Indian Pediatr 2010;47: 33-37
Vaccines as Tools to Reduce ARI Burden: Merits
and Some Inherent Verticality in the Debate
Professor of Community Medicine, University College of
Medical Sciences and GTB Hospital, Delhi, India.
Correspondence to: Dr Sanjay Chaturvedi, E-15, GTB
Hospital Campus, Dilshad Garden, Delhi 110 095, India.
Acute respiratory infections (ARI) continue
to stay among the main causes of child mortality. Even in the general
population, they are the leading cause of acute morbidities globally.
Developing countries are the worst sufferers where they top the list of
causes of disability adjusted life years (DALYs) lost. Estimates suggest
that the incidence density of ARI in underfive children among developing
and industrialized world is 0.29 and 0.05 episodes per child-year,
accounting for 151 million and 5 million new episodes each year,
respectively. India (43 million), China (21 million), Pakistan (10
million), and Bangladesh (5.6 million) bear the maximal brunt(1).
Pneumonia, influenza, tuberculosis, and bronchiolitis are the chief
contributors to ARI related mortality for it is the lower respiratory
infection (LRI) that leads to severe forms of clinical presentations. Most
vulnerable to develop a fatal ARI are very young, elderly and the
immuno-compromized and in this context, a child with suboptimal immunity
for any reason is doubly at risk. While early detection and treatment with
antimicrobials significantly reduces mortality, the advantage is blunted
by lack of access to care, treatment delays and treatment failures because
of rising resistance to commonly used antimicrobials. Preventive
modalities like immunization, improved nutrition and reduced indoor air
pollution offer a proactive and cost-effective line of intervention(2).
Tuberculosis, for its inherent chronicity and BCG vaccine, for a plethora
of rather noisy evidence, deserve a dedicated space. Here, we restrict
ourselves to certain innovations in the existing immunization program as
well as some newer vaccines to be used for a sustained reduction in the
incidence of ARI.
The chief pathogens responsible for ARI in children are
Streptococcus pneumoniae, Haemo-philus influenzae type b (Hib),
Staphylococcus aureus, respiratory syncytial virus (RSV), measles
virus, human influenza virus A/H1N1, and parainfluenza viruses (PIV-1,
PIV-2 and PIV-3). Influenza virus has an added threat of novel strains
causing pandemic waves - presently novel A/H1N1 with a potential threat of
A/H5N1. Of these, licensed vaccines recommended by both the global as well
as national expert bodies are available against measles, Hib,
Streptococcus pneumoniae, and seasonal human influenza A/H1N1. One
opportunity for the measles containing vaccine (MCV-1) is a part of
national immunization schedule since mid eighties, and soon the Hib
vaccine may join the universal immunization programme (UIP) as an
ingredient of multi-dose liquid pentavalent vaccine (DPT-HepB-Hib)(3).
Availability of acellular pertussis (aP) has added to UIP options. Among
the non-UIP group, pneumococcal vaccines are making a very strong case for
inclusion and influenza vaccines are seeking immediate attention.
The fact file of measles in India raises several
concerns. Our surveillance is largely outbreak-centric and the mortality
associated with measles gets underrepresented for even in the health
system data and verbal autopsies, several cases are recorded as pneumonia
deaths. With the rejuvenated efforts to eliminate measles, India is the
only country in the region not offering the second opportunity for measles
containing vaccine (MCV-2). Now, the National Technical Advisory Group on
Immunization (NTAGI) has recommended its delivery through supplementary
immunisation activities (SIA) for children aged 9 months to 10 years in
the states with ³80%
MCV-1 coverage; and through measles-rubella (MR) or measles-mumps-rubella
(MMR) vaccine during second year of life in the states with sustained
MCV-1 coverage(4). The strategies are technically correct but in view of
the fatigue and social resistance seen with polio eradication initiative,
any campaign mode SIA may place the measles elimination program in a
social and political hotspot. The phenomenology illustrated by qualitative
evidence from western Uttar Pradesh may have a bearing on the
measles-centric verticality as well(5). Ordinary people have something
very meaningful to share with us. Some of them are shouting from the
rooftop but we are reluctant to listen. If we do, we would realize that
population-based disease control activities are much more than a technical
mission. It is being argued that the phenomenal social mobilization and
energized health machinery of pulse polio should be exploited for measles
agenda as well. Under the pressure of international advocacy and the
cultural verticality of national experts, we may continue to ignore the
voices of most peripheral health workers and people.
The scheduling of MCV-1 at 9 months has an ethical
issue also that we have been ignoring for a decade. A small proportion of
measles infection is borne by children between 6 to 9 months. These young
children suffer with the disease before reaching the eligibility for
immunization. In developing countries, maternal antibody levels against
measles may be low and severe outbreaks of measles can occur in younger
infants. The standard Edmonston-Zagreb vaccine that we have today has
shown 94% protective efficacy even among infants aged 4.5 months(6). This
age group may look small in size but ethically, we are denying vaccination
to some children at a higher risk. Epidemiologically too, this
constituency will become significant as we approach elimination. Immediate
goal of high coverage should not be delinked from the need for timely
immunization. There is a case for advancing the age of first opportunity
for measles vaccination, not as substitute but as supplement to the
vaccine given at 9-15 months(7).
Acellular pertussis (aP) vaccines containing purified
antigens are better tolerated than whole-cell vaccines (wP), and are now
used in all regions of the world. Both the types have comparable efficacy
and it would be prudent to gradually replace wP with aP. The higher cost
of aP may be the only impeding factor(8). Since the immunity after early
childhood immunization with DTwP/DTaP wanes over a decade and evidence
from industrialized countries has shown a rising secular trend of
pertussis in adolescents and adults, a single dose of Tdap (standard
quantity tetanus toxoid, reduced quantity diphtheria toxoid and three
acellular pertussis components in reduced quantities viz. pertussis toxoid,
filamentous hemagglutinin and pertactin) is being recommended at 10-12
years instead of Td alone(9).
The conjugate Hib vaccines have demonstrated safety and
efficacy world over, including India, and there is a global consensus that
lack of local surveillance data should not delay the introduction of these
vaccines in all infant immunization schedules(10). They have also
demonstrated a substantive herd effect. NTAGI was concerned about reports
of adverse events following immunization (AEFI) from Sri Lanka but the
investigations conducted by WHO did not reveal any causal association
between the events and the Hib containing vaccine(4). Hib vaccines are
available as monovalent, tetravalent (DTwP-Hib) and penta-valent (DTwP-HepB-Hib)
formulations, and in similar combinations with triple vaccine containing
acellular pertussis (DTaP). They fit into the 6-10-14 week primary
vaccination schedule followed by a booster at 15-18 months with triple
vaccine and oral polio. Several Indian manufacturers are producing Hib
vaccines and with sufficient lead time, would be able to meet the domestic
demand by scaling up the production(11). The planned nationwide roll out
of pentavalent vaccine by 2012 is supported by sound arguments and
evidence(3). However, it may be logistically challenging to launch it
across the country in a single phase. States with high under-5 mortality
should be given priority, especially the districts with low routine
immunization (RI) coverage. This will help the most vulnerable children
both by the direct and herd effect even if there is no drastic improvement
in the RI. A close monitoring of roll out projects and adverse events
following immunisation (AEFI) would ensure the managerial and technical
correctness of the initiative but carefully planned strategies for
communication and partnership with people and civil society, especially
involving non-utilizer clients, are going to be critical.
Pneumococcal vaccines are knocking at the door for
quite sometime. Both the unconjugated polysaccharide vaccine (PPV) as well
as conjugate pneumococcal vaccines (PCV) are available. PPV, a 23 valent
vaccine, has low efficacy and does not induce herd immunity. Poor
immunogenicity of this vaccine among the under-2 children, who are at
higher risk for pneumococcal disease, was the primary reason why conjugate
PCVs were developed(12). Nevertheless, PPV 23 has retained its relevance
for its broad serotype coverage and is recommended to be administered with
PCV in high risk children. The 7 valent pneumococcal conjugate vaccine (PCV
7) containing polysaccharide antigen of serotypes 4, 6B, 9V, 14, 18C, 19F
and 23 linked to a protein carrier has shown remarkable safety and
efficacy. The vaccine has also demonstrated some herd effect resulting
from reduced nasopharyngeal carriage(9). Evidence of protection from other
pneumococcal illnesses like meningitis and otitis media is not robust as
yet, and on the safety front - there have been some concerns about the
possible rise in reactive airway disease. Based on experience from over 25
developed countries and risk-benefit ratio, WHO has recommended its
inclusion in the national immunization programs on a priority basis,
especially in countries with above 50 under-5 mortality rate(13). PCV 9,
PCV 10 and PCV 13 are also in the advanced stages of trials. In the case
of PCV too, the 6-10-14 week routine immunization and a booster at 15-18
months fits well with the UIP schedule. Since the maximal force of
infection and virulence of pneumococcal disease is borne by
underprivileged and high risk children, the PCV should be offered to them
first. Cost should not be used as a deterrent – and it is not that
prohibitive either. GAVI has offered to supply PCV at a cost of Rs.
15/dose, till 2015(9).
The major concern is the coverage of circulating
serotypes in India. In the evolving scenario of serotype composition of
PCVs, NTAGI has rightly applied a cautious approach. The group has
recommended that the vaccine to be introduced in the national program
should cover more than 70% of the circulating serotypes in India. PCV7
offers only 55% coverage in this regard. It also needs to be explored
whether this can be achieved with minimal number of serotypes included in
the vaccine. That would be the appropriate product to be piloted. NTAGI
has also recommended that the indigenous manufacturers should be
encouraged to develop such a vaccine(4). This will reduce the cost and
make the program self reliant in post 2015 scenario. An assessment of
joint introduction of Hib vaccines with newer 10 and 13 valent PCVs for
mortality impact would answer several questions, as both are effective
against pneumonia and meningitis(4,11). Advocacy to establish Hib and
pneumococcal disease surveillance system for baseline measure-ment of
disease and impact monitoring has its technical merit but when seen with
the similar demands for a verticality in the surveillance of other
important diseases like measles, the proposal does not look feasible.
Although many feel that the present format of Integrated Disease
Surveillance Project (IDSP) does not suitably inform immuni-zation
program, the general consensus favors the integrated approach to
surveillance. Newer infor-mation needs of UIP will have to be woven around
an augmented IDSP.
Seasonal influenza is neither a serious child health
problem in India nor there are clearly defined influenza seasons across
the country – inspite of winter peaks in the north(14). What brings
urgency to this agenda is the ongoing pandemic caused by novel A/H1N1.
Vaccination against seasonal human influenza is a relatively complex
process. The subjects are to be immunized every year with a newer vaccine.
This process of constant change is informed by a global surveillance of
viral drift. Both killed and live attenuated vaccines are available but
only the killed vaccine is licensed in India. Both have good safety
records but their efficacy in India would only be based on an informed
guess. Current evidence does not suggest that seasonal influenza
vaccination either decreases or increases the risk for acquiring pandemic
H1N1 illness(15). Pandemic vaccines from several manufacturers are now
available within the developed world. Although all of them are based on
the initial isolate A/California/7/2009(H1N1), they are likely to be
effective since no significant genetic or antigenic drift has occurred
till now(16). With present constraints and availability, the pandemic
vaccine can only be recommended to groups at very high risk. In-country
production of pandemic vaccine, considered by NTAGI, may not be a
pragmatic response to emerging situation. Haridwar Maha-Kumbh
2010, the biggest human congregation on earth, coinciding with the
dreaded second wave in the northern hemisphere, is already on and by the
time we have an indigenous vaccine – 6 months after having new isolate, it
may be too little, too late. Non-pharmaceutical interventions would be the
only preventive modality available in large parts of India(17). We can
only hope that the second wave is as muted as its predecessor. Many argue
that the global antigenic surveillance machinery is tuned to inform
vaccine needs for North America and Europe, and even if some reference
laboratories in the developing world detect a local strain, it will have a
low probability of inclusion in the newer vaccine. These concerns get
neutralized by the communicability of influenza virus added with the level
of civil aviation that we have today. Seasonal, pre-pandemic or pandemic,
the idea of having a region specific vaccine would be self defeating. The
challenges posed by any local drift would be instantly made global by
today’s civil aviation. The developed countries know it fully well.
All this debate and advocacy on inclusion of newer
vaccines to child immunization schedule is to be seen in the context of
weak infrastructure of primary care delivery and poor RI coverage. Several
undocumented reports of non-inclusion of sizeable areas in the RI
microplanning also need to be factored here. With only 43.5% fully
immunized children - and serious rural-urban, inter-state and
inter-district divide in this ‘documented’ universe and percentages(18,19)
– widening the spectrum of diseases to be covered by available UIP and
non-UIP vaccines would not only result into suboptimal impact but may also
end up highlighting the health inequities across class, strata and
regions. Indiscriminate advertisements of several vaccines by the
manufacturers, often promoted by reach and credibility of child health
clinics, also needs to be regulated. Although cutting edge technology and
equity in health care are not mutually exclusive, one may be forced to ask
– will this public health grammar always favor the class that has power to
access and purchase? An argument that sounds specious from this side of
the table may prove quite robust from the other side. Even a vaccine made
universally available may continue to deny several children’s right to get
immunized. Access remains a result of privileges.
Competing interests: None stated.
1. World Health Organization. Acute Respiratory
Infections (Update September 2009). http://www.who.int/vaccine_research/diseases/ari/en/print.html.
Accessed 4 November, 2009.
2. Niessen L, Hove AT, Hilderink H, Weber M,
Mulhollande K, Ezzati M. Comparative impact assessment of child pneumonia
interventions. Bull World Health Organ 2009; 87: 472-480.
3. WHO India. Pneumonia a major killer in children;
prevention possible with safe & effective vaccines. http://www.whoindia.org/EN/Section6/Section453.htm.
Accessed 4 November, 2009.
4. Ministry of Health and Family Welfare, Govt. of
India. Minutes of the meeting of the National Technical Advisory Group on
Immunization (NTAGI), New Delhi: 3 Aug 2009.
5. Chaturvedi S, Dasgupta R, Adhish V, Ganguly KK, Rai
S, Sushant L, et al. Deconstructing social resistance to pulse
polio campaign in two North Indian Districts. Indian Pediatr 2009; 46:
6. Martins CL, Garly ML, Balé C, Rodrigues A, Ravn H,
Whittle HC, et al. Protective efficacy of standard Edmonston-Zagreb
measles vaccination in infants aged 4.5 months: interim analysis of a
randomised clinical trial. BMJ 2008; 337: a661.
7. Broutin H, Miller MA. Early vaccination against
measles in developing countries. BMJ 2008; 337: a406.
8. World Health Organization. WHO position on pertussis
vaccines. Wkly Epidemiol Rec 2005; 80: 37-39.
9. Indian Academy of Pediatrics Committee on
Immunization (IAPCOI). Consensus Recommen-dations on Immunization, 2008.
Indian Pediatr 2008; 45: 635-648.
10. World Health Organization. WHO position paper on
Haemophilus influenzae type b conjugate vaccines. Wkly Epidemiol Rec
2006; 81: 445-452.
11. Subcommittee on Introduction of Hib Vaccine in
Universal Immunization Program, National Technical Advisory Group on
Immunization, India. NTAGI subcommittee recommendations on Haemophilus
influenzae Type b (Hib) vaccine introduction in India. Indian Pediatr
2009; 46: 945-954.
12. Advisory Committee on Immunization Practices.
Preventing pneumococcal disease among infants and young children.
Recommendations of the Advisory Committee on Immunization Practices (ACIP).
MMWR Recomm Rep 2000; 49 (RR-9): 1-35.
13. World Health Organization. Pneumococcal conjugate
vaccine for childhood immunization – WHO position paper. Wkly Epidemiol
Rec 2007; 82: 93-104.
14. Mathew JL. Influenza vaccination for children in
India. Indian Pediatr 2009; 46: 304-307.
15. Centers for Disease Control and Prevention (CDC).
Effectiveness of 2008-09 trivalent influenza vaccine against 2009 pandemic
influenza A (H1N1) - United States, May-June 2009. MMWR Morb Mortal Wkly
Rep 2009; 58:1241-1245.
16. Johansen K, Nicoll A, Ciancio BC, Kramarz P.
Pandemic influenza A(H1N1) 2009 vaccines in the European Union. Euro
Surveill 2009; 14: 19361.
17. Chaturvedi S. Pandemic influenza: imminent threat,
preparedness and the divided globe. Indian Pediatr 2009; 46: 115-121.
18. Ministry of Health and Family Welfare, Govt. of
India. National family health survey, 2005-2006 (NFHS-3): National fact
sheet. http://www.nfhsindia.org/pdf/IN.pdf. Accessed 4 November, 2009.
19. Ministry of Health and Family Welfare, Govt. of India. District
level household and facility survey, 2007-2008 (DLHS-3). http://www.rchiips.org/state-fact-sheet-rch3.html.
Accessed 4 November , 2009.