Costs of congenital rubella syndrome (CRS) in Oman: Evidence based on long-term follow-up of 43 children

Abstract

As part of the national plan for elimination of rubella and congenital rubella syndrome (CRS), Oman established a national registry of CRS cases. As of May 2005, the registry included 43 surviving CRS cases, with a mean age of 11.9 years. Clinical examinations found that 84% had ocular defects, 84% had auditory/speech defects, 70% had neurological manifestations, and 42% had cardiac defects. Lifetime medical, special education, and rehabilitation costs were assessed. Using a discount rate of 3%, the average direct lifetime cost per surviving CRS patient was estimated at 18,644 US dollars. When including predicted lost productivity due to CRS, the average discounted direct and indirect lifetime costs per surviving CRS patient amounted to 98,734 US dollars.

Full text

Vaccine 24 (2006) 6437–6445
Costs of congenital rubella syndrome (CRS) in Oman: Evidence
based on long-term follow-up of 43 children
Salah Al-Awaidy a,∗, Ulla K. Griffiths b, Hosammudin Mohammed Nwara,
Shyam Bawikar a, Masoud Salim Al-Aisiric, Rajiv Khandekard,
Ali Jaffer Mohammade, Susan E. Robertson f
aDepartment of Communicable Disease Surveillance and Control, Directorate General of Health Affairs,
Ministry of Health, Muscat, Sultanate of Oman
bHealth Policy Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
cDepartment of Financial Planning, Directorate General of Health Affairs, Ministry of Health, Muscat, Sultanate of Oman
dEye and Ear Health Care, Department of Noncommunicable Diseases, Directorate General of Health Affairs,
Ministry of Health, Muscat, Sultanate of Oman
eMinistry of Health, Muscat, Sultanate of Oman
fDepartment of Immunization, Vaccines and Biologicals, World Health Organization, Geneva 27, CH-1211 Switzerland
Received 14 December 2005; received in revised form 22 May 2006; accepted 23 May 2006
Available online 13 June 2006
Abstract
As part of the national plan for elimination of rubella and congenital rubella syndrome (CRS), Oman established a national registry of
CRS cases. As of May 2005, the registry included 43 surviving CRS cases, with a mean age of 11.9 years. Clinical examinations found
that 84% had ocular defects, 84% had auditory/speech defects, 70% had neurological manifestations, and 42% had cardiac defects. Lifetime
medical, special education, and rehabilitation costs were assessed. Using a discount rate of 3%, the average direct lifetime cost per surviving
CRS patient was estimated at US$ 18,644. When including predicted lost productivity due to CRS, the average discounted direct and indirect
lifetime costs per surviving CRS patient amounted to US$ 98,734.
© 2006 Elsevier Ltd. All rights reserved.
Keywords: Congenital rubella syndrome; Cost study; Disability
1. Introduction
WHO estimates indicate that there are still more than
100,000 new cases of congenital rubella syndrome (CRS)
occurring each year [1]. Children with CRS suffer from
multiple birth defects, including deafness, blindness, con-
genital heart disease, and mental retardation. While some
CRS defects are readily identified in infants, others are hard
to diagnose until older ages (i.e. deafness) and some of the
problems associated with CRS are known to have late onset
(i.e. diabetes, thyroid disorders). A global review of stud-
∗Corresponding author. Tel.: +96 82 460 1921; fax: +96 82 460 1832.
E-mail addresses: awadymoh@omantel.net.om (S. Al-Awaidy),
robertsons@who.int (S.E. Robertson).
ies assessing the costs of CRS was published in 2002 [2].
Altogether 22 studies were identified, including 10 from
developing countries. The review concluded that more CRS
costing studies from developing countries should be encour-
aged, and that such studies should use standardized economic
methods. The need for standardised methods was emphasized
in an accompanying editorial [3].
