Trends in severe gastroenteritis among young children according to socio-economic characteristics before and after implementation of a rotavirus vaccination program in Quebec.

Gosselin, Virginie ; Petit, Genevieve ; Gagneur, Arnaud 等

Rotavirus is the main cause of acute gastroenteritis (AGE) among children under five years of age worldwide. (1) In developed countries, hospitalizations related to rotavirus gastroenteritis (RVGE) generate important costs for society. (2) Before the arrival of rotavirus vaccines in Canada, there were on average 7,500 to 10,500 estimated hospitalizations for RVGE annually. (3,4) Rotavirus infections were responsible for up to 72% of AGE hospitalizations during winter months. (5) Rotavirus season started in December and ended in May, with a peak incidence observed in March and April. (4)

In Canada, two rotavirus vaccines, RotaTeq[R] and Rotarix[R], were approved in 2006 and 2007, and were recommended by the National Advisory Committee on Immunization in July 2010 to prevent RVGE in young children. (6) Both vaccines showed high clinical efficacy in upper-middle and high-income countries, reducing RVGE hospitalizations by 85%-100%. (7,8) On November 1, 2011, the monovalent rotavirus vaccine Rotarix[R] (RV1), offered to all infants in two doses and administered orally at two and four months of age, was introduced into the publicly funded vaccination program in Quebec. This program primarily aims at reducing gastroenteritis morbidity in the general population, including vulnerable subgroups.

After implementation of rotavirus vaccination programs, many studies from the US, Australia and the European Union documented significant declines in AGE and RVGE hospitalization rates. (9-11) Globally, they observed a 30%-60% decline in AGE hospitalization rates. Only two studies from Mexico analyzed relative reductions according to socio-economic status. (12,13) They found lower, but still significant, reductions in diarrhea-related hospitalizations and deaths in states with low socio-economic status. To date, no studies have assessed the impact of the rotavirus immunization program in Quebec since its implementation in 2011. In Canada, where people benefit from the universal health care system, an impact study could be highly relevant in describing the burden of severe rotavirus infections over time, before and after implementation of universal rotavirus immunization, and could therefore assess its public health benefits in the general population as well as in socio-economic subgroups.

The aim of this study was to assess the impact of the rotavirus routine immunization program on gastroenteritis morbidity and health inequalities among young children living in the Eastern Townships (QC, Canada). More specifically, AGE and RVGE hospitalization rates in post-program years were compared with those of the pre-program years, overall and according to individual- and neighbourhood-level socio-economic characteristics. Rotavirus vaccine coverage was also examined in the post-program period overall and according to the same characteristics.

METHODS

Study setting

The Eastern Townships, a southern region of Quebec with 320,000 residents in 2014 (4% of the Quebec population), is composed of a mix of urban, semi-urban and rural communities. (14) One central city, named Sherbrooke (Quebec's sixth largest city), has half of the regional population. This city contains one central tertiary hospital, the Centre hospitalier universitaire de Sherbrooke (CHUS), where 95% of deliveries in the Eastern Townships occur and where nearly 100% of pediatric beds for acute care in the region are held. (4) Therefore, the vast majority of children living in the Eastern Townships requiring hospitalization for AGE attend the CHUS.

Data sources

Data on all births and hospitalizations occurring at the CHUS were obtained from CIRESSS (Centre informatise de recherche evaluative en services et soins de sante), which is a local data warehouse based at the CHUS that has contained exhaustive data since 1991. Vaccination data were obtained from LOGIVAC, an immunization registry unique to the Eastern Townships in which all births in the region and all vaccines administered to the residents have been recorded since 1998, even for those born outside the region. Thus, all children born in the region, regardless of their vaccination status, are included in LOGIVAC.

Study population

This longitudinal descriptive study included all children born at the CHUS between June 1999 and May 2014 and living in the Eastern Townships at birth, in order to assess gastroenteritis hospitalization rates among children younger than five years from 2004 to 2014. This birth cohort, extracted from the hospital database CIRESSS, was followed up from birth (or from the start of the study for children born before June 2004) to the age of five years (or until the end of the study for children born after May 2009) with respect to all AGE hospitalizations. Data were then linked to LOGIVAC to obtain the rotavirus vaccination status of newborns. After the pairing, all data were denominalized. The final cohort consisted of 37,757 newborns.

