- Email: [email protected]
Racial disparities in diarrhea-associated hospitalizations among children in five US States, before and after introduction of rotavirus vaccine
Vaccine 28 (2010) 7423–7426
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Racial disparities in diarrhea-associated hospitalizations among children in five US States, before and after introduction of rotavirus vaccine Catherine Yen a,∗ , Claudia A. Steiner b , Marguerite Barrett c , Aaron T. Curns a , Katherine Hunter d , Emily Wilson d , Umesh D. Parashar a a
National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA Healthcare Cost and Utilization Project, Center for Delivery, Organization and Markets, Agency for Healthcare Research and Quality, Rockville, MD, USA M.L. Barrett, Inc., Del Mar, CA, USA d Thomson Reuters, Santa Barbara, CA, USA b c
a r t i c l e
i n f o
Article history: Received 15 June 2010 Received in revised form 20 August 2010 Accepted 25 August 2010 Available online 15 September 2010 Keywords: Gastroenteritis Rotavirus Vaccines Health disparities
a b s t r a c t Racial differences in diarrheal disease have not been systematically examined, and the impact of rotavirus vaccine on these differences has not been assessed. We compared diarrhea-associated hospitalizations by race/ethnicity among children <5 years pre- (2000–2006) and post- (2007 and 2008) rotavirus vaccine introduction in five US states. Pre-vaccine hospitalization rates were greater among whites versus blacks and Hispanics. However, black (versus non-black) infants <6 months and white (versus non-white) children ≥1 year had higher rates. In 2008, racial disparities for children 12–35 months resolved, but higher hospitalization rates among black infants <6 months persisted, highlighting the need for timely vaccination. Published by Elsevier Ltd.
1. Introduction Rotavirus is the leading cause of severe diarrheal illness among infants and young children worldwide [1]. Prior to the implementation of routine rotavirus vaccination of United States (US) infants in 2006, rotavirus gastroenteritis caused an estimated 55,000–70,000 hospitalizations, 205,000–270,000 emergency department (ED) visits, and 410,000 outpatient visits annually among US children <5 years of age [2]. A few studies have examined racial disparities in diarrheaassociated morbidity among US children. Pont et al. examined nationally representative data from 1995 to 2004 and demonstrated that black children <5 years of age had higher rates of diarrhea-associated ED visits (28% of which were attributed to rotavirus infection) compared to white children [3]. Brandt et al. observed a higher prevalence of rotavirus gastroenteritis in hospitalized black infants <6 months of age compared to non-black infants [4]; similar observations were made by Fischer et al. in
Abbreviations: AHRQ, Agency for Healthcare Research and Quality; CI, confidence interval; ED, emergency department; HCUP, Healthcare Cost and Utilization Project; SID, State Inpatient Databases. ∗ Corresponding author at: Centers for Disease Control and Prevention, 1600 Clifton Road NE, MS A-47, Atlanta, GA, USA. Tel.: +1 404 639 1726; fax: +1 404 639 8665. E-mail address: [email protected] (C. Yen). 0264-410X/$ – see front matter. Published by Elsevier Ltd. doi:10.1016/j.vaccine.2010.08.094
an analysis of multistate hospital discharge data for the period 1993–2003 [5]. Higher rates of diarrhea-associated hospitalization in American Indian/Alaska Native infants compared to all US infants have also been documented [6]. To date, however, no study has systematically examined diarrhea-associated hospitalization rates in US children by age group to accurately ascertain patterns of diarrhea morbidity by race/ethnicity. Furthermore, since reductions in racial disparities in invasive pneumococcal infections between black and white children have been observed following the introduction of the pneumococcal conjugate vaccine in the US, it is possible that other vaccines may have the same impact [7]. Given the recent introduction of rotavirus vaccine, it is of interest to ascertain whether vaccination has impacted race/ethnicity-based differences in diarrhea morbidity in US children. We conducted this study to better examine racial disparities in diarrhea-associated hospitalizations among US children <5 years of age before introduction of rotavirus vaccine and to assess if the introduction of rotavirus vaccine affected these disparities. 2. Methods 2.1. Hospitalization data We analyzed data from the State Inpatient Databases (SID), maintained by the Healthcare Cost and Utilization Project (HCUP),
7424
C. Yen et al. / Vaccine 28 (2010) 7423–7426
to perform a retrospective study of diarrhea-associated hospitalizations among children <5 years of age for the pre-vaccine rotavirus seasons 2000–2006 and post-vaccine licensure seasons of 2007 and 2008. Sponsored by the Agency for Healthcare Research and Quality (AHRQ), the HCUP is a collection of health care databases that provides multistate, discharge-level health care data through a federal–state–industry partnership [8]. The SID contain inpatient discharge data from 40 participating states, comprising about 90% of all community hospital discharges in the US. Typically, these data are available with a 1–2 year time delay. However, after the introduction of rotavirus vaccine in 2006, AHRQ, 18 HCUP partners, and the Centers for Disease Control and Prevention (CDC) entered an agreement for accelerated data collection from October 2007 to June 2008. We limited the analysis to the 5 states that provided data encoding race/ethnicity for >92% of their discharge records during the study period (California, Florida, Maryland, Missouri, and South Carolina). Statewide quarterly hospitalization data for January–June were obtained for the 2008 rotavirus season while yearly data were obtained for the 2000–2007 seasons. For this analysis, a diarrhea-associated hospitalization was defined as a hospitalization with any of the following International Classification of Diseases, Ninth Edition, Clinical Modification (ICD9-CM) codes listed as a primary or secondary discharge diagnosis [9]: • Diarrhea of determined etiology: Bacterial (001–005 and 008.0–008.5) excluding localized Salmonella infections (003.2), viral (008.6 and 008.8) including rotavirus (008.61), and parasitic (006–007) excluding amebic liver, lung, and brain abscesses and amebic skin ulceration (006.3–006.6), and • Diarrhea of undetermined etiology: Infectious (009.0–009.3) and noninfectious (558.9, 787.91). 2.2. Population data We calculated hospitalization rates using the National Center for Health Statistics’ Bridged-Race population estimates for 2000–2007 as the denominator data [10]. Since population data were not yet available for the 2008 season, we used 2007 population data for all 2008 rate calculations.
