SUPPLEMENT

Reduction of Diarrhea-associated Hospitalizations AmongChildren Aged �5 Years in Panama Following the Introduction

of Rotavirus VaccineYadira Molto, MD,* Jennifer E. Cortes, MD,†‡ Lucia Helena De Oliveira, RN, MSc,§ Adrianna Mike, RN,*

Itzel Solis, RN,* Onix Suman, RN,¶ Luis Coronado, MD,¶ Manish M. Patel, MSc, MD,†Umesh D. Parashar, MB BS, MPH,† and Margaret M. Cortese, MD†

Background: In March 2006, rotavirus vaccine (Rotarix, RV1) wasintroduced into the Panamanian national immunization program. We as-sessed the effect of vaccine on diarrhea-associated hospitalizations amongyoung Panamanian children.Methods: We obtained monthly numbers of diarrhea-associated hospi-talizations among children aged �5 years during 2003 and 2008 from5 health regions in Panama, representing 53% of the birth cohort. Wecompared the number of diarrhea-associated hospitalizations during thepostvaccine years of 2007 and 2008 with the prevaccine mean numbers2003–2005 among children �1 year and those 1 to 4 years of age.Administrative data were used to estimate national rotavirus vaccinecoverage.Results: During prevaccine years, diarrhea-associated hospitalizationsamong children �5 years in the 5 regions averaged 4057 annually.After the vaccine introduction, a decrease in diarrhea-associated hos-pitalizations of 22% (898 fewer) occurred in 2007 and 37% (1502fewer) in 2008. Greater reductions were observed during Januarythrough June, the months presumed to have high rotavirus activity inprevaccine years (33% reduction in 2007 and 58% in 2008, comparedwith prevaccine mean). Reduction estimates were similar among infantsand those aged 1– 4 years of age, even though only 25% of the lattergroup was likely to have received vaccine by early 2008. Estimatedcoverage with �1 dose of rotavirus vaccine among infants increasedfrom 63% at the end of 2006 to 94% at the end of 2008.Conclusions: RV1 appears to have had a substantial impact on diarrhea-associated hospitalizations among young children in Panama.

Key Words: rotavirus, vaccines, diarrhea, hospitalizations, Panama,children

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Rotavirus is the leading cause of severe childhood diarrheaworldwide, resulting in approximately 2 million hospitaliza-

tions and more than 600,000 deaths in children �5 years of age.1,2

In Latin America and the Carribean, Rotavirus is estimated tocause approximately 40% of all diarrhea-associated hospitaliza-tions and deaths in children, and a quarter of ambulatory visits fordiarrhea in children, resulting in approximately 2 million outpa-tient visits, 190,000 hospitalizations, and 5,000 deaths annually.2,3

In March 2006, Panama became one of the first countries tointroduce rotavirus vaccine into its national immunization pro-gram. Little baseline information about diarrhea disease burden inPanama is available, and there have been few studies on the effectof rotavirus vaccine since introduction.4 We examined data onrotavirus vaccine coverage and diarrhea-associated hospitaliza-tions before and after vaccine introduction to assess the effect ofvaccine on diarrhea epidemiology in Panama.

METHODS

Setting and Study DesignPanama is an upper-middle income Latin American country

with an annual birth cohort of approximately 70,000. Healthcare isprovided through the public (Ministry of Health and Social Secu-rity Fund) and private sectors. Panama maintains national surveil-lance for diarrhea as it is one of the leading causes of morbidity inchildren. Hospital admissions and ambulatory visits for diarrheaare aggregated at the regional level and submitted monthly to theMinistry of Health, which maintains the national data. Vaccinesfor children aged �5 years are provided to all Panamanian chil-dren at no cost. The monovalent rotavirus vaccine (RV1) wasadded to the national vaccination program in March 2006, withdoses recommended at ages 2 and 4 months, and a maximum ageof 24 weeks for the second dose.