Variables

Dependent Variables

In this study, three dependent variables were examined: 1) AGE hospitalization rates among children younger than five years (a proxy for severe gastroenteritis), 2) RVGE hospitalization rates among children younger than five years and 3) rotavirus vaccine coverage. Hospitalizations for AGE that occurred between June 1, 2004 and May 31, 2014, were identified in CIRESSS using the following International Classification of Diseases, 9th Revision and 10th Revision, Canada (ICD-9/10-CA) codes: AGE of determined etiology (bacterial [003.0, 004, 005, 008.0-008.5/A02.0, A03-A05], parasitic [006.0-006.1, 007/A06.0-A06.3, A07] and viral [008.6-008.8/A08, including rotavirus code 008.61/A08.0]), AGE of undetermined etiology (presumed infectious [009/A09] and presumed noninfectious [558.4-558.9/K52.8-K52.9]) and noninfective neonatal AGE (P78.3). Hospitalizations for RVGE were identified in CIRESSS using laboratory data of positive stool analyses for rotavirus. Laboratory-confirmed RVGE hospitalizations represent a more specific and complete definition of severe RVGE than RVGE-coded hospitalizations, because some patients with rotavirus-positive test results are not assigned a rotavirus code, as has been documented in the US health care system. (15) Both primary and secondary diagnoses were considered, and two hospitalizations for the same infant occurring in less than 14 days were considered as one event. Hospitalizations rates were calculated by dividing the number of hospitalizations that occurred among children aged less than five years by the total number of children of the same age group in the birth cohort over a specified period.

LOGIVAC provided information about rotavirus vaccines, including name, date of administration and number of doses received. Coverage was first calculated at the age of three months to assess the coverage of [greater than or equal to] 1 dose of rotavirus vaccine since the approval of the two vaccines in 2006 and 2007. Coverage of eligible infants in the funded vaccination program was also assessed at the end of the period study, on May 31, 2014. Coverage was defined as the receipt of [greater than or equal to] 1 dose among children born between August 1, 2011 and February 28, 2014 (aged between 3 and 33 months).

Individual Covariates

Several covariates were available in the CIRESSS database. Birth date allowed age to be calculated at the end of each "rotavirus" year (i.e., May 31), and this was then used to determine the denominators of age-specific hospitalization and vaccine coverage rates (<1, 1-2 and 3-4 years). Birth characteristics (all dichotomized) were sex, maternal age at birth (<25 vs. [greater than or equal to] 25 years), gestational age at birth (<37 weeks [preterm infant] vs. [greater than or equal to] 37 weeks [term infant]) and birth weight (<2500 g [low birth weight] vs. [greater than or equal to] 2500 g [normal birth weight]). Place of residence, defined as eastern, central (i.e., Sherbrooke city) and western territories, was determined by the municipality of residence at birth.

Ecological Covariates

The population density (i.e., number of people per square kilometre), the rate of low-income families (i.e., families having an annual income below the low-income cut-off), the unemployment rate among people [greater than or equal to] 25 years, the rate of single mothers (i.e., not living with a partner) and the proportion of mothers without a high school diploma (i.e., <11 school years completed), derived from the National Census (2006) and the Live Births File (2002-2010), were measured at the dissemination area (DA) level. DA is the smallest geostatistical unit available from the census (approximately 400-700 persons by DA). (16) The six-digit residential postal codes at birth, provided by CIRESSS, were geocoded in order to assign a DA to each participant (total of 519 DAs), allowing pairing of the five ecological variables to respective children. These ecological variables were then categorized into tertiles (T1, T2, T3), T3 representing the highest rate or proportion of poor socio-economic indicators. In the absence of individual measures, these neighbourhood-level variables were used as proxy measures for the socio-economic status of participants, T1, T2 and T3 representing advantaged, middle and disadvantaged socio-economic groups.

Statistical analyses

Monthly and annual AGE and RVGE hospitalization rates were examined to observe rotavirus seasonal patterns and long-term trends between June 2004 and May 2014. For further analyses, the focus was on AGE hospitalizations, which were considered to be more appropriate for assessing the overall trends in severe rotavirus infections, since laboratory-confirmed RVGE is less sensitive and may underestimate the rotavirus infections burden. (17) Focusing on AGE rather than RVGE also increased the statistical power to detect differences between subgroups. To compute the relative reduction in hospitalization rates between pre- and post-program periods, the mean annual AGE hospitalization rates were compared for years 2004/2005-2010/2011 versus years 2011/2012-2013/2014, using this formula: ([pre-program rate - post-program rate]/pre-program rate) x 100. Mean annual hospitalization and vaccine coverage rates were calculated overall and according to demographic and socio-economic characteristics measured at individual and ecological levels. Children with missing variables were excluded only in the specific analyses involving those variables. Statistical comparisons of rates within subgroups in each study period were made using the chi-square test with significance level set at 0.05 (two-sided). Data were analyzed using SPSS. The research project was approved by the CHUS Ethics Committee.