Fig. 1. Diarrhea-associated hospitalization rates among children <5 years of age by age group in months for rotavirus seasons 2000–2006 (A), 2007 (B), and 2008 (C). Source: Agency for Healthcare Research and Quality, Center for Delivery, Organization, and Markets, Healthcare Cost and Utilization Project (HCUP), State Inpatient Databases, 2000–2007. 2008 quarterly data provided by five HCUP partners.
3. Results 2.3. Data analysis Although the primary goal of this analysis was to estimate rates of rotavirus hospitalizations by race/ethnicity and the impact of vaccination on existing disparities, hospitalizations coded specifically as rotavirus underestimate the true disease burden as testing for rotavirus is not part of routine clinical practice [5]. Therefore, we examined all diarrhea-associated hospitalizations during rotavirus seasons, which were defined as the months of January–June, similar to the approach used by another study [11]. National laboratory surveillance data and active surveillance studies have shown that rotavirus activity across the US almost exclusively occurred during this 6-month period in the pre-vaccine era. While the onset and peak of the rotavirus season was delayed after vaccine introduction in 2008 to the months of February–March, the season was shorter and ended by June 2008 [12]. Thus, the months of January–June reliably captured rotavirus seasons for our entire study period. We calculated race-specific, diarrhea-associated hospitalization rates among children <5 years of age for the 2000–2008 rotavirus seasons. To compare pre-vaccine and post-vaccine licensure hospitalization rates, we used the median hospitalization rate for the 2000–2006 rotavirus seasons. We then compared race-specific hospitalization rates and rate ratios by age group using Poisson regression analysis [13].
In the pre-vaccine period of 2000–2006, the overall rate of diarrhea-associated hospitalization among all children <5 years of age was slightly greater among white children compared with black or Hispanic children (P < .0001; Fig. 1, panel A). However, examination of race-specific rates by age showed some notable patterns. Black infants <6 months of age had higher rates of diarrheaassociated hospitalization when compared with white or Hispanic infants (P < .0001). In contrast, white children >11 months of age had higher rates of hospitalization when compared with black (P < .0001) or Hispanic children (P < .01). In 2007, the first rotavirus season after vaccine introduction, age-related racial disparities in diarrhea-associated hospitalization rates seen in the pre-vaccine years persisted despite a moderate decline in overall rates (Fig. 1, panel B). In 2008, marked declines were observed in overall diarrhea-associated hospitalization rates among children <5 years of age (Fig. 1, panel C). While blacks continued to have higher rates of hospitalization when compared with whites or Hispanics among infants <6 months of age in 2008, racial disparities disappeared among children aged 12–35 months and for the overall hospitalization rate for children <5 years of age. Rate ratios comparing hospitalization rates for black children and white children also demonstrate that black infants <6 months of age were more likely to be hospitalized in all time periods
C. Yen et al. / Vaccine 28 (2010) 7423–7426
7425
Table 1 Diarrhea-associated hospitalization rates per 10,000 children for blacks compared to whites, by age group. Age group (months)
2000–2006
0–2 3–5 6–11 12–17 18–23 24–35 36–47 48–59 Total a b
2007 a
2008 a
White
Black
Rate ratio (95% CI )
White
Black
Rate ratio (95% CI )
White
Black
Rate Ratio (95% CIa )
165.8 136.3 190.3 196.7 157.5 92.6 55.7 36.2 107.1
235.8 223.3 196.2 150.1 111.2 62.2 35.4 22.6 95.7
1.42 (1.26–1.60)b 1.64 (1.45–1.86)b 1.03 (0.95–1.13) 0.76 (0.69–0.84)b 0.71 (0.63–0.79)b 0.67 (0.60–0.75)b 0.64 (0.55–0.73)b 0.62 (0.52–0.74)b 0.89 (0.86–0.93)b
148.5 99.9 146.9 172.0 133.6 76.8 42.9 27.7 87.8
206.6 170.4 160.3 127.9 87.1 55.8 27.4 20.8 78.5
1.39 (1.23–1.57)b 1.71 (1.48–1.96)b 1.09 (0.99–1.20) 0.74 (0.67–0.82)b 0.65 (0.58–0.74)b 0.73 (0.65–0.81)b 0.64 (0.54–0.75)b 0.75 (0.63–0.91)b 0.89 (0.86–0.93)b
107.6 82.0 82.6 76.6 62.9 42.5 25.8 18.3 49.4
160.0 114.0 97.6 76.9 59.5 37.2 17.9 12.0 51.4
1.49 (1.29–1.71)b 1.39 (1.18–1.64)b 1.18 (1.04–1.34)b 1.00 (0.88–1.15) 0.95 (0.81–1.10) 0.88 (0.76–1.01) 0.69 (0.57–0.84)b 0.65 (0.51–0.83)b 1.04 (0.98–1.09)
CI = confidence interval. P < .05.
