Anticipating rotavirus vaccines – a pre-vaccine assessment of incidence and economic burden of rotavirus hospitalizations among children < 5 year of age in Libya, 2012-13
Alkoshi et al. BMC Public Health
Anticipating rotavirus vaccines - a pre-vaccine assessment of incidence and economic burden of rotavirus hospitalizations among children < 5 year of age in Libya, 2012-13
Salem Alkoshi 0 1
Eyal Leshem 2
Umesh D Parashar 2
Maznah Dahlui 1
0 17-4 pangasapuri permai putera , Jalan 13D, Desa Permai, Taman Dato, Ahmed Razali, 68000 Ampang Selangor , Malaysia
1 Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya , Kuala Lumpur , Malaysia
2 National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention , Atlanta, Georgia , USA
Background: Libya introduced rotavirus vaccine in October 2013. We examined pre-vaccine incidence of rotavirus hospitalizations and associated economic burden among children < 5 years in Libya to provide baseline data for future vaccine impact evaluations. Methods: Prospective, hospital-based active surveillance for rotavirus was conducted at three public hospitals in two cities during August 2012 - April 2013. Clinical, demographic and estimated cost data were collected from children <5 hospitalized for diarrhea; stool specimens were tested for rotavirus with a commercial enzyme immunoassay. Annual rotavirus hospitalization incidence rate estimates included a conservative estimate based on the number of cases recorded during the nine months and an extrapolation to estimate 12 months incidence rate. National rotavirus disease and economic burden were estimated by extrapolating incidence and cost data to the national population of children aged <5 years. Results: A total of 410 children <5 years of age with diarrhea were enrolled, of whom 239 (58%) tested positive rotavirus, yielding an incidence range of 418-557 rotavirus hospitalizations per 100,000 children <5 years of age. Most (86%) rotavirus cases were below two years of age with a distinct seasonal peak in winter (December-March) months. The total cost of treatment for each rotavirus patient was estimated at US$ 679 (range: 200-5,423). By extrapolation, we estimated 2,948 rotavirus hospitalizations occur each year in Libyan children <5 years of age, incurring total costs of US$ 2,001,662 (range: 1,931,726-2,094,005). Conclusions: Rotavirus incurs substantial morbidity and economic burden in Libya, highlighting the potential value of vaccination of Libyan children against rotavirus.
Diarrhea; Rotavirus; Hospitalization; Incidence rate; Treatment cost; Libya
Rotavirus is a major cause of severe diarrhea and
hospitalization among children aged < 5 years worldwide. In
2008, globally rotavirus caused an estimated 453,000
deaths among children in this age group ; more than
half of these deaths occurred in sub-Saharan Africa. In
Libya, health service facilities in Libya are publicly
owned and managed by the Ministry of Health. Public
hospitals provide preventive and curative treatment to
all citizens free of charge. While the Libyan government
encourages the expansion of private health, private
facilities have insufficient infrastructure to provide a full
treatment service to severe diarrhea patients such as
admission for intravenous fluid (IVF). Rotavirus disease
accounted for 24 – 45% of diarrheal hospitalizations among
children <5 during the period 1980-2009 [2,3]. The
economic burden of rotavirus infections includes hospital
costs, as well as indirect costs incurred by the society [4,5].
The World Health Organization (WHO) Strategic
Advisory Committee on Immunization (SAGE) recommended
adding rotavirus vaccine to all national immunization
programmes, especially where the mortality rate of diarrhea
affected up approximately 10% among children aged below 5
years [6-9]. Two live attenuated vaccines have been
approved for global use: RotaTeq (RV5, Merck, Whitehouse
Station, NJ, USA) is a pentavalent (G1, G2, G3, G4, P)
human-bovine reassortant vaccine and Rotarix (RV1,
GlaxoSmithKline Biologicals, Rixensart, Belgium) is a
monovalent (G1P) vaccine derived from an attenuated
human strain [10,11]. RotaTeq is administered at 2nd, 4th
and 6th months of age, while Rotarix is administered at
2nd and 4th months of age. In 2009, the World Health
Organization recommended the inclusion of rotavirus
vaccine in the national immunization programs of all countries
globally and particularly in those countries with high child
mortality due to diarrhea . In Libya, a live attenuated
pentavalent vaccine based on a human rotavirus strain
(RV5; RotaTeq™, Merck & Co. Inc., West Point, PA, USA)
was introduced during October 1, 2013.