RESULTS

Ten-year trends in hospitalization rates and vaccine coverage

In the cohort of 37,757 newborns, 882 hospitalizations for AGE were observed before the age of five years between June 2004 and May 2014. During the pre-program years, AGE hospitalization rates were characterized by a sharp increase between January and May (Figure 1). A similar seasonal pattern was observed for RVGE hospitalizations. In post-program years, AGE and RVGE hospitalization rates significantly decreased, particularly in the last year under investigation (2013/2014). The mean peaks of AGE and RVGE hospitalizations, observed in April for the pre-program period, were both dramatically flattened during the post-program period (Figures 2A and 2B). Furthermore, monthly vaccine coverage of >1 dose was very low before the arrival of the rotavirus vaccination program, ranging from 0% to 4%. Soon after the program implementation, vaccine uptake increased markedly and was maintained during the following years to an average of 81% (Figure 1).

[FIGURE 1 OMITTED]

[FIGURE 2 OMITTED]

Pre- and post-program AGE hospitalization trends

In the whole cohort of newborns, annual AGE hospitalization rates significantly decreased from 81/10,000 in the pre-program period to 46/10,000 in the post-program period, representing an overall relative reduction of 43% (95% confidence interval [CI]: 33-51) (Table 1). Less than 2% of children had missing information regarding sex, maternal age at birth or postal code. For all individual-level variables examined, each subgroup showed a decline in hospitalization rates during the post-program years in comparison with the pre-program years. However, lower relative and non-significant reductions were observed in specified subgroups, including children aged three and four years, children having a young mother and preterm children (26%, 19%, and 26% respectively). Regarding DA-level characteristics, all socio-economic strata showed a significant relative reduction in the post-program period (Table 2). However, the lowest relative reductions were generally observed among the most urban and the most socio-economically disadvantaged areas (T3). Indeed, children from densest DAs (T3) had a 27% reduction in hospitalization rates, whereas those living in DAs with low (T1) and medium (T2) population density had a much greater reduction (47% and 53% respectively). In the same vein, hospitalization rates declined less sharply in DAs with higher unemployment rates, higher low-income family rates and higher single mother rates (relative reductions of 35%, 26% and 30% respectively) than more advantaged DAs. It is noteworthy that some of the observed differences in AGE hospitalization rates among subgroups in post-program years were not present in pre-program years.

Post-program vaccine coverage

In post-program years, coverage of [greater than or equal to] 1 dose for all infants eligible for free vaccination was 81% (Table 1). RV1 was the vaccine administered to 99.9% of these cases. Coverage in each socioeconomic subgroup ranged from 75% to 85%. Regarding individual characteristics, infants aged <1 year at admission, children having a young mother, normal birth weight children and those living in Sherbrooke were among the most frequently vaccinated. No significant differences were observed between DA-level subgroups.

DISCUSSION

This longitudinal study based on a large birth cohort was the first to examine the simultaneous evolution over the last decade of gastroenteritis hospitalization and rotavirus vaccine coverage rates among young children, overall and according to various socioeconomic characteristics. The substantial decline in AGE and RVGE pediatric hospitalizations in post-program years is consistent with that observed in previous impact studies conducted in industrialized countries, where a sustained reduction has been observed since the beginning of the rotavirus vaccination program. (18-21) Reductions over three consecutive years simultaneously occurring with the rapid increase in vaccine coverage indicates that these changes are likely due to the new rotavirus vaccination program. However, an important reduction in hospitalizations for gastroenteritis was also observed in 2009-2010, before the implementation of the program. This unexpected decline could possibly be explained by the natural fluctuation in rotavirus activity related to different rotavirus strains (22) or by the increase in general hygiene measures following the 2009 H1N1 influenza pandemic. Indeed, the 2010 weak rotavirus season was preceded by a strong rotavirus season in 2009, reflecting the biennial seasonal pattern of rotavirus. (23)