(P < .0001, Table 1). In contrast, the higher likelihood of hospitalization seen among white children 12–35 months of age in 2000–2006 and 2007 became non-significant in the 2008 season. Rate ratios comparing hospitalization rates for Hispanic children and white children demonstrate significantly greater hospitalization rates for Hispanic children 3–5 months (P < .0001) and for white children ≥12 months (P < .01) in 2000–2006 and 2007, with the differences in rates largely disappearing in 2008 (Table 2). 4. Discussion Our analysis demonstrates that in the pre-vaccine era, diarrheaassociated hospitalization rates were significantly greater among black infants <6 months of age compared with whites and Hispanics, whereas rates among older children were greater among whites compared with blacks and Hispanics. The higher rates of hospitalization in black infants <6 months compared to white and Hispanic infants persisted following the introduction of rotavirus vaccine in the US, despite a large overall decline in hospitalization rates and resolution of disparities in rates between older white children and black and Hispanic children. Thus, while rotavirus vaccination seems to have had a considerable impact on rates of diarrhea-associated hospitalization among children overall, the racial disparity seen among the youngest children persists. Our finding of higher rates of hospitalization in black infants <6 months of age compared to white infants during both preand post-vaccine periods and of older white children compared to black children in the pre-vaccine period is consistent with previous observations; several hypotheses have been postulated to explain this phenomenon. Biologic factors, such as higher rates of low birth weight and prematurity, may lead to increased vulnerability of minority infants with early onset and severe complications of diarrhea and increased risk for diarrheal death [14,15]. Race may to some extent be a proxy for socioeconomic status, and environmental factors, such as crowding and poor sanitation, could
generate a higher force of infection. Insurance status or low level of maternal education may lead to delays in seeking healthcare and therefore more severe disease [3,14]. Ma et al. observed that in the pre-vaccine years of 2000 and 2003, children receiving Medicaid assistance had a greater rates of rotavirus gastroenteritisassociated hospitalizations when compared to a non-Medicaid population [16]. Regardless of the cause, clinicians should be aware of the greater risk of severe disease resulting in hospitalization when considering the management of diarrhea in young minority children, and timely vaccination of infants with rotavirus vaccine, particularly of black infants, should be emphasized since it may help prevent these early infections. This study has several limitations. First, data from only 5 states were analyzed and therefore cannot be generalized to all children <5 years of age living in the US. Nevertheless, these states account for one-quarter of US children <5 years of age and have diverse populations reflective of the nation’s population. Second, analysis including other racial groups that have been noted to have higher rates of diarrhea-associated hospitalization among young infants compared to all US infants, such as American Indians and Alaska Natives, was not possible because of small numbers, patient privacy considerations, and exclusion of Indian Health Service hospitals [6]. Additionally, misclassification of race/ethnicity when methods other than self-reporting are used is possible. However, we were unable to assess to what degree this may have occurred in our study population. Third, because of probable incomplete testing and coding of rotavirus, we used all-cause diarrhea hospitalizations during the winter season as a proxy for rotavirus hospitalizations. This is reasonable as rotavirus accounts for a majority of diarrheaassociated hospitalizations during these months [5]. However, variability in hospitalizations for gastroenteritis due to other infectious agents with winter seasonality, such as norovirus, may have impacted our results [5,17]. Fourth, we are unable to account for missing race/ethnicity data, which may potentially affect our findings, and were unable to conduct a formal sensitivity analysis for
Table 2 Diarrhea-associated hospitalization rates per 10,000 children for Hispanics compared to whites, by age group. Age group (months)
0–2 3–5 6–11 12–17 18–23 24–35 36–47 48–59 Total a b
2000–2006
2007
2008
White
Hispanic
Rate ratio (95% CI )
White
Hispanic
Rate ratio (95% CI )
White
Hispanic
Rate ratio (95% CIa )
165.8 136.3 190.3 196.7 157.5 92.6 55.7 36.2 107.1
163.5 182.1 196.7 179.7 122.9 70.7 37.7 26.0 97.8
0.99 (0.89–1.09) 1.34 (1.20–1.48)b 1.03 (0.97–1.11) 0.91 (0.85–0.98)b 0.78 (0.72–0.85)b 0.76 (0.71–0.83)b 0.68 (0.61–0.75)b 0.72 (0.64–0.81)b 0.91 (0.87–0.94)b
148.5 99.9 146.9 172.0 133.6 76.8 42.9 27.7 87.8
146.3 120.3 137.8 131.5 93.3 56.7 30.8 20.8 73.3
0.99 (0.89–1.09) 1.20 (1.07–1.36)b 0.94 (0.87–1.01) 0.76 (0.71–0.82)b 0.70 (0.64–0.76)b 0.74 (0.68–0.80)b 0.72 (0.64–0.80)b 0.75 (0.66–0.86)b 0.83 (0.81–0.86)b
107.6 82.0 82.6 76.6 62.9 42.5 25.8 18.3 49.4
102.4 93.7 88.4 77.8 61.3 40.1 21.6 15.4 49.3
0.95 (0.84–1.08) 1.14 (1.00–1.31)b 1.07 (0.97–1.18) 1.02 (0.92–1.12) 0.97 (0.87–1.09) 0.94 (0.85–1.04) 0.84 (0.73–0.96)b 0.84 (0.72–0.99)b 1.00 (0.96–1.04)
CI = confidence interval. P < .05.