Oman experienced large rubella epidemics in 1987–1989
[4] and 1992–1994 [5]. Since then there has been a dramatic
decline in the incidence of rubella following widespread
use of rubella vaccine. In March 1994, there was a national
campaign to deliver measles–rubella (MR) vaccine to the
target group aged 15 months–18 years. Some 700,000 per-
sons received MR vaccine during the campaign, with 94%
coverage of the target age group. At the same time as the cam-
0264-410X/$ – see front matter © 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.vaccine.2006.05.089

6438 S. Al-Awaidy et al. / Vaccine 24 (2006) 6437–6445
paign, a dose of MR vaccine was introduced into the routine
immunization schedule for children at age 15 months. This
decision was based on the results of a clinical trial conducted
in 1992–1993, which showed excellent seroconversion of
Omani children to rubella vaccine at age 15 months [6].In
1997, MR vaccine was changed to measles–mumps–rubella
(MMR) vaccine. Coverage with the 15 month vaccine dose
has been 97% or higher since 1994. In addition, postpartum
rubella vaccination has been a national policy since 2001
and a nationwide coverage survey in 2004 demonstrated that
99.5% of postpartum women had received rubella vaccine
[7].
Oman has a target for elimination of rubella and CRS in
2005 [7,8]. In April 1996, Oman initiated a fever and rash ill-
ness surveillance system. Since 1997, blood specimens have
been collected from >95% of suspected patients with rash
and fever. The specimens are first tested for measles IgM
antibody and, if negative, for rubella IgM antibody by the
national measles/rubella laboratory. There have been fewer
than 10 confirmed rubella cases each year since 1997. As part
of the national plan for rubella and CRS elimination, a reg-
istry of CRS cases was established in 2000, which includes
all children with CRS reported to the Ministry of Health since
1988 [8]. This paper reports on data collected in the national
CRS registry as of May 2005, findings of follow-up clinical
assessments of the CRS cases, and estimates of the direct and
indirect costs of CRS in Oman.
2. Methods
2.1. Registration of CRS cases and follow-up
examinations
In Oman, the Ministry of Health set up a registry for
CRS cases in 2000. CRS cases that have been reported to
the national surveillance system since 1988 are included in
the registry. At the start of 2000, a total of 79 CRS cases
had been reported, but more cases were identified following
a National Workshop on Rubella and CRS held for medi-
cal officers from all regions of the country in October 2000
[8]. Since 2001, surviving children with CRS have been
scheduled for biannual detailed clinical assessments using
standardized forms. The assessments include a general phys-
ical examination, as well as examinations by ophthalmology,
audiology, otorhinolaryngology, pediatrics, cardiology, neu-
rology, and endocrinology specialists. We analysed the results
of the follow-up examinations and used these to estimate life-
time treatment and rehabilitation costs. The cost analysis was
undertaken from a societal viewpoint.
2.2. Medical resources used during treatment of CRS
cases
Inpatient hospital resources used to treat CRS cases
were identified from patient medical records. Major resource
items, such as the number of days in hospital, type of surgery,
and type of laboratory tests, were recorded. Resource use
from neonatal hospital stay, outpatient visits and special edu-
cation were estimated by interviewing medical and educa-
tional staff caring for children with CRS.
2.2.1. Newborn evaluation
For each child with CRS the local birth registry was con-
sulted for information on birth weight and neonatal risk
factors. Hospital neonatologists and paediatricians estimated
that each newborn with low birth weight (<2500g) or other
serious risks would have spent an average of 14 days in the
neonatal intensive care unit, with one follow-up visit to a
neonatologist.
2.2.2. Eye disease
An ophthalmologist examined each child with CRS.
Where feasible, a complete eye examination, including
dilated retinal assessment, was carried out. Available inpa-
tient medical records for CRS patients who had eye surgery
were reviewed. An ophthalmologist estimated that all patients
with eye surgery or serious eye disease would require follow-
up consultation with an ophthalmologist once a year for the
first 15 years after the surgery and every 3 years thereafter.
Children with visual impairment (as assessed at the most
recent examination) were assumed to require a new low vision
device (spectacles, magnifying lens, etc.) once a year for the
first 15 years of life and every 3 years thereafter.
2.2.3. Hearing loss/speech defects
An otorhinolaryngologist and an audiologist examined
each child with CRS. Where the child was cooperative, pure
tone audiometric testing was carried out. Hearing impair-
ments were classified as sensorineural, conductive, or mixed.
The average age at detection of hearing impairment was
assumed to be 2 years. Children with hearing aids were
assumed to require check ups at the ear clinic once every
6 months for the first 15 years and every 5 years there-
after; they were assumed to receive eight hearing aids during
their lifetime. Speech was also assessed, noting impairments
and delays. Optimal treatment of speech impairment involves
speech therapy for approximately 45 min once a week; how-
ever, as there are only two speech therapists working in the
whole of Oman, it was assumed that children would receive
speech therapy once a month for a period of 3 years.