The observed vaccine coverage of [greater than or equal to] 1 dose in 81% of children aged 3-33 months during the post-program period is consistent with estimates from a recent survey conducted in children of one and two years old in Quebec (81%-88% for [greater than or equal to] 1 dose) as well as with reported coverage among children aged 0-2 years in the Eastern Townships on the basis of LOGIVAC data (75% for 2 doses). (24,25) The estimated coverage in the present study is slightly higher because coverage of [greater than or equal to] 1 dose was assessed instead of a full series and possibly because our birth cohort did not include children born in birthing centres or at home. Indeed, a previous study found an association between assisted delivery by a midwife and incomplete immunization status (i.e., not all the recommended vaccines received). (26)

Among children younger than five years, AGE hospitalization rates were significantly reduced in the post-program period (43%). This reduction corresponds to that observed in many studies in industrialized countries, ranging from 30% to 60%. (9-11,18-21) However, our study went further than previous studies by examining these trends according to several individual- and neighbourhood-level characteristics. As expected, children less than three years, who were eligible to receive the funded rotavirus vaccine, had the highest reductions, suggesting that the observed decline in gastroenteritis hospitalizations was due to rotavirus vaccine. Interestingly, children aged three and four years, too old to receive the rotavirus vaccine, still had a relative reduction of 26%. Although it did not reach statistical significance, this observation suggests a herd immunity effect of the vaccine, also observed in many other studies. (18-21) Children living in Sherbrooke, which is the most central and most populous city, as well as those living in the densest DAs, had the lowest reductions in AGE hospitalization rates in comparison with children living in more rural areas. Urban clusters with high population density could increase the potential for transmission of rotavirus or other gastrointestinal pathogens, explaining the lower reduction in AGE hospitalizations in urban areas despite high vaccine coverage.

For socio-economic ecological-level variables, the most disadvantaged subgroups generally showed the lowest rate reductions in post-program years. This may have been caused by factors other than vaccination itself as no significant difference in vaccine coverage according to socio-economic subgroups was observed in the present study. Indeed, people with low socioeconomic status generally differ from more well-off ones according to their living conditions (e.g., household crowding), their physical health (e.g., weaker immune status, smoking habits), their nutritional status and their health seeking behaviour. (27) A study from southern Israel showed similar results to ours in two distinct populations, and the authors suggested that the differential reduction could be partially explained by socio-economic conditions. (28) Moreover, because disadvantaged parents generally have fewer resources and may be less knowledgeable about the causes and cures of symptoms, (27) doctors tend to hospitalize these children more in order to achieve recovery. In Quebec, this practice was previously observed among asthmatic children, as those whose fathers held economically disadvantaged occupations were more likely to be hospitalized. (29) This differential management from doctors may be a complementary hypothesis for the lower reduction in AGE hospitalizations observed in disadvantaged subgroups.

This study had some limitations. Temporal trends could have been influenced by factors other than vaccination, such as natural variation in rotavirus activity and testing practices. However, the observed rate reductions were sustained over three consecutive years, suggesting that declines were most likely attributable to the vaccination program. For trends in RVGE hospitalizations, laboratory testing practices were probably similar over the study period, as the proportion of requests among hospitalized children was equivalent in pre- and post-program periods (data not shown). Concerning CIRESSS and LOGIVAC, both databases had no information about whether a child had moved out of the Eastern Townships after birth. This had the potential effect of underestimating gastroenteritis hospitalizations and vaccine coverage. However, this bias was presumably non-differential according to the birth and family characteristics or the outcomes examined, and did not preclude comparison of rates between pre- and post-program periods. Finally, the socio-economic status of parents was not available in both databases, but several proxies, measured at the finest ecological level available, were used to obtain the socio-economic level of the child's neighbourhood.

CONCLUSIONS

This impact study strongly suggests that the publicly funded rotavirus vaccination program significantly reduced gastroenteritis hospitalizations in young children. Moreover, Quebec's universal vaccination program demonstrated equitable access to rotavirus vaccine among different socio-economic subgroups. However, disadvantaged subgroups experienced a less pronounced AGE reduction, suggesting that factors other than vaccination may influence part of the reduction in hospitalization for gastroenteritis among young children. Based on the present study, a forthcoming study will assess vaccine effectiveness directly among children eligible for the rotavirus vaccination program, overall and according to socio-economic characteristics, to further explore the present findings.