a
a
7426
C. Yen et al. / Vaccine 28 (2010) 7423–7426
these data as denominator data were unavailable for those children with unknown race classification. Of note, the mean proportion of records missing race/ethnicity data among the five states ranged from 3.7 to 4.8% for the study period. These missing data could potentially result in the over- or underestimation of hospitalization rates of children within specific race categories. Fifth, we used 2007 population data to calculate hospitalization rates for 2008. Given a growing population, our calculated hospitalization rates for 2008 would likely be an overestimation and therefore an underestimation of the decline in hospitalizations and of vaccine impact. Finally, the lack of concomitant vaccine coverage data limits our ability to correlate the post-vaccine trends seen in this analysis with vaccine uptake, although the relatively similar levels of declines seen across age groups suggest fairly consistent impact of vaccination. 5. Conclusion A substantial overall decline in diarrhea-associated hospitalization rates among children aged <5 years of all races/ethnicities examined in this study has occurred since the introduction of rotavirus vaccine. However, black infants <6 months of age continue to have higher rates of hospitalization compared to non-black infants, whereas disparities in rates among older children have largely resolved. The persistent, greater rate of hospitalization among black infants <6 months of age highlights the need for timely rotavirus vaccination. Continued surveillance as vaccine coverage improves and additional studies to explore the reasons for the observed racial disparities are warranted. Disclaimer The findings and conclusions of this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention or the Agency for Healthcare Research and Quality. Acknowledgments We sincerely would like to thank and acknowledge the following HCUP state partners for their active support of this study: Arizona Department of Health Services, Office of Statewide Health Planning and Development (CA), Florida Agency for Health Care Administration, Georgia Hospital Association, Hawaii Health Information Corporation, Indiana Hospital Association, Iowa Hospital Association, Kentucky Cabinet for Health and Family Services, Maine Health Data Organization, Maryland Health Services Cost Review Commission, Michigan Health & Hospital Association, Minnesota Hospital Association, Hospital Industry Data Institute (MO), Nevada
Department of Health and Human Services, New York State Department of Health, South Carolina State Budget & Control Board, Washington State Department of Health, and West Virginia Health Care Authority. References [1] Parashar UD, Gibson CJ, Bresee JS, Glass RI. Rotavirus and severe childhood diarrhea. Emerg Infect Dis 2006;12(February (2)):304–6. [2] Cortese MM, Parashar UD. Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2009;58(February 6 (RR-2)):1–25. [3] Pont SJ, Grijalva CG, Griffin MR, Scott TA, Cooper WO. National rates of diarrheaassociated ambulatory visits in children. J Pediatr 2009;155(July (1)):56–61. [4] Brandt CD, Kim HW, Rodriguez WJ, Arrobio JO, Jeffries BC, Stallings EP, et al. Pediatric viral gastroenteritis during eight years of study. J Clin Microbiol 1983;18(1):71–8. [5] Fischer TK, Viboud C, Parashar U, Malek M, Steiner C, Glass R, et al. Hospitalizations and deaths from diarrhea and rotavirus among children <5 years of age in the United States, 1993–2003. J Infect Dis 2007;195(April 15 (8)):1117–25. [6] Singleton RJ, Holman RC, Yorita KL, Holve S, Paisano EL, Steiner CA, et al. Diarrhea-associated hospitalizations and outpatient visits among American Indian and Alaska Native children younger than five years of age, 2000–2004. Pediatr Infect Dis J 2007;26(November (11)):1006–13. [7] Flannery B, Schrag S, Bennett NM, Lynfield R, Harrison LH, Reingold A, et al. Impact of childhood vaccination on racial disparities in invasive Streptococcus pneumoniae infections. JAMA 2004;291(May 12 (18)):2197–203. [8] Steiner C, Elixhauser A, Schnaier J. The Healthcare Cost and Utilization Project: an overview. Eff Clin Pract 2002;5(May–June (3)):143–51. [9] Public Health Service and Healthcare Financing Administration. ICD-9-CM international classification of diseases, ninth revision, clinical modification, 6th ed. NCHS CD-ROM 1997, no 1. Official ed. Washington, DC: U.S. Dept. of Health and Human Services; 2007. [10] National Center for Health Statistics. Estimates of the July 1, 2000–July 1, 2007, United States resident population from the Vintage 2007 postcensal series by county, age, sex, race, and Hispanic origin, prepared under a collaborative arrangement with the U.S. Census Bureau; 2008 [cited 2009 10/21/2009]. Available from: http://www.cdc.gov/nchs/about/major/dvs/popbridge/popbridge. htm. [11] Curns AT, Steiner CA, Barrett M, Hunter K, Wilson E, Parashar UD. Reduction in acute gastroenteritis hospitalizations among US children after introduction of rotavirus vaccine: analysis of hospital discharge data from 18 US states. J Infect Dis 2010;201(11):1617–24. [12] Reduction in rotavirus after vaccine introduction—United States, 2000–2009. MMWR Morb Mortal Wkly Rep 2009;58((October 23) 41):1146–9. [13] Kleinbaum DG, Kupper LL, Muller KE, Nizam A. Applied regression analysis and other multivariable methods. Pacific Grove, CA: Brooks/Cole; 1998. [14] Ho MS, Glass RI, Pinsky PF, Young-Okoh NC, Sappenfield WM, Buehler JW, et al. Diarrheal deaths in American children. Are they preventable? JAMA 1988;260(December 9 (22)):3281–5. [15] Parashar UD, Kilgore PE, Holman RC, Clarke MJ, Bresee JS, Glass RI. Diarrheal mortality in US infants Influence of birth weight on risk factors for death. Arch Pediatr Adolesc Med 1998;152(January (1)):47–51. [16] Ma L, El Khoury AC, Itzler RF. The burden of rotavirus hospitalizations among Medicaid and non-Medicaid children younger than 5 years old. Am J Public Health 2009;99(October (2)):S398–404. [17] Jin S, Kilgore PE, Holman RC, Clarke MJ, Gangarosa EJ, Glass RI. Trends in hospitalizations for diarrhea in United States children from 1979 through 1992: estimates of the morbidity associated with rotavirus. Pediatr Infect Dis J 1996;15(May (5)):397–404.
