review on child health priorities |
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Indian Pediatr 2011;48:
191-218 |
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Acute Respiratory Infection and Pneumonia in
India: A Systematic Review of Literature for Advocacy and
Action: UNICEF-PHFI Series on Newborn and Child Health, India |
Joseph L Mathew, *Ashok K Patwari, ¶Piyush Gupta, ¶Dheeraj
Shah, $Tarun Gera, **Siddhartha Gogia, ¶¶Pavitra
Mohan, $$Rajmohan Panda and $$ Subhadra Menon
From Advanced Pediatrics Center, PGIMER, Chandigarh;
*Research Professor, International Health, Center for Global Health &
Development, School of Public Health, Boston University; ¶University
College of Medical Sciences, New Delhi; $Fortis Hospital, New
Delhi; **Max Hospital, Gurgaon, Haryana; ¶¶UNICEF, India; and
$$Public Health Foundation of India, New Delhi, India.
Correspondence to: Joseph L Mathew, Advanced Pediatrics
Center, PGIMER, Chandigarh 160 012, India.
Email: [email protected]
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Background: Scaling up of evidence-based management of
childhood acute respiratory infection/pneumonia, is a public health
priority in India, and necessitates robust literature review, for advocacy
and action.
Objective: To identify, synthesize and summarize
current evidence to guide scaling up of management of childhood acute
respiratory infection/pneumonia in India, and identify existing knowledge
gaps.
Methods: A set of ten questions pertaining to the
management (prevention, treatment, and control) of childhood ARI/pneumonia
was identified through a consultative process. A modified systematic
review process developed a priori was used to identify, synthesize
and summarize, research evidence and operational information, pertaining
to the problem in India. Areas with limited or no evidence were identified
as knowledge gaps.
Results: Childhood ARI/pneumonia is a significant
public health problem in India, although robust epidemiological data is
not available on its incidence. Mortality due to pneumonia accounts for
approximately one-fourth of the total deaths in under five children, in
India. Pneumonia affects children irrespective of socioeconomic status;
with higher risk among young infants, malnourished children,
non-exclusively breastfed children and those with exposure to solid fuel
use. There is lack of robust nation-wide data on etiology; bacteria
(including Pneumococcus, H. influenzae, S. aureus and Gram
negative bacilli), viruses (especially RSV) and Mycoplasma, are the
common organisms identified. In-vitro resistance to cotrimoxazole
is high. Wheezing is commonly associated with ARI/pneumonia in children,
but difficult to appreciate without auscultation. The current WHO
guidelines as modified by IndiaCLEN Task force on Penumonia (2010), are
sufficient for case-management of childhood pneumonia. Other important
interventions to prevent mortality are oxygen therapy for those with
severe or very severe pneumonia and measles vaccination for all infants.
There is insufficient evidence for protective or curative effect of
vitamin A; zinc supplementation could be beneficial to prevent pneumonia,
although it has no therapeutic benefit. There is insufficient evidence on
potential effectiveness and cost-effectiveness of Hib and Pneumococcal
vaccines on reduction of ARI specific mortality. Case-finding and
community-based management are effective management strategies, but have
low coverage in India due to policy and programmatic barriers. There is a
significant gap in the utilization of existing services, provider
practices as well as family practices in seeking care.
Conclusion: The systematic review summarizes
current evidence on childhood ARI and pneumonia management and provides
evidence to inform child health programs in India
Keywords: Action, Advocacy, ARI, Child health, Pneumonia,
Systematic reviews.
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Childhood Acute Respiratory Infection (ARI) is the largest cause of
morbidity among under-five children across the world. Pneumonia - the most
serious presentation - is singly responsible for almost one-fifth of total
mortality in this vulnerable age group. Therefore the importance of ARI
and pneumonia cannot be over-emphasized. Consequently, global health-care
agencies such as the World Health Organization (WHO), United Nations
Children’s Fund (UNICEF), national and state Governments, as well as
international and local agencies involved with aid, academics, and
research- have all focused on this area. In India, ARI has been given top
priority in all Government programs including the current Reproductive and
Child Health Program, Phase-II (RCH-II).
The successful management of childhood pneumonia at a
programmatic level revolves around four prongs viz. rapid and
accurate detection of pneumonia in children, early treatment/management
with specific therapy, management of co-morbid conditions, and efforts at
primary prevention. These basic tenets are utilized to varying degrees in
different programmes to manage the burden of childhood pneumonia at the
national and international levels. However, there are several challenges
in implementing and managing a successful program to reduce the mortality
and morbidity due to childhood pneumonia, necessitating periodic review
and rethinking.
This systematic review of literature was undertaken to
provide evidence-based guidance for advocacy and action towards the
management of childhood pneumonia in India. The specific objective was to
identify, synthesize and summarize current best evidence pertaining to ARI/pneumonia.
The review further aimed to identify knowledge gaps in the issues
considered, with particular reference to the Indian context.
Methods
The format for the Systematic Review Methodology has
been presented earlier [1]. The search term "ARI" in Medline MeSH revealed
7 categories, none of which included acute respiratory infection. The term
"acute respiratory infection" yielded no output, but the list of
Suggestions included "respiratory infection". Exploding this term yielded
the sub-category of "Respiratory Tract Infections" with 22 further
sub-categories, one of which was "Pneumonia". Since most of the other
terms did not cover acute respiratory infection, "Pneumonia" was chosen as
the term for searching literature through Medline.
