Impact of Rotavirus Vaccination on Diarrheal Hospitalizations in Children Aged <5 Years in Lusaka, Zambia
Impact of Rotavirus Vaccination on Diarrheal Hospitalizations in Children Aged <5 Years in Lusaka, Zambia
Correspondence: E. M. Mpabalwani 1 4
University Teaching Hospital 1 4
Department of Paediatrics 1 4
Child Health 1 4
PO Box 1 4
Lusaka 1 4
Zambia (). Clinical Infectious Diseases® 1 4
0 World Health Organization , Regional Office for Africa, Brazzaville , Republic of Congo
1 The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions , e-mail
2 Virology Laboratory, University Teaching Hospital , Lusaka , Zambia
3 Department of Paediatrics and Child Health
4 Evans M. Mpabalwani
5 Centers for Disease Control and Prevention , Atlanta , Georgia
6 World Health Organization Country Office , Lusaka , Zambia
Background. Monovalent rotavirus vaccine was introduced in the routine public health immunization program in Lusaka, Zambia, in January 2012 and was rolled out countrywide in November 2013. We examined the effect of rotavirus vaccination on hospitalization for all-cause acute gastroenteritis (AGE) and rotavirus-specific AGE at a large referral hospital in Lusaka. Methods. Data were derived from ongoing hospital-based AGE surveillance from January 2009 to December 2014. Pre-rotavirus vaccine introduction (2009-2011) and post-rotavirus vaccine introduction (2013-2014) periods were compared for annual changes in hospitalizations for AGE and rotavirus; 2012 was excluded as a transition year. Hospital administrative discharge data were used to compare trends in all-cause diarrhea discharges and in-hospital diarrhea deaths captured by HIMS pre- and post-rotavirus vaccine introduction. Results. Between January 2009 and December 2014, 5937 children <5 years of age presenting with AGE had their stools collected and tested for rotavirus by enzyme immunoassay. The rotavirus positivity rate declined from 40.1% (449/1121) in prevaccine years to 30.2% (250/828; P < .001) in 2013 and 24.7% (157/635; P < .001) in 2014. The greatest reduction was noted in infants, with the rotavirus positivity rate in this age group declining from 40.9% in prevaccine years to 34.0% (P = .009) in 2013 and 26.2% (P < .001) in 2014. Following rotavirus vaccine introduction, seasonal peaks of rotavirus and all-cause AGE were dwarfed. From HIMS data, compared to the prevaccine era, reductions of 18%-29% in all-cause diarrhea hospitalizations and 27%-33% in-hospital diarrhea deaths among children <1 year of age were observed in 2013 and 2014. Conclusions. We observed a significant reduction in AGE-associated in-hospital morbidity and mortality following rotavirus vaccine introduction. The greatest reduction was seen in infants <1 year who accounted for 84.4% of rotavirus hospitalizations prior to vaccine
Rotavirus is the most common cause of severe acute
gastroenteritis (AGE) in young children. With the introduction of
rotavirus vaccine in routine public health immunization programs
], declines in the burden of severe childhood AGE have been
documented in early vaccine-introducing countries, such as the
United States [
], Australia , and several countries in South
] and Europe [
]. Rotavirus vaccines are
expected to have the highest impact on AGE morbidity and
mortality in Africa, where the burden of disease is the greatest ,
but data from African countries on vaccine impact are sparse
given the more recent introduction of vaccines in the region.
Given the lower efficacy of rotavirus vaccines in developing
countries compared with developed countries in clinical trials
], assessing impact of routine rotavirus vaccination in
developing settings is important.
The Zambian government through the Ministry of
Community Development, Mother and Child Health with the assistance
of Gavi, the Vaccine Alliance rolled out an oral monovalent
rotavirus vaccine (Rotarix; GlaxoSmithKline Biologicals)
countrywide in November 2013 [
]. The vaccine was initially
introduced in Lusaka province as a pilot demonstration project
in January 2012 [
] (E. M. Mpabalwani, C. J. Simwaka, M.
Monze, B. Matapo, J. M. Mwenda, unpublished data). The
monovalent rotavirus vaccine is given at 6 and 10 weeks of
age (without a catch-up dose) together with oral polio vaccine
types 1 and 2, respectively. The first dose of monovalent
rotavirus vaccine is administered early in life (6 weeks) due to early
exposure of rotavirus infection [
] (E. M. Mpabalwani, C. J.
Simwaka, M. Monze, B. Matapo, J. M. Mwenda, unpublished
Rotavirus surveillance among children admitted with AGE
has been in existence at the University Teaching Hospital (UTH)
in Lusaka since 2009. In this study, we report the early impact of
rotavirus vaccine introduction on all-cause diarrhea and
rotavirus AGE hospitalizations and in-hospital deaths for diarrhea at
the UTH in Lusaka, Zambia.