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Racial disparities in diarrhea-associated hospitalizations among children in five US States, before and after introduction of rotavirus vaccine Catherine Yen a,∗ , Claudia A. Steiner b , Marguerite Barrett c , Aaron T. Curns a , Katherine Hunter d , Emily Wilson d , Umesh D. Parashar a a
National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA Healthcare Cost and Utilization Project, Center for Delivery, Organization and Markets, Agency for Healthcare Research and Quality, Rockville, MD, USA M.L. Barrett, Inc., Del Mar, CA, USA d Thomson Reuters, Santa Barbara, CA, USA b c
a r t i c l e
i n f o
Article history: Received 15 June 2010 Received in revised form 20 August 2010 Accepted 25 August 2010 Available online 15 September 2010 Keywords: Gastroenteritis Rotavirus Vaccines Health disparities
a b s t r a c t Racial differences in diarrheal disease have not been systematically examined, and the impact of rotavirus vaccine on these differences has not been assessed. We compared diarrhea-associated hospitalizations by race/ethnicity among children <5 years pre- (2000–2006) and post- (2007 and 2008) rotavirus vaccine introduction in five US states. Pre-vaccine hospitalization rates were greater among whites versus blacks and Hispanics. However, black (versus non-black) infants <6 months and white (versus non-white) children ≥1 year had higher rates. In 2008, racial disparities for children 12–35 months resolved, but higher hospitalization rates among black infants <6 months persisted, highlighting the need for timely vaccination. Published by Elsevier Ltd.
1. Introduction Rotavirus is the leading cause of severe diarrheal illness among infants and young children worldwide [1]. Prior to the implementation of routine rotavirus vaccination of United States (US) infants in 2006, rotavirus gastroenteritis caused an estimated 55,000–70,000 hospitalizations, 205,000–270,000 emergency department (ED) visits, and 410,000 outpatient visits annually among US children <5 years of age [2]. A few studies have examined racial disparities in diarrheaassociated morbidity among US children. Pont et al. examined nationally representative data from 1995 to 2004 and demonstrated that black children <5 years of age had higher rates of diarrhea-associated ED visits (28% of which were attributed to rotavirus infection) compared to white children [3]. Brandt et al. observed a higher prevalence of rotavirus gastroenteritis in hospitalized black infants <6 months of age compared to non-black infants [4]; similar observations were made by Fischer et al. in
Abbreviations: AHRQ, Agency for Healthcare Research and Quality; CI, confidence interval; ED, emergency department; HCUP, Healthcare Cost and Utilization Project; SID, State Inpatient Databases. ∗ Corresponding author at: Centers for Disease Control and Prevention, 1600 Clifton Road NE, MS A-47, Atlanta, GA, USA. Tel.: +1 404 639 1726; fax: +1 404 639 8665. E-mail address: [email protected] (C. Yen). 0264-410X/$ – see front matter. Published by Elsevier Ltd. doi:10.1016/j.vaccine.2010.08.094
an analysis of multistate hospital discharge data for the period 1993–2003 [5]. Higher rates of diarrhea-associated hospitalization in American Indian/Alaska Native infants compared to all US infants have also been documented [6]. To date, however, no study has systematically examined diarrhea-associated hospitalization rates in US children by age group to accurately ascertain patterns of diarrhea morbidity by race/ethnicity. Furthermore, since reductions in racial disparities in invasive pneumococcal infections between black and white children have been observed following the introduction of the pneumococcal conjugate vaccine in the US, it is possible that other vaccines may have the same impact [7]. Given the recent introduction of rotavirus vaccine, it is of interest to ascertain whether vaccination has impacted race/ethnicity-based differences in diarrhea morbidity in US children. We conducted this study to better examine racial disparities in diarrhea-associated hospitalizations among US children <5 years of age before introduction of rotavirus vaccine and to assess if the introduction of rotavirus vaccine affected these disparities. 2. Methods 2.1. Hospitalization data We analyzed data from the State Inpatient Databases (SID), maintained by the Healthcare Cost and Utilization Project (HCUP),
7424
C. Yen et al. / Vaccine 28 (2010) 7423–7426
to perform a retrospective study of diarrhea-associated hospitalizations among children <5 years of age for the pre-vaccine rotavirus seasons 2000–2006 and post-vaccine licensure seasons of 2007 and 2008. Sponsored by the Agency for Healthcare Research and Quality (AHRQ), the HCUP is a collection of health care databases that provides multistate, discharge-level health care data through a federal–state–industry partnership [8]. The SID contain inpatient discharge data from 40 participating states, comprising about 90% of all community hospital discharges in the US. Typically, these data are available with a 1–2 year time delay. However, after the introduction of rotavirus vaccine in 2006, AHRQ, 18 HCUP partners, and the Centers for Disease Control and Prevention (CDC) entered an agreement for accelerated data collection from October 2007 to June 2008. We limited the analysis to the 5 states that provided data encoding race/ethnicity for >92% of their discharge records during the study period (California, Florida, Maryland, Missouri, and South Carolina). Statewide quarterly hospitalization data for January–June were obtained for the 2008 rotavirus season while yearly data were obtained for the 2000–2007 seasons. For this analysis, a diarrhea-associated hospitalization was defined as a hospitalization with any of the following International Classification of Diseases, Ninth Edition, Clinical Modification (ICD9-CM) codes listed as a primary or secondary discharge diagnosis [9]: • Diarrhea of determined etiology: Bacterial (001–005 and 008.0–008.5) excluding localized Salmonella infections (003.2), viral (008.6 and 008.8) including rotavirus (008.61), and parasitic (006–007) excluding amebic liver, lung, and brain abscesses and amebic skin ulceration (006.3–006.6), and • Diarrhea of undetermined etiology: Infectious (009.0–009.3) and noninfectious (558.9, 787.91). 2.2. Population data We calculated hospitalization rates using the National Center for Health Statistics’ Bridged-Race population estimates for 2000–2007 as the denominator data [10]. Since population data were not yet available for the 2008 season, we used 2007 population data for all 2008 rate calculations.