REFERENCES

(1.) Parashar UD, Gibson CJ, Bresse JS, Glass RI. Rotavirus and severe childhood diarrhea. Emerg Infect Dis 2006;12(2):304-06. PMID: 16494759. doi: 10.3201/eid1202.050006.

(2.) Kilgore A, Donauer S, Edwards KM, Weinberg GA, Payne DC, Szilagyi PG, et al. Rotavirus-associated hospitalization and emergency department costs and rotavirus vaccine program impact. Vaccine 2013;31(38):4164-71. PMID: 23845802. doi: 10.1016/j.vaccine.2013.06.085.

(3.) Morton VK, Thomas MK, McEWEN SA. Estimated hospitalizations attributed to norovirus and rotavirus infection in Canada, 2006-2010. Epidemiol Infect 2015:143(16):3528-37. PMID: 25991407. doi: 10.1017/S0950268815000734.

(4.) Bernard S, Valiquette L, De Wals P, Nault V, Babakissa C, Cyr C, et al. Burden of rotavirus disease: A population-based study in Eastern Townships, Quebec. Can J Infect Dis Med Microbiol 2013;24(3):138-42. PMID: 24421824.

(5.) Rivest P, Proulx M, Lonergan G, Lebel MH, Bedard L. Hospitalisations for gastroenteritis: The role of rotavirus. Vaccine 2004;22(15-16):2013-17. PMID: 15121314. doi: 10.1016/j.vaccine.2003.10.029.

(6.) National Advisory Committee on Immunization. Updated statement on the use of rotavirus vaccines. Can Commun Dis Rep 2010;36(ACS-4):1-37.

(7.) Vesikari T, Matson DO, Dennehy P, Van Damme P, Santosham M, Rodriguez Z, et al. Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine. N Engl J Med 2006;354(1):23-33. PMID: 16394299. doi: 10.1056/NEJMoa052664.

(8.) Ruiz-Palacios GM, Perez-Schael I, Velazquez FR, Abate H, Breuer T, Clemens SC, et al. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med 2006;354(1):11-22. PMID: 16394298. doi: 10.1056/NEJMoa052434.

(9.) Karafillakis E, Hassounah S, Atchison C. Effectiveness and impact of rotavirus vaccines in Europe, 2006-2014. Vaccine 2015;33(18):2097-107. PMID: 25795258. doi: 10.1016/j.vaccine.2015.03.016.

(10.) Rha B, Tate JE, Payne DC, Cortese MM, Lopman BA, Curns AT, et al. Effectiveness and impact of rotavirus vaccines in the United States--2006-2012. Expert Rev Vaccines 2014;13(3):365-76. PMID: 24392657. doi: 10.1586/14760584.2014.877846.

(11.) Giaquinto C, Dominiak-Felden G, Van Damme P, Htar Myint TT, Maldonado YA, Spoulou V, et al. Summary of effectiveness and impact of rotavirus vaccination with the oral pentavalent rotavirus vaccine: A systematic review of the experience in industrialized countries. Hum Vaccin 2011; 7(7):734-48. PMID: 21734466. doi: 10.4161/hv.7.7.15511.

(12.) Esparza-Aguilar M, Gastanaduy PA, Sanchez-Uribe E, Desai R, Parashar UD, Richardson V, et al. Diarrhoea-related hospitalizations in children before and after implementation of monovalent rotavirus vaccination in Mexico. Bull World Health Organ 2014;92(2):117-25. PMID: 24623905. doi: 10.2471/BLT.13.125286.

(13.) Gastanaduy PA, Sanchez-Uribe E, Esparza-Aguilar M, Desai R, Parashar UD, Patel M, et al. Effect of rotavirus vaccine on diarrhea mortality in different socioeconomic regions of Mexico. Pediatrics 2013;131(4):e1115-20. PMID: 23460689. doi: 10.1542/peds.2012-2797.

(14.) Roy M, Genereux M, Laverdiere E, Vanasse A. Surveillance of social and geographic inequalities in housing-related issues: The case of the Eastern Townships, Quebec (Canada). Int J Environ Res Public Health 2014;11(5): 4825-44. PMID: 24806192. doi: 10.3390/ijerph110504825.

(15.) Hsu VP, Staat MA, Roberts N, Thieman C, Bernstein DI, Bresee J, et al. Use of active surveillance to validate international classification of diseases code estimates of rotavirus hospitalizations in children. Pediatrics, 2005;115(1): 78-82. PMID: 15629984.

