12 months in the
presence of a well-performing surveillance system. Recently, the eleven
member states of World Health Organization South-East Asia Region (WHO
SEAR) have committed to eliminate measles by 2020 at the 66th session of
the WHO regional committee [1]. As per WHO’s recommendation, all
available measles vaccines are safe, effective and protect equally well
against all wild type measles genotypes [2]. In the phased manner, the
Government of India (GoI) is working for measles elimination. GoI
introduced second dose of measles in 2010, and recently announced to
introduce the rubella vaccine in its Universal Immunization Program
(UIP) [3]. Indian Academy of Pediatrics (IAP) supports elimination of
measles and rubella but also of mumps in the form of two doses of
affordable measles-mumps-rubella (MMR) vaccine [4].
Measles is reported to be cause of considerable
morbidity and mortality in India. In 2005, an estimated 92000 deaths
occurred in India due to measles, predominantly in children aged less
than 5 years. Estimates from year 2008 indicate that 77% of global
measles mortality was in the WHO SEAR, the majority from India. An
update on 1st dose of measles-containing vaccine coverage, progress in
implementing a 2nd dose of measles-containing vaccine coverage and
measles outbreak surveillance activities was conducted during years 2006
to 2010 in the eight Indian States [5]. This report highlights that the
pace of implementation of measles mortality reduction is variable across
the States.
A model to estimate the progress made towards the
global measles-mortality reduction goal emphasizes need to
intensify control measures and further commitments on the
political/financial issues [6]. Updated estimates of measles case
fatality rates (CFR) are critical for monitoring progress towards
measles elimination goals. A retrospective cohort study to estimate
measles CFR and its risk factors for measles death in the State of Bihar
has been recently reported [7]. Report indicates higher CFR in the
children less than 5 years of age (1.22%), and amongst children
belonging to scheduled castes/tribes (1.72%). A review of Indian
community-based measles CFR studies conducted between year 1975 and 2008
indicates significantly higher CFR in rural population, and
further emphasizes to enhance measles vaccine coverage and routine
supplementation of vitamin A in the outbreak settings [8]. Recent
estimates indicate that over 100,000 children died due to measles in
India during 2005 [9]. The majority of measles deaths occurred in the
States of Uttar Pradesh, Bihar and Madhya Pradesh. Estimate also shows
that girls were at higher risk of mortality compared to boys. All these
reports show need of supplementary immunization activity in the high
burden districts.
The feasibility of measles elimination and the
possible challenges in India to achieve this important goal have been
described earlier [10]. This review also describes the National
Technical Advisory Group of India’s (NTAGI) strategies on routine
measles vaccine coverage and introduction of supplementary immunization
activity (SIA) in a phased manner. However, measles-mortality reduction
remains the top priority. The Government of India had introduced
two-dose strategy for measles vaccine in the UIP [11]. As per the
revised routine immunization schedule, every child should get two doses
of measles vaccine: first at the age of 9-12 months and 2nd at the age
of 16-24 months. If a child missed any of these doses, these can be
offered up to 5 years of age maintaining a gap of at least 4 weeks
between the doses. Recent reports [12,13] on the measles outbreak
investigations indicate need to improve measles vaccine coverage and
community participation. Use of vitamin A during outbreak management and
supplemental immunization is essential to improve the control measures
in the outbreak settings [14]. Vitamin A deficiency contributes to
delayed recovery and high rate of post-measles complications. The
beneficial effect of two doses of vitamin A during treatment of measles
is well established, and WHO recommends administration of vitamin A to
all patients with measles [2].
Between January 2013 and June 2014, Maharashtra State
health agencies have investigated 197 suspected measles outbreaks in the
28 districts. Of these outbreaks, 138 were confirmed as measles, 18 were
confirmed as rubella, 31 were mixed outbreaks, and nine outbreaks
remained unconfirmed (Unpublished data). During this investigation, few
adult measles cases were also reported; majority were among unimmunized.
Recently, three outbreaks of measles in adults (medical cadets, medical
students and nursing students) were reported from the State of
Maharashtra, Karnataka and Andhra Pradesh. The possibility of shift in
age for measles is likely, necessitating further such studies. Primary
vaccine failure or waning immunity in adults may also be the likely
cause. In the developed countries, measles outbreak-based (or
case-based) surveillance coupled with genotyping of virus strains have
generated data for tracking the transmission routes, documenting the
elimination of endemic virus strains, and indicating any risk groups.
In India, data on the circulation of measles strains
was generated during 2005-10 by establishing national network (i.e.
MeaslesNetIndia) of 27 centers and sentinel practitioners in 21 States
and 2 Union Territories of India [15]. Phylogenetic studies revealed
circulation of measles genotype D4 and D8 strains. This project has
created support and capabilities for countrywide measles molecular
surveillance. Measles genotype D7 was detected from two classical
measles cases from the Chennai and Pune cities, and in a fulminant SSPE
case from the Bangalaru city [16]; circulation of this genotype was not
detected afterwards. Molecular studies from the States of Uttar Pradesh
[17,18] and Tamil Nadu [19] indicate presence of measles genotype D8
strains. India’s measles virus sequencing data now cover different
regions of the country (Table I). Recently,
circulation of measles genotype B3 was reported from Thiruvananthapuram,
Kerala [20] indicating either importation from other countries or
unidentified indigenous measles strain. Thus, studies on the genetic and
antigenic properties of circulating wild type viruses will be important
in context of measles elimination.
TABLE I Measles Virus Strains Detected in Different Parts of the Country (1996-2014)
State/Union Territory |
Genotype D4 |
Genotype D8 |
Total |
Andaman and Nicobar |
- |
7 |
7 |
Andhra Pradesh |
7 |
15 |
22 |
Arunachal Pradesh |
12 |
7 |
19 |
Assam |
1 |
7 |
8 |
Bihar |
1 |
5 |
6 |
Chattisgarh |
- |
2 |
2 |
Delhi |
- |
9 |
9 |
Gujarat |
10 |
2 |
12 |
Haryana |
- |
2 |
2 |
Himachal Pradesh |
2 |
- |
2 |
Jammu and Kashmir |
8 |
- |
8 |
Jharkhand |
1 |
- |
1 |
Karnataka |
11 |
21 |
32 |
Kerala |
- |
4 |
4 |
Madhya Pradesh |
3 |
- |
3 |
Maharashtra |
32 |
49 |
81 |
Manipur |
- |
4 |
4 |
Meghalaya |
- |
1 |
1 |
Nagaland |
- |
6 |
6 |
Odisha |
- |
3 |
3 |
Rajasthan |
2 |
5 |
7 |
Sikkim |
6 |
1 |
7 |
Tamil Nadu |
9 |
48 |
57 |
Tripura |
- |
1 |
1 |
Uttar Pradesh |
3 |
44 |
47 |
Uttarakhand |
5 |
6 |
11 |
West Bengal |
- |
4 |
4 |
Total |
113 |
253 |
366 |
A longitudinal follow-up study conducted during 1995
shows that measles containing vaccine (MMR) had excellent
immunogenicity, low reactogenicity and good seroconversion rate (75% to
100%) in previously vaccinated children [21]. The persistence of
measles IgG antibodies was studied up to 6 years post-vaccination, that
revealed 88% measles seropositivity, and suggests 2nd dose of measles
for the boost-up [22]. A study conducted on 84 children (aged 4-6 years)
from the State of Delhi shows increased seropositivity for measles (21.4
to 72.6%), mumps (87.4 to 100%) and rubella (75.7 to 100%) after
introduction of 2nd dose of MMR vaccine [23]. However, large-scale
studies are necessary to understand the level of sero-protection, and
ultimately to understand the impact of measles immunization.
Limited sero-epidemiological studies on measles are
available from India. The prevalence of serological susceptibility to
measles was 9.5% in 790 health science students [24]. Additional efforts
are needed to generate more information to understand the real impact of
measles immunization. For the large-scale studies, alternative
neutralization assays that utilize a 96-well tissue culture plate format
would be preferred [25]. However, commercially available more rapid
enzyme linked immunosorbent assays (EIA) do not differentiate
neutralizing and non-neutralizing antibodies. For the characterization
of vaccine or wild type-induced immune response, rapid and reliable
neutralization tests are essential. Therefore, the focus reduction
neutralization tests (FRNT) for measles, mumps and rubella viruses have
been developed [26].
The major challenges to achieve measles elimination
goal in India are as follows:
Vaccine Procurement and Supply
WHO estimates shows that US$ 800 million are required
for the SEAR to achieve the target of measles elimination before 2020.
Thus, for the procurement of measles vaccine, there is a need to find
funding source from the State Governments, Central Government and other
national or international agencies. Similarly, efforts are required to
tie up with the vaccine manufacturers for adequate and timely vaccine
supply. Maintenance of cold chain during the transportation and vaccine
storage facilities may be the key issue in the South-East Asian
countries. Similarly, adequate supply of syringes and needles, and their
proper disposal is an important issue.
Efforts to Maintain High Vaccine Coverage
The prime target is to achieve >95% population
immunity with high vaccine coverage by two doses of measles and/or by
supplementary immunization activities. For this, trained staff would be
required for vaccine delivery, and to mobilize the community
participation. More attention is needed in the tribal areas, hilly
regions, and migrant population.
Active Surveillance
In order to succeed, country must plan a surveillance
system that detects all cases of measles. For this purpose, a case-based
measles surveillance needs to be established, and if possible,
laboratory confirmation of the representative cases/circulating wild
type viruses should be undertaken. Few States have already established
measles outbreak-based surveillance system and in near future, these
States may enter into the case-based surveillance. To date, GoI have not
introduced the measles case-based surveillance. However, States that can
utilize their existing surveillance system (like Integrated Disease
Surveillance Program or National Polio Surveillance Project network) may
enter into a measles case-based surveillance.
Strengthening of Laboratory Facilities
To strengthen laboratory capacities, WHO has
recognized 11 national laboratories (MeaslesLabNet) in different States
of India. These laboratories perform serological (IgM antibody
detection) and molecular testing (measles virus detection and
genotyping). For the measles virus sequencing, PCR products have been
referred to the Reference laboratory at NIV Pune. As work load
increases, there is need to create more laboratories without
compromising on the WHO’s accreditation criteria. Recently, Indian
Council of Medical Research have identified 150 virus diagnostic
laboratories across the country, and attempts are going on to strengthen
them. These laboratories can be included in the MeaslesLabNet for the
measles and rubella diagnosis. Role of laboratories is crucial in
documenting interruption of endemic transmission of the circulating
(indigenous) measles viruses.
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