Memorial (RFM) Hospital). Both hospitals are located in urban areas and have bed capacities of 575 and 350, respectively. Mbabane Government Referral Hospital serves a population of 86,647 and RFM serves a population of 141,244; these health facilities also serve as referral facilities for other hospitals in the country thus increasing the catchment areas.
Children under the age of five years who presented with acute gastroenteritis (AGE), defined as the occurrence of >3 episodes of diarrhoea (stools of less formed character than usual) within 24 hour period of ≤7 days duration as a primary illness, and were admitted to a hospital ward or treated at the emergency unit at 1 of the 2 sentinel hospitals during the period January 2013 – December 2016, were enrolled in the surveillance program. Stool specimens were collected as in the standard guidelines [18]. All information regarding inclusion criteria and basic demographic and clinical information for each case was captured on the standard rotavirus case investigation form. Data collected from the sentinel hospitals was entered into Epi- Info software (Centres for Disease Control and Prevention).
Stool specimens were screened for the presence of group A rotavirus antigen using the commercially available ProSpecT™ Rotavirus enzyme immunoassay kit (Oxoid Ltd, UK) according to the manufacturer’s instructions. Samples were prepared following manufacturer’s protocol.
January 2013 to December 2014 served as the pre-vaccine introduction baseline and the post-vaccine introduction period was defined as January to December 2016. 2015 was considered a transition year as vaccine was introduced in May 2015 and coverage among eligible children reached 36%.
3. RESULTS
Overall prevalence of rotavirus among children < 5 years old
Between January 2013 – December 2016, 596 children below the age of five years were hospitalized for management of diarrhea in the two sentinel site hospitals. All cases had stool samples collected and tested for rotavirus. Of the total samples tested, 277 (32%) were positive for rotavirus. In 2013, rotavirus positives were 54/144 (38%). In 2014, rotavirus positivity was higher 118/194 (61%). In 2016, rotavirus positives were the lowest at 24/82 29% (Figure 1).
Figure 1: All-cause diarrhea hospitalizations, rotavirus positives and percent rotavirus positives among children <5 years old, Swaziland, 2013 – 2016.
The median age of rotavirus positive children increased from an average of 10.0 months in 2013 – 2014 (n=338) to 13.7 months (n=106) in 2016 (Table 1). The number of all diarrhea hospitalizations in children 0 – 11 months and 12 – 23 months decreased to its lowest level in 2016 as compared to the pre-vaccine periods (Table 2).
Table 1:
Under 5 years acute gastroenteritis (AGE) hospitalizations and rotavirus positives by year, Swaziland, 2013 – 2016
| Year | Tested samples (N) | Number of positive | Positive Rotavirus (%) | Median age of positive children (months) |
|---|---|---|---|---|
| 2013 | 144 | 54 | 38% | 9.8 |
| 2014 | 194 | 118 | 61% | 10.3 |
| 2015 | 176 | 81 | 46% | 10.2 |
| 2016 | 82 | 24 | 29% | 13.7 |
| Total | 596 | 277 | 32% | 10.6 |
Table 2:
All diarrhea hospitalization and rotavirus test results by age group and by year, 2013 – 2016, Swaziland
| 0–11 months | 12–23 months | 24–59 months | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Year | Rota Positive | Rota Negative | All enrolled & tested diarrhoea hospitalizations | Rota Positive | Rota Negative | All enrolled & tested diarrhoea hospitalizations | Rota Positive | Rota Negative | All enrolled & tested diarrhoea hospitalizations |
| 2013 | 41 | 66 | 107 | 10 | 19 | 29 | 3 | 5 | 8 |
| 2014 | 75 | 54 | 129 | 32 | 15 | 47 | 11 | 7 | 18 |
| 2015 | 64 | 62 | 126 | 16 | 26 | 42 | 1 | 6 | 7 |
| 2016 | 15 | 30 | 45 | 6 | 17 | 23 | 3 | 11 | 14 |
Prevalence of rotavirus hospitalizations by age group
Diarrhea hospitalizations were common among children under the age of five years; and the majority of children hospitalized for diarrhea 548/595 (92%) were below the age of 2 years. In 2016, rotavirus infection rate decreased in all age groups (Figure 2). A major reduction in rotavirus positivity was observed in the 0–23 months age groups.
Figure 2: Rotavirus infections by age group, Swaziland, 2013 – 2016.