(16.) Statistics Canada. Dissemination Area (DA). 2011 Census Dictionary. Ottawa, ON: Statistics Canada, 2012. Available at: http://www12.statcan.gc.ca/censusrecensement/2011/ref/dict/geo021-eng.cfm (Accessed November 24, 2015).

(17.) Bettinger JA, Wills K, Le Saux N, Scheifele DW, Halperin SA, Vaudry W. Heterogeneity of rotavirus testing and admitting practices for gastroenteritis among 12 tertiary care pediatric hospitals: Implications for surveillance. Can J Infect Dis Med Microbiol 2011;22(1):15-8. PMID: 22379483.

(18.) Desai R, Curns AT, Steiner CA, Tate JE, Patel MM, Parashar UD. All-cause gastroenteritis and rotavirus-coded hospitalizations among US children, 2000-2009. Clin Infect Dis 2012;55(4):e28-34. PMID: 22543022. doi: 10.1093/cid/cis443.

(19.) Yen C, Tate JE, Wenk JD, Harris JM, Parashar UD. Diarrhea-associated hospitalizations among US children over 2 rotavirus seasons after vaccine introduction. Pediatrics 2011;127(1):e9-15. PMID: 21172995. doi: 10.1542/peds.2010-1393.

(20.) Dey A, Wang H, Menzies R, Macartney K. Changes in hospitalisations for acute gastroenteritis in Australia after the national rotavirus vaccination program. Med J Aust 2012;197(8):453-57. PMID: 23072242. doi: 10.5694/mja12.10062.

(21.) Clarke MF, Davidson GP, Gold MS, Marshall HS. Direct and indirect impact on rotavirus positive and all-cause gastroenteritis hospitalisations in South Australian children following the introduction of rotavirus vaccination. Vaccine 2011;29(29-30):4663-67. 21575665. doi: 10.1016/j.vaccine.2011.04.109.

(22.) Payne DC, Szilagyi PG, Staat MA, Edwards KM, Gentsch JR, Weinberg GA, et al. Secular variation in United States rotavirus disease rates and serotypes: Implications for assessing the rotavirus vaccination program. Pediatr Infect Dis J 2009;28(11):948-53. PMID: 19859013. doi: 10.1097/INF.0b013e3181a6ad6e.

(23.) Aliabadi N, Tate JE, Haynes AK, Parashar UD. Centers for Disease Control and Prevention (CDC). Sustained decrease in laboratory detection of rotavirus after implementation of routine vaccination-United States, 2000-2014. MMWR Morb Mortal WklyRep 2015;64(13):337-42. PMID: 25856253.

(24.) Boulianne N, Audet D, Ouakki M. Enquete sur la couverture vaccinale des enfants de 1 an et 2 ans au Quebec en 2014. Quebec : Institut national de sante publique, 2015. Available at: http://www.inspq.qc.ca/pdf/publications/1973_Enquete_Couverture_Vaccinale_Enfants.pdf (Accessed August 19, 2015).

(25.) Poirier B. Rapport de la couverture vaccinale des 0-2 ans en Estrie. Sherbrooke, QC : Direction de sante publique de l'Estrie, 2015. Available at: http://www.santeestrie.qc.ca/sante_publique/protection_maladies_infectieuses/ vaccination/documents/RapportCV2014_Estrie_VFACCWeb.pdf (Accessed August 19, 2015).

(26.) Guay M, Gallagher F, Petit G, Menard S, Clement P, Boyer G. Pourquoi les couvertures vaccinales chez les nourrissons de l'estrie sont-elles sous-optimales? Quebec : CSSS-IUGS, 2009. Available at: http://www.santeestrie.qc.ca/publication_documentation/documents/ etude_couvertures_vaccinales_chez_les_nourrissons_sous-optimales.pdf (Accessed August 19, 2015).

(27.) Bradley RH, Corwyn RF. Socioeconomic status and child development. Annu Rev Psychol 2002;53:371-99. PMID: 11752490. doi: 10.1146/annurev.psych.53.100901.135233.

(28.) Givon-Lavi N, Ben-Shimol S, Cohen R, Greenberg D, Dagan R. Rapid impact of rotavirus vaccine introduction to the National Immunization Plan in Southern Israel: Comparison between 2 distinct populations. Vaccine 2015; 33(16):1934-40. PMID: 25744226. doi: 10.1016/j.vaccine.2015.02.062.