Data Collection and AnalysisWe estimated 1- and 2-dose national RV1 coverage for

2006 –2008 as the total number of first and second dosesactually administered to children, on the basis of the data fromthe Panama Expanded Program for Immunizations, divided bythe number of live births for that calendar year. We assumedthat all doses were given to infants in accordance with the agerecommendations. In a similar manner, we estimated 1- and2-dose pentavalent vaccine (DTP-HepB-Hib) coverage, whichhas a recommended administration scheduled at the same agesas rotavirus vaccine (at ages 2 and 4 months) for doses 1 and 2and which had stable uptake during the study period.

To evaluate the effect of rotavirus vaccine on diarrhea-associated hospitalizations, our goal was to obtain the monthlynumber of diarrhea-associated hospitalizations for childrenaged �5 years on the basis of available age groups (�1 yearand 1– 4 years) during 2003–2008 from each of the 14 healthregions. We defined a diarrhea-associated hospitalization as anyhospitalization with an ICD-10 code for diarrhea (bacterialA00.0-A05.9, parasitic A06.0-A07.9, viral A08.0-A08.5, and

Accepted for publication September 28, 2010.From the *Ministry of Health, Panama City, Panama; †National Center for

Immunization and Respiratory Diseases, Centers for Disease Control andPrevention, Atlanta, GA; ‡Epidemic Intelligence Service, Office of Work-force and Career Development, Centers for Disease Control and Prevention,Atlanta, GA; §Pan American Health Organization, Washington, DC; and¶El Hospital del Nino, Panama City, Panama.

The findings and conclusions in this report are those of the authors and do notnecessarily represent the views of the Centers for Disease Control andPrevention (CDC).

Address for correspondence: Margaret M. Cortese, MD, National Center forImmunization and Respiratory Diseases, Centers for Disease Control andPrevention, 1600 Clifton Road, NE, MS A47, Atlanta, GA 30333. E-mail:mcortese@cdc.gov.

Copyright © 2010 by Lippincott Williams & WilkinsISSN: 0891-3668/11/3001-0016DOI: 10.1097/INF.0b013e3181fefc68

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presumed infectious diarrhea A09) or one collected as part ofthe required national diarrhea surveillance at a regional level.There was no overlap between definitions as reporting hospitalsor regions used either the ICD-10 code or national surveillancedata, but not both. Data from regions that contributed informa-tion for each year during 2003–2008 and that averaged at least50 diarrhea-associated hospitalizations annually during prevac-cine years were used in the study. Six hospitals representing 5(Bocas del Toro, Chiriquí, Los Santos, Metropolitan region, andSan Miguelito) of the 14 health regions in Panama met thesecriteria. These regions when combined include approximately53% of the annual national birth cohort, with Metropolitanregion representing 17%; San Miguelito, 16%; Chiriqui, 12%;Bocas del Toro, 6%; and Los Santos, 2%. Of the total diarrhea-associated hospitalizations at the 6 hospitals, 60% occurred inthe Metropolitan region. Two pediatric referral hospitals, elHospital del Nino and el Hospital de Especialdades Pediatricas,are located in the metropolitan region. The larger of the two, theHospital del Nino, contributed 65% of the data for the regionand 45% of the overall data.

We used the data from these regions to examine trends ofdiarrhea-associated hospitalizations on the basis of month, year,and age group. We also obtained total number of hospitalizations

by month and year for children aged �5 years and subtracted thenumber of diarrheal hospitalizations from the total to obtain thenumber of nondiarrheal hospitalizations.

We compared monthly trends in the number of diarrhea-associated hospitalizations during the postvaccine years of 2007 and2008 with the prevaccine mean number of diarrhea-associated hospi-talizations from the years 2003–2005. Data from the transitional year2006 were excluded from calculations as vaccine was introducedduring that year. We calculated the percent reduction of diarrhea-associated hospitalizations in 2007 and 2008 from the baseline meanby age group annually (January through December) and during thefirst half of the year (January through June) when the incidence ofrotavirus disease is expected to be high on the basis of seasonality datafrom nearby countries5–8 and the prevaccine data (monthly counts ofdiarrhea-associated hospitalizations exceeding the mean). To furtherexamine trends, we also assessed the ratio of the annual number ofdiarrhea-associated hospitalizations per annual number of nondiar-rheal hospitalizations for each region during the pre- and postvaccineperiods, to help account for any changes in general hospitalizationpractices or catchment areas.