In February 2011, ongoing rotavirus surveillance
activities in Libya were interrupted due to civil unrest. Our
objective was to re-establish rotavirus surveillance to
provide up-to-date estimates of the baseline pre-vaccine
incidence of rotavirus hospitalizations among children
aged < 5 years, and economic burden, in order to allow
vaccine impact evaluations in the future.
Study design and setting
We conducted prospective, active, hospital-based
surveillance for rotavirus-associated diarrheal hospitalizations
among children < 5 years of age at three hospitals in two
cities in Northwest Libya during the 9-month period
from August 2012 to April 2013. These 3 hospitals are
the only hospitals for treatment of severe diarrhea
patients in the two cities, Khoms (estimated population
235,894) and Zliten (estimated population 239,860), which
include a combined catchment population of 57,180
children aged < 5 years .
Surveillance and data collection
Children <5 years of age with diarrhea symptoms (three
or more instances of liquid stool in a day) who sought
therapy in the pediatric ward at the study hospitals were
identified and parental/guardian consent was obtained.
Trained nurses collected stool samples from the suspected
patients, whereas the staff researcher collected the
demographic, clinical and economic data from patient’s files.
The stool samples were transferred to the national
laboratory at the National Center for Diseases Control (NCDC)
where an enzyme immunoassay (ProSpect Rotavirus Test,
Oxoid Ltd, UK) was used to detect Group A rotavirus.
Treatment cost of hospitalized rotavirus patients was
calculated from perspectives of hospital (direct cost) and
patient (indirect cost). Hospital cost was conducted only in
Zliten hospital because all studied hospitals are reimbursed
by the same source, Ministry of health and covered closely
similar population. Hospital cost included three
components: bed-day (Per Diem), medication and laboratory
investigation tests. The cost of bed-day in the hospital
includes the cost of staff salaries and the hotel cost,
consisting of furniture, foods, laundry, disposal, cleaning,
operation and maintenance. The cost of bed-day was calculated
by dividing annual expenditure at the pediatric ward (US$
983,015) by the number of patient’s days in the pediatric
ward (accounted at 8,470 patient days in 2012). The cost of
bed-day in the pediatric ward was provided from the
financial management at the Zliten hospital during 2012.
Medication cost was obtained from the central pharmacy, which
was calculated separately for each patient, and the cost of
laboratory tests were provided by the main laboratory in
Several cost elements from the patient perspective
were obtained from parents, including 1) the
transportation cost for trips to the hospital when bringing or
visiting the admitted patient; 2) household cost of
expenditures related to the treatment of hospitalized
rotavirus patients such as hygiene items for baby such as
diapers; and 3) lost income of caregivers during the
We compared demographic and clinical characteristics of
children hospitalized due to rotavirus diarrhea (stool tested
positive for rotavirus) and diarrhea-hospitalizations not
associated with rotavirus (tested negative for rotavirus). The
annual incidence of rotavirus hospitalizations was
calculated by dividing the number of rotavirus diarrhea
hospitalizations by the number of children < 5 years of age
residing in the catchment area of studies hospitals. We
Table 1 Conservative estimated number of rotavirus hospitalizations
Estimated number of rotavirus hospitalizations
(95% confidence interval)
Annual estimated incidence/100,000 of rotavirus
hospitalizations (95% confidence interval)
Zliten and Khoms
Figure 1 Age distribution of positive and negative rotavirus cases association with hospitalization.
provided a conservative estimate calculated using the
number of cases during the 9 months of enrolment as
numerator (not inflating the number of rotavirus
hospitalizations) to calculate annual incidence. Importantly, the
historical months of the peak rotavirus season in Libya
were captured during the 9 months of enrollment. Lastly,
to estimate the annual number of rotavirus hospitalization
countrywide and their associated costs, the conservative
incidence and costs of rotavirus hospitalization from this
study was extrapolated to the national population of
705,190 children <5 years of age in 2012 in Libya.