2.2.4. Congenital heart disease
Each child with CRS was assessed by a paediatrician or
cardiologist for cardiac history and current cardiac status.
Available inpatient medical records for CRS patients who
have had cardiac surgery were reviewed. It was assumed that
patients who had surgical correction of patent ductus arterio-
sus alone would require one follow-up consultation with a
cardiologist, whereas patients with other types of congenital
heart disease would require annual follow-up consultations
with a cardiologist.

S. Al-Awaidy et al. / Vaccine 24 (2006) 6437–6445 6439
2.2.5. Neurological disease
Each child with CRS was assessed by a paediatrician or
a neurologist for microcephaly, cerebral palsy, seizure disor-
der, mental impairment, and any other neurological disease.
The assessment included information on whether the child
required special schooling. For cerebral palsy, it was assumed
that either the patient would attend a special rehabilitation
centre for cerebral palsy or the patient would require 40 visits
for rehabilitation therapy, 4 visits to an orthopaedics special-
ist, and annual follow-up visits to a neurologist. For seizure
disorder, diagnostic procedures include an electroencephalo-
gram and a magnetic resonance imaging scan. Drug therapy
is required lifelong and there are annual follow-up visits to
the neurologist.
2.2.6. Other manifestations
Each child with CRS was assessed by a paediatrician for
diabetes, other endocrine disorders, and any other medical or
surgical disorders.
2.3. Unit costs of health resource items and discounting
of future costs
The unit costs of the resource items identified from the
patient records were retrieved from a detailed cost-accounting
system maintained at the Ministry of Health. For health cen-
tres, the average costs per visit are reported. For regional and
national hospitals the costs per bed-day are specified accord-
ing to cost centre, e.g. general surgery, neurology, paediatrics,
etc. Moreover, the cost-accounting system provides the unit
cost of various surgical procedures. The unit cost measures
account for all expenses, including staff time, drugs, food,
administration, etc. The annual cost of attendance at a special
school was obtained from the Ministry of Education [9] and
the annual cost of attendance at a community-based reha-
bilitation centre was obtained from the Ministry of Social
Development. All unit cost data were in Omani rials and
reported for the year 2001. We converted the cost data to US$
by using the average 2001 exchange rate of 0.385 rials per
US$ [10]. The unit costs most frequently used in the analysis
are summarised in Table 1.
We chose the year 2001 as the base year, as this was the la-
test year with final cost data from the cost-accounting system.
However, very few of the costs were actually incurred in 2001.
Most of the children received surgery during the first 5 years
of life and the follow-up visits take place for their remaining
lifetime. Hence, the resource use is a mixture of past and
future costs. We estimated all costs in 2001 values without
attempting to predict changes in real unit costs over time. All
future costs were discounted by 3% per year. A picture of the
future stream of costs after year 2001 was established from the
patient records review, the follow-up examinations and from
interviews with specialists. We assumed a life expectancy
of 50 years for the CRS patients with cerebral palsy. For the
remaining patients, we assumed a life expectancy of 74 years;
similar to the rest of the Omani population in year 2002 [11].
Table 1
Unit cost estimates most frequently used in the analysis, in US$ 2001 values
Type Cost item Unit cost (US$)
Surgery Cardiac surgery 1111
Eye surgery 498
Hospital cost per bed day Neonatal intensive care
department
208
Pediatric surgery
department
167
Eye surgery department 103
Diagnostic procedure Magnetic resonance
imaging scan
312
Electroencephalogram 44
Rubella IgM ELISA test 11
Outpatient visit Neonatology clinic 154
Paediatric surgery clinic 151
Ophthalmology clinic 112
Physical therapy clinic 105
Paediatrics clinic 60
Orthopedics clinic 37
Audiology clinic 21
Speech therapy clinic 21
Drugs Thyroxine (per day) 0.021
Tegretol (per day) 2.09
Equipment Low vision aid (including
glasses)
52
Hearing aid, both ears 532
The results are presented with and without discounting of
future costs, and we undertook a sensitivity analysis using a
10% discount rate per annum.