RESULTSEstimated RV1 coverage increased rapidly after vaccine

introduction in 2006. Coverage with 1 dose of RV1 was 66% atthe end of 2006 and increased to 93% by the end of 2007, whichwas similar to the pentavalent (DTP-HepB-Hib) 1-dose cover-age of 94%, and remained stable in 2008 (Table 1). Two-doseRV1 coverage was lower than 1-dose coverage, increasing from32% at the end of 2006 to 72% by the end of 2008, but stilllagging behind the 91% coverage with 2 doses of pentavalentvaccine.

During the study period, 21,771 diarrhea-associated hos-pitalizations and 123,323 nondiarrheal hospitalizations for chil-dren aged �5 years were recorded. Before the introduction ofRV1, diarrhea-associated hospitalizations among Panamanianchildren peaked (ie, exceeded the monthly mean for each year)during the first half of the year (Fig. 1). A similar pattern wasobserved in 2006. Diarrhea-associated hospitalizations during

TABLE 1. Rotavirus and Pentavalent (DTP-HepB-Hib) Vaccine Coverage Among Children �1 Year ofAge—Panama, 2006–2008*

Year

Vaccine Coverage, %

Dose 1 Dose 2

Rotavirus Pentavalent Rotavirus Pentavalent

2006 66 95 32 862007 93 94 65 892008 94 97 72 91

*Vaccine coverage was calculated from administrative data as the number of dosesof vaccine administered during the year divided by the number of live births per year.

FIGURE 1. Monthly number of diarrhea-associated hospitalizations by year among children �5 years of age—Panama,2003–2008. Contributing regions include Metropolitan Region, Chiriqui, Bocas del Toro, San Miguelito, and Los Santos.The number of diarrhea-associated hospitalizations from the Hospital de Especialdades Pediatricas (1 of 2 hospitals contrib-uting data from the Metropolitan region) was not available for the month of January 2003 and was estimated as the meannumber of admissions during the month of January 2004–2006.

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the first half of the year decreased in 2004 and 2005, butsubsequently increased in 2006, consistent with secular varia-tion. In 2007, the peak for diarrhea-associated hospitalizationsoccurred later in the year, between April and August. In 2008,the seasonality of diarrhea hospitalizations was less well-de-fined with peak number occurring in September. During Octo-ber 2006 through March 2007, and during October 2007through June 2008, the numbers of diarrhea-associated hospi-talizations among children aged �5 years were less than thelowest of the prevaccine years (Fig. 2).

Diarrhea-associated hospitalizations among childrenaged �5 years averaged 4057 per year before the introductionof RV1 (Table 2). Compared with this prevaccine average, adecrease in hospitalizations of 22% (898 fewer hospitalizations)occurred in 2007 and 37% (1502 fewer) in 2008. The number ofdiarrhea-associated hospitalizations in 2008 was lower than thatin the lowest prevaccine year for which data were available(2005) in both age groups. Greater reductions were observedduring the first half of each year (33% reduction in 2007 and

58% in 2008, compared with prevaccine mean) and were similaramong infants and those 1– 4 years of age (Table 2). In 2007and 2008, The number of diarrhea-associated hospitalizationsduring January through June was also lower as compared withthe lowest prevaccine year available for both age groups.

When data on number of diarrhea-associated hospitalizationsfor children �5 years of age were examined by region, annualreductions occurred in 3 of 5 regions in 2007 and 4 of 5 in 2008(Table 3). In the 3 regions with the lower number of prevaccinehospitalizations (Bocas del Toro, Los Santos, and San Miguelito), theannual number of diarrhea-associated hospitalizations increased in2007 compared with prevaccine mean, but only the region with thelowest prevaccine number, Los Santos, also had an increase in 2008.In the January through June assessment, 4 of the 5 regions had areduction in 2007 and all 5 had a reduction in 2008 (range, 19%–74%)(Table 3). Reductions were greatest during January through June,2008, in the 2 regions with the greatest number of prevaccinehospitalizations: Chiriqui experienced a 74% reduction and the Met-ropolitan region had a decline of 59%.