However, "ARI" frequently appears as a term in other
documents including the World Health Organization (WHO) reports,
Government of India documents, National Family Health Survey (NFHS)
report, etc. Therefore, the term "ARI" also was used when searching these
sources.
Results
Details of the search output in terms of citations
identified, titles screened, abstracts short-listed and full-text examined
are shown in WebTable I.
Literature searches were carried out during April 2010; and updated on15
February 2011.
1. Epidemiology
Burden of disease in India
There was no systematic review or nation-wide cohort
study addressing this issue. Nation-wide data, collected prospectively
from a representative sample of the Indian population, through the serial
National Family Health Survey (NFHS) studies [2-4] reported an overall ARI
prevalence of 6.5%, 19.0% and 5.8% among under-five children in the
preceding two weeks before the survey in three surveys at three
time-periods over last two decades (Table I). The
inexplicable three-fold higher prevalence in the second survey compared to
the first is inadequately explained; it is stated that the difference is
on account of different time-periods at which surveys were conducted. The
National Health Profile of India report published by the Central Bureau of
Health Intelligence [5] mentions 26 544 613 cases of ARI across all age
groups with only 2813 deaths; although the source and methodology are not
described.
A research paper reporting global estimates projected
44 million cases per year in India [6]. A previous estimate based on the
same data projected 43 million episodes per year [7]. A recent
secondary analysis pointed out that both are likely to be over-estimates
based on out-dated data and/or highly sensitive diagnosis [8].
Among the small-scale primary studies, a
community-based study in Udupi [9] among children less than five years old
recorded overall ARI incidence of 6.42 episodes per child per year;
however only 51 of 584 episodes (8.7%) were pneumonia (which works out to
0.52 episodes per child per year) and only 3 of 584 ARI episodes (0.5%)
were severe pneumonia. A small ARI survey conducted in Tripura [10] among
400 rural and 400 urban slum children below five years of age, reported
the incidence of ARI over 18 months as 23% in rural areas, and 17.7% in
urban areas. A study from Lucknow [11] reported 17 episodes of pneumonia
among 1061 children, giving an annual incidence rate of 0.096 (95% CI
0.057 to 0.16) per child year. The same study [11] also reported the
annual incidence rate of respiratory disease (other than pneumonia) as 167
(95% 149-185) per 100 child-years, suggesting that just under 10%
‘respiratory disease’ is ‘pneumonia’. A 20 year old study from AIIMS New
Delhi [12] followed 5335 children in villages of Ballabhgarh block for one
year and reported 834 episodes of pneumonia. The authors calculated the
attack rate as 0.29/child/year among under-five children. Severe cases
constituted only 0.5%.
A recent study [13] published during the process of
this systematic review evaluated the incidence of hospitalised pneumonia
and meningitis in infants below 2 years old. Severe pneumonia was defined
to match the WHO criteria (cough or difficult breathing or tachypnea and
at least one clinical sign among intercostal retractions, nasal flaring,
grunting, central cyanosis, inability to feed, lethargy, unconsciousness,
or head nodding). Radiographic evidence of consolidation as per the WHO
criteria was labelled as Radiological pneumonia. A total of 589 episodes
of pneumonia were suspected among 17951 children. The incidence of
physician diagnosed pneumonia at discharge per child-year in the three
study sites was 0.030 (95% CI 0.025-0.034) at Chandigarh, 0.080 (95% CI
0.071-0.091) at Kolkata and 0.037 (95% CI 0.030-0.045) at Vellore.
Age-specific calculations showed that the incidence of severe clinical
hospitalized pneumonia was highest in infants less than 5 months old,
declining with increasing age. Only 11.3% of 434 readable radiographs were
consistent with radiological pneumonia; although there was significant
variation among the three study sites.
Conclusions and Comments
• The precise magnitude of childhood ARI and/or
pneumonia in India is not known. ARI and pneumonia have been used
interchangeably in some studies although the two are not synonymous.
• Most of the available data is based on small-scale
community and hospital-based studies, and hence may not be
representative of the whole population. It appears that a little less
than 10% of ARI are pneumonia.
• The burden of disease in terms of episodes per
child per year in small scale studies ranges from 0.03 to 0.52.
Knowledge gap
• Childhood community acquired pneumonia is an
important public health problem, though the precise burden is not known.
Mortality
The Registrar General of India conducts the Sample
Registration System (SRS) in randomly selected sample units all over India
to calculate multiple demographic indicators. A study based [14] on a
sample from the 1991 census (about 6 million people in 1.1 million
households) used an enhanced format of verbal autopsy (abbreviated as
RHIME for routine, reliable, representative, resampled household
investigation of mortality with medical evaluation) to estimate cause
specific mortality in the selected sample. Families were interviewed and
cause of death assigned by physicians, providing cause-specific mortality
rates for 2005. Pneumonia was identified using 32 codes of the
International Classification of Diseases tenth revision (ICD-10). Using
data from this study, respiratory infection was reported as the cause of
22% mortality among 0-4 year old children for the period 2001-03. For the
age group 1-4 years, respiratory infections were responsible for 22.5%
deaths.