2.4. Indirect costs of CRS
Indirect costs of CRS include the time lost from productive
activities of the patient as well as time lost by parents to care
for their child. In light of the severity of the cases, indirect
costs are undoubtedly high for the families of children with
CRS. There are three recognised methods for quantifying the
value of productivity costs: “the human capital approach”,
“the friction cost approach” and the “US Panel approach”
[12]. The human capital approach focuses on the impact of
health care on lost work time, whether through illness or
death, and is the most commonly used method. Normally,
work time is valued according to the gross wage rate. In the
friction cost approach, the existence of involuntary unem-
ployment limits production losses due to death and illness
to the period required to replace the deceased worker from
the ranks of the unemployed. This approach arose as a cri-
tique to the human capital approach, as it is argued that this
approach provides an estimate of potential lost production as
a result of disease, rather than the loss that would be expe-
rienced in practice. In the US Panel approach health state
values, such as the Quality Adjusted Life Year, are used to
implicitly incorporate the impact of illness on the ability to
work and financial loss [13]. As there are recognized short-
comings to all the methods used for attaching an economic

6440 S. Al-Awaidy et al. / Vaccine 24 (2006) 6437–6445
value to a life, we present the total cost estimates with and
without inclusion of productivity costs. We used the human
capital method for estimating lost productivity and we only
included the loss to the CRS case and not to the parents of the
child. The average market wage in Oman in 2001 was used
to approximate the value of an individual’s productive output
during their working years. This was estimated as US$ 6464
per capita per year [14]. We assumed that a person works
from age 20 to 60 years.
3. Results
3.1. Patient registration and follow-up
Altogether there were 94 CRS cases reported to the
national surveillance system in Oman since 1988, and all
these cases were enrolled in the National CRS Registry
(Fig. 1). Twenty-seven CRS patients (29%) had laboratory
confirmed CRS based on a positive rubella-specific IgM test,
and the remaining cases were confirmed clinically. Of the 94
CRS cases 37% were female and 63% were male. The report-
ing sources were tertiary care hospitals for 61 cases (Royal
Hospital: 31 patients, Sultan Qaboos University Hospital: 17
patients, Al Nadha Hospital: 13 patients) and regional hos-
pitals for 33 cases. CRS patients were reported from every
region of the country except Musandam Region, a sparsely
populated area isolated from the mainland of Oman. The
regional distribution of CRS cases was: Dhofar: 24 cases,
Muscat: 19 cases, N. Sharqiyah: 12 cases, N. Batinah: 11
cases, Dakhliyah: 9 cases, S. Batinah: 7 cases, Dhahirah: 6
cases, S. Sharqiya: 4 cases, and Al Wostah: 2 cases.
As of May 2005, contact had been re-established with
families of 70 children with CRS, but 24 cases were lost
to follow-up. Of the 70 cases where the family contact was
reestablished 43 children were available for follow-up exam-
inations and 27 had died. For the children who died, 85%
of the deaths occurred in infancy, most within a few months
after birth. Older children were more likely to be lost-to-
follow-up: 58% of CRS cases born during a rubella outbreak
in 1987–1989 could not be traced, compared with 16% of
CRS cases born during a rubella outbreak in 1992–1994.
The 43 surviving CRS cases include 14 females and 29
males. In May 2005, the mean age of this group was 11.9
years (range 3–19 years). Speciality examinations for the
43 children found that 84% had ocular defects, 84% had
auditory and/or speech defects, 69% had neurological man-
ifestations, and 42% had cardiac defects (Table 2). Twenty-
two of the children had undergone surgery; six children had
undergone both cardiac and eye surgery, although these oper-
ations were performed during different hospital admissions.
By institution and type of surgical procedure these included:
Royal Hospital, Muscat: 13 children with cardiac surgery; Al
Nahdha Hospital, Muscat: 7 children with eye surgery; Sul-
tan Qaboos University Hospital, Muscat: 4 children with eye
surgery; regional hospitals: 4 children with eye surgery. For
the 13 patients with cardiac surgery, 9 were operated at <12
months of age. For the 15 patients with eye surgery, 5 were
operated at <12 months of age, 7 at age 1–2 years, and 3 at
age 3–9 years.
3.2. Direct treatment costs
3.2.1. Neonatal treatment
Of the 43 surviving children, birth weight data was avail-
able for 31, of whom 16 had low birth weight (<2500 g).
