Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine Health Policy

cy and Planning 2013;28:51–61

ß The Author 2012; all rights reserved. Advance Access publication 8 March 2012 doi:10.1093/heapol/czs025

Cost-effectiveness of Haemophilus influenzae

type b (Hib) vaccine introduction in the
universal immunization schedule in
Haryana State, India
Madhu Gupta,* Shankar Prinja, Rajesh Kumar and Manmeet Kaur

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School of Public Health, Post Graduate Institute of Medical Education and Research, Chandigarh, India
*Corresponding author. Madhu Gupta, MD, Assistant Professor of Community Medicine, School of Public Health, Post Graduate
Institute of Medical Education and Research, Chandigarh 160 012, India. Tel: þ91-9876732629, þ91-9914208226
E-mail: madhugupta21@gmail.com.

Accepted 5 December 2011

Objective In India, Haemophilus influenzae type b (Hib) vaccine introduction in the

universal immunization programme requires evidence of its potential health
impact and cost-effectiveness, as it is a costly vaccine. Since childhood mortality,
vaccination coverage and health service utilization vary across states, the
cost-effectiveness of introducing Hib vaccine was studied in Haryana state.
Methodology A mathematical model was used to compare scenarios with and without Hib
vaccination to estimate the cost-effectiveness of Hib vaccine in Haryana from
2010 to 2024. Demographic and National Family Health Surveys were used
to estimate vaccination coverage and mortality rates among children under 5.
Hib pneumonia, Hib meningitis and invasive Hib disease incidence were based
on Indian studies. Vaccine and syringe prices of the UNICEF supply division
were used. Cost-effectiveness from government and societal perspectives
was calculated as the net incremental cost per unit of health benefit gained
[disability-adjusted life years (DALYs) averted, life years saved, Hib cases
averted, Hib deaths averted]. Sensitivity analysis was done using variation in
parameter estimates among different states of India.
Findings The incremental cost of Hib vaccine introduction from a government and a
societal perspective was estimated to be US$81.4 and US$27.5 million,
respectively, from 2010 to 2024. Vaccination of 73.3, 71.6 and 67.4 million
children with first, second and third dose of pentavalent vaccine, respectively,
would avert 7 067 817 cases, 31 331 deaths and 994 564 DALYs. Incremental cost
per DALY averted from a government (US$819) and a societal perspective
(US$277) was found to be less than the per capita gross national income of
India in 2009. In sensitivity analysis, Hib vaccine introduction remained
cost-effective for India.

Conclusion Hib vaccine introduction is a cost-effective strategy in India.