FIGURE 2. Monthly number of diarrhea-associated hospitalizations after RV1 introduction compared with the monthly pre-vaccine mean and range among children �5 years of age—Panama, 2003–2008. Contributing regions include Metropoli-tan Region, Chiriqui, Bocas del Toro, San Miguelito, and Los Santos. The number of diarrhea-associated hospitalizationsfrom the Hospital de Especialdades Pediatricas (1 of 2 hospitals contributing data from the Metropolitan region) was notavailable for the month of January 2003 and was estimated as the mean number of admissions during the month of Janu-ary 2004–2006.

TABLE 2. Number of Diarrhea-associated Hospitalizations and PercentReduction Before and After Rotavirus Vaccine Introduction, by Age Group

Age Group 2003–2005Mean (Range)

2007 2008

n %Reduction n %

Reduction

AnnualAll �5 yr 4057 (3260–5059) 3159 22 2555 37�1 yr 1359 (1090–1633) 1155 15 941 311–4 yr 2698 (2170–3425) 2004 26 1614 40

January–JuneAll �5 yr 2406 (1712–3263) 1604 33 1013 58�1 yr 776 (542–1041) 491 37 352 551–4 yr 1630 (1170–2221) 1113 32 661 59

Contributing regions include Metropolitan Region, Chiriqui, Bocas del Toro, San Miguelito, and Los Santos.The number of diarrhea-associated hospitalizations from the Hospital de Especialdades Pediatricas (1 of 2 hospitals

contributing data from the Metropolitan region) was not available for the month of January 2003 and was estimated as themean number of admissions during the month of January 2004–2006.

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During this time of reduction in diarrhea-associated hos-pitalizations, an increase in total number of annual nondiarrhealhospitalizations occurred. Annual nondiarrheal hospitalizationsaveraged 19,380 (range, 18,631–20,703) during prevaccineyears and increased 2% (n � 20,285) in 2007 and 15% (n �22,715) in 2008. However, some individual regions experienceda decrease in nondiarrheal hospitalizations in 2007 and 2008.When the ratio of the annual number of diarrhea-associatedhospitalizations to nondiarrheal hospitalizations in 2007 wascompared with the prevaccine mean for each region, only SanMiguelito demonstrated a notable increase (having had anincrease in diarrhea-associated hospitalizations with a decreasein nondiarrheal hospitalizations); Bocas del Tora demonstrateda 1% increase, whereas Los Santos showed a reduction (32%).In 2008, compared with the prevaccine mean, all regionsdemonstrated a reduction in the ratio of diarrhea-associatedhospitalizations to nondiarrheal hospitalizations, including SanMiguelito (25%), Bocas del Tora (28%), and Los Santos (36%).Chiriqui and the Metropolitan region demonstrated a reductionin this ratio in 2007 and 2008 that was within 3 percentagepoints of the reduction estimate using absolute counts of diar-rhea hospitalizations (data not shown).

DISCUSSIONRV1 appears to have had a substantial impact on diar-

rhea-associated hospitalizations among young Panamanian chil-dren. Although rotavirus-specific data with laboratory confir-mation were not available, the data examined support that theburden of severe rotavirus disease has declined in Panama afterthe introduction of rotavirus vaccine. Reductions were greaterin the second year (2008), with an additional cohort of vacci-nated children. Furthermore, reductions were greater in theJanuary to June period, the period encompassing months withhigh rotavirus activity in nearby countries5– 8 and the periodwhen diarrhea hospitalizations were most common in the pre-vaccine years. These reductions in diarrhea-associated hospi-talizations during the postvaccine period coincided with anoverall modest increase in nondiarrheal hospitalizations. Wehave no reason to believe that the latter finding was a result ofrotavirus vaccine introduction. Therefore, if the reductionsin diarrhea-associated hospitalizations from the regions ana-lyzed are representative of the other regions in Panama, rota-virus vaccine may have prevented an additional 6% of totalhospitalizations from occurring in 2008 among children aged�5 years.