Fig. 1. Diarrhea-associated hospitalization rates among children <5 years of age by age group in months for rotavirus seasons 2000–2006 (A), 2007 (B), and 2008 (C). Source: Agency for Healthcare Research and Quality, Center for Delivery, Organization, and Markets, Healthcare Cost and Utilization Project (HCUP), State Inpatient Databases, 2000–2007. 2008 quarterly data provided by five HCUP partners.
3. Results 2.3. Data analysis Although the primary goal of this analysis was to estimate rates of rotavirus hospitalizations by race/ethnicity and the impact of vaccination on existing disparities, hospitalizations coded specifically as rotavirus underestimate the true disease burden as testing for rotavirus is not part of routine clinical practice [5]. Therefore, we examined all diarrhea-associated hospitalizations during rotavirus seasons, which were defined as the months of January–June, similar to the approach used by another study [11]. National laboratory surveillance data and active surveillance studies have shown that rotavirus activity across the US almost exclusively occurred during this 6-month period in the pre-vaccine era. While the onset and peak of the rotavirus season was delayed after vaccine introduction in 2008 to the months of February–March, the season was shorter and ended by June 2008 [12]. Thus, the months of January–June reliably captured rotavirus seasons for our entire study period. We calculated race-specific, diarrhea-associated hospitalization rates among children <5 years of age for the 2000–2008 rotavirus seasons. To compare pre-vaccine and post-vaccine licensure hospitalization rates, we used the median hospitalization rate for the 2000–2006 rotavirus seasons. We then compared race-specific hospitalization rates and rate ratios by age group using Poisson regression analysis [13].
In the pre-vaccine period of 2000–2006, the overall rate of diarrhea-associated hospitalization among all children <5 years of age was slightly greater among white children compared with black or Hispanic children (P < .0001; Fig. 1, panel A). However, examination of race-specific rates by age showed some notable patterns. Black infants <6 months of age had higher rates of diarrheaassociated hospitalization when compared with white or Hispanic infants (P < .0001). In contrast, white children >11 months of age had higher rates of hospitalization when compared with black (P < .0001) or Hispanic children (P < .01). In 2007, the first rotavirus season after vaccine introduction, age-related racial disparities in diarrhea-associated hospitalization rates seen in the pre-vaccine years persisted despite a moderate decline in overall rates (Fig. 1, panel B). In 2008, marked declines were observed in overall diarrhea-associated hospitalization rates among children <5 years of age (Fig. 1, panel C). While blacks continued to have higher rates of hospitalization when compared with whites or Hispanics among infants <6 months of age in 2008, racial disparities disappeared among children aged 12–35 months and for the overall hospitalization rate for children <5 years of age. Rate ratios comparing hospitalization rates for black children and white children also demonstrate that black infants <6 months of age were more likely to be hospitalized in all time periods
C. Yen et al. / Vaccine 28 (2010) 7423–7426
7425
Table 1 Diarrhea-associated hospitalization rates per 10,000 children for blacks compared to whites, by age group. Age group (months)
2000–2006
0–2 3–5 6–11 12–17 18–23 24–35 36–47 48–59 Total a b
2007 a
2008 a
White
Black
Rate ratio (95% CI )
White
Black
Rate ratio (95% CI )
White
Black
Rate Ratio (95% CIa )
165.8 136.3 190.3 196.7 157.5 92.6 55.7 36.2 107.1
235.8 223.3 196.2 150.1 111.2 62.2 35.4 22.6 95.7
1.42 (1.26–1.60)b 1.64 (1.45–1.86)b 1.03 (0.95–1.13) 0.76 (0.69–0.84)b 0.71 (0.63–0.79)b 0.67 (0.60–0.75)b 0.64 (0.55–0.73)b 0.62 (0.52–0.74)b 0.89 (0.86–0.93)b
148.5 99.9 146.9 172.0 133.6 76.8 42.9 27.7 87.8
206.6 170.4 160.3 127.9 87.1 55.8 27.4 20.8 78.5
1.39 (1.23–1.57)b 1.71 (1.48–1.96)b 1.09 (0.99–1.20) 0.74 (0.67–0.82)b 0.65 (0.58–0.74)b 0.73 (0.65–0.81)b 0.64 (0.54–0.75)b 0.75 (0.63–0.91)b 0.89 (0.86–0.93)b
107.6 82.0 82.6 76.6 62.9 42.5 25.8 18.3 49.4
160.0 114.0 97.6 76.9 59.5 37.2 17.9 12.0 51.4
1.49 (1.29–1.71)b 1.39 (1.18–1.64)b 1.18 (1.04–1.34)b 1.00 (0.88–1.15) 0.95 (0.81–1.10) 0.88 (0.76–1.01) 0.69 (0.57–0.84)b 0.65 (0.51–0.83)b 1.04 (0.98–1.09)
CI = confidence interval. P < .05.