The Million Death Study [15] reported that, 27·6% (99%
CI 31·8%-34·1%) deaths were attributable to pneumonia among a total of
12260 deaths in children from 1-59 months. This outweighed the deaths due
to diarrhea (22·6% with 99% CI 21·5%-23·7%), making pneumonia the leading
cause of childhood mortality in India. In this study, pneumonia was
identified by verbal autopsy and labeled by physicians.
Using the SRS data, the Million Death Study group
applied the proportions of each cause of childhood mortality to the
independent UN Population Division estimate of India’s total live births
(27·3 million) and under-five childhood mortality (2·35 million) for the
year 2005; to estimate age-specific and gender-specific mortality rates
(per 1000 live births) as well as absolute number of deaths by specific
causes [15]. Mortality due to pneumonia comprised 24·9% (99% CI
21·4-28·8%) of 1113 deaths in urban areas; and 28·0% (99% CI 26·8-29·2) of
11147 deaths in rural children. The proportion of deaths due to pneumonia
was highest in Jammu and Kashmir, and Delhi; and lowest in Tamil Nadu. The
study projected the collected data for the whole country and estimated
that 13·5% (99% CI 13·0-14·1) of under five mortality is attributable to
pneumonia; accounting for 369000 annual deaths. It also reported that the
mortality due to pneumonia among girls was higher than boys (16.0% vs
11.2%) [15].
The Central Bureau of Health Intelligence of the MoHFW
reported ARI mortality ranging from 3200 to 6900 each year [5], giving a
mortality rate of 0.32 to 0.61 deaths per l00,000 population. The
WHO-UNICEF estimated that approximately 408000 under-five deaths in India
are contributed by pneumonia [6]. If this is true, it works out to a ARI
case fatality rate of 0.93% [8]. A large modelling analysis of data from
193 countries calculated that pneumonia contributes 18% of a total of
8.795 million under-five deaths [16].
A recently published systematic review [17] examined
causes of child deaths in India over the past 25 years. The authors
included 12 data sources reporting pneumonia mortality in children beyond
the neonatal age group. Although the terms ARI, respiratory infection, and
pneumonia were defined differently in various studies, mortality
attributable to these conditions ranged from 10 to 33%. Based on SRS data
calculations, respiratory infection was listed as the leading cause in
infants as well as children from 1 to 5 years of age [18].
The recently published multicentric study among
hospitalized children in Chandigarh, Kolkata and Vellore reported
pneumonia case fatality ratios as 1.01%, 2.35% and 0.77% respectively. The
respective mortality rates in severe clinical pneumonia were 1.35%, 3.32%
and 0.89% [13].
A community based study in Ballabhgarh villages [12]
followed over 5000 under five children and estimated overall case fatality
rate due to pneumonia as 1.26%; it also reported that mortality rate was
1% in moderate cases and 50% in severe cases, although the severity
grading was not defined.
An AIIMS study [19] of hospitalized children (<5 years
with WHO defined severe pneumonia) reported 21 deaths among 200
hospitalized children (10.5%). The SPEAR study [20] in children with very
severe community acquired pneumonia, hospitalized across several
developing countries including India, reported a mortality rate of 24
among 958 children enrolled (2.5%). Naturally, these are not necessarily
representative of the mortality rate in the community.
An older study in urban slum children of Delhi (2 weeks
to 5 years old) admitted in the Pediatric Emergency with ALRI reported
case fatality rate by severity of pneumonia [21] as 11.1% among those with
no pneumonia (n=18), 0% among those with pneumonia (n=45),
8.7% among those with severe pneumonia (n=104) and 47% in very
severe pneumonia (n=9). Another study in 28 urban slums of Lucknow
[22] identified 71 deaths among 2796 children (2.5%), among which
pneumonia was the major cause (19.7%), followed by diarrhea (18.3%) and
measles (11.4%). Yet another study in over 24000 children residing in
slums, used verbal autopsy to determine cause of death and reported that
among 1171 deaths, the most important cause beyond the neonatal period was
pneumonia (23.4%), diarrhea (20.9%), and malnutrition and/or anaemia
(11.4%) [23].
Conclusions and Comments
• In India, pneumonia is the single most important
cause of death among children in the post-neonatal period, contributing
as much as 27.5% of total under-five mortality according to one
estimate.
• Older studies reported around 10% case fatality
rate in children hospitalized with severe pneumonia and upto 50% with
very severe pneumonia. Recent data in tertiary care hospitals reports
lower mortality (1-3%) in severe and very severe pneumonia. Mortality
calculated from hospital-based studies could be higher than
community-based mortality owing to sicker children being taken to
hospital; on the other hand, it is possible that very sick children die
even before they reach the hospital.
Knowledge gap
• Longitudinal, community and hospital-based
surveillance is required to understand the true picture of childhood
pneumonia mortality in India.
Time trends
Table I shows the trend in ARI prevalence over
the past 1.5 decades through the NFHS series [2-4]; there is an
inexplicable three-fold rise between the first and second survey, with
return to baseline during the third survey. The reason(s) for this is/are
not clear; although it is stated that the surveys were conducted at
different times of the year. Comparison of ARI NFHS-3 data with NFHS-2
survey may not be practical also because the questions to estimate ARI
changed between the two surveys, and the surveys took place at different
times of the year.
Conclusion and Comment
• Identification of trend over time is fraught with
the problem of diverse definitions used. Even the NFHS data using fairly
similar definitions over time cannot be used to reliably assess time
trends.
Risk factors for incidence and mortality
The community-based NFHS-3 survey [4] reported that ARI
affects all children, irrespective of socioeconomic status; however
prevalence is slightly higher among boys, in rural areas, among
scheduled-tribe children, and those residing in lower standard of living
households. The prevalence is lower among children of mothers who have at
least completed high school and those living in households that use piped
drinking water and water filter for the purification of water. A
community-based study [12] among 5000 <5 children reported that infants
with all forms of pneumonia had nearly twice higher attack rate
(0.59/child/year), although females had higher case fatality rate than
males (1.5% vs 1.1%). A case-control study in hospitalized children
[24] reported solid fuel use (OR 3.97, CI 2.00-7.88), history of asthma
(OR 5.49, CI 2.37-12.74), poor economic status (OR 4.95, CI 2.38-10.28)
and keeping large animals (OR 6.03, CI 1.13-32.27) as risk factors.
Subgroup analysis of the SRS data from 1.1 million households across India
analyzed a total of 6790 child deaths by the household usage of solid
fuel. The investigators noted that solid fuel use was associated with
increased child mortality among 1-4 year old children (prevalence ratio
among boys 1.30, 95% CI 1.08-1.56 and girls: 1.33, 95% CI 1.12-1.58).
Solid fuel use was also associated with non-fatal pneumonia in boys
(prevalence ratio 1.54 95% CI 1.01-2.35) as well as girls (prevalence
ratio 1.94 95% CI 1.13-3.33) [25].
The WHO 2008 report [6] cited and categorized risk
factors as: (i) Definite risk factors: malnutrition (weight-for-age
z-score < -2), low birth weight, lack of exclusive breastfeeding
during first 4 months, lack of measles immunization, indoor air pollution,
crowding; (ii) Likely risk factors: parental smoking, zinc
deficiency, maternal inexperience, co-morbidities; and (iii) Possible
risk factors: maternal illiteracy, day-care attendance, rainfall
(humidity), high altitude (cold air), vitamin A deficiency, higher birth
order, outdoor air pollution.
A systematic review of mortality risk in pneumonia
identified 16 studies across several countries and reported that
malnourished children had higher mortality; RR 2.9-121.2 with severe
malnutrition, and 1.2-36.5 with moderate malnutrition [26].
Among Indian studies, risk factors of mortality in
children with severe pneumonia [19] were reported as presence of head
nodding (RR 8.34, 95% CI 2.71-12.77), altered sensorium (RR 5.44, 95% CI
1.34-17.56), abnormal leukocyte counts (RR 5.85, 95% CI 1.36-17.14), and
pallor (RR 10.88, 95% CI 2.95-20.40). Among children with pneumonia
(severe and very severe cases) admitted in the Emergency department of a
teaching hospital in Delhi [21], risk factors for mortality included age
less than 1 year (OR 23.1, 95% CI 2.7-197.5), inability to feed (OR 6.2,
95% CI 1.3-30.7), malnutrition defined by weight for age Z score <-3.0 (OR
3.9, 95%CI 1.01-9.7), and presence of bandemia on peripheral smear (OR
1.1, 95% CI 1.05-1.2). The presence of concomitant diarrhea was also an
independent predictor of mortality (OR 5.1, 95% CI 1.2-27.3).
A hospital-based case control study [27] identified
severe pneumonia (OR 4.2; CI 1.2-14.4), marasmic status (OR 2.9, CI
1.5-5.7), age under 6 months (OR 2.8, CI 1.3-5.7), and associated
illnesses, as risk factors for death.
Conclusions and Comments
• ARI (and therefore pneumonia) in India affects
children irrespective of socioeconomic status.
• Malnourished state, younger age and concomitant
illnesses are associated with higher mortality.
• Lack of breast feeding, younger age (less than one
year), lack of measles immunization, and solid fuel use are additional
risk factors for pneumonia morbidity and/or mortality.
Knowledge gaps
• The net effect/impact of a set of multiple risk
factors, for an individual child to develop ARI/pneumonia and/or
response to treatment, is not known.
• Feasibility and effectiveness of interventions to
reduce exposure to some of the risk factors is not known.
2. Etiology
Etiology of Childhood Pneumonia in India
There is no systematic review or nation-wide study of
etiology in India. A prospective study [28] of microbiology of
nasopharyngeal aspirates and, serology in children with severe ALRI (n=95)
reported viruses from NP aspirate in 38%, bacterial isolates from blood
cultures in only 16%, Mycoplasma in 24%, Chlamydia in 11% by
serological testing, and mixed infections in 9%.
Additional tests like latex agglutination test (LA) for
H. influenzae and S. pneumoniae; immunofluorescent technique
(IFAT) and enzyme immunoassay (EIA) for respiratory syncytial virus (RSV)
in another study [29] isolated Haemophilus influenzae in 15%, RSV
in 14%, Klebsiella in 13%, and S. pneumoniae in 12%. Among
young infants < 3 months, E. coli was the commonest organism,
followed by RSV. In older infants (7-24 months), RSV and H. influenzae
were relatively more common. Among those older than five years, S.
aureus and S. pneumoniae were isolated in 40% and 20%
respectively by culture.