(29.) Amre DK, Infante-Rivard C, Gautrin D, Malo J-L. Socioeconomic status and utilization of health care services among asthmatic children. J Asthma 2002; 39(7):625-31. PMID: 12442952. doi:10.1081/JAS-120014927.

Received: September 16, 2015

Accepted: January 17, 2016

Virginie Gosselin, BSc, [1] Genevieve Petit, MD, MSc, FRCPC, [1,2] Arnaud Gagneur, MD, PhD, [3] Melissa Genereux, MD, MSc, FRCPC [1,2]

Author Affiliations

[1.] Community Health Sciences Department, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC

[2.] Eastern Townships Public Health Department, ClUSSS de l'Estrie-CHUS, QC

[3.] Pediatrics Department, Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, QC

Correspondence: Dr. Melissa Genereux, Eastern Townships Public Health Department, ClUSSS de l'Estrie-CHUS, 300 King Est, bureau 300, Sherbrooke, QC J1G 1B1, Tel: 819 829-3400, ext. 42453, E-mail: Melissa.Genereux@USherbrooke.ca

Acknowledgements: We thank Beatrice Poirier of the Eastern Townships Public Health Department for LOGIVAC data extraction, and Jean-Michel Gagnon of the CHUS for ClRESSS extraction and linkage between the two administrative databases.

Source of funding: VG was supported by the Eastern Townships Public Health Scholarship from the Fellowship Program of Graduate Studies of the University of Sherbrooke. The funding source had no involvement in any part of the study.