Data was analyzed by SPSS version 16. Chi-Square and
P values <0.05 were considered statistically significant.
Statistical tests were Chi-Square, X2 and t-test to obtain
the outcomes such as mean, range and standard deviation.
ANOVA or Mann–Whitney’s test were used to make a
comparison between positive and negative-rotavirus cases.
Mean, range and standard deviation were identified in
University of Malaya Medical Ethics Committee (IRP
908.6), NCDC in Libya, and study hospitals provided
ethical clearance to conduct the study.
A total of 410 children hospitalized due to diarrhea were
enrolled, of whom 239 (58%) tested positive for rotavirus.
Based on the catchment population in the studied hospitals
(57,180 children aged < 5 years) in 2012, the unadjusted
(conservative) incidence rate of rotavirus associated with
hospitalization in the studied hospitals during the study
period (9 months) was 418 per 100,000 (95% confidence
interval, 405-431 per 100,000, Table 1). Applying the
Aug 12 Sep 12 Oct 12 Nov 12 Dec 12 Jan 13 Feb 13 Mar 13 Apr 13
Figure 2 Monthly distribution of positive and negative rotavirus cases association with hospitalization.
conservative estimate for incidence rate to whole
population of Libya (705,190 children aged <5 years) was yielded
an estimate of 2,948 (95% confidence interval, 2,845-3,048)
national hospitalized rotavirus patients associated with
hospitalization in 2012. Most (86%) patients with rotavirus
diarrhea patients were under two years of age (Figure 1)
and the disease showed a distinct winter seasonal peak
during the months from December to March (Figure 2).
Compared with rotavirus-negative patients, those who
were rotavirus-positive were significantly more likely
to suffer severe dehydration and vomiting (Table 2).
Median duration of hospitalization of rotavirus patients
was 3 days (range 1-15) as compared with 2 days (range
1-13) among rotavirus negative patients (p = 0.05), and
nearly all patients receive intravenous fluids. No deaths
Table 2 Basic characteristics of positive and negative
rotavirus diarrhea associated with hospitalization below
5 years of age
Duration of Symptoms
2 weeks and Above 6 (3)
Length of Hospital Stay
8 Days and Above Fever Vomiting Dehydration Degree
Severe Dehydration 97 (41)
Treatment with IVF
Treatment with ORT 2 (1)
From the hospital perspective, the total expenditure to
treat each rotavirus patient in the hospital was calculated
to be US$ 488 (Intra quartile range [IQR], 318-541), the
mean cost for each bed-day (Per Diem) was US$ 116
(Table 3), and the mean cost of medication was US$ 108
(IQR, 43-94). The most expensive medications were
intravenous fluids and antibiotics which were given to
99% and 56% of rotavirus patients, respectively.
From the family perspective, the mean cost for each
hospitalized patient was approximately US$ 191 (IQR,
74-220). Family costs combined with hospital costs
yielded an overall cost to treat each rotavirus patient of
US$ 679 (IQR, 476-737).
Overall, hospital costs comprised 72% of the total
expenditure, and family cost made up 28%. Hospital cost
included bed-day (51%), medication (16%) and
laboratory investigations (5%). Considering the family cost,
transportation, household costs, and lost incomes were
12%, 10% and 6% of total cost, respectively (Table 4).
National burden and costs of rotavirus hospitalization in
Applying the conservative incidence rate for one year of
surveillance yielded an estimate of 2,948 rotavirus
hospitalizations annually in Libyan children <5 years of age.