Keywords Cost-effectiveness, Hib, vaccine, India, model, incremental cost

51
52 HEALTH POLICY AND PLANNING
KEY MESSAGES
 Hib vaccine introduction in the universal immunization schedule was found to be cost-effective, from both societal and
government perspectives, in Haryana State, India.
 The incremental cost-effectiveness ratio per DALY averted from a government (US$819) and a societal (US$277)
perspective was less than the per capita gross national income of India in 2009.
 Policy makers should therefore introduce the Hib vaccine into the universal immunization programme.
Introduction
Infections due to the bacterium Haemophilus influenzae type b
(Hib) represent a serious cause of vaccine-preventable morbid-
ity and mortality among children worldwide (Levine et al.
1998). Peltola (1999) found that Hib is responsible for 30–50%
of confirmed bacterial meningitis and is the second leading
cause of bacterial pneumonia among children under 5 years of
age in Asia. In India, the Invasive Bacterial Infections
Surveillance Group (IBIS Group 1998) has shown that Hib
meningitis is severe (case fatality ratio of 25%), occurs primarily
in infants (76% cases) and that 40–50% of isolates are resistant
to first-line antibiotics. Minz et al. (2008) found that the annual
incidence of Hib meningitis was at least 32 per 100 000 in
infants aged 0–11 months and 19 per 100 000 among children
aged 12–23 months in a south Indian community of Vellore.
The safety and immunogenicity of Hib vaccine has been
demonstrated worldwide (Adams et al. 1993). Evidence from
two randomized controlled trials by Mulholland et al. (1997)
and Levine et al. (1999) reveals that 20–25% of radiologically
confirmed pneumonia cases with consolidation can be pre-
vented with use of Hib conjugate vaccine. Moreover, it has been
observed by Adegbola et al. (2005) and Lewis et al. (2008) that
with relatively high vaccination coverage rates, near elimination
of Hib disease had been achieved after introduction of Hib
vaccine in the Gambia and Uganda. Although vaccination has
been recognized as one of the most cost-effective health
interventions to improve child survival, financial and program-
matic constraints are often cited as important operational
bottlenecks for the introduction of newer vaccines into the
routine immunization schedule (Darmstadt et al. 2005). This is
particularly relevant to Hib vaccine given its relatively high
retail cost. In Kenya, Akumu et al. (2007) has shown that Hib
vaccine is highly cost-effective and would be cost saving if the
vaccine price was less than half of the present level. Despite the
existence of Hib disease in India and documented evidence of
preventable burden after the introduction of Hib vaccine in
other developing countries, policy makers need reassurance that
this vaccine represents a cost-effective health intervention.
Considering the marked variability in childhood mortality
rates, vaccination coverage and treatment-seeking behaviour of
the population in various states of India, cost-effectiveness
analysis should ideally be considered at the state level. This
study estimated the cost-effectiveness of introducing Hib
vaccine in the north Indian state of Haryana. This is one of
the wealthiest states of India, having the third highest per
capita income in the country, and also one of the most
economically developed regions in South Asia because of
sustained growth of its agricultural and manufacturing industry
(Byres et al. 1999; Government of Haryana 2010a).
Methods
A mathematical model, developed at the London School of
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Hygiene and Tropical Medicine (LSHTM), was used to track
costs and health benefits for children born in the state of
Haryana from 2010 to 2024, as shown in Figure 1 (Hib
Initiative 2009). The model was prepared using MS-Excel
spreadsheet software. We followed a birth cohort in the year
2010, for a period of 15 years, with the addition of children
born in subsequent years and removing those who die as a
result of Hib diseases or all-cause mortality at different age
groups. Two scenarios were compared, i.e. (1) using a penta-
valent (DPT-HBV-Hib) vaccine, and (2) the current strategy in
Haryana, where children are immunized with DPT
(diphtheria-pertussis-tetanus) and HBV (hepatitis B virus)
vaccine. Children in both arms were then followed to study
the outcomes in terms of Hib diseases, i.e. Hib meningitis,
clinical pneumonia due to Hib and invasive Hib disease
(non-pneumonia and non-meningitis). Clinical pneumonia
was further stratified into severe and non-severe.
Health-seeking behaviour estimates from a Haryana study
were used to estimate the number of children who report to
a health facility to seek care (ICMR 2008). Further, the visits to
a health facility were categorized into those at private
(non-medical faith healer, pharmacy, clinic and hospital) and
public (clinic, primary health care, secondary and tertiary
hospital) facilities. Cost at each facility per child treated was
used to estimate the cost of treatment (Hussain et al. 2006;
Madsen et al. 2009). Both health system and out-of-pocket costs
were considered.
Cost of immunization in each arm was estimated based on
the vaccines delivered, i.e. pentavalent (DPT-HBV-Hib) vs DPT
and HBV vaccine. Costs of delivering vaccination in terms of
unit price of vaccine, cost of syringes, safety boxes, wastage
factor, handling and freight charges were included. Overall,
costs in terms of delivering the immunization programme and
treating children with Hib diseases were compared in the two
arms. Incremental benefits were computed as the difference in
cumulative cases, deaths and disability-adjusted life years
(DALYs), respectively, in the two comparator scenarios. Net
incremental cost of Hib vaccination was calculated by subtract-
ing the projected treatment cost savings from the total
incremental vaccination cost. Cost-effectiveness was then
calculated as the net incremental cost per unit of health
benefit (DALYs gained, life years saved, Hib cases averted, Hib
deaths averted). DALYs were age weighted and future costs and
health benefits were discounted back to the year 2010 using a
discount rate of 3% per year. Age weighting has been done as
per the methodology described by Murray and Lopez (1996) in
the methods for the Global Burden of Disease study. We have
 COST-EFFECTIVENESS OF HIB VACCINE INTRODUCTION
Figure 1 Model structure for cost-effectiveness of Hib vaccine in Haryana State, India
Notes: NPNM=non-pneumonia, non-meningitis; PHC=primary health centre
used age weights and a normalization constant of 0.04 and
0.1658, respectively. We assumed a median age of onset of
disability of 2.5 years and a life expectancy of 64 years. The
2010 average exchange rate of Indian Rupees (INR) 46.0 to
US$1.0 was used in all calculations. Parameters and assump-
tions used in the mathematical model to estimate the incre-
mental cost-effectiveness ratio (ICER) before and after the
introduction of Hib vaccine from a government as well as a
societal perspective are described below (Table 1).
Demography
Demographic parameters were based on census projections for
Haryana state. According to the 2001 census, Haryana had a
population of 21.14 million and a decadal growth rate of 28%
(Registrar General of India 2001). The projected population for
2010 has been estimated as 25 million (Registrar General of
India 2006). In 2008, the birth rate of Haryana was 23/1000
population (20.4/1000 urban, 24.2/1000 rural) and the infant
mortality rate was 54/1000 live births (43/1000 urban, 58/1000
rural) (Registrar General of India 2009). Fifty-three per cent
and 63.5% of infant mortality was among neonates in urban
and rural areas, respectively. The urban to rural ratio of
mortality among infants and among children aged 12–59
months was 0.8 and 0.4, respectively, according to the
National Family Health Survey (NFHS-3) conducted in 2005–
06 (IIPS 2007).
53
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Vaccine coverage
Hib vaccine will be delivered along with DPT through the
existing health system. The National Family Health Survey
(NFHS) and District Level Household Survey (DLHS) estimates
of DPT vaccine coverage were used to estimate historical
vaccination coverage and as a basis for extrapolating the
future trend from 2010 to 2024 (MOHFW 2006; IIPS 2007).
Annual projections were made on the basis of the parameter
‘percentage increase in DPT1 coverage per year’. We assumed
that coverage level should rise to cover all children, i.e. 99%. In
order to achieve this we assumed that the incremental
improvement in coverage will be gradual. This annual incre-
mental change has been assumed to be 2% of the gap between
current coverage level and desired peak (99%). With these
assumptions, our DPT coverage levels for Haryana peak at
about 88% in 2015 and go further to reach 92% if extrapolated
till 2049. The base year for these reductions was 2000 and a
benchmark check made against the reported NFHS-3 coverage
figure for the year 2005 showed that the trend was plausible.
Coverage of DPT2 and DPT3 was calculated by multiplying
the DPT1 coverage by the DPT1 to DPT2 and DPT1 to DPT3
dropout rate, respectively, as estimated in NFHS-3. It has been
assumed, that due to greater focus brought by the introduction
of a new vaccine, there will be a relative decline in the DPT1 to
DPT3 drop-out rate of about 2%. With this assumption, the
drop-out rate in our model for Haryana declines from 10% to
8% between 2010 and 2024. Based on these assumptions, our
54 HEALTH POLICY AND PLANNING
Table 1 Parameters used for estimating Hib disease burden before and after introduction of pentavalent vaccine in Haryana, India
Parameter Base case Range used in
value uncertainty
analysis
Birth rate per 1000 mid-year population 23 14.3–29.1
Vaccine coverage of 1st dose of DPT (%) 84 55.7–98.1
Vaccine coverage of 3rd dose of DPT (%) 74 28.7–95.7
Burden of Hib disease
Annual Hib meningitis incidence 7 3.1–14
per 100 000 children <5yrs
Annual severe clinical pneumonia 2717 2313–9000
per 100 000 children <2yrs
Vaccine costs
DTP-HepB-Hib (liquid) per dose (US$) 1.5 1.0–3.6
Vaccine efficacy
Hib vaccine (%) 95 67–99
results match UNICEF coverage evaluation survey results for
2010 (UNICEF 2010b). Rural to urban ratios of coverage rates
of DPT 1, 2 and 3 were taken as 0.87, 0.91 and 0.84,
respectively, as per the NFHS-3 survey (IIPS 2007). We
assumed phased introduction of Hib vaccine in the national
immunization schedule as a pentavalent vaccine, i.e. 6% in
2010, 8% in 2011, 60% in 2012, 80% in 2013 and 85% in 2014.
The immunization coverage rates thus assumed were similar to
rates from the NFHS-3 and those obtained by Prinja et al.
(2010) in Haryana.
Hib disease incidence
Invasive Hib disease manifests in three forms: (1) Hib pneu-
monia, (2) Hib meningitis and (3) non-pneumonia and
non-meningitis invasive Hib disease (Hib NPNM). Incidence
of Hib pneumonia among children under 5 years has been
estimated from severe clinical pneumonia incidence in Haryana.
A multicentre surveillance study, where one centre was
Khizrabad block in Yamunanagar district in Haryana (Gupta
et al. 2010), found incidence of severe clinical pneumonia was
at least 2717/100 000 child years of observation among children
under 2 years in Haryana. Incidence of acute lower respiratory
tract infection (ALRI)/pneumonia was taken as 10 times the
incidence of severe clinical pneumonia based on studies by
Datta et al. (1987) and Acharya et al. (2003). The urban to rural
ratio of the burden of ALRI cases and deaths was found to be
0.2 (Registrar General of India 2009). Hib is responsible for
between 13 and 19% of pneumonia and lower lung disease in
Indian studies (Kumar and Ayyagari 1984; Bahl et al. 1995;
Patwari et al. 1996). In our model, we used a base assumption
of the proportion of Hib cases among total pneumonia and
lower lung disease cases of 13%. The case fatality ratio (CFR) of
Hib pneumonia was assumed to be 16% based on a study by
the Invasive Bacterial Infections Surveillance Group (IBIS
Group 2002). The fraction of under-5 deaths due to ALRI was
taken as 19% as per the World Health Organization (WHO)
‘Mortality country fact sheet’ of 2006 and the Million Death
Study (WHO 2006a; Million Death Study Collaborators 2010).
Reference
Sample Registration System (Registrar General of India 2009)
National Family Health Survey 2005–06 (IIPS 2007)
National Family Health Survey 2005–06 (IIPS 2007)
Minz et al. (2008)
Gupta et al. (2010)
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UNICEF vaccine projections (UNICEF 2008)
Mulholland et al. (1997)
Severe pneumonia was defined as cough or difficult breathing
or tachypnea and at least one of the following symptoms/signs:
lower chest wall in-drawing, nasal flaring, grunting, central
cyanosis, inability to feed, lethargy, unconsciousness or head
nodding. Radiological pneumonia was defined as severe pneu-
monia with radiographic evidence of consolidation meeting the
WHO clinical trialist group primary endpoint criteria (WHO
2001).
The incidence of Hib meningitis in under-5s was estimated to
be 7.1 [95% confidence interval (CI) 3.1 to 14] per 100 000 child
years of observation based on a prospective surveillance study
in Vellore, Tamil Nadu during 1997 and 1999 (Minz et al. 2008).
The ratio of Hib meningitis to other forms of invasive Hib
disease (or non-pneumonia, non-meningitis) was assumed to
be 0.05 based on global estimates by Watt et al. (2009). Kabra
et al. (1991) and Chinchankar et al. (2002) reported a CFR of
20–29% for Hib meningitis in India. A review by WHO (2006b)
found a CFR of between 16% and 20% for invasive Hib disease
(including meningitis) in the Western Pacific Region.
The age distribution of all invasive Hib disease cases was
assumed to be 60% aged <12 months, 30% aged 12–23 months,
5% 24–35 months, 4% 36–47 months and 1% aged 48–59
months, based on the study by the Invasive Bacterial Infections
Surveillance Group (IBIS Group 2002). Using evidence from a
local study in Chandigarh, India, by Singhi et al. (2007), we
assumed that 40% of survivors of Hib meningitis would develop
a permanent lifelong disability and 30% of those lifelong
sequelae would be ‘major’. Major sequelae included persistent
seizures, mental retardation and hearing loss. We assumed
Global Burden of Disease disability weights (fraction of healthy
time lost to disability) of 0.28 and 0.61 for pneumonia and
meningitis/NPNM, respectively (Murray and Lopez 1996). For
non-severe pneumonia we assumed a weight of 0.14, assuming
half of the reported weight for pneumonia. For minor and
major sequelae, we assumed weights of 0.20 and 0.46, respect-
ively, as per the WHO Global Burden of Disease 2004 update
(WHO 2004). The mean duration of illness for Hib non-severe
pneumonia, Hib severe pneumonia, Hib meningitis, Hib NPNM
 COST-EFFECTIVENESS OF HIB VACCINE INTRODUCTION 55

Table 2 Treatment-seeking behaviour for pneumonia and meningitis and minor and major sequelae among children, by type of facility in Haryana,
2006

Health facility Percentage of the patients visiting the health facility

Non-severe pneumonia Severe pneumonia Meningitis NPNM Sequelae minor Sequelae major
Government
Sub-centre 0.4 1 0 0 0.4 0
PHC 13 14 14 14 13 14
CHC/district hospital 2 2 2 2 2 2
Tertiary care hospital 1 1 1 1 1 1
Private
Pharmacy 72 10 10 10 72 10

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Private clinic/hospital 11.6 73 73 73 11.6 73
Total 100 101 100 100 100 100

Source: Estimating the preventable burden of Haemophilus influenza type b, Meningitis and Pneumonia in India, Report Part A (ICMR 2008).
Notes: NPNM ¼ non-pneumonia, non-meningitis; PHC ¼ primary health centre; CHC ¼ community health centre.

was assumed to be 7, 15, 20 and 30 days, respectively, based on
a 2008 surveillance report of pneumonia and meningitis in
Haryana (ICMR 2008).
Vaccine efficacy
Efficacy against Hib disease from one, two and three doses of
Hib vaccine was assumed to be 47%, 75% and 95%, respectively
(Eskola et al. 1990; Booy et al. 1994; Mulholland et al. 1997).
Incremental cost of introducing Hib vaccine
We estimated the cost-effectiveness of pentavalent Hib vaccine
(DPTþHepBþHib) introduction in Haryana. We used the 2009
vaccine and syringe prices of UNICEF supply division for a
10-dose vial (liquid) (UNICEF 2009). However, we assumed
that the cost for this vaccine would be US$1.5 per dose in India
(a decline in the vaccine price is expected due to the large
number of children to be vaccinated in India). Vaccine delivery
cost includes the price of vaccines, administering syringes,
safety boxes, percentage waste factor, handling and freight
charges. Based on discussions with the national EPI Manager,
we assumed there would be no other major incremental vaccine
delivery costs to the programme for introducing Hib vaccine
into the national immunization programme. This assumes that
training and communication costs would be minimal, and that
there is currently enough space in the cold-chain to accommo-
date the pentavalent vaccine. Moreover, evidence from Akumu
et al. (2007) from Kenya shows that such costs account for
0.13% of total incremental costs of vaccine delivery. We also
estimated the variation in the ICER with a change in the cost of
pentavalent vaccine (DPTþHepBþHib).
pneumonia and meningitis among children by type of facility
is given in Table 2.
Cost of treatment in formal care was estimated for the
following diseases: non-severe pneumonia, severe pneumonia,
Hib meningitis and Hib NPNM cases, Hib minor sequelae and
Hib major sequelae. Travel cost to the health facility and cost of
treatment was obtained from the local surveillance report of
pneumonia and meningitis in Khizrabad block, Haryana (ICMR
2008). The information on costs of treatment was supple-
mented with the results of the 61st round of the National
Sample Survey (NSSO 2006), a study in south India (Madsen
et al. 2009) and a study from a neighbouring country with
similar socio-demographic characteristics and treatment-
seeking practices (Hussain et al. 2006). The estimated costs of
treatment in US dollars (US$) from a government and a
societal perspective are given in Table 3.
Sensitivity analysis
We undertook a univariate sensitivity analysis to assess the
impact of uncertainty in parameter values on cost-effectiveness
estimates. Ranges of parameters used in uncertainty analysis
are given in Table 1. The uncertainty range for parameter base
values was derived using variation in parameter estimates
among different states in India, so as to assess the generaliz-
ability of the Haryana study to other Indian states. Since there
are significantly lower estimates of Hib disease burden reported
from other settings such as Gambia and Indonesia, we varied
our assumption of the fraction of Hib cases among total
pneumonia cases from 5% to 15% (Watt et al. 2009), to assess
the cost-effectiveness of Hib vaccine in conditions of lower
disease burden.

Health service utilization and costs

Information on access to health services was obtained from a
local surveillance report of pneumonia and meningitis in
Haryana (ICMR 2008). Government facilities included only
outpatient departments/clinics and indoor facilities at primary,
secondary and tertiary level. Private facilities included pharma-
cies and outpatient departments with indoor facilities in urban
and rural areas. The treatment-seeking behaviour for
Results
Hib disease incidence
According to model estimates, there would be about 1500 cases
of Hib meningitis (incidence 9.8/10 000) among children under
5 years without Hib vaccination in Haryana, which would
reduce to 67 cases (incidence 0.3/10 000) in the year 2024
56 HEALTH POLICY AND PLANNING

Table 3 Estimated cost of treatment from government and societal perspectives (US$)

Health facility Travel Total drugs and diagnostics cost

cost Non-severe Severe Meningitis NPNM Sequelae Sequelae
pneumonia pneumonia Minor Major
Cost to government
Government cost per patient per outpatient visit
Sub-centre 1.5 0.2 0.5 0.6 0.6 0.2 0.5
Primary health care facility 1.0 0.2 0.5 0.6 0.6 0.2 0.5
Secondary health care facility 1.4 3.0 6.0 7.2 7.2 3.0 6.0
Tertiary health care facility 2.1 17.0 87.0 104.4 104.4 17.0 87.0
Government cost per inpatient bed day

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Primary health care facility 4.6 10.0 25.0 30.0 30.0 10.0 25.0
Secondary health care facility 6.1 25.0 84.0 100.8 100.8 25.0 84.0
Tertiary health care facility 8.3 71.0 147.0 176.4 176.4 71.0 147.0
Cost to household
Household cost per patient per outpatient visit
Government health centre / private pharmacy 1.0 1.2 3.0 3.6 3.6 1.2 3.0
Government primary hospital 2.0 1.2 3.0 3.6 3.6 1.2 3.0
Government secondary hospital 3.0 95.0 192.0 230.4 230.4 95.0 192.0
Government tertiary hospital / private health facility 6.0 150.0 250.0 300.0 300.0 150.0 250.0
Household cost per inpatient bed day
Government primary hospital 2.0 1.0 5.0 6.0 6.0 1.0 5.0
Government secondary hospital 3.0 1.0 36.0 43.2 43.2 1.0 36.0
Government tertiary hospital / private health facility 6.0 5.0 129.0 154.8 154.8 5.0 129.0

Sources: ICMR (2008), Madsen et al. (2009), Hussain et al. (2006), NSSO (2006).
Note: NPNM ¼ non-pneumonia, non-meningitis.

following Hib vaccine introduction in the national immuniza-
tion programme. Similarly, incidence of severe Hib pneumonia
would reduce from 831/10 000 cases to 52/10 000 cases among
children under 5. There would be a 93% reduction in the
number of deaths due to severe Hib pneumonia and a 95%
reduction in deaths due to Hib meningitis. The number of
life years saved would be about 0.1 million in the year 2024
(Table 4).
Cost-effectiveness
It was estimated that, by 2024, the incremental cost from
government and societal perspectives would be US$81.4 million
and US$27.5 million, respectively. Mortality and morbidity
averted as a result of Hib vaccination would include 7 067 817
cases and 31 331 deaths (994 564 DALYs). This gives a ratio of
about 31.7 DALYs per death averted. With the introduction of
the Hib vaccine, the Government of Haryana would spend an
additional US$819 per DALY averted, US$885 per life year
gained or US$115 per Hib case averted. From a societal
perspective, the incremental cost of Hib vaccine introduction
would be US$277, US$300 and US$39 per DALY averted, life
year gained and Hib case averted, respectively (Table 5).
Sensitivity analysis
Incidence of acute lower respiratory infections (ALRI) and Hib
vaccine cost were found to be the most important determinants
of cost-effectiveness. However, even with the extremes of
variation in cost of vaccine per dose and ALRI incidence, Hib
vaccination was found to be cost-effective from both govern-
ment and societal perspectives. Hib vaccination would cost the
Government of Haryana an additional US$165 to US$551 per
DALY averted when the cost of Hib vaccine ranged from US$1
to US$3.5 per dose, respectively (Figures 2 and 3). Assuming
high Hib burden and low vaccine cost, i.e. high ALRI incidence
and low estimate for Hib vaccine cost, Hib vaccination is a
cost-saving intervention and dominates the scenario with
‘no-vaccination’ from a societal perspective.
We also varied the base assumption of the percentage of total
pneumonia cases that are due to Hib from 6% to 15%; and
found the ICER per DALY averted varied from US$1089 to
US$168, respectively, from a societal perspective. With a per
capita GDP of US$1176 for India, Hib vaccine introduction
remains a very cost-effective option even in a scenario of lower
Hib disease burden. With Hib cases accounting for only 5% of
the total ALRI burden, introduction of Hib vaccine in the
universal immunization programme will cost US$1336 per
DALY averted, which is also within cost-effective bounds
according to the WHO threshold (between 1 to 3 times per
capita GDP).
In order of decreasing importance, other determinants of
cost-effectiveness included vaccination coverage, efficacy of
vaccine and incidence of Hib meningitis (Figure 2). Variations
in other model parameters were found to have insignificant
 COST-EFFECTIVENESS OF HIB VACCINE INTRODUCTION 57

Table 4 Model-estimated incident number of Hib disease events and Table 5 Cost-effectiveness of pentavalent vaccine (DPTþHepBþHib) in
life years in 2024, with and without Hib vaccine in universal immun- Haryana, 2010 to 2024
ization programme, Haryana, India
Parameter Value
Parameter Without Hib With Hib Incremental cost
vaccination vaccination
Government perspective US$81.4 million
Year 2024 2024
Societal perspective US$27.5 million
Vaccine coverage 0% >85%
Incremental benefit
Total acute cases 749 948 46 876
DALYs gained 994 564
Hib non-severe pneumonia 598 695 37 444
Hib cases averted 7 067 817
Hib severe pneumonia 149 674 9361
Hib deaths averted 31 331
Hib meningitis 1504 67
Life years gained 920 512
Hib NPNM 75 3

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Incremental cost-effectiveness ratio
Total deaths 3286 201
Government perspective
Hib non-severe pneumonia 0 0
US$ per DALY averted 819
Hib severe pneumonia 2993 187
US$ per life year gained 885
Hib meningitis 279 13
US$ per Hib case averted 115
Hib NPNM 14 1
US$ per Hib death averted 26 004
Total sequelae 489 21
Societal perspective
Minor 367 16
US$ per DALY averted 277
Major 122 5
US$ per life year gained 300
Total disability-adjusted 104 181 6317
life years lost US$ per Hib case averted 39
Acute disease 3386 211 US$ per Hib death averted 8809
Minor sequelae 2163 95 Note: DALY ¼ disability-adjusted life years.
Major sequelae 1691 75
Premature death 96 940 5937

Note: NPNM ¼ non-pneumonia, non-meningitis.
effects on the estimate of cost-effectiveness. Although high
levels of vaccine efficacy (95%) have been observed with three
doses of pentavalent vaccine, a variation of between 67% and
99% efficacy has been documented in the literature
(Mulholland et al. 1997). With this variation in vaccine efficacy,
cost per DALY averted ranged from US$791 to US$370,
respectively, from a health system perspective, and from
US$373 to US$248, respectively, from a societal perspective.
Discussion
This study has demonstrated that the introduction of Hib
vaccine in the universal immunization schedule is cost-effective
in Haryana state of India. According to the World Country
Classification System, which uses 2008 gross national income
(GNI) per capita (in US$) calculated using the World Bank
Atlas method, India is a lower-middle-income country with a
GNI between US$996 and US$3945 (World Bank 2010).
According to WHO vaccine introduction guidelines, any inter-
vention is cost-effective if the cost-effectiveness ratio of that
intervention is less than three times the per capita GNI of that
nation (WHO 2005). This classification has been used by WHO
in their review of Hib disease burden and Hib vaccine
cost-effectiveness in the Western Pacific Region (WHO
2006b). The net cost per DALY gained is estimated as US$277
in the present study, which is less than the GNI of India and
hence Hib vaccine introduction is a cost-effective intervention.
The State government of Haryana has allocated US$2283
million for its annual budget plan 2010–11, of which about
US$245 million (10.7%) will be spent on health (Government of
Haryana 2010b). The incremental cost (US$6.6 million) of
introducing pentavalent Hib vaccine appears to be affordable
from a fiscal perspective. According to the Disease Control
Priority Project’s cost-effectiveness estimation for adding penta-
valent Hib vaccine, the incremental discounted cost per death
averted is US$10 950 for South Asia (DCPP 2006). This cost was
estimated to be higher (US$26 004) in Haryana. This could be
due to relatively lower incidence of Hib disease in Haryana state
(Gupta et al. 2010), which means vaccine introduction would be
even more cost-effective in other parts of India which have
higher incidence levels.
Further, our analysis has shown that introduction of Hib
vaccine is more cost-effective from a societal perspective, as
80% of households pay out-of-pocket for treatment of pneu-
monia and meningitis. Hence the introduction of this vaccine
will not only help in reducing the disease burden, but it will
also prevent the regressive effects of high out-of-pocket
payments for health care in India.
The current price of pentavalent vaccine in India is US$1.75
(UNICEF 2010a). GAVI has reported a decline of 14% in the
price of pentavalent vaccine from 2009 to 2010 (GAVI 2009)
and UNICEF has registered an annual decline of 20.4% during
this period (UNICEF 2009; UNICEF 2010a). A vaccine price
estimate of US$1.5 was used in this study because when India
plans to introduce the vaccine into its national immunization
schedule, the additional demand of nearly 75 million doses
58 HEALTH POLICY AND PLANNING

ALRI Incidence

Societal
Vaccine cost perspective

DPT3 coverage Government

perspective
DPT1 coverage

Vaccine efficacy

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Hib Meningitis incidence

-400 0 400 800 1200 1600 2000 2400 2800

USD per DALY averted
Figure 2 Univariate sensitivity analysis of incremental cost-effectiveness ratio (US$ per DALY averted) with respect to DPT 1st and DPT 3rd dose
coverage, incidence of acute lower respiratory infections (ALRI) and Hib meningitis, Hib vaccine cost and efficacy

800
Incremental cost (USD) per DALY gained

700

600

500

400

300

200

100

0
1 1.5 2 2.5 3 3.5
Cost of pentavalent vaccine per dose (USD)
Figure 3 Incremental cost-effectiveness ratio per disability-adjusted life year (DALY) averted from a government perspective with respect to cost of
pentavalent (DPTþHepBþHib) vaccine per dose (US$)

(based on birth cohort size) should lead to a higher rate of
decline in vaccine prices. Moreover, sensitivity analysis revealed
that even at a price of US$3.5 per dose, the introduction of Hib
vaccine in the universal immunization schedule remains
cost-effective.
Various studies elsewhere have also found the introduction of
Hib vaccine into national immunization schedules to be
cost-effective. In Kenya, Akumu et al. (2007) found that
vaccination of children with Hib vaccine in one area was
cost-effective in comparison to a control area without the
vaccination. A ratio of about 30 DALYs per Kenyan child death
averted was observed, similar to that in the present study. In
Colombia, a Hib vaccination programme could prevent around
25 000 cases of invasive disease per year, 700 deaths per year
and save 44 054 years of life per year, representing a cost saving
of at least US$15 million annually (Alvis et al. 2006).
An assessment of the value of Hib conjugate vaccine in Asia
using a model predicted that approximately 136 000 (87%) Hib
deaths could be prevented annually with incorporation of Hib
vaccine into the Expanded Program for Immunization based on
current vaccination coverage rates for the individual countries
considered (Miller 1998). For each of the countries, routine
vaccination with Hib would cost between 0.1% and 3.0% of per
capita gross national product per child under 5 years. According
to the assessment, Hib vaccine was considered to be a
cost-effective public health intervention, but was likely to be
cost-prohibitive to implement in the lowest income countries
without initial donor assistance.
In Santiago, Chile, Levine et al. (1993) compared the potential
benefits to the Chilean Ministry of Health in terms of treatment
costs averted by prevention of Haemophilus influenzae type b
invasive disease, and the costs of adding Hib conjugate vaccine
 COST-EFFECTIVENESS OF HIB VACCINE INTRODUCTION
to the DPT immunization routinely administered to infants.
Assuming a cost of US$1 for a full three-dose regimen of
vaccine, they find a benefit/cost ratio of 1.66, with a net
discounted saving of over US$40 322, which shows Hib vaccine
to be cost-beneficial.
In the model in the present study, assumptions about Hib
disease in Haryana were based on minimal incidence of Hib
meningitis in Tamil Nadu (Minz et al. 2008) and of pneumonia
in Haryana (Gupta et al. 2010). However, the methodology used
by Minz et al. to determine the minimal incidence of Hib
meningitis in Tamil Nadu was less than ideal, i.e.
hospital-based surveillance. With such methodology, many
cases of disease can be missed due to poor health-seeking
behaviour and barriers to access in poor developing country
contexts. This is corroborated by findings from a study in
Lombok (Gessner et al. 2005). Minz et al. also report that eight
children in the study area, who did not use medical care in
study hospitals, died with signs suggestive of central nervous
system (CNS) infection. Moreover, due to a poor
patient–physician ratio, some cases could not be subjected to
lumber puncture, especially outside routine working hours.
Hence, the base estimates for Hib disease incidence used in
our model could be considered on the low side of what may be
the true burden of disease, making the vaccine even more
cost-effective.
The 15-year time horizon used in our study was based on
the epidemiology of Hib. Risk of falling ill as a result of Hib
disease peaks at mid-infancy or early childhood, and gradually
wanes thereafter. Worldwide, most cases of H. influenzae occur
between the ages of 2 months and 3 years; it is unusual beyond
5 years of age (Wenger 1998). According to the Invasive
Bacterial Infections Surveillance Group study from India, 90%
of H. influenzae cases (pneumonia, meningitis and invasive
Hib disease) occurred among children under 15 years, of
which more than 96% were under 5 (IBIS Group 2002). There is
minimal risk of Hib disease beyond the age of 15. Hence, a
15-year time horizon gives a proxy for an analysis which
provides life-time benefits.
In India, since Hib vaccination is not done routinely, a
cost-effectiveness study can be useful for policy makers in
deciding whether to introduce the vaccine in the universal
immunization schedule. In its position paper on Hib conjugate
vaccine, WHO has recommended inclusion of Hib vaccination
in all countries (WHO 2006c), but since it is an expensive
vaccine, governments are hesitant to introduce it at national
level; they would like information on its cost-effectiveness. A
literature review reveals that the Hib burden is best estimated
using vaccine probe studies (Mulholland et al. 1997; Levine et al.
1999), but a vaccine probe study in which only one group will
be given the vaccine will be ethically problematic in light of the
WHO recommendation. Hence, cost-effectiveness analysis based
on a model remains one way to inform policy makers in their
decision-making on the introduction of Hib vaccine into routine
immunization.
A limitation of this study is that the cost of additional
training for implementing the vaccine as part of routine immun-
ization was considered minimal. As vaccines will be delivered in
the routine programme rather than through a social mobiliza-
tion campaign, interpersonal communication by health workers
59
during their routine duties was considered to be enough.
Evidence from Kenya indicates that the cost of additional
training and community sensitization was about US$100 000.
Assuming this amount will last over a period of 15 years, and
discounting for future costs at 5%, the annualized value
(US$9634) is 0.13% of the total incremental cost of imple-
menting pentavalent Hib vaccine in Kenya (Akumu et al. 2007).
Our base estimate results show Hib vaccine to be a
cost-effective option for preventing childhood morbidity, dis-
ability and deaths in Haryana. We carried out a sensitivity
analysis using the uncertainty range for different parameters,
which was reflective of state-wise differences in the parameter
estimates in India. Using uncertainty around all model param-
Downloaded from https://academic.oup.com/heapol/article/28/1/51/644753 by guest on 14 December 2023
eters, our results from univariate sensitivity analysis show that
Hib vaccine introduction in the national immunization schedule
as a pentavalent vaccine is cost-effective in India. It is even
more cost-effective in states which have a higher burden of
acute lower respiratory infections. Hence, policy makers should
consider introduction of Hib vaccine in the universal immun-
ization schedule of India.
Acknowledgements
We thank Dr Ulla Griffiths, Lecturer at the London School
of Hygiene and Tropical Medicine and Director of cost-
effectiveness for The Hib Initiative, and Mr Andrew Clark
from the London School of Hygiene and Tropical Medicine for
the sharing of and training in the mathematical model for
cost-effective analysis.
Funding
There was no source of funding for this study.
Conflict of interest
None declared.
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