(P < .0001, Table 1). In contrast, the higher likelihood of hospitalization seen among white children 12–35 months of age in 2000–2006 and 2007 became non-significant in the 2008 season. Rate ratios comparing hospitalization rates for Hispanic children and white children demonstrate significantly greater hospitalization rates for Hispanic children 3–5 months (P < .0001) and for white children ≥12 months (P < .01) in 2000–2006 and 2007, with the differences in rates largely disappearing in 2008 (Table 2). 4. Discussion Our analysis demonstrates that in the pre-vaccine era, diarrheaassociated hospitalization rates were significantly greater among black infants <6 months of age compared with whites and Hispanics, whereas rates among older children were greater among whites compared with blacks and Hispanics. The higher rates of hospitalization in black infants <6 months compared to white and Hispanic infants persisted following the introduction of rotavirus vaccine in the US, despite a large overall decline in hospitalization rates and resolution of disparities in rates between older white children and black and Hispanic children. Thus, while rotavirus vaccination seems to have had a considerable impact on rates of diarrhea-associated hospitalization among children overall, the racial disparity seen among the youngest children persists. Our finding of higher rates of hospitalization in black infants <6 months of age compared to white infants during both preand post-vaccine periods and of older white children compared to black children in the pre-vaccine period is consistent with previous observations; several hypotheses have been postulated to explain this phenomenon. Biologic factors, such as higher rates of low birth weight and prematurity, may lead to increased vulnerability of minority infants with early onset and severe complications of diarrhea and increased risk for diarrheal death [14,15]. Race may to some extent be a proxy for socioeconomic status, and environmental factors, such as crowding and poor sanitation, could
generate a higher force of infection. Insurance status or low level of maternal education may lead to delays in seeking healthcare and therefore more severe disease [3,14]. Ma et al. observed that in the pre-vaccine years of 2000 and 2003, children receiving Medicaid assistance had a greater rates of rotavirus gastroenteritisassociated hospitalizations when compared to a non-Medicaid population [16]. Regardless of the cause, clinicians should be aware of the greater risk of severe disease resulting in hospitalization when considering the management of diarrhea in young minority children, and timely vaccination of infants with rotavirus vaccine, particularly of black infants, should be emphasized since it may help prevent these early infections. This study has several limitations. First, data from only 5 states were analyzed and therefore cannot be generalized to all children <5 years of age living in the US. Nevertheless, these states account for one-quarter of US children <5 years of age and have diverse populations reflective of the nation’s population. Second, analysis including other racial groups that have been noted to have higher rates of diarrhea-associated hospitalization among young infants compared to all US infants, such as American Indians and Alaska Natives, was not possible because of small numbers, patient privacy considerations, and exclusion of Indian Health Service hospitals [6]. Additionally, misclassification of race/ethnicity when methods other than self-reporting are used is possible. However, we were unable to assess to what degree this may have occurred in our study population. Third, because of probable incomplete testing and coding of rotavirus, we used all-cause diarrhea hospitalizations during the winter season as a proxy for rotavirus hospitalizations. This is reasonable as rotavirus accounts for a majority of diarrheaassociated hospitalizations during these months [5]. However, variability in hospitalizations for gastroenteritis due to other infectious agents with winter seasonality, such as norovirus, may have impacted our results [5,17]. Fourth, we are unable to account for missing race/ethnicity data, which may potentially affect our findings, and were unable to conduct a formal sensitivity analysis for
Table 2 Diarrhea-associated hospitalization rates per 10,000 children for Hispanics compared to whites, by age group. Age group (months)
0–2 3–5 6–11 12–17 18–23 24–35 36–47 48–59 Total a b
2000–2006
2007
2008
White
Hispanic
Rate ratio (95% CI )
White
Hispanic
Rate ratio (95% CI )
White
Hispanic
Rate ratio (95% CIa )
165.8 136.3 190.3 196.7 157.5 92.6 55.7 36.2 107.1
163.5 182.1 196.7 179.7 122.9 70.7 37.7 26.0 97.8
0.99 (0.89–1.09) 1.34 (1.20–1.48)b 1.03 (0.97–1.11) 0.91 (0.85–0.98)b 0.78 (0.72–0.85)b 0.76 (0.71–0.83)b 0.68 (0.61–0.75)b 0.72 (0.64–0.81)b 0.91 (0.87–0.94)b
148.5 99.9 146.9 172.0 133.6 76.8 42.9 27.7 87.8
146.3 120.3 137.8 131.5 93.3 56.7 30.8 20.8 73.3
0.99 (0.89–1.09) 1.20 (1.07–1.36)b 0.94 (0.87–1.01) 0.76 (0.71–0.82)b 0.70 (0.64–0.76)b 0.74 (0.68–0.80)b 0.72 (0.64–0.80)b 0.75 (0.66–0.86)b 0.83 (0.81–0.86)b
107.6 82.0 82.6 76.6 62.9 42.5 25.8 18.3 49.4
102.4 93.7 88.4 77.8 61.3 40.1 21.6 15.4 49.3
0.95 (0.84–1.08) 1.14 (1.00–1.31)b 1.07 (0.97–1.18) 1.02 (0.92–1.12) 0.97 (0.87–1.09) 0.94 (0.85–1.04) 0.84 (0.73–0.96)b 0.84 (0.72–0.99)b 1.00 (0.96–1.04)
CI = confidence interval. P < .05.