Among children <5 years of age, rotavirus positivity reduced from an average of 51% (172/338) in 2013 – 2014 to 29% (24/82) in 2016 (percent reduction 43%, p-value=0.0005). In 2013, infants (0–11 months of age) and young children (12–23 months) had similar proportions of diarrhea hospitalizations due to rotavirus 45/107 (38%) and 10/29 (34%), respectively. During the rotavirus epidemic in 2014 and in 2015, over half of diarrhea hospitalizations 75/129 (58%) and 64/126 (51%) respectively in infants were due to rotavirus. Young children aged 12–23 months were also highly affected by rotavirus in 2014 with 32/47 (68%) of diarrhea hospitalizations due to rotavirus. In 2016, rotavirus positives in children 0–11 months reduced to 15/45 (33%) of diarrhea compared to a pre-vaccine average of 116/236 (49%) (p-value=0.05) and among children 12–23 months from a pre-vaccine average of 42/76 (55%) to 6/23 (26%) (P-value=0.02) (Figure 2).
Seasonality of diarrhoea hospitalizations
Diarrhea hospitalizations among under five year olds occurred all year round with the highest numbers seen between June – August (Figure 3). In 2013, 18/24 (43%) – 8/31 (74%), in 2014, 15/24 (63%) – 95/107 (89%), in 2015 15/27 (56%) – 55/74 (74%) of diarrhea hospitalizations in June – August tested positive for rotavirus which accounted for 44/54 (81%), 111/118 (94%), and 70/81 (86%) of all rotavirus hospitalizations in 2013, 2014, and 2015, respectively. The seasonal peaks coincided with the winter season in Swaziland. In 2016, the number of rotavirus positives was very low and the peaks were substantially blunted in all age groups (Figures 3 and 4). From June – August 2016, the proportion of diarrhea hospitalizations due to rotavirus was 5/11 (45%) – 5/6 (83%) and 16/24 (67%) of total rotavirus hospitalizations occurred during these months.
Figure 3: Seasonality of diarrhoea and rotavirus hospitalizations in under 5 year olds, Swaziland, 2013 – 2016.
Figure 4: Seasonality of diarrhoea hospitalizations in under 5 year olds, by age groups, Swaziland, 2013 – 2016.
4. DISCUSSION
The sentinel surveillance data from Swaziland showed evidence of early impact of rotavirus vaccine in the first full season following vaccine introduction with a significant reduction in overall diarrhea hospitalizations as well as in rotavirus positives. Rotavirus positivity among diarrhea hospitalizations reduced from an average of 51% pre vaccine to 29% post vaccine introduction, a 35% reduction in rotavirus positivity post-vaccine introduction.
The high number of diarrhea hospitalizations in 2014 among all age groups in Swaziland was associated with the rotavirus outbreak in that year which affected all under five year olds. In 2014, 118/194 (61%) of diarrhea hospitalizations in Swaziland were positive for rotavirus (the highest in all years of 2013 – 2016) and resulted in the death of 6/149 (4%) of the affected children where outcome (live or dead (was documented). The rotavirus outbreak prompted rotavirus vaccine introduction which in turn resulted in reducing the burden of all diarrhea and rotavirus.
The epidemiology of rotavirus infection two years before vaccine introduction and the year of vaccine introduction was characterized by peaks in the winter period from June to August. However, in the corresponding period of the first full calendar year post-vaccine introduction, this peak did not happen. The reduction in diarrhea hospitalizations was also associated with a shift in the median age of rotavirus positives from 10 months in the pre-vaccine era to 13.7 months post rotavirus vaccine in addition to the blunting of the number of diarrhea hospitalizations in the peak seasons. The substantial reduction of hospitalization in children younger than 12 months after vaccine introduction further supports the hypothesis that the observed decline in rotavirus hospitalizations can be attributed to the introduction of rotavirus vaccination in the routine immunization program. Similar results were also observed in South Africa [19] and other African countries following the introduction of rotavirus vaccination in the routine immunization [20] [21].
We acknowledge that the post-vaccine introduction data is limited to one year. However, given the dramatic reduction of rotavirus infection rate, our data suggests a substantial early impact of vaccine on rotavirus diarrhea and all diarrhea hospitalizations in Swaziland. Further, the sentinel surveillance facilities were located in urban areas and the majority of their catchment population resided in urban areas and thus may not be representative of the entire country. However, these facilities served as referral hospitals and did admit children from all over the country.
Sentinel surveillance showed the high prevalence of rotavirus infection among children hospitalized for gastroenteritis in Swaziland and the impact of rotavirus vaccine in reducing all diarrhea hospitalizations as well as rotavirus diarrhea. However, continued surveillance and monitoring of vaccine impact is needed to ensure that these reductions are sustained over time.
5. ACKNOWLEDGEMENT
The authors would like to thank the Ministry of Health of Swaziland, World Health Organization and other partners for material and technical support to the rotavirus sentinel surveillance system which produced these results. The clinical and laboratory staffs of Mbabane Government Referral Hospital, National Reference Laboratory (NRL) and Raleigh Fitkin Memorial hospital are highly appreciated for collecting the surveillance data. The authors also appreciate the support from MRC Diarrhoeal pathogens research unit, University of Limpopo (MEDUNSA) in genotyping the samples.
Footnotes
6. COMPETING INTERESTS
No competing interest
Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention (CDC).
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