Combining these burden figures with cost data yielded a
national economic burden of US$ 2,001,692 (range:
Our prospective, active, hospital-based surveillance for
rotavirus shows that, prior to rotavirus vaccine
introduction, 58% of diarrheal hospitalizations among
children < 5 years of age in Northwest Libya were caused by
rotavirus. Each rotavirus hospitalization incurred a total
cost of US$ 679, of which 72% were costs of hospital
Table 3 Variables used to calculate the per diem (Bed-Day)
cost for hospitalized patients at Zliten Public Hospital, in
Staff Salaries (US$)
752,266 (77%) Zliten Hospital Management
Hotel Cost (US$)
230,750 (23%) Zliten Hospital Management
Total Per Diem Cost (US$) 983,015
Costs per Day for each
Hotel Cost includes: Furniture, Equipment, Foods, Laundry, Disposal, Cleaning,
Operation and Maintenance Costs.
Zliten Hospital Management
Zliten Hospital Management
Table 4 Treatment cost for hospitalized children
associated with rotavirus diarrhea per each patient
Mean cost (US$) %
SD (US$) Range (US$)
Laboratory Tests 31.16
expenditures. By extrapolation, we estimated that nearly
3000 hospitalizations for rotavirus diarrhea occur each
year in Libyan children 5 years of age or 1 in 50 children
born each year is hospitalized for rotavirus by age 5,
incurring total costs of US$ 2,001,662. This tremendous
morbidity and economic burden highlights the potential
value of vaccination of Libyan children against rotavirus.
Reports from Libya during the period 1980-2009 showed
a rotavirus detection rate of 24% to 45% among children <5
years of age hospitalized with diarrhea [2,3,14-19], which
were slightly lower compared with our data. This difference
may have resulted from not including 3 months in our
study during which rotavirus rates are usually lower,
thereby increasing the proportion of rotavirus cases among
the studied population; however, the detection rate of
rotavirus in our study is also similar to other regional countries
such as Oman (70%) and Iran (58%) . Characteristics of
rotavirus infection such as vulnerable ages to the disease,
season of increased infection, difference in gender (male
and female) and places of residence (urban and rural areas)
were also comparable to previous reports of rotavirus
disease in Libya [3,14,17-19].
Previous studies have not assessed the economic
burden of rotavirus hospitalizations in Libya. Hospital costs
in this study represented 72% of total costs of disease,
which was higher than that reported in the U.S (66%)
, but lower than in Brazil (86%) . Lost income of
caretaker in Hong Kong represented 10% of monthly
income , while it was about 7% in Libya. These data
illustrate the substantial economic burden of rotavirus on
both the health care system and families.
Our study has some limitations. Notably, we had planned
to continue surveillance for collection of data for at least
one full calendar year; however, due to the political and
security situation after the Libyan revolution, the study was
interrupted in April 2013. Since the 3 months of data that
we were not able to capture were late spring/summer
months with lower rotavirus prevalence in previous years
. Also, since we conducted surveillance in only 2 cities
in Libya, our findings may not be representative of the
entire population. Nevertheless, these are among two of the
large cities in Libya and their population structure and
composition is similar to the rest of the country.
We documented pre-vaccine incidence of rotavirus
hospitalization in Libyan children and their associated costs
to provide baseline data for future vaccine impact
evaluations. Further studies of rotavirus disease burden among
hospitalized children, in the form of active hospital based
surveillance in Libya, will be crucial to understand the
effect of introducing the vaccine into national childhood
immunization, to provide scientific evidence for continued
immunization efforts and identification of barriers for
vaccine impact and effectiveness [24,25].
The authors declare that they have no competing interests.
SA and MD conceived the study and participated in its design. SA collected
the data. SA, MD, EL and UP analyzed and helped to draft the manuscript.
All authors interpreted the findings, and contributed to critical revision of the
manuscript. All authors read and approved the final manuscript.
Authors appreciate the great help for the national laboratory at the NCDC,
staffs at the hospitals. We are grateful to the parents who participated in the
study. The study was supported by the University of Malaya/Ministry of
Higher Education (UM/MOHE) High Impact Research Grant (E000010-20001),
Malaysia, and also supported by the AADUN RP026-2012C grant.
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