In the ISCAP trial [30], among 2188 under-five children
with non-severe pneumonia there were 878 isolates of S. pneumoniae
and 496 isolates of H. influenzae at enrollment. A total of 513
samples (23%) tested positive for RSV.
A serotyping study [31] reported that among 150
clinical isolates from invasive and other clinically significant
pneumococcal infections, 59.3% belonged to serotypes 1, 6, 19, 5, 23 and
7. Serotype 1 was the commonest isolate in meningitis and empyema. In
another study [32], among 42 pneumococcal strains, over one-third in
children and nearly half in adults were serotypes 5, 6 and 7. The
remaining 11 of 14 strains in children and 20 of 28 strains in adults
belonged to 8 serogroups/types, namely 3, 4, 10, 11, 12, 13, 19 and 20.
The IBIS study [33,34] was a prospective hospital-based
surveillance for H. influenzae and invasive pneumococcal disease (IPD)
in 6 teaching/referral hospitals across India. Children (1mo-12y) as well
as older patients with radiologic or clinical pneumonia, fever, suspected
meningitis or suspected sepsis; underwent microbial culture. Among a total
of 3441 patients, the majority were children and 2324 had pneumonia. A
total of 182 S. pneumoniae and 58 H. influenzae were
isolated. Of the 58 H. influenzae isolated, 96% were serotype b.
Among patients with H. influenzae infection 40 had meningitis, and
only 11 had pneumonia; whereas patients with S. pneumoniae on
culture had pneumonia and meningitis in almost equal proportions (about
one-third). Nearly all isolates were from children <5 years old, majority
from <1 yr. It is believed that the true prevalence of Hib disease may not
be identified by culture; antigen testing and PCR increase yield in CSF by
1.3-5.5-fold, compared with culture alone [35]; this suggests that the
prevalence of Hib disease is significantly higher than that reported by
studies isolating the organism by culture methods.
Studies targeted towards isolation of atypical
organisms by serological tests or indirect immunofluorescence identified
M. pneumoniae in 17 of 62 children and C. pneumoniae in 4
[36]. A recent study identified RSV in 29 of 67 (43.3%) children with
clinically defined pneumonia, although the age range was not restricted to
under-five children [37]. A hospital-based study [38] applied viral
culture and immunofluorescence techniques in 736 children <5 years of age
with ARI (pneumonia 39%, upper respiratory infection 38%, croup or
bronchiolitis 23%). Among those with pneumonia, viruses were detected in
66 of 287 (23%) cases. The isolates included measles (33%), adenovirus
(18%), RSV (14%), influenza (18%) and parainfluenza (17%). In contrast,
among children hospitalized with very severe pneumonia, the SPEAR study
[20] reported RSV positive in only 47 of 724 (6.4%) samples, suggesting
that severe disease is less likely to be viral.
The WHO Bulletin 2008 report [6] identified
Streptococcus pneumoniae and Haemophilus influenzae, Staphylococcus
aureus and Klebsiella pneumoniae as the major bacterial causes
of childhood pneumonia. It also mentioned H. influenzae as an
important cause in developing countries. The report cited older data to
show that Pneumococcus is responsible for 30–50% cases, H. influenzae
type b for 10–30% cases, followed by S. aureus and K.
pneumoniae.
A systematic review [26] of mortality risk in children
with pneumonia identified 16 studies, and reported that among severely
malnourished children, Klebsiella pneumoniae, Staphylococcus
aureus, Streptococcus pneumoniae, Escherichia coli, and
Haemophilus influenzae are the common organisms in that order.
Conclusions and Comments
• Most studies are not designed to identify the
etiology of pneumonia, but restricted to detection of one or more
micro-organisms through non-invasive methods; hence may not reflect true
etiology.
• Childhood pneumonia in India is caused by bacteria,
viruses, atypical organisms like Chlamydia and Mycoplasma,
although the precise proportions in community and hospital-based studies
is not clear. However, it appears that about 10-15% of childhood
pneumonias are caused by H. influenzae and RSV each; and 12-35%
by pneumococcus. Other important causes include S. aureus, Gram
negative organisms (especially in younger infants), Mycoplasma
and Chlamydia.
• Serotypes of S. pneumoniae causing childhood
pneumonia are also not well identified; limited data suggests that
around 50% are covered by the 7-valent Pneumococcal conjugate vaccine.
Knowledge gap
• India’s large size and diverse socio-economic,
cultural, climatic influences and variable service delivery systems;
mandate that surveillance systems are set up for identifying etiology of
childhood pneumonia at the community and health facility levels.
Antimicrobial resistance pattern
This section includes data on antimicrobial
susceptibility of organisms that are responsible for pneumonia, but not
necessarily isolated from children with pneumonia.
The IBIS study [33,34] reported that more than 50% of
57 H. infleunzae isolates were intermediately or fully resistant to
chloramphenicol, and 38 to 41% were resistant to cotrimoxazole, ampicillin
or erythromycin. None of the isolates showed resistance to a third
generation cephalosporin. Among S. pneumoniae, there was 56%
cotrimoxazole resistance. However, resistance to penicillin was rare
(1.3%), and none of the isolates was resistant to injectable third
generation cephalosporins. Amongst H. influenzae, resistance was
common both to co-trimoxazole (45%) and ampicillin (38%) [34].
In the ISCAP trial [30] the resistance pattern of
S.pneumoniae to various antibiotics was: cotrimoxazole 66.3%,
chloramphenicol 9.0%, oxacillin 15.9% and erythromycin 2.8%. The
respective resistance rates among H. influenzae were 57.7%, 24.7%,
29.0% and 18.2%.
Among 150 clinical isolates from invasive and other
clinically significant pneumococcal infections, only 11 (7.3%) isolates
were relatively resistant to penicillin, although 64 were resistant to one
or more antibiotics especially cotrimoxazole, tetracycline and
chloramphenicol [31]. In 464 South Indian infants (2-6 months) [39],
pneumococci isolated from nasopharynx were tested for resistance to three
common antibiotics (penicillin, cotrimoxazole and erythromycin). When
tested individually, there was no resistance to penicillin. However, when
tested together, overall resistance to penicillin was 3.4%, cotrimoxazole
81% and erythromycin 37%. Serotypes most frequently resistant were 6, 9,
14, 19 and 23; although less than 1% isolates were multi-drug resistant. A
similar study [40] in 100 infants detected colonization with Pneumococcus
on at least one occasion in 81 infants. Resistance to penicillin,
chloramphenicol, cotrimoxazole and erythromycin was observed in 0%, 6% and
3% isolates, respectively.
The IBIS study [34] reported 60% resistance to
chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole, or
erythromycin; with 32% isolates resistant to more than 3 antimicrobial
drugs; among 125 isolates. None were resistant to third-generation
cephalosporins. Another study from Lucknow [41] reported the resistance
pattern of 90 Haemophilus isolates among patients with ARI of all
age groups as: cotrimoxazole 33.3%, ampicillin 21.1%, cephalexin 7.8%,
chloramphenicol 7.8%, ciprofloxacin 2.5% erythromycin and tetracycline 5%
each. In a limited study [42] with 12 Hib isolates, 8 (67%) were multiply
resistant to ampicillin, chloramphenicol and cotrimoxazole, but all were
susceptible to cefotaxime and erythromycin.
Among older children, a study [43] in 5-10 year old
school children identified 1001 H. influenzae isolates from 2400
nasopharyngeal swabs; Hib constituted 316 (31.6 %). Of these, 44.0 % were
ampicillin resistant, although only 13.1 % non-type b H. influenzae
isolates were ampicillin resistant. 196 of 229 ampicillin resistant
isolates were positive for beta-lactamase. This suggests that these
antibiotics may not be the most appropriate first choice in this age
group.
Among Gram negative organisms, tertiary-care center
hospital data from Lucknow [44] reported resistance patterns of E. coli
and Klebsiella from various body fluids of patients with
septicaemia in all age groups as amikacin 15%, gentamicin 67%,
trimethoprim/sulphamethoxazole 79% and ciprofloxacin 94%. Extended
spectrum beta-lactamases (ESBL) were found in 64% of 143 E. coli
isolates and 67% of 57 K. pneumoniae isolates. In a study [45] of
100 clinical isolates of Klebsiella spp. from cases of neonatal
septicaemia, 58 were reported to be ESBL positive. In a retrospective
study of community acquired as well as nosocomial septicemia [46], a total
of 4027 samples were obtained from children less than 15 years of age.
Among 736 positive cultures, Gram negative organisms predominated (66%)
followed by Gram positive (33.5%) and fungi (1%). Among the Gram negative
bacteria, Klebsiella pneumoniae (22.4%) and E. coli (12.6%)
predominated followed by Acinetobacter (9.3%) and Salmonella
typhi (5.4%). Both Klebsiella and E. coli showed 70-80%
resistance to amoxicillin and cephalexin, and minimum resistance to
cefotaxime (23%) and ciprofloxacin (12%).
Conclusions and Comments
• There is variable in-vitro resistance to
common antibiotics among organisms implicated in childhood pneumonia;
however penicillin resistance is uniformly low and cotrimoxazole
resistance high.
• Research studies published after 2000 show higher
resistance to cotrimoxazole among Pneumococci and H. influenzae,
than earlier studies.
• Gram negative organisms are also showing increasing
resistance to common antibiotics; this needs to be factored in as they
are implicated in childhood pneumonia in India.
• The use of antibiotics is recommended for all
children with Acute Lower Respiratory Infection (ALRI) based on fast
breathing. On one hand, this guideline results in early treatment (and
recovery) of pneumonia; on the other hand it may result in overtreatment
increasing antibiotic resistance.
• In view of increasing reports of in-vitro
cotrimoxazole resistance it may be prudent to use amoxicillin as the
first-line antibiotic, monitor the sensitivity patterns, and use an
antibiotic rotation policy, in tune with surveillance data.
Knowledge gaps
• An antibiotic surveillance system is required to
identify the antimicrobial sensitivity patterns (in vitro and
in vivo), and modify recommendations for public health programs
based on changing patterns.
• The degree of match between in vitro and
in vivo results; and data from large hospitals versus the spectrum
within the community, are not clear.
• The level of resistance at which, one antibiotic
should be abandoned in favor of another (in a national program) is not
known.
3. Management
Chest radiography is not routinely indicated for
children with community acquired pneumonia. Hence data pertaining to
radiography has not been included in this review.
Antibiotic therapy
As it is inappropriate to examine data comparing
antibiotic versus placebo/no treatment in childhood pneumonia, such
studies are not included.
Choice of antibiotic: A recent Cochrane review [47]
updated an older Cochrane review [48] on antibiotic therapy for childhood
pneumonia. The latest conclusions are that for non-severe pneumonia,
cotrimoxazole and amoxicillin have comparable treatment failure rate (OR
0.92, 95% CI 0.58-1.47) and cure rate (OR 1.12, 95% CI 0.61-2.03). The two
antibiotics appear to have similar failure rate for severe pneumonia
diagnosed clinically (OR 1.71, 95% CI 0.94-3.11) or radiologically (OR
2.14, 95% CI 0.96-4.78). Mortality with the two antibiotics is also
comparable (OR 2.08, 95% CI 0.22-20.06). These findings are in line with
data from an effectiveness study [49] that reported no difference in
effectiveness of oral cotrimoxazole versus amoxicillin for (non-severe)
pneumonia.
The Cochrane review [47] reported cotrimoxazole to be
comparable to procaine penicillin in terms of cure rate (OR 1.58, 95% CI
0.26-9.69), hospitalization rate (OR 2.52, 95% CI 0.88-7.25) and mortality
(OR 3.09, 95% CI 0.13-76.13). Coamoxiclav is reported to be comparable to
amoxicillin for multiple outcomes including cure rate (OR 10.44, 95% CI
2.85-38.21), complications (OR 5.21, 95% CI 0.24-111.24) and side effects
(OR 5.21, 95% CI 0.24-111.24).
In severe pneumonia, the Cochrane review [47] reported
that chloramphenicol resulted in greater treatment failure rate on
multiple days of treatment as compared to a combination of ampicillin and
gentamicin (OR 1.51, 95% CI 1.04-2.19 on day 5, OR 1.46, 95% CI 1.04-2.06
on day 10, and OR 1.43, 95% CI 1.03-1.98 on day 21). The necessity to
change antibiotics was also higher with chloramphenicol than the
combination. Mortality showed a trend of being higher with chloramphenicol
(OR 1.65, 95% CI 0.99-2.77). In very severe pneumonia, chloramphenicol was
reported to be comparable to penicillin plus gentamicin in terms of
mortality (OR 1.25, 95% CI 0,76-2.07), need to change antibiotics (OR
0.80, 95% CI 0.54-1.18) and adverse events (OR 1.26, 95% CI 0.96-1.66).
However odds of treatment failure were higher with chloramphenicol (OR
1.61, 95% CI 1.02-2.55).
The multi-nation SPEAR trial [20] comparing 5 day
treatment with injectable ampicillin plus gentamicin vs
chloramphenicol in children aged 2-59 months with very severe pneumonia
reported greater treatment failure with chloramphenicol at day 5 (RR 1.43,
95% CI 1.03-1.97) and also by days 10 and 21.
Another multi-center study [50] in eight developing
countries in Africa, Asia, and South America, among children aged 3-59
months with severe pneumonia, evaluated 48 hour hospitalization followed
by 5-day course of oral amoxicillin at home. In-hospital treatment was
either oral amoxicillin (n=857) or parenteral penicillin (n=845).
Treatment failure (persistence of lower chest indrawing or new danger
signs) was 19% in each group. Age <12 months (OR 2.72, 95% CI 1.95-3.79),
very fast breathing (OR 1.94, 95% CI 1.42-2.65), and hypoxia at baseline
(OR 1.95, 95% CI 1.34-2.82) predicted treatment failure by multivariate
analysis. An older randomized-controlled trial [51] compared 10 days of
treatment with penicillin G and chloramphenicol vs ceftriaxone and
found similar cure rates.
A 2003 WHO meeting [52] concluded that for (non-severe)
pneumonia, three days therapy with oral antibiotics is sufficient in
countries where HIV is not a major public health problem. Oral amoxicillin
is a superior choice in countries where cotrimoxazole resistance is high.
Oral amoxicillin can be used twice daily instead of thrice. Children
presenting with wheeze and pneumonia should be given a trial of rapid
acting bronchodilator (where feasible) before an antibiotic is prescribed.
For severe pneumonia, if HIV infection is clinically suspected or
confirmed, routine WHO ARI case-management should not be used.
A recent Cochrane review [53] extracted data pertaining
to children with Mycoplasma pneumonia to evaluate whether
macrolides are superior to other antibiotics (especially coamoxyclav). In
most trials, clinical response was comparable with macrolide and non-macrolide
antibiotic.
In older children and adolescents, for non severe
cases, oral amoxicillin or coamoxyclav are the first choices; severe cases
require injectable antibiotics. Crystalline penicillin is an appropriate
starting choice. Cloxacillin should be added if Staphylococcal disease is
suspected clinically. Atypical organisms such as Mycoplasma are
fairly common in this age group and treatment is with macrolide [54]. The
current guideline for patients >18 years of age with community
acquired pneumonia [55] also recommends beta-lactams as the first line,
since it covers the most common pathogens responsible; however the
resistance rate is reportedly higher than in children. It is not clear
whether such guidelines can be extrapolated to adolescents.
In a recent trial in Bangladesh [56], children (2-59
months old) with severe pneumonia (WHO criteria) but without severe
malnutrition and/or other complications, were randomized to be treated
with injectable ceftriaxone either as ‘day-care’ or hospitalized. After
treatment, both groups had comparable duration of symptoms, oxygen therapy
and duration of stay; suggesting that severe pneumonia without
malnutrition could be managed as day-care without admission.
Route of antibiotic: A Cochrane review [57]
compared effectiveness and safety of oral versus parenteral
antibiotics for treatment of severe pneumonia in children (3mo-5y),
although meta-analysis was not performed owing to limited data. One of the
trials found similar treatment failure rate with oral cotrimoxazole vs
intramuscular procaine penicillin followed by oral ampicillin in 134
children. Another larger trial (n=1702) reported similar results. A
recent cost-minimisation economic analysis [58] among children
hospitalized with CAP who were randomized to receive either oral
amoxicillin or i.v. benzyl penicillin; reported that parenteral treatment
was significantly more expensive than oral owing to cost of therapy and
greater length of stay. Unfortunately the equivalent costs in a developing
country setting are not mentioned.
Dose of antibiotic: A RCT in Pakistan [59] compared
45 mg/kg/day versus 90 mg/kg/day oral amoxicillin for 3 days, among
children aged 2-59 months with non-severe pneumonia. There was no
significant difference in treatment failure between the groups. The COMET
study [60] reported that treatment failure rate in children with
non-severe pneumonia receiving double dose of cotrimoxazole (8 mg
trimethoprim plus 40 mg sulfamethoxazole/kg) was comparable (RR 1.10; 95%
CI 0.87–1.37) to those receiving standard dose (4 mg trimethoprim plus 20
mg sulfamethoxazole/kg).
Duration of therapy: A Cochrane review [61]
comparing short versus standard duration of therapy identified 3 trials
(5763 children) and showed no significant difference in clinical cure,
treatment failure and relapse rate after seven days of clinical cure with
shorter durations of therapy. A meta-analysis [62] comparing short ( £7
days) versus long (³2
days difference) course therapy for CAP in children 2-59 month old did not
find any differences. The MASCOT trial [63] compared 3-day vs 5-day
oral amoxicillin in (non-severe) pneumonia among 2000, 2-59 month old
children. Treatment failure was similar: 209 (21%) with 3-day vs
202 (20%) with 5-day treatment. Relapse rate also was similar between the
groups (1% in each group).
Prophylactic antibiotics following measles: A
Cochrane review [64] with 7 trials (1385 children) reported no difference
in the incidence of pneumonia with antibiotics (OR 0.28; 95% CI 0.06-1.25)
when all trials were compared. Removing an outdated trial (1942) that
showed increase in pneumonia, resulted in strong evidence of reduction in
incidence (OR 0.17; 95% CI 0.05-0.65; NNT 24). The incidence of
complications was lower with antibiotics: purulent otitis media (OR 0.34;
95% CI 0.16-0.73) and tonsillitis (OR 0.08; 95% CI 0.01-0.72), although
there was no difference in conjunctivitis (OR 0.39; 95% CI 0.15-1.0),
diarrhea (OR 0.53; 95% CI 0.23-1.22) or croup (OR 0.16; 95% CI 0.01-4.06).
Conclusions and Comments
• There is adequate data to support the choice of
antibiotics recommended in the IAP-IndiaCLEN 2010 guideline.
• Oral route can be used for most childhood pneumonia
in the community; severe and very severe cases require injectable
antibiotics. Successful trials of oral therapy in severe pneumonia may
not give similar results unless research setting level of
follow-up/monitoring can be maintained.
• For (non-severe) pneumonia, 3 days therapy appears
sufficient.
• Children with measles can be offered antibiotics to
prevent pneumonia and/or complications.
Knowledge gap
• Treating all children with rapid breathing
(pneumonia as per the WHO criteria) can result in antibiotic over-use
and its consequences; however the short and long term impacts of this
are not known.
Oxygen therapy
Prevalence of hypoxemia in pneumonia: A
systematic review [65] reported the median prevalence of hypoxemia among
studies in children with severe pneumonia as 9.4% (IQR 7.5-18.5%); it was
13% for combined severe and very severe pneumonia defined by the WHO
criteria. Another older systematic review [66] to determine the prevalence
of hypoxemia in under-five children with ALRI (17 cohort studies, 4021
children) reported low risk (6-9%) of hypoxemia among out-patient children
and those with upper respiratory infection. The prevalence was 31-43% in
emergency departments; and 47% among hospitalized children and highest
(72%) in those with radiographically confirmed pneumonia.
Prospective data from Papua New Guinea in hospitalized
children (including pneumonia) [67], reported hypoxemia in 384 of 1313
children (29.25%, 95% CI 26.8-31.8); oxygen was not available on the day
of admission for 22% of children including 13% of all children with
hypoxemia. Oxygen was less available in remote rural district hospitals
than in provincial hospitals in regional towns. Clinical signs proposed by
WHO as indicators for oxygen would miss 29% of children with hypoxemia and
using the signs, 30% of non-hypoxemic children would receive oxygen. In a
Nepal study [68], the prevalence of hypoxemia (SpO2 <90%) in 150 children
with pneumonia was 38.7%. Of them 100% of very severe pneumonia, 80% of
severe and 17% of pneumonia patients were hypoxic. Clinical predictors
significantly associated with hypoxemia on