An additional nine children had other neonatal risk factors
related to CRS, including congenital heart disease and severe
intrauterine growth retardation. The costs of admission to the
neonatal care intensive unit for an average of 14 days with a
Fig. 1. CRS cases in national registry, by year of birth, and annual incidence of CRS per 100,000 live births, Oman, 1985–2004.

S. Al-Awaidy et al. / Vaccine 24 (2006) 6437–6445 6441
Table 2
Clinical manifestations, 43 children with CRS, Oman
Type of clinical manifestation No. of unilateral No. of bilateral Total Total (%)
Ocular manifestations
Any ocular defect 36 83.7
Retinopathy 3 18 21 48.8
Microphthalmos 3 7 10 23.3
Cataract 6 8 14 32.6
Glaucoma 1 4 5 11.6
Eye surgery 15 34.9
Auditory manifestations
Any auditory/speech defect 36 83.7
Sensorineural hearing loss 4 23 27 62.8
Conductive hearing loss 1 1 2 4.7
Mixed hearing loss 0 1 1 2.3
Speech impairment/delay 26 60.4
Cardiac manifestations
Any congenital heart defect 18 41.9
Patent ductus arteriosus 8
Patent ductus arteriosus and ventricular septal defect 4
Patent ductus arteriosus and pulmonary stenosis 1
Pulmonary stenosis and tricuspid regurgitation 1
Venticular septal defect 1
Ventricular septal defect and pulmonary atresia 1
Ventricular septal defect, pulmonary
stenosis, and double outlet right ventricle
1
Details of heart defect not available 1
Cardiac surgery 13 30.2
Neurologic manifestations
Any neurologic manifestation 30 69.7
Microcephaly 26 60.4
Mental retardation 22 53.4
Cerebral palsy 18 41.9
Seizure disorder 1 2.3
Other manifestations
Hypospadias 1 2.3
Syndactyly with surgical correction 1 2.3
Thyroiditis 1 2.3
Educational status
Normal school 9 20.9
Special school for deaf or blind 3 7.0
Community-based rehabitation centre 10 23.3
Cerebral palsy rehabilitation centre 2 4.7
Under 5 years of age 3 7.0
Not in school 16 37.2
follow-up outpatient visit to the neonatologist, amounted to
US$ 3066 per child.
3.2.2. Eye disease
A total of 36 children (84%) had any eye disease. Two
of the conditions – retinopathy (21 children) and microph-
thalmos (10 children) – have no specific treatment. Serious
eye diseases included cataract (14 children) and glaucoma (5
children). Altogether 15 children received eye surgery, and
hospitalization records were available for 8 of them: 6 with
cataract and 2 with glaucoma. For eye surgery, the average
length of stay in hospital was 7 days. The average discounted
cost of eye surgery (including hospital bed days) per patient
was US$ 2462 (range US$ 824–5122). The future discounted
costs of follow-up ophthalmologic care and low vision aids
for children with serious eye disease were US$ 1117 per
patient (Table 3).
3.2.3. Hearing/speech impairment
Six children were uncooperative with hearing testing. Of
the 37 children who could be tested, 27 had sensorineural
hearing impairment, 2 had conductive hearing impairment,
and 1 had mixed hearing impairment. The degree of hearing
loss in the best ear during the most recent examination was
severe–profound for 17 children and moderate for 3 chil-
dren. Discounted lifetime treatment costs for a child with
severe–moderate hearing loss were estimated at US$ 4519.
Altogether 26 children had speech delays or speech defects;

6442 S. Al-Awaidy et al. / Vaccine 24 (2006) 6437–6445
Table 3
Direct costs with and without discounting (3% per year) for 43 children with CRS, Oman
Disease category, type of treatment No. of
children
Per child
non-discounted
direct lifetime cost
Total
non-discounted
direct lifetime cost
Per child
discounted direct
lifetime cost
Total discounted
direct lifetime
cost
Neonatal risk factors
Neonatal intensive care 25 3066 76,650 3066 76,650
Eye disease
Eye surgery 15 2709 40,632 2462 36,923
Eye disease follow-up 19 4130 79,093 1117 21,218
Auditory/speech defects
Treatment of auditory defects 20 5164 103,274 4519 90,385
Speech therapy 20 748 14,955 726 14,524
Congenital heart disease
Cardiac surgery (including hospitalization) 13 4668 60,685 4202 54,631
Patent ductus arteriosus follow-up 8 151 1209 136 1088
Other congenital heart disease follow-up 10 5803 58,026 1363 13,629
Neurological disease/special education
Cerebral palsy, individual treatment programme 16 7348 117,568 2780 44,483
Cerebral palsy, rehabilitation centre 2 36,585 73,170 32,600 65,200
Seizure disorder, controlled with medication 1 61,247 61,247 25,437 25,437
Special school for deaf or blind 3 109,305 327,915 97,399 292,197
Community-based rehabilitation centre 9 41,950 377,550 6729 60,557
Other medical problems
Syndactyly, surgical correction 1 3227 3227 2703 2703
Thyroiditis, controlled with medication 1 5007 5007 2062 2062
Total costs
Total costs for 43 patients 43 –a1,399,578 –a801,688
Average cost per patient 32,548 18,644
aNot applicable.