Conflict of Interest: None to declare. Table 1. Mean annual AGE hospitalization rates in pre-and post-program periods and vaccine coverage in the post- program period, according to individual-level characteristics, cohort of 37,757 children under five years, Eastern Townships, Quebec (Canada), 2004-2014 2004/2005-2010/2011 AGE hospitalization Mean rate ([double dagger]) p (total n) ([section]) Total (<5 years) 80.5 (700) Sex Male 89.5 (404) 0.002# Female 70.8 (296) Age at admission <1 year 135.7 (244) <0.001# 1-2 years 101.3 (355) 3-4 years 29.7 (101) Maternal age at birth <25 years 89.5 (199) 0.086 [greater than or equal to] 25 years 77.5 (501) Gestational age at birth <37 weeks 125.1 (92) <0.001# [greater than or 76.4 (608) equal to] 37 weeks Birth weight <2500 g 148.1 (81) <0.001# [greater than or 76.0 (619) equal to] 2500 g Place of residence at birth East 79.3 (151) 0.007# Central 87.4 (432) West 63.2 (117) 2011/2012-2013/2014 AGE hospitalization Mean rate ([double dagger]) p (total n) ([section]) Total (<5 years) 46.0 (182) Sex Male 49.0 (100) 0.360 Female 42.7 (82) Age at admission <1 year 87.8 (68) <0.001# 1-2 years 49.6 (79) 3-4 years 22.0 (35) Maternal age at birth <25 years 72.3 (61) <0.001# [greater than or equal to] 25 years 38.8 (121) Gestational age at birth <37 weeks 92.1 (28) <0.001# [greater than or 42.1 (154) equal to] 37 weeks Birth weight <2500 g 75.8 (18) 0.027# [greater than or 44.1 (164) equal to] 2500 g Place of residence at birth East 41.2 (35) 0.015# Central 53.4 (125) West 28.7 (22) Vaccine coverage * (%) p ([section]) Total (<5 years) 80.6 Sex Male 80.5 0.852 Female 80.7 Age at admission <1 year 84.2 <0.001# 1-2 years 79.1 3-4 years NA Maternal age at birth <25 years 84.3 <0.001# [greater than or equal to] 25 years 79.7 Gestational age at birth <37 weeks 78.5 0.191 [greater than or 80.8 equal to] 37 weeks Birth weight <2500 g 76.4 0.022# [greater than or 80.9 equal to] 2500 g Place of residence at birth East 78.2 0.030# Central 81.4 West 80.7 Rate reduction (95% CI), % Total (<5 years) 43 (33-51) Sex Male 45 (32-56) Female 40 (23-53) Age at admission <1 year 35 (16-51) 1-2 years 51 (38-62) 3-4 years 26 (-8-50) Maternal age at birth <25 years 19 (-8-39) [greater than or equal to] 25 years 50 (39-59) Gestational age at birth <37 weeks 26 (-12-52) [greater than or 45 (34-54) equal to] 37 weeks Birth weight <2500 g 49 (15-69) [greater than or 42 (31-51) equal to] 2500 g Place of residence at birth East 48 (25-64) Central 39 (25-50) West 55 (29-71) NOTE: Bold values are statistically significant (p < 0.05). * Vaccine coverage is defined as reception of [greater than or equal to] 1 rotavirus vaccine doses on May 31, 2014, among the children eligible for the vaccination program (children aged between 3 and 33 months). ([dagger]) Rate reductions were calculated by comparing the pre-program rates and post-program rates. ([double dagger]) Mean annual rates per 10,000 children <5 years of age. ([section]) [chi square] test used to compare rates among subgroups for a respective study period. AGE, acute gastroenteritis; CI, confidence interval; NA, not applicable. NOTE: Statistically significant (p < 0.05) are indicated with #. Table 2. Mean annual AGE hospitalization rates in pre-and post-program periods and vaccine coverage of post-program period, according to ecological-level * characteristics, cohort of 37,757 children under five years, Eastern Townships, Quebec (Canada), 2004-2014 2004/2005- 2010/2011 AGE hospitalization Mean rate p ([section]) ([parallel]) (total n) Population density T1 (low) 71.0 (205) 0.088 T2 83.6 (240) T3 (high) 86.3 (253) Unemployment rate T1 (low) 81.3 (229) 0.581 T2 76.4 (219) T3 (high) 84.0 (251) Low-income family rate T1 (low) 72.2 (207) 0.136 T2 85.2 (243) T3 (high) 85.0 (249) Single mother rate T1 (low) 72.4 (205) 0.139 T2 87.1 (247) T3 (high) 81.9 (248) Proportion of mothers without high school diploma T1 (low) 81.6 (226) 0.327 T2 74.6 (218) T3 (high) 85.4 (256) 2011/2012- 2013/2014 AGE hospitalization Mean rate p ([section]) ([parallel]) (total n) Population density T1 (low) 37.9 (50) 0.005# T2 39.2 (53) T3 (high) 62.6 (79) Unemployment rate T1 (low) 43.6 (62) 0.287 T2 41.7 (54) T3 (high) 54.3 (66) Low-income family rate T1 (low) 41.4 (54) 0.003# T2 35.6 (49) T3 (high) 63.1 (78) Single mother rate T1 (low) 38.0 (52) 0.060 T2 43.9 (58) T3 (high) 57.5 (72) Proportion of mothers without high school diploma T1 (low) 40.5 (57) 0.151 T2 55.5 (72) T3 (high) 42.8 (53) Vaccine coverage ([dagger]) Mean rate p ([section]) ([parallel]) (total n) Population density T1 (low) 79.7 0.168 T2 80.1 T3 (high) 81.9 Unemployment rate T1 (low) 80.8 0.885 T2 80.2 T3 (high) 80.4 Low-income family rate T1 (low) 81.0 0.625 T2 80.5 T3 (high) 79.8 Single mother rate T1 (low) 80.8 0.855 T2 80.1 T3 (high) 80.5 Proportion of mothers without high school diploma T1 (low) 81.2 0.567 T2 80.2 T3 (high) 80.0 Rate reduction ([double dagger]) (95% CI), % Population density T1 (low) 47 (27-61) T2 53 (37-65) T3 (high) 27 (7-44) Unemployment rate T1 (low) 46 (29-59) T2 45 (26-59) T3 (high) 35 (15-51) Low-income family rate T1 (low) 43 (23-58) T2 58 (43-69) T3 (high) 26 (4-42) Single mother rate T1 (low) 47 (29-61) T2 50 (33-62) T3 (high) 30 (9-46) Proportion of mothers without high school diploma T1 (low) 50 (34-63) T2 26 (3-43) T3 (high) 50 (33-63) NOTE: Bold values are statistically significant (p < 0.05). * Ecological variables were calculated according to the dissemination area of residence at the birth of the child. They are presented in tertiles, T1 representing the lowest rate. ([dagger]) Vaccine coverage is defined as reception of >1 rotavirus vaccine doses on May 31, 2014, among children eligible for the vaccination program (children aged between 3 and 33 months). ([double dagger]) Rate reductions were calculated by comparing the pre-program rates and post-program rates. ([section]) Mean annual rates per 10,000 children <5 years of age. ([parallel]) [chi square] test used to compare rates among subgroups for a respective study period. AGe, acute gastroenteritis; CI, confidence interval. NOTE: Statistically significant (p < 0.05) are indicated with #.