Patients and Methods
UTH is a 2000-bed hospital with >500 bed spaces in the
Department of Paediatrics and Child Health. More than 95% of the
patients attended to in the Department are referred from
community district hospitals in the greater city of Lusaka, which has
an under-5 population of about 402 500 (E. M. Mpabalwani,
C. J. Simwaka, M. Monze, B. Matapo, J. M. Mwenda,
The period from January 2009 to December 2011 was defined
as the pre–vaccine introduction period and the period from
January 2013 to December 2014 was defined as the post–
vaccine introduction period. The year 2012 was excluded as a
transition year with low vaccine uptake.
A suspected case of rotavirus AGE was defined as a child <5
years of age who was hospitalized for treatment of acute watery
diarrhea and/or vomiting of <7 days’ duration [
Children aged <5 years hospitalized for AGE were recruited
to the surveillance for rotavirus by dedicated research nurses
under the guidance of a pediatrician. Demographic and clinical
data were collected using a case investigation form adapted from
World Health Organization generic guidelines for rotavirus
A stool sample was collected within 48 hours of admission
and transported to the virology laboratory within 24 hours.
Stool samples were tested for group A rotavirus using an
enzyme immunoassay (EIA; Dako).
Hospital discharge administrative data for all-cause diarrhea
discharges and in-hospital diarrhea deaths for children <1
year of age were abstracted from the hospital’s HIMS. These
data are routinely captured from case files on discharge/death
on the wards daily and aggregated weekly and monthly by the
HIMS unit. The summarized data are entered into a computer
database using discharge codes of the International
Classification of Diseases, Tenth Revision (ICD-10). The ICD-10 codes
used were A00.9 (cholera, unspecified), A03.9 (shigellosis,
unspecified), A09 (infectious gastroenteritis and colitis, unspecified),
and K52.9 (noninfective gastroenteritis and colitis, unspecified).
Data were analyzed using Epi Info version 184.108.40.206. We analyzed
AGE hospitalizations due to rotavirus before and after the
vaccine was introduced. We also examined total hospital admissions
for diarrhea pre– and post–vaccine introduction and calculated
the percentage of decline in all-cause diarrhea hospitalizations
and in-hospital diarrhea deaths. We used Microsoft Excel to
calculate the median number of tests performed and number of
positive tests pre–vaccine introduction. We examined the percentage
of decline in the total number of samples tested and the number
rotavirus positive before and after the vaccine was introduced. We
also calculated the percentage of decline in proportions that were
rotavirus positive before and after the vaccine was introduced and
compared the proportions positive using χ2 tests.
Active Surveillance Data
From January 2009 through December 2014, 5936 children <5
years of age with AGE were enrolled in active surveillance, and
5853 (98.6%) had their stools tested for rotavirus by EIA. In
the pre–rotavirus vaccine introduction period (2009–2011), a
median of 40.1% (449/1121) of children with AGE tested positive
for rotavirus annually (Table 1). In the post–rotavirus vaccine
<5 y of age
<1 y of age
1 y of age
2–4 y of age
period, the rotavirus positivity rate declined to 30.2% (250/828;
P < .001) in 2013 and to 24.7% (157/635; P < .001) in 2014
(Figure 1). The declines in rotavirus positivity rates were associated
with a corresponding decline in the total number of children
tested and the number of children with a positive result (Table 1).
The greatest reduction in rotavirus positivity between the pre–
and post–rotavirus vaccine introduction was noted in infants <12
months of age (Table 1 and Figure 1). Compared with the
prevaccine median rotavirus positivity rate of 44.6%, the
rotaviruspositive rate declined to 34.0% (P = .009) in 2013 and 26.2%
(P < .001) in 2014 (Table 1). Smaller declines in the total number
of children enrolled and the number rotavirus positive, and the
percentage rotavirus positive were observed in children 1 year of
age. No declines were observed in children 2–4 years of age.
Prior to rotavirus vaccine introduction, 84.4% (1133/1342)
of rotavirus-positive cases occurred in children <1 year of age,
14% (195/1342), occurred in children 1 year of age, and 0.9%
(13/1342) occurred in children 2–4 years of age. Post–rotavirus
vaccine introduction in 2013 and 2014, 75.1% (307/409;
P < .001) of rotavirus-positive cases occurred in children <1 year
of age, 21% (86/409; P = .002) occurred in children 1 year of age,
and 3.9% (16/409; P < .001) occurred in children 2–4 years of age.
Prior to vaccine introduction, rotavirus AGE exhibited a
distinct seasonality, usually with 2 obvious peaks of
rotavirusassociated diarrhea during the months of May–June and
September–October. Following rotavirus vaccine introduction,
seasonal peaks of rotavirus and all-cause AGE were dwarfed,
especially the smaller peak toward the end of the year (Figure 2).
A reduction in all-cause diarrhea hospitalizations and in-hospital
deaths among children <1 year of age was also observed in the
post–rotavirus introduction era (Figure 3). All-cause diarrhea
hospitalizations declined 29% in 2013, from a median of 1143
in 2009–2011 to 817, and 18% to 942 in 2014. Similarly, a
reduction of 27% and 33% among in-hospital deaths for all-cause
diarrhea among children <1 year of age occurred in 2013 (from 114
to 83) and in 2014 (from 114 to 76), respectively, compared to the
pre–vaccine introduction median from 2009 to 2011.
Following the introduction of monovalent rotavirus vaccine in
January 2012, all-cause diarrhea and rotavirus AGE
hospitalizations as well as in-hospital diarrhea deaths declined at a large
referral hospital in Lusaka, Zambia, over 2 consecutive
postvaccine years (2013 and 2014). These overall declines were
associated with a blunting of the characteristic seasonal peaks of
rotavirus AGE in Zambia, further supporting that the declines
are attributable to the effect of vaccination. The monovalent
rotavirus vaccine coverage in infants was 39% in 2013 and 77% in
2014 in Lusaka district (Lusaka Provincial Health Office,
Ministry of Health, Zambia, personal communication). As the
coverage rates of 2 doses of rotavirus vaccine reach the oral polio
vaccine type 2 coverage of 83% (2014), we anticipate even
greater declines in the burden of severe AGE in Zambian children.
The declines in rotavirus AGE were particularly evident in
infants, in whom a marked reduction was observed in the
rotavirus positivity rate from 44.6% to 26.2% in the pre– and
post–rotavirus vaccine eras, respectively, representing a reduction
of 51%. As rotavirus disease burden, including mortality, is
highest in infants in low-resource countries (E. M. Mpabalwani, C. J.
Simwaka, M. Monze, B. Matapo, J. M. Mwenda, unpublished
], this decline is particularly noteworthy. In
1-yearolds, rotavirus positivity rates also declined by 31.4% from
prevaccine vs postvaccine years. Although rotavirus positivity
rates increased post–vaccine introduction in children 2–4 years
of age compared with prevaccine year, this age group only
accounted for 1% of all rotavirus hospitalizations in the prevaccine
era. Thus, this increase in older children is not particularly
concerning, but should be further monitored, particularly as vaccine
coverage increases in older children.
Rotavirus vaccine implementation has been associated with a
reduction in all-cause AGE mortality in several middle-income
countries in the Americas [
]. Our analyses of administrative
data are among the first to demonstrate a potential impact of
vaccination on in-hospital diarrhea mortality in African
children. We observed a reduction of 27% and 33% in 2013 and
2014, respectively, compared to prevaccine years.
An ecological observational study such as ours has a number
of limitations. First, the observed reduction in all-cause diarrhea
did not take into account seasonal trends of other causes of
diarrhea or other interventions that may have impacted diarrhea
6, 9, 15
]. Nonetheless, our data have
demonstrated significant reductions in rotavirus AGE and all-cause
diarrhea hospitalizations, and we attribute these declines to
rotavirus introduction in the routine public health
immunization program. The investigators had no control on the quality
of the hospital administrative data, but the data were robust
enough to support reductions in all-cause diarrhea. However,
the quality of these data needs to be improved. Finally, our
study has not evaluated rotavirus vaccine immunization status
of each individual child.
In conclusion, within 2 years following rotavirus vaccine
introduction in Lusaka, Zambia, we observed a significant decline
in all-cause AGE morbidity and mortality at a large referral
hospital in Lusaka. The greatest reductions were seen in children <1
year of age, who accounted for 84.4% of rotavirus
hospitalizations in this age group prior to vaccine introduction. Our
data support the financial investment in rotavirus vaccine by
the government of the Republic of Zambia and should
encourage other low-income countries to consider adopting rotavirus
vaccination for prevention of severe childhood AGE.
Acknowledgments. The authors acknowledge Gavi, the Vaccine Alliance
for financial support to the World Health Organization to support new vaccine
surveillance, and support from the Ministry of Community Development,
Mother and Child Health through the National Expanded Programme on
Immunization. We also thank the Ministry of Health through the UTH
management for the support and for creating a hospital environment conducive to
carrying out new vaccine surveillance. We also thank the children and their
parents/guardians who have continued to participate in rotavirus disease
surveillance study since 2006. The research nurses on the ward deserve credit for
their dedication in recruiting children with AGE to the study.
Disclaimer. The findings and conclusions of this report are those of the
authors and do not necessarily represent the official position of the Centers
for Disease Control and Prevention (CDC). The views expressed by the
authors do not necessarily reflect the views of PATH, the CDC Foundation, the
Bill and Melinda Gates Foundation, or GAVI, the Vaccine Alliance.
Supplement sponsorship. This article appears as part of the supplement
“Health Benefits of Rotavirus Vaccination in Developing Countries,”
sponsored by PATH and the CDC Foundation through grants from the Bill and
Melinda Gates Foundation and GAVI, the Vaccine Alliance.
Potential conflicts of interest. All authors: No reported conflicts. All
authors have submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest. Conflicts that the editors consider relevant to the content
of the manuscript have been disclosed.
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