Reductions of diarrhea-associated hospitalizations wereprominent across both age groups, even though approximately75% of children in the older age group (1– 4 years) never hadthe opportunity to receive the vaccine, as they were alreadyabove the first-dose age limit when RV1 was introduced in2006. The reduction in diarrhea hospitalizations of approxi-mately 58% in the January through June 2008 period forchildren 1 through 4 years of age could indicate that theyounger children in the age group (with high rotavirus vaccinecoverage overall per administrative data) contributed most ofthe rotavirus burden prevaccine and directly protecting thesechildren alone resulted in the large reduction in hospitalizations. Itis also possible that older children in the 1 through 4-year agegroup who would not have directly received vaccine may haveexperienced reductions in diarrhea burden as possible indirectbenefits of rotavirus vaccine. This has been observed in othercountries after rotavirus vaccine introduction.9–12 Collecting datafor each 1-year cohort in Panama would be valuable. Particularlyfor the smaller regions, some regional variation was observed inthe level of reduction for diarrhea-associated hospitalizations. Thiscould be related to secular trends of rotavirus disease within thecountry, local differences in the burden of other diarrhea pathogensduring these years, regional differences in hospitalization practicesand healthcare seeking behaviors, or differences in vaccinecoverage.

There are several limitations to this study. First, not allregions of the country contributed data; however, the regionsthat experience the highest numbers of pediatric hospitaliza-tions (Metropolitan region and Chiriqui) were represented.Second, we evaluated all diarrhea-associated hospitalizations,but could not assess rotavirus-specific hospitalizations as rota-virus testing was not performed. Therefore, we could neitherassess whether there was a postvaccine delay in the onset of therotavirus season in addition to disease reduction (as seen in theUnited States)10 –12 nor the etiology of the diarrhea casesobserved in mid 2007. Third, these data are not population-based, as the catchment areas for the hospitals were unknown.To help address this, we examined the change in ratio ofdiarrhea-associated hospitalizations to nondiarrheal hospitaliza-tions for each region, and the reductions observed support theconclusion that the burden of severe diarrhea illness decreased aftervaccine introduction. Finally, due to the ecological nature of the study,we could not be certain that reductions in diarrhea-associated hospi-talizations were solely because of vaccine effect.

TABLE 3. Annual and January through June Number of Diarrhea-associated Hospitalizations and PercentReduction Among Children �5 Years of Age, by Health Region, Panama, 2007 and 2008

Region

Annual January–June

Prevaccine Mean*n % Reduction

Prevaccine Mean*n % Reduction

2007 2008 2007 2008 2007 2008 2007 2008

All regions 4057 3159 2555 22 37 2406 1604 1013 33 58Metropolitan region 2401 1766 1604 26 33 1381 973 561 30 59

Hospital del Niño 1747 1402 1244 20 29 1024 801 444 22 57Esp Pediatricas† 654 364 360 44 45 357 172 117 52 67

Chiriqui 841 393 285 53 66 565 177 147 69 74Bocas del Toro 424 453 342 �7 20 253 210 173 17 32San Miguelito 316 451 227 �43 28 159 215 94 �36 41Los Santos 76 96 97 �26 �27 47 29 38 38 19

*Prevaccine mean calculated as the average of the number of diarrhea-associated hospitalizations during 2003–2005 annually and January through June.†The number of diarrhea-associated hospitalizations from the Hospital de Especialdades Pediatricas (1 of 2 hospitals contributing data from the Metropolitan region) was not

available for the month of January 2003 and was estimated as the mean number of admissions during the month of January 2004–2006.

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In conclusion, diarrhea-associated hospitalizations amongPanamanian children aged �5 years have decreased substantiallyin 2 consecutive seasons after the introduction of rotavirus vaccinein 2006. Further studies on vaccine effectiveness and healthcareutilization for rotavirus-specific diarrhea will be useful to fullyassess the impact of rotavirus vaccine in Panama.

ACKNOWLEDGMENTSWe thank Drs. Gregory Armstrong and Susan Goldstein for

their careful review of the manuscript and the regional epidemi-ology staff in Panama for providing the data.

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