a
a
7426
C. Yen et al. / Vaccine 28 (2010) 7423–7426
these data as denominator data were unavailable for those children with unknown race classification. Of note, the mean proportion of records missing race/ethnicity data among the five states ranged from 3.7 to 4.8% for the study period. These missing data could potentially result in the over- or underestimation of hospitalization rates of children within specific race categories. Fifth, we used 2007 population data to calculate hospitalization rates for 2008. Given a growing population, our calculated hospitalization rates for 2008 would likely be an overestimation and therefore an underestimation of the decline in hospitalizations and of vaccine impact. Finally, the lack of concomitant vaccine coverage data limits our ability to correlate the post-vaccine trends seen in this analysis with vaccine uptake, although the relatively similar levels of declines seen across age groups suggest fairly consistent impact of vaccination. 5. Conclusion A substantial overall decline in diarrhea-associated hospitalization rates among children aged <5 years of all races/ethnicities examined in this study has occurred since the introduction of rotavirus vaccine. However, black infants <6 months of age continue to have higher rates of hospitalization compared to non-black infants, whereas disparities in rates among older children have largely resolved. The persistent, greater rate of hospitalization among black infants <6 months of age highlights the need for timely rotavirus vaccination. Continued surveillance as vaccine coverage improves and additional studies to explore the reasons for the observed racial disparities are warranted. Disclaimer The findings and conclusions of this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention or the Agency for Healthcare Research and Quality. Acknowledgments We sincerely would like to thank and acknowledge the following HCUP state partners for their active support of this study: Arizona Department of Health Services, Office of Statewide Health Planning and Development (CA), Florida Agency for Health Care Administration, Georgia Hospital Association, Hawaii Health Information Corporation, Indiana Hospital Association, Iowa Hospital Association, Kentucky Cabinet for Health and Family Services, Maine Health Data Organization, Maryland Health Services Cost Review Commission, Michigan Health & Hospital Association, Minnesota Hospital Association, Hospital Industry Data Institute (MO), Nevada
Department of Health and Human Services, New York State Department of Health, South Carolina State Budget & Control Board, Washington State Department of Health, and West Virginia Health Care Authority. References [1] Parashar UD, Gibson CJ, Bresee JS, Glass RI. Rotavirus and severe childhood diarrhea. Emerg Infect Dis 2006;12(February (2)):304–6. [2] Cortese MM, Parashar UD. Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2009;58(February 6 (RR-2)):1–25. [3] Pont SJ, Grijalva CG, Griffin MR, Scott TA, Cooper WO. National rates of diarrheaassociated ambulatory visits in children. J Pediatr 2009;155(July (1)):56–61. [4] Brandt CD, Kim HW, Rodriguez WJ, Arrobio JO, Jeffries BC, Stallings EP, et al. Pediatric viral gastroenteritis during eight years of study. J Clin Microbiol 1983;18(1):71–8. [5] Fischer TK, Viboud C, Parashar U, Malek M, Steiner C, Glass R, et al. Hospitalizations and deaths from diarrhea and rotavirus among children <5 years of age in the United States, 1993–2003. J Infect Dis 2007;195(April 15 (8)):1117–25. [6] Singleton RJ, Holman RC, Yorita KL, Holve S, Paisano EL, Steiner CA, et al. Diarrhea-associated hospitalizations and outpatient visits among American Indian and Alaska Native children younger than five years of age, 2000–2004. Pediatr Infect Dis J 2007;26(November (11)):1006–13. [7] Flannery B, Schrag S, Bennett NM, Lynfield R, Harrison LH, Reingold A, et al. Impact of childhood vaccination on racial disparities in invasive Streptococcus pneumoniae infections. JAMA 2004;291(May 12 (18)):2197–203. [8] Steiner C, Elixhauser A, Schnaier J. The Healthcare Cost and Utilization Project: an overview. Eff Clin Pract 2002;5(May–June (3)):143–51. [9] Public Health Service and Healthcare Financing Administration. ICD-9-CM international classification of diseases, ninth revision, clinical modification, 6th ed. NCHS CD-ROM 1997, no 1. Official ed. Washington, DC: U.S. Dept. of Health and Human Services; 2007. [10] National Center for Health Statistics. Estimates of the July 1, 2000–July 1, 2007, United States resident population from the Vintage 2007 postcensal series by county, age, sex, race, and Hispanic origin, prepared under a collaborative arrangement with the U.S. Census Bureau; 2008 [cited 2009 10/21/2009]. Available from: http://www.cdc.gov/nchs/about/major/dvs/popbridge/popbridge. htm. [11] Curns AT, Steiner CA, Barrett M, Hunter K, Wilson E, Parashar UD. Reduction in acute gastroenteritis hospitalizations among US children after introduction of rotavirus vaccine: analysis of hospital discharge data from 18 US states. J Infect Dis 2010;201(11):1617–24. [12] Reduction in rotavirus after vaccine introduction—United States, 2000–2009. MMWR Morb Mortal Wkly Rep 2009;58((October 23) 41):1146–9. [13] Kleinbaum DG, Kupper LL, Muller KE, Nizam A. Applied regression analysis and other multivariable methods. Pacific Grove, CA: Brooks/Cole; 1998. [14] Ho MS, Glass RI, Pinsky PF, Young-Okoh NC, Sappenfield WM, Buehler JW, et al. Diarrheal deaths in American children. Are they preventable? JAMA 1988;260(December 9 (22)):3281–5. [15] Parashar UD, Kilgore PE, Holman RC, Clarke MJ, Bresee JS, Glass RI. Diarrheal mortality in US infants Influence of birth weight on risk factors for death. Arch Pediatr Adolesc Med 1998;152(January (1)):47–51. [16] Ma L, El Khoury AC, Itzler RF. The burden of rotavirus hospitalizations among Medicaid and non-Medicaid children younger than 5 years old. Am J Public Health 2009;99(October (2)):S398–404. [17] Jin S, Kilgore PE, Holman RC, Clarke MJ, Gangarosa EJ, Glass RI. Trends in hospitalizations for diarrhea in United States children from 1979 through 1992: estimates of the morbidity associated with rotavirus. Pediatr Infect Dis J 1996;15(May (5)):397–404.