6 of these children were severely retarded, but the other 20
children were eligible for speech therapy. Discounted life-
time treatment costs for a child with treatable speech defects
were estimated at US$ 726.
3.2.4. Congenital heart disease
Altogether 18 children had congenital heart disease. Of
these, 13 underwent surgery; hospital records were available
for 7 of these children. For cardiac surgery, the average length
of stay in hospital was 16 days. The average discounted costs
per patient for surgery (including hospital bed days) amount
to US$ 4202 (range US$ 2810–11,353). There was a wide
variation in the costs of surgery, as some cases are more
complicated than others. For patients without patent ductus
arteriosus as the sole cardiac anomaly the future discounted
costs of follow-up amounted to US$ 1363 per patient.
3.2.5. Neurological manifestations
Of the 43 children, 26 had microcephaly, for which no
treatment is required. Eighteen children had cerebral palsy,
and two of these children were permanently bedridden. One
child had a seizure disorder, controlled on medication. For a
patient with cerebral palsy, the discounted average lifetime
costs of physical therapy, orthopedics, and neurology visits
were estimated at US$ 2780. For a patient with seizure dis-
order controlled on medication, the discounted lifetime cost
for diagnosis and treatment was estimated at US$ 25,437.
Twenty-two children had mental retardation, which was
severe-profound in seven children. Sixteen children do not
attend school and are cared for at home; 3 children are too
young to attend school (e.g. 5 years or younger); 10 children
attend normal school. Three children attend Ministry of Edu-
cation special schools at an annual cost of US$ 12,145 per
child with 9 years attendance. Two children attend special
rehabilitation centres for cerebral palsy run by the Ministry
of Social Development or NGOs; the annual per child costs
of such centres is US$ 6493 and US$ 1636, respectively. Nine
children attend community-based rehabilitation centres run
by the Ministry of Social Development; average annual per
child cost is US$ 839.
3.2.6. Other manifestations
One child developed thyroiditis, which is controlled on
medication; discounted lifetime treatment costs were esti-
mated at US$ 2062. One child was born with syndactyly of
both hands due to CRS, and the surgical costs of correct-
ing these deformities amounted to US$ 3227. One child has
hypospadias, which does not require treatment.
3.2.7. Total direct costs
The figures generated by using the average costs of treat-
ment summarised above were applied for all patients with the
respective clinical features (Table 3). The total direct lifetime
medical, rehabilitation, and special education costs of the 43

S. Al-Awaidy et al. / Vaccine 24 (2006) 6437–6445 6443
surviving CRS patients amounted to US$ 1,399,578 without
discounting and US$ 801,688 with discounting at a 3% rate.
The average direct lifetime cost per surviving CRS patient
was US$ 18,644 using a 3% discount rate.
3.3. Indirect costs of CRS
The lifetime productivity loss of a patient with 100% dis-
ability amounted to US$ 265,000 without discounting future
values and to US$ 109,330 discounting at 3% per year.
Among the 43 children in the surviving cohort, 24 were
judged to have multiple handicaps so severe that they would
not be able to work at all (100% disability), and 15 were
judged to have 50% disability. Thus, for the entire cohort
of 43 survivors the discounted indirect lifetime costs were
US$ 3,443,883. In addition there were 27 children with CRS
who died, discounted indirect costs due to their lost lifetime
productivity amounted to US$ 2,951,910.
The average, lifetime productivity costs lost per surviving
CRS patient amounted to US$ 80,090 with a discount rate of
3% per year.
3.4. Sensitivity analysis
Using a 10% annual discount rate, the average direct life-
time treatment cost was US$ 14,365 and the average lifetime
productivity cost lost per surviving CRS patient amounted to
US$ 16,263. Thus the senitivity analysis found that the total
average direct and indirect costs for a surviving CRS patient
were US$ 30,628 with a 10% discount rate.
4. Discussion
There has been great progress toward elimination of
rubella and CRS in Oman, with no CRS cases identified
since 2001. Nevertheless, the burden of blindness, deaf-
ness, cardiac and neurological complications will continue
for the lifetime of the CRS patients born in the past. For
the 43 surviving Omani children with CRS, the average
discounted direct lifetime cost of treatment, special educa-
tion, and rehabilitation is estimated at US$ 18,644 per child,
while the average discounted indirect costs per child were
US$ 80,090. The base case used a discount rate of 3%.
A sensitivity analysis using a discount rate of 10% found
the average discounted direct and indirect lifetime costs
per surviving CRS patient remained impressively high at
US$ 30,628.
Direct health care costs – e.g. medical visits, diagnostic
tests, surgery, hearing aids, speech therapy, and low vision
aids – may vary widely from country to country. Nevertheless,
these are generally high for CRS because many of the children
have multiple handicaps. A recent study from Brazil assessed
only direct costs in the first year of life of CRS patients, and
these amounted to US$ 2072 per child [15]. In Oman, many of
the children with CRS had surgical procedures after the first
year of life. Moreover, many of the CRS survivors have seri-
ous disabilities – such as deafness, blindness, cerebral palsy,
and mental retardation – that necessitate special education
and rehabilitation services. Altogether in Oman the average
discounted direct and indirect lifetime costs were US$ 98,734
per surviving CRS patient (in 2001 US$). These findings can
be compared with results of other CRS costing studies from
developing countries (Table 4). A study in Guyana in 1997
found direct and indirect costs amounted to US$ 63,990 per
CRS patient [17].
By 2004, 116 (60%) of all 192 WHO member states
included rubella vaccine in their routine national immuniza-
tion programme [20]. A WHO position paper on rubella
vaccines provides detailed guidance for countries on spe-
cific points to consider before introducing rubella vaccine
[21]. The national decision will be further informed by an
Table 4
Estimated costs of congenital rubella syndrome (CRS) in developing countries
Country Average cost per
CRS case (US$)
Method Comments Reference
Barbados, 1997 50,000 Lifetime: direct costs [16]
Brazil, 1999–2000 2072 First year of life:
direct costs
Direct costs include hospitalization, diagnostic
tests, treatment, and follow-up but do not include
cochlear implants, hearing aids, or spectacles.
[15]
Guyana, 1997 63,990 Lifetime: direct and
indirect costs
Direct costs include overseas surgery for heart
disease. Indirect costs include missed wages for
single parent households and lifetime earning
loss for disabled patients.
[17]
Jamaica, 1997 13,482 Annual: direct costs Direct costs include health care, institutional
care, and special education.
[18]
Oman, 2001 18,644 Lifetime: direct costs Direct costs do not include cochlear implants. Al-Awaidy et al.
(present study)
98,734 Lifetime: direct and
indirect costs
Panama, 1989 2291 First year of life:
direct costs
Direct costs do not include surgical
interventions, rehabilitation, or medications.
[19]

6444 S. Al-Awaidy et al. / Vaccine 24 (2006) 6437–6445
assessment of the cost-effectiveness of rubella vaccination
compared to other health interventions [2,3]. In a concise
cost-effectiveness analysis of rubella vaccine an estimate of
the economic burden of CRS, as presented in the present
study from Oman, should be included. Although such esti-
mates need to take into account country-specific health care
costs and the local costs of lost work time, the example of
Oman should prove useful.
In industrialized countries there are a number of CRS
patient registries, including Australia [22–24], Canada [25],
and the United Kingdom [26]. To our knowledge, the Oman
registry is the only one located in a developing country.
The Oman CRS registry includes a substantial cohort of
CRS survivors with long-term follow-up and comprehen-
sive clinical assessments. Previous papers based on data
from the Oman CRS registry have documented the devel-
opment of the registry [7] and explored the ophthalmologic
outcomes of CRS patients [27]. The Ministry of Health of
Oman intends to continue medical follow-up of this cohort
in future years. Further late onset manifestations of CRS
may be expected in some children. In Canada, long-term
follow-up of 100 CRS survivors for a mean of 34 years has
identified the following late manifestations, all of which were
detected after 5 years of age: 23% seizure disorder, 21% glau-
coma, 12% diabetes mellitus, and 10% thyroid dysfunction
[25].
Of the entire group of 94 Omani children reported since
1988 with CRS, there were 27 children (28.7%) who died
and 24 children (25.5%) lost to follow-up. While these pro-
portions seem high, a number of previous studies have also
reported high mortality with CRS and high attrition in long-
term follow-up of CRS survivors. Early studies from the
USA during the 1969 pandemic include several reports of
high mortality. Cooper et al. reported 35% mortality dur-
ing the first year of life in one group of 58 infants with
neonatal thrombocytopenic purpura due to CRS [28]. Among
children reported to a USA national surveillance system
during 1969–1973, 18% had died by the time their case
reports were submitted, most within the first few months
after birth [29]. O’Neill followed a group of CRS patients
with eye disease and 26% died, with two-thirds of the
deaths before 16 months of age [30]. In Panama, among a
cohort of 54 infants with CRS born in 1986–1987, 14 (26%)
died with 11 deaths in the neonatal period and the remain-
ing 3 deaths within the first 4 months [19]. A prospective
cohort study at Johns Hopkins University during 1963–1964
enrolled 328 children with CRS; at follow-up 7 years later,
15 (5%) were dead, and 70 (21%) were lost to follow-up
[31].
The 94 patients reported to the Oman CRS registry most
likely represent only the “tip of the iceberg” of all individuals
in the country with CRS. First, there is a striking dispropor-
tion by sex, with only one-third of CRS cases reported in
girls. Other data from Oman show that among 697 students
enrolled in special schools in 2004, only 37% were girls [9].
It is thought that in more rural areas of the country, families
worry that identification of a daughter as “disabled” through
attendance at a special school may detract from her chances
for a good marriage. In addition, the majority of patients in
the Oman registry have severe presentations of CRS, and it
seems likely that many children with milder manifestations
of CRS were not detected.
A limitation in our cost estimates is that we assume
that treatment practices and services for people with dis-
abilities will remain at a 2001 level in future years. We
have not taken into account a likely increase in costs due
to improved services. In particular, we did not include the
costs of cochlear implants, which are now widely used in
industrialized countries, where an estimated 50,000 patients
– including children with congenital deafness – have received
implants [32]. Cochlear implants have begun to be carried out
in Oman, at a price of US$ 23,000–26,000 per ear; however,
currently this procedure is reserved for patients who have
no neurological problems. To date, cochlear implant proce-
dures have not been carried out for any of the CRS cases in
Oman.
A large proportion of the Omani cohort of CRS survivors
had central nervous system defects, including mental retar-
dation. Children with blindness alone or deafness alone may
attend special schools, but children who are deaf and blind
or deaf–blind and mentally retarded may require special
care during their entire lifetime [33]. In Western countries
such children typically receive long-term care in institu-
tions, which is extremely expensive with costs exceeding US$
100,000 per year [34]. In Oman, family-based care remains
the norm for severely disabled persons. In keeping with this
tradition, the Omani Ministry of Social Development has
established 19 community-based rehabilitation centres in dif-
ferent regions of the country, which offer day-care services
and outreach services to some 1500 disabled individuals. An
Omani nongovernmental organization, the Association for
the Welfare of Handicapped Children, has established 6 cen-
tres that offer day-care services for some 300 disabled indi-
viduals. Of the cohort of 43 child-survivors of CRS described
in this paper, about one-quarter participate in governmen-
tal or nongovernmental community-based rehabilitation. The
Omani system is much less costly than institutionalization. It
may offer a culturally appropriate model for other countries
in the Middle East, Africa, and Asia which place a high value
on family centered support systems for multiply handicapped
persons.
Acknowledgements
The authors are grateful to the families of the Omani chil-
dren with CRS for their cooperation. This project was carried
out with scientific oversight from the Steering Committee on
Epidemiology and Field Research of the WHO Department
of Immunization, Vaccines and Biologicals. Thanks to Dr
F.Z. El Samani and Dr J. Vandelaer for critical review of the
manuscript.

S. Al-Awaidy et al. / Vaccine 24 (2006) 6437–6445 6445
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