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15 Journal of Natural Science, Biology and Medicine | January 2014 | Vol 5 | Issue 1
Acute respiratory infections among under-5
children in India: A situational analysis
Abstract
Acute respiratory infections (ARIs) are the leading cause of death among children less than 5 years in India. Emergence of
newer pathogenic organisms, reemergence of disease previously controlled, wide spread antibiotic resistance, and suboptimal
immunization coverage even after many innovative efforts are major factors responsible for high incidence ofARI. Drastic reduction
in the burden of ARI by low-cost interventions such as hand washing, breast feeding, availability of rapid and feasible array of
diagnostics, and introduction of pentavalent vaccine under National Immunization Schedule which are ongoing are necessary
for reduction of ARI.
Key words: Acute respiratory infections, control of acute respiratory infection, disease burden, National Immunization
Schedule, pneumonia, under-5 children, vaccine status
Department of Preventive and Social Medicine, Jawaharlal Institute of Post Graduate Medical
Education and Research, Puducherry, 1
Dept of Community medicine,
Indira Gandhi Medical College
and Research Institute, Puducherry, Puducherry, India
Address for correspondence:
Dr. Kalaiselvi Selvaraj, Department of Preventive and Social Medicine, Jawaharlal Institute of Post
Graduate Medical Education and Research, Puducherry - 605 009, India.
E-mail: Kalaiselvi.dr@gmail.com
INTRODUCTION
Acute respiratory infections (ARIs) contribute to major
disease associated mortality and morbidity among children
under 5 years. The existing evidences on ARI are focused
on the burden of illness around urban slums and hence
lack representative and reliable data resulting in under
estimation of ARI prevalence. Shift in the infectious disease
etiology from gram positive to gram negative organisms
is not well-recognized by health care providers who often
under utilize novel rapid diagnostic methods and/or
irrationally use antibiotics leading to increased burden
of ARI. Although a few studies have claimed efficacy
and impact of vaccines (Hemophilus influenza (Hib),
pneumococcal vaccines) in reducing the respiratory
infections,[1-4]
ignorance and other competing priorities are
major hurdles against implementing the newer vaccines in
control of ARI. Within these circumstances, this review
is focused toward the sensitization on disease burden,
etiology, and state of newer vaccines against ARI in India.
METHODS
We searched PubMed, Google Scholar and official web sites
of WHO, UNICEF, and MOHFW between 01/01/2013
and 28/02/2013. Articles were restricted to last 15 years
pertaining to Indian context. Key words used for search
are acute respiratory tract infections, pneumonia, upper
respiratory infections, lower respiratory infections,
influenza like illnesses, risk factors, and preventive
interventions for respiratory illnesses, vaccine efficacy, and
zinc prophylaxis. This review is organized in the sequence
of current mortality burden, incidence of disease burden
from Indian studies, risk factors, and preventive measures.
Mortality
ARIs are the major cause of mortality among children
aged less than 5 years especially in developing countries.
Worldwide, 20% mortality among children aged
less than 5 years is attributed to respiratory tract
Kalaiselvi Selvaraj,
Palanivel Chinnakali1
,
Anindo Majumdar,
Iswarya Santhana
Krishnan
Review Article
Access this article online
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Website:
www.jnsbm.org
DOI:
10.4103/0976-9668.127275
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Selvaraj, et al.: Acute respiratory infections among children in India
16Journal of Natural Science, Biology and Medicine | January 2014 | Vol 5 | Issue 1
infections (predominantly pneumonia associated). If
we include the neonatal pneumonia also in the pool, the
burden comes around to be 35-40% mortality among
children aged less than 5 years accounting for 2.04 million
deaths/year. Southeast Asia stands first in number for
ARI incidence,[5]
accounting for more than 80% of all
incidences together with sub-Saharan African countries.[6]
In India, more than 4 lakh deaths every year are due to
pneumonia accounting for 13%-16% of all deaths in the
pediatric hospital admissions.[7,8]
Million deaths study
based on the register general of India mortality statistics
had reported 369,000 deaths due to pneumonia among
children 1-59 months at the rate of 13.5/1000 live births.
More number of deaths due to pneumonia was reported
from central India.[9]
Morbidity
Estimating the morbidity burden has inherent challenges
due to lack of uniformity in study definitions, spectral
nature of illness and misclassification errors. Recent
estimates suggest 3.5% of the global burden of disease is
caused by ARI.[10]
In developing countries, on an average
every child has five episodes of ARI/year accounting
for 30%-50% of the total pediatric outpatient visits
and 20%-30% of the pediatric admissions.[10]
Recent
community-based estimates from prospective study report
70% of the childhood morbidities among children aged
less than 5 years are due to ARI.[11]
While in developing
country, a child is likely to have around 0.3 episodes of
pneumonia/year, in developed countries it is 0.03 episodes
per child/year.[10]
On this basis, India is predicted to have
over 700 million episodes of ARI and over 52 million
episodes of pneumonia every year. A study from Haryana
by Broor et al., had reported 2387, 536, and 43 episodes of
acute upper respiratory infections, acute lower respiratory
infections, and severe acute lower respiratory infections
respectively per 1000 child years. Table 1 shows the burden
of disease from various parts of India at different periods
of time.[10,12-19]
It is important to note that ARI include spectrum of severity
within it as a result majority of the milder infections may go
undetected. Thus incidence of respiratory infections can
be relied only from community-based longitudinal cohorts
rather than hospital-based studies. Majority of studies
regarding etiology of ARI were conducted 2 decades back
and studies on etiology at present are lacking. Without
representative community-based studies on etiology of
ARI, it is difficult to recognize the intensity of this problem.
Although some hospital-based studies have shown the
emergence of different set of pathogen contributing to
significant burden of ARI.[20,21]
Also, the reemergence
of already controlled diseases such as pertussis has
necessitated revision in National Immunization Schedule.
Even some of the developed countries have suggest
booster dose of acellular pertussis at the age of 10-12 years.
Recent evidences from Delhi shows Chlamydia, Escherichia
coli, and Mycoplasma cause more than 10% of pneumonia
individually, where the past evidences describes them as
rare pathogens.[20,21]
In clinical practice, this shift in etiology
from gram positive to gram negative organisms needs to
be considered. Scientific advances in laboratory diagnostic
methods like antigen assays, rapid diagnostic kits, and
noninvasive procedures like urinary antigen detection test
have demonstrated successful identification of respiratory
pathogens.[22]
In some of the developed countries, the
availability of multiplex real time Polymerase chain reaction
assays have made diagnosis and etiology identification of
Table 1: Incidence of acute respiratory infections in India
Author Year Study setting Results
Deb[12]
1998 North-east region Incidence of ARI=2 0%
3% of ARI in rural and 7% of ARI in urban area was
progressed into pneumonia
Sharma et al.,[13]
1999 Urban slums of Sunderpur Varanasi 6.11 episodes/children/year
NFHS I*
NFHS II
NFHS III
1994-95
1998-99
2005−06
Nationwide surveys 6.5%
19.0%
5.8%
Acharya et al.,[14]
2003 Community-based Longitudinal
study from Udupi district, Karnataka
6.42 episodes of ARI/child/year
86% URI
Rest LRI, less than 0.5% causes severe pneumonia
Jain and Khan[15]
2006 Rajasthan Attack rate-11.5%
2.9 episodes/child/year
Broor et al.,[16]
2009 Ballabgarh block in Haryana 2387 episodes of URI/1000 children years
LRI: 536/1000 children years
Severe LRI: 43 episodes/1000 children
Rudan et al.,[10]
2008 SEAR 0.36 episodes of pneumonia/child/year
Gladstone et al.,[17]
2008 Urban slums of Vellore district 7.4 episodes ARI/child year
Gladstone et al.,[18]
2010 Urban slums around Vellore ARI contribute to 58.2% of childhood morbidities
Sarkar et al.,[19]
2013 Semiurban slums-surrounding the
Vellore district
ARI contributes to 60.2% of self reported morbidities among
children. 7.5 episodes/child year. 98% of ARIs were URI
*National Family Health Survey, ARI: Acute respiratory infection, LRI: Lower respiratory tract infection, URI: Upper respiratory tract infection
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Selvaraj, et al.: Acute respiratory infections among children in India
17 Journal of Natural Science, Biology and Medicine | January 2014 | Vol 5 | Issue 1
ARI efficient. All these advancements are farther from
reach of primary health care and even clinical diagnosis of
pneumonia and empirical management based on Integrated
Management of Neonatal and Childhood Illness (IMNCI)
could save more lives.
Risk factors and determinants of ARI
Several small scale community-based studies have
reported poor socioeconomic factors; low level of literacy,
suboptimal breast feeding, malnutrition, unsatisfactory
level of immunization coverage, cooking fuel used other
than liquefied petroleum gas as risk factors contributing to
increasing burden of ARI among children.[14,23,24]
Prevention and control of respiratory infections
Breast feeding
In developing countries, children who are exclusive
breast fed for 6 months had 30%-42% lower incidence
of ARI compared to children who did not received for
same duration of breast feeding.[25]
A recent research
report from longitudinal cohort by Mihrshahi et al.,[26]
reported the increased risk of ARI (relative risk = 2.3)
among children not breast fed adequately. Breast feeding
is included under one of the life-saving tool in prevention
of various childhood diseases.[27]
Hence, breast feeding
is among the WHO/UNICEF global action plan to
stop pneumonia. In addition, hand washing, improved
nutrition, and reduction of indoor air pollution are
suggested as primary strategies to protect from pneumonia
among children under 5 years age.[5]
Hand washing and respiratory infections
Quantitative systematic review of studies from developed
countries estimated hand washing reduces the incidence
of respiratory infections by 24% (ranging from 6% to
44%).[28]
Evidences from developing countries are lacking
on this issue.
Indoor air pollution from solid bio mass fuel
Exposure to indoor air pollution has 2.3 (1.9-2.7) times
increased risk of respiratory infections (especially lower
respiratory tract infections).[25]
Hence, use of cleaner fuels
or improvised stoves have proven to be the cost-effective
interventions to reduce incidence of indoor air pollution.[29]
Million deaths study has also reported increasing prevalence
ratio (PR = 1.54 among males, 1.94 among females) of
respiratory infections due to use of solid fuel.[30]
Vaccines in preventing respiratory tract infections
Severity and transmissibility of respiratory tract infections
by major pathogens, limited availability of laboratory
diagnostics, and antibiotic resistance to wide range of drugs
makes vaccines as a potential intervention against ARI.
While conventional fatality due to pertussis, diphtheria,
and measles is reduced by routine immunization, infections
due to other bacterial organisms such as H. influenza,
Streptococcus pneumonia remains responsible for major burden
of the disease. Despite the proven efficacy of vaccines
and assistance through Global Alliance for Vaccines and
Immunization (GAVI), wide scale implementation is
lacking due to non availability of community-based studies
to establish the evidence of ARI/pneumonia due to above
organisms.
Vaccines against pertussis
Reemergence of increasing number of pertussis cases
are evident. This has led to the change in National
Immunization Schedule to introduce Diphtheria, Pertussiss
and Tetanus, (DPT-booster) at 5 years of age instead of
Diphtheria and Tetanus DT and raising the upper age limit
for DPT vaccine to 7 years of age.[31]
Measles
The recent multiyear strategic plan of India gives an
opportunity for Indian children to receive the second dose
of measles vaccine. According to this plan, Measles, Mumps
and Rubella (MMR) at 15-18 months of age is suggested
in states with >80% immunization coverage, while catch
up campaigns are suggested in states where less than 80%
routine coverage is reported.[31]
Influenza vaccine among children
For children 6-23 months, two doses of trivalent influenza
vaccine is recommended if country can afford, make it
feasible, and cost-effective analysis is made in favor of
vaccination. Children less than 6 months are exempted from
vaccination, but protection of mother during pregnancy is
recommended as a means to protect these young infants.
However, for developing countries appropriate target
groups for influenza vaccination is not well-defined.[32]
Vaccines against H. influenza-immediate candidate
to be included in National Immunization Schedule
More than 95% H. influenza infections occur only among
children. According to the recent estimates H. influenza
contributes to annual burden of 8.13 million serious
illnesses and 371,000 deaths worldwide.[33]
From the first
H. influenza vaccine trial conducted in 1973-74 showed
the efficacy of vaccine against all types of invasive
pathogens.[2,34]
Conjugated vaccines are shown to be more
immunogenic and less reactogenic.[35]
Various vaccine
trials reported efficacy in the range of 98%-100% after
three doses of vaccination, in contrast 35%-47% of the
children had low level of immunoglobulin G antibodies
against this organism when they did not receive any
booster dose.[36]
The estimated overall efficacy for
three doses of Polyribosylribitol Phosphate-Tetanus
Conjugate (Hib) Vaccine was 98.1% (95% confidence
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Selvaraj, et al.: Acute respiratory infections among children in India
18Journal of Natural Science, Biology and Medicine | January 2014 | Vol 5 | Issue 1
interval 97.3%-98.7%).[37]
Efficacy in infants aged
5-11 months was 99.1%, 12-23 months 97.3%, and
24-35 months 94.7%. This vaccine not only protects against
severe pneumonia but also prevents the colonization,
thereby helping in prevention of disease transmission.[38]
In spite of its safety, efficacy, feasibility to insert in routine
immunization schedule and protection against huge
number of avertable deaths most of the developing
countries are hesitant to adopt this mode of intervention.
Only impediment factor is cost and fear of reactions.
Despite financial and technical assistance offered by GAVI
introduction of this vaccine in National Immunization
Schedule is slow due to questionable affordability toward
long-term commitment. A recent study has shed some
insight into vaccine safety wherein use of 1.25 g dose
of vaccine has given equivalent sero conversion with less
reaction compared to conventional 5 g doses. This dose
reduction can further reduce cost of vaccination.[3]
Pneumococcal vaccines
Scope for inclusion under National Immunization
Schedule: Pneumococcal infections alone contribute
to 11% of all deaths among children under 5 years of
age.[39]
Randomized trial reports from nationwide Finish
group of children had proven 100% efficacy of vaccine
against vaccine serotypes when the 3 + 1 schedule
(6, 10, 14 weeks infant series and 1 year post toddler) was
adopted.[40]
Vaccine efficacy against this 2 + 1 schedule
was reported to be 92%.[41]
Safety profiles were confirmed
from many trials including the recent trial reported from
12 sites in India.[41-43]
Like Hib vaccines, this also prevents
colonization thereby facilitates the protection against the
disease transmission.[44,45]
While the currently available
PCV 7 gives protection against only seven serotypes, rest
of the serotypes are left out. Unfortunately, vaccine which
covers all 23 serotypes cannot be used among children
under 2 years which is a most vulnerable period to get
this disease. To widen the protection against additional
serotypes PCV-13 is suggested. Trial reports from various
countries again confirmed the safety profile and added
protection by PCV13 compared to PCV 7.[42]
However,
issues on revaccination of children in 5 years age group
remains a challenge. With these scientific evidences,
political commitment toward acceptance for inclusion
under routine vaccination is yet to be achieved.
MMR and chickenpox vaccine
Secondary pneumonia due to exanthematous illnesses like
measles and chicken pox are next common cause for ARI
among children. Despite their high incidence, prevention
efforts with these vaccines are not under priority since
other vaccines like H. influenza, Hep B are yet to be
included in nationwide plan. Varicella and MMR can be
given in two ways. Giving vaccines to adolescents and adults
alone will protect the vulnerable group without changing
the epidemiology of disease. Vaccination of children
without focusing for high coverage level (coverage < 80%)
will result in epidemiological shift leading to onset of
cases (rubella and varicella) at adult age group which is more
harmful than the existing scenario. For countries like India
where second dose of measles is proposed recently (MMR
at the age of 15-18 months) is recommended with
emphasis on high coverage. Vaccine against varicella is not
recommended at present under National Immunization
Schedule considering the other priorities. Adults who are
at risk of contacting varicella are advised to get vaccinated
within 48 hrs of exposure. This prophylactic method has
the proven efficacy of 90%.[46,47]
Mile stones in control of ARI in India
On the basis of burden and effectiveness of simple primary
health care interventions shown from the field, ARI control
program was started in India during 1990. Since then,
various community-based interventions are implemented
under ARI control program. Identification of severe
respiratory infections by health care worker from rural area,
wide access to antibiotics, and its administration by health
care workers, was seen as a successful model [Gadchiroli
project, management of childhood illness by holistic
approach of IMNCI]. Increasing coverage of vaccines
against major vaccine-preventable diseases through various
strategies under National Rural Health Mission, measles
second dose implementation and newer introduction of
pentavalent vaccines are the major primary health care
measures currently implemented in India. Table 2 shows the
factors favoring introduction of these newer vaccines under
National Immunization Schedule. Algorithm development
and respiratory tract infection group education modules
are the major steps taken by professional bodies toward
management of ARI and irrational use of antibiotics.
Role of zinc in prevention of ARI
Controversial evidences are reported over the effect of
zinc in prevention of ARI. While some of the evidences
support its impact on reducing acute lower respiratory tract
infections[48]
other studies contradict this.[49,50]
Considering
the tolerability and high threshold for toxic effects, the
further recommendations on zinc in ARI will be based on
the conclusions from ongoing community trials. However,
global action plan to prevent pneumonia by WHO/
UNICEF insists on routine zinc prophylaxis for children
affected by acute diarrheal diseases.
For developing countries to take decision on various
modes of interventions against ARI, cost-effective
analysis is necessary. The assessment of various
interventions against ARI has shown the high impact from
interventions like breast feeding, zinc prophylaxis, access
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Selvaraj, et al.: Acute respiratory infections among children in India
19 Journal of Natural Science, Biology and Medicine | January 2014 | Vol 5 | Issue 1
to clean fuel for cooking, and community/facility-based
case management. These interventions are applicable
even in resource poor settings to combat the burden of
ARI drastically.[51]
CONCLUSION
Incidence of respiratory infections cannot be reduced
without an overall increase in social and economic
development. But enormous evidences have shown
various measures to reduce this disease mortality. Every
reduction in death due to ARI would give an incremental
benefit toward achieving the Millennium Development
Goal (MDG 4). Final step toward control of ARI
would be commitment to implement these proven and
evidence-based interventions.
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Table 2: Vaccines against major respiratory pathogens
Name of
the vaccine
Burden of
diseases
Schedule Safety Efficacy Cost Impedance Adaptability to
routine immune
system
Hib 3 million cases and
3,86000 deaths
every year
Country-specific
data not available
6,10,14 weeks Rare
Local
reaction
98-100% against
invasive diseases
if three 1°doses
are complete
≈1$
child/dose
Cost analysis to
assess feasibility for
implementation in
developing countries
not available
Perfectly adapts with
routine DPT vaccine
schedule
PCV Infant series
(6, 10, 14 weeks)
Toddler dose at
one year of age
Local
reaction
50-80% ≈2$
child/dose
Cost
PCV 23 cannot be used
for children less than
two years
PCV 7 protects only
against seven
sero types
Infant series
(6,10,14 weeks) is
feasible.
Toddler dose (1 year)
needs additional visit
Influenza A
and B
Annual attack
rate-20-30% among
children
10% of OP visit and
6.5% of hospital
admission in children
Developing countries risk group not defined
Hib: Haemophilus Influenza type B, PCV-13: Pneumococcal ConjugateVaccine (13-valent) OP-out patient
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nan IS. Acute respiratory infections among under-5 children in India: A
situational analysis. J Nat Sc Biol Med 2014;5:15-20.
Source of Support: Nil. Conflict of Interest: None declared.
[Downloaded free from http://www.jnsbm.org on Wednesday, March 16, 2016, IP: 117.211.48.144]

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Rf prevention control of ari

  • 1. 15 Journal of Natural Science, Biology and Medicine | January 2014 | Vol 5 | Issue 1 Acute respiratory infections among under-5 children in India: A situational analysis Abstract Acute respiratory infections (ARIs) are the leading cause of death among children less than 5 years in India. Emergence of newer pathogenic organisms, reemergence of disease previously controlled, wide spread antibiotic resistance, and suboptimal immunization coverage even after many innovative efforts are major factors responsible for high incidence ofARI. Drastic reduction in the burden of ARI by low-cost interventions such as hand washing, breast feeding, availability of rapid and feasible array of diagnostics, and introduction of pentavalent vaccine under National Immunization Schedule which are ongoing are necessary for reduction of ARI. Key words: Acute respiratory infections, control of acute respiratory infection, disease burden, National Immunization Schedule, pneumonia, under-5 children, vaccine status Department of Preventive and Social Medicine, Jawaharlal Institute of Post Graduate Medical Education and Research, Puducherry, 1 Dept of Community medicine, Indira Gandhi Medical College and Research Institute, Puducherry, Puducherry, India Address for correspondence: Dr. Kalaiselvi Selvaraj, Department of Preventive and Social Medicine, Jawaharlal Institute of Post Graduate Medical Education and Research, Puducherry - 605 009, India. E-mail: Kalaiselvi.dr@gmail.com INTRODUCTION Acute respiratory infections (ARIs) contribute to major disease associated mortality and morbidity among children under 5 years. The existing evidences on ARI are focused on the burden of illness around urban slums and hence lack representative and reliable data resulting in under estimation of ARI prevalence. Shift in the infectious disease etiology from gram positive to gram negative organisms is not well-recognized by health care providers who often under utilize novel rapid diagnostic methods and/or irrationally use antibiotics leading to increased burden of ARI. Although a few studies have claimed efficacy and impact of vaccines (Hemophilus influenza (Hib), pneumococcal vaccines) in reducing the respiratory infections,[1-4] ignorance and other competing priorities are major hurdles against implementing the newer vaccines in control of ARI. Within these circumstances, this review is focused toward the sensitization on disease burden, etiology, and state of newer vaccines against ARI in India. METHODS We searched PubMed, Google Scholar and official web sites of WHO, UNICEF, and MOHFW between 01/01/2013 and 28/02/2013. Articles were restricted to last 15 years pertaining to Indian context. Key words used for search are acute respiratory tract infections, pneumonia, upper respiratory infections, lower respiratory infections, influenza like illnesses, risk factors, and preventive interventions for respiratory illnesses, vaccine efficacy, and zinc prophylaxis. This review is organized in the sequence of current mortality burden, incidence of disease burden from Indian studies, risk factors, and preventive measures. Mortality ARIs are the major cause of mortality among children aged less than 5 years especially in developing countries. Worldwide, 20% mortality among children aged less than 5 years is attributed to respiratory tract Kalaiselvi Selvaraj, Palanivel Chinnakali1 , Anindo Majumdar, Iswarya Santhana Krishnan Review Article Access this article online Quick Response Code: Website: www.jnsbm.org DOI: 10.4103/0976-9668.127275 [Downloaded free from http://www.jnsbm.org on Wednesday, March 16, 2016, IP: 117.211.48.144]
  • 2. Selvaraj, et al.: Acute respiratory infections among children in India 16Journal of Natural Science, Biology and Medicine | January 2014 | Vol 5 | Issue 1 infections (predominantly pneumonia associated). If we include the neonatal pneumonia also in the pool, the burden comes around to be 35-40% mortality among children aged less than 5 years accounting for 2.04 million deaths/year. Southeast Asia stands first in number for ARI incidence,[5] accounting for more than 80% of all incidences together with sub-Saharan African countries.[6] In India, more than 4 lakh deaths every year are due to pneumonia accounting for 13%-16% of all deaths in the pediatric hospital admissions.[7,8] Million deaths study based on the register general of India mortality statistics had reported 369,000 deaths due to pneumonia among children 1-59 months at the rate of 13.5/1000 live births. More number of deaths due to pneumonia was reported from central India.[9] Morbidity Estimating the morbidity burden has inherent challenges due to lack of uniformity in study definitions, spectral nature of illness and misclassification errors. Recent estimates suggest 3.5% of the global burden of disease is caused by ARI.[10] In developing countries, on an average every child has five episodes of ARI/year accounting for 30%-50% of the total pediatric outpatient visits and 20%-30% of the pediatric admissions.[10] Recent community-based estimates from prospective study report 70% of the childhood morbidities among children aged less than 5 years are due to ARI.[11] While in developing country, a child is likely to have around 0.3 episodes of pneumonia/year, in developed countries it is 0.03 episodes per child/year.[10] On this basis, India is predicted to have over 700 million episodes of ARI and over 52 million episodes of pneumonia every year. A study from Haryana by Broor et al., had reported 2387, 536, and 43 episodes of acute upper respiratory infections, acute lower respiratory infections, and severe acute lower respiratory infections respectively per 1000 child years. Table 1 shows the burden of disease from various parts of India at different periods of time.[10,12-19] It is important to note that ARI include spectrum of severity within it as a result majority of the milder infections may go undetected. Thus incidence of respiratory infections can be relied only from community-based longitudinal cohorts rather than hospital-based studies. Majority of studies regarding etiology of ARI were conducted 2 decades back and studies on etiology at present are lacking. Without representative community-based studies on etiology of ARI, it is difficult to recognize the intensity of this problem. Although some hospital-based studies have shown the emergence of different set of pathogen contributing to significant burden of ARI.[20,21] Also, the reemergence of already controlled diseases such as pertussis has necessitated revision in National Immunization Schedule. Even some of the developed countries have suggest booster dose of acellular pertussis at the age of 10-12 years. Recent evidences from Delhi shows Chlamydia, Escherichia coli, and Mycoplasma cause more than 10% of pneumonia individually, where the past evidences describes them as rare pathogens.[20,21] In clinical practice, this shift in etiology from gram positive to gram negative organisms needs to be considered. Scientific advances in laboratory diagnostic methods like antigen assays, rapid diagnostic kits, and noninvasive procedures like urinary antigen detection test have demonstrated successful identification of respiratory pathogens.[22] In some of the developed countries, the availability of multiplex real time Polymerase chain reaction assays have made diagnosis and etiology identification of Table 1: Incidence of acute respiratory infections in India Author Year Study setting Results Deb[12] 1998 North-east region Incidence of ARI=2 0% 3% of ARI in rural and 7% of ARI in urban area was progressed into pneumonia Sharma et al.,[13] 1999 Urban slums of Sunderpur Varanasi 6.11 episodes/children/year NFHS I* NFHS II NFHS III 1994-95 1998-99 2005−06 Nationwide surveys 6.5% 19.0% 5.8% Acharya et al.,[14] 2003 Community-based Longitudinal study from Udupi district, Karnataka 6.42 episodes of ARI/child/year 86% URI Rest LRI, less than 0.5% causes severe pneumonia Jain and Khan[15] 2006 Rajasthan Attack rate-11.5% 2.9 episodes/child/year Broor et al.,[16] 2009 Ballabgarh block in Haryana 2387 episodes of URI/1000 children years LRI: 536/1000 children years Severe LRI: 43 episodes/1000 children Rudan et al.,[10] 2008 SEAR 0.36 episodes of pneumonia/child/year Gladstone et al.,[17] 2008 Urban slums of Vellore district 7.4 episodes ARI/child year Gladstone et al.,[18] 2010 Urban slums around Vellore ARI contribute to 58.2% of childhood morbidities Sarkar et al.,[19] 2013 Semiurban slums-surrounding the Vellore district ARI contributes to 60.2% of self reported morbidities among children. 7.5 episodes/child year. 98% of ARIs were URI *National Family Health Survey, ARI: Acute respiratory infection, LRI: Lower respiratory tract infection, URI: Upper respiratory tract infection [Downloaded free from http://www.jnsbm.org on Wednesday, March 16, 2016, IP: 117.211.48.144]
  • 3. Selvaraj, et al.: Acute respiratory infections among children in India 17 Journal of Natural Science, Biology and Medicine | January 2014 | Vol 5 | Issue 1 ARI efficient. All these advancements are farther from reach of primary health care and even clinical diagnosis of pneumonia and empirical management based on Integrated Management of Neonatal and Childhood Illness (IMNCI) could save more lives. Risk factors and determinants of ARI Several small scale community-based studies have reported poor socioeconomic factors; low level of literacy, suboptimal breast feeding, malnutrition, unsatisfactory level of immunization coverage, cooking fuel used other than liquefied petroleum gas as risk factors contributing to increasing burden of ARI among children.[14,23,24] Prevention and control of respiratory infections Breast feeding In developing countries, children who are exclusive breast fed for 6 months had 30%-42% lower incidence of ARI compared to children who did not received for same duration of breast feeding.[25] A recent research report from longitudinal cohort by Mihrshahi et al.,[26] reported the increased risk of ARI (relative risk = 2.3) among children not breast fed adequately. Breast feeding is included under one of the life-saving tool in prevention of various childhood diseases.[27] Hence, breast feeding is among the WHO/UNICEF global action plan to stop pneumonia. In addition, hand washing, improved nutrition, and reduction of indoor air pollution are suggested as primary strategies to protect from pneumonia among children under 5 years age.[5] Hand washing and respiratory infections Quantitative systematic review of studies from developed countries estimated hand washing reduces the incidence of respiratory infections by 24% (ranging from 6% to 44%).[28] Evidences from developing countries are lacking on this issue. Indoor air pollution from solid bio mass fuel Exposure to indoor air pollution has 2.3 (1.9-2.7) times increased risk of respiratory infections (especially lower respiratory tract infections).[25] Hence, use of cleaner fuels or improvised stoves have proven to be the cost-effective interventions to reduce incidence of indoor air pollution.[29] Million deaths study has also reported increasing prevalence ratio (PR = 1.54 among males, 1.94 among females) of respiratory infections due to use of solid fuel.[30] Vaccines in preventing respiratory tract infections Severity and transmissibility of respiratory tract infections by major pathogens, limited availability of laboratory diagnostics, and antibiotic resistance to wide range of drugs makes vaccines as a potential intervention against ARI. While conventional fatality due to pertussis, diphtheria, and measles is reduced by routine immunization, infections due to other bacterial organisms such as H. influenza, Streptococcus pneumonia remains responsible for major burden of the disease. Despite the proven efficacy of vaccines and assistance through Global Alliance for Vaccines and Immunization (GAVI), wide scale implementation is lacking due to non availability of community-based studies to establish the evidence of ARI/pneumonia due to above organisms. Vaccines against pertussis Reemergence of increasing number of pertussis cases are evident. This has led to the change in National Immunization Schedule to introduce Diphtheria, Pertussiss and Tetanus, (DPT-booster) at 5 years of age instead of Diphtheria and Tetanus DT and raising the upper age limit for DPT vaccine to 7 years of age.[31] Measles The recent multiyear strategic plan of India gives an opportunity for Indian children to receive the second dose of measles vaccine. According to this plan, Measles, Mumps and Rubella (MMR) at 15-18 months of age is suggested in states with >80% immunization coverage, while catch up campaigns are suggested in states where less than 80% routine coverage is reported.[31] Influenza vaccine among children For children 6-23 months, two doses of trivalent influenza vaccine is recommended if country can afford, make it feasible, and cost-effective analysis is made in favor of vaccination. Children less than 6 months are exempted from vaccination, but protection of mother during pregnancy is recommended as a means to protect these young infants. However, for developing countries appropriate target groups for influenza vaccination is not well-defined.[32] Vaccines against H. influenza-immediate candidate to be included in National Immunization Schedule More than 95% H. influenza infections occur only among children. According to the recent estimates H. influenza contributes to annual burden of 8.13 million serious illnesses and 371,000 deaths worldwide.[33] From the first H. influenza vaccine trial conducted in 1973-74 showed the efficacy of vaccine against all types of invasive pathogens.[2,34] Conjugated vaccines are shown to be more immunogenic and less reactogenic.[35] Various vaccine trials reported efficacy in the range of 98%-100% after three doses of vaccination, in contrast 35%-47% of the children had low level of immunoglobulin G antibodies against this organism when they did not receive any booster dose.[36] The estimated overall efficacy for three doses of Polyribosylribitol Phosphate-Tetanus Conjugate (Hib) Vaccine was 98.1% (95% confidence [Downloaded free from http://www.jnsbm.org on Wednesday, March 16, 2016, IP: 117.211.48.144]
  • 4. Selvaraj, et al.: Acute respiratory infections among children in India 18Journal of Natural Science, Biology and Medicine | January 2014 | Vol 5 | Issue 1 interval 97.3%-98.7%).[37] Efficacy in infants aged 5-11 months was 99.1%, 12-23 months 97.3%, and 24-35 months 94.7%. This vaccine not only protects against severe pneumonia but also prevents the colonization, thereby helping in prevention of disease transmission.[38] In spite of its safety, efficacy, feasibility to insert in routine immunization schedule and protection against huge number of avertable deaths most of the developing countries are hesitant to adopt this mode of intervention. Only impediment factor is cost and fear of reactions. Despite financial and technical assistance offered by GAVI introduction of this vaccine in National Immunization Schedule is slow due to questionable affordability toward long-term commitment. A recent study has shed some insight into vaccine safety wherein use of 1.25 g dose of vaccine has given equivalent sero conversion with less reaction compared to conventional 5 g doses. This dose reduction can further reduce cost of vaccination.[3] Pneumococcal vaccines Scope for inclusion under National Immunization Schedule: Pneumococcal infections alone contribute to 11% of all deaths among children under 5 years of age.[39] Randomized trial reports from nationwide Finish group of children had proven 100% efficacy of vaccine against vaccine serotypes when the 3 + 1 schedule (6, 10, 14 weeks infant series and 1 year post toddler) was adopted.[40] Vaccine efficacy against this 2 + 1 schedule was reported to be 92%.[41] Safety profiles were confirmed from many trials including the recent trial reported from 12 sites in India.[41-43] Like Hib vaccines, this also prevents colonization thereby facilitates the protection against the disease transmission.[44,45] While the currently available PCV 7 gives protection against only seven serotypes, rest of the serotypes are left out. Unfortunately, vaccine which covers all 23 serotypes cannot be used among children under 2 years which is a most vulnerable period to get this disease. To widen the protection against additional serotypes PCV-13 is suggested. Trial reports from various countries again confirmed the safety profile and added protection by PCV13 compared to PCV 7.[42] However, issues on revaccination of children in 5 years age group remains a challenge. With these scientific evidences, political commitment toward acceptance for inclusion under routine vaccination is yet to be achieved. MMR and chickenpox vaccine Secondary pneumonia due to exanthematous illnesses like measles and chicken pox are next common cause for ARI among children. Despite their high incidence, prevention efforts with these vaccines are not under priority since other vaccines like H. influenza, Hep B are yet to be included in nationwide plan. Varicella and MMR can be given in two ways. Giving vaccines to adolescents and adults alone will protect the vulnerable group without changing the epidemiology of disease. Vaccination of children without focusing for high coverage level (coverage < 80%) will result in epidemiological shift leading to onset of cases (rubella and varicella) at adult age group which is more harmful than the existing scenario. For countries like India where second dose of measles is proposed recently (MMR at the age of 15-18 months) is recommended with emphasis on high coverage. Vaccine against varicella is not recommended at present under National Immunization Schedule considering the other priorities. Adults who are at risk of contacting varicella are advised to get vaccinated within 48 hrs of exposure. This prophylactic method has the proven efficacy of 90%.[46,47] Mile stones in control of ARI in India On the basis of burden and effectiveness of simple primary health care interventions shown from the field, ARI control program was started in India during 1990. Since then, various community-based interventions are implemented under ARI control program. Identification of severe respiratory infections by health care worker from rural area, wide access to antibiotics, and its administration by health care workers, was seen as a successful model [Gadchiroli project, management of childhood illness by holistic approach of IMNCI]. Increasing coverage of vaccines against major vaccine-preventable diseases through various strategies under National Rural Health Mission, measles second dose implementation and newer introduction of pentavalent vaccines are the major primary health care measures currently implemented in India. Table 2 shows the factors favoring introduction of these newer vaccines under National Immunization Schedule. Algorithm development and respiratory tract infection group education modules are the major steps taken by professional bodies toward management of ARI and irrational use of antibiotics. Role of zinc in prevention of ARI Controversial evidences are reported over the effect of zinc in prevention of ARI. While some of the evidences support its impact on reducing acute lower respiratory tract infections[48] other studies contradict this.[49,50] Considering the tolerability and high threshold for toxic effects, the further recommendations on zinc in ARI will be based on the conclusions from ongoing community trials. However, global action plan to prevent pneumonia by WHO/ UNICEF insists on routine zinc prophylaxis for children affected by acute diarrheal diseases. For developing countries to take decision on various modes of interventions against ARI, cost-effective analysis is necessary. The assessment of various interventions against ARI has shown the high impact from interventions like breast feeding, zinc prophylaxis, access [Downloaded free from http://www.jnsbm.org on Wednesday, March 16, 2016, IP: 117.211.48.144]
  • 5. Selvaraj, et al.: Acute respiratory infections among children in India 19 Journal of Natural Science, Biology and Medicine | January 2014 | Vol 5 | Issue 1 to clean fuel for cooking, and community/facility-based case management. These interventions are applicable even in resource poor settings to combat the burden of ARI drastically.[51] CONCLUSION Incidence of respiratory infections cannot be reduced without an overall increase in social and economic development. But enormous evidences have shown various measures to reduce this disease mortality. Every reduction in death due to ARI would give an incremental benefit toward achieving the Millennium Development Goal (MDG 4). Final step toward control of ARI would be commitment to implement these proven and evidence-based interventions. REFERENCES 1. Swingler G, Fransman D, Hussey G. Conjugate vaccines for preventing Haemophilus influenzae type B infections. Cochrane Database Syst Rev 2007;18:CD001729. 2. Vadheim CM, Greenberg DP, Partridge S, Jing J, Ward JI. Effectiveness and safety of an Haemophilus influenzae type b conjugate vaccine (PRP-T) in young infants. Kaiser-UCLA Vaccine Study Group. Pediatrics 1993;92:272-9. 3. Punjabi NH, Richie EL, Simanjuntak CH, Harjanto SJ, Wangsasaputra F, Arjoso S, et al. Immunogenicity and safety of four different doses of Haemophilus influenzae type b-tetanus toxoid conjugated vaccine, combined with diphtheria-tetanus-pertussis vaccine (DTP-Hib), in Indonesian infants. Vaccine 2006;24:1776-85. 4. Amdekar YK, Lalwani SK, Bavdekar A, Balasubramanian S, Chhatwal J, Bhat SR, et al. Immunogenicity and Safety of a 13-Valent Pneumococcal Conjugate Vaccine in Healthy Infants and Toddlers Given with Routine Vaccines in India. Pediatr Infect Dis J 2012. 5. Wardlaw TM, Johansson EW, Hodge MJ. World Health Organization. Pneumonia: The Forgotten Killer of Children. UNICEF, 2006. Available from: http://www.who.int/maternal_child_adolescent/ documents/9280640489/en/[Last accessed on 2013 Mar 13]. 6. The State of Asia-Pacific’s Children 2008: Child Survival. Unicef, 2008. Available from: http://www.unicef.org/sapc08/report/report. php [Last accessed on 2013 Mar 13]. 7. Jain N, Lodha R, Kabra SK. Upper respiratory tract infections. Indian J Pediatr 2001;68:1135-8. 8. Vashishtha VM. Current status of tuberculosis and acute respiratory infections in India: Much more needs to be done! Indian Pediatr 2010;47:88-9. 9. Causes of neonatal and child mortality in India: A nationally representative mortality survey-Causes-of-neonatal-and-child- mortality-in-India-2010.pdf. Available from: http://cghr.org/ wordpress/wp-content/uploads/Causes-of-neonatal-and- child-mortality-in-India-2010.pdf [Last accessed on 2013 Mar 11]. 10. Rudan I, Boschi-Pinto C, Biloglav Z, Mulholland K, Campbell H. Epidemiology and etiology of childhood pneumonia. Bull World Health Organ 2008;86:408-16. 11. Dongre AR, Deshmukh PR, Garg BS. Health expenditure and care seeking on acute child morbidities in peri-urban Wardha: A prospective study. Indian J Pediatr 2010;77:503-7. 12. Deb SK. Acute respiratory disease survey in Tripura in case of children below five years of age. J Indian Med Assoc 1998;96:111-6. 13. Sharma AK, Reddy DC, Dwivedi RR. Descriptive epidemiology of acute respiratory infections among under five children in an urban slum area. Indian J Public Health 1999;43:156-9. 14. Acharya D, Prasanna KS, Nair S, Rao RS. Acute respiratory infections in children: A community based longitudinal study in south India. Indian J Public Health 2003;47:7-13. 15. Jain SK, Khan JA. Epidemiological study of acute diarrhoeal disease and acute respiratory infection amongst under-five children inAlwar district (Rajasthan), India. Indian J Practising Doctor 2006;3 (5):11-2. 16. BroorS,ParveenS,BharajP,PrasadVS,SrinivasuluKN,SumanthKM, et al. A prospective three-year cohort study of the epidemiology and virology of acute respiratory infections of children in rural India. PLoS One 2007;2:e491. 17. Gladstone BP, Das AR, Rehman AM, Jaffar S, Estes MK, Muliyil J, et al. Burden of illness in the first 3 years of life in an Indian slum. J Trop Pediatr 2010;56:221-6. 18. Gladstone BP, Muliyil JP, Jaffar S, Wheeler JG, Le Fevre A, Iturriza-Gomara M, et al. Infant morbidity in an Indian slum birth cohort. Arch Dis Child 2008;93:479-84. 19. Sarkar R, Sivarathinaswamy P, Thangaraj B, Sindhu KN, Ajjampur SS, Muliyil J, et al. Burden of childhood diseases and Table 2: Vaccines against major respiratory pathogens Name of the vaccine Burden of diseases Schedule Safety Efficacy Cost Impedance Adaptability to routine immune system Hib 3 million cases and 3,86000 deaths every year Country-specific data not available 6,10,14 weeks Rare Local reaction 98-100% against invasive diseases if three 1°doses are complete ≈1$ child/dose Cost analysis to assess feasibility for implementation in developing countries not available Perfectly adapts with routine DPT vaccine schedule PCV Infant series (6, 10, 14 weeks) Toddler dose at one year of age Local reaction 50-80% ≈2$ child/dose Cost PCV 23 cannot be used for children less than two years PCV 7 protects only against seven sero types Infant series (6,10,14 weeks) is feasible. Toddler dose (1 year) needs additional visit Influenza A and B Annual attack rate-20-30% among children 10% of OP visit and 6.5% of hospital admission in children Developing countries risk group not defined Hib: Haemophilus Influenza type B, PCV-13: Pneumococcal ConjugateVaccine (13-valent) OP-out patient [Downloaded free from http://www.jnsbm.org on Wednesday, March 16, 2016, IP: 117.211.48.144]
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How to cite this article: Selvaraj K, Chinnakali P, Majumdar A, Krish- nan IS. Acute respiratory infections among under-5 children in India: A situational analysis. J Nat Sc Biol Med 2014;5:15-20. Source of Support: Nil. Conflict of Interest: None declared. [Downloaded free from http://www.jnsbm.org on Wednesday, March 16, 2016, IP: 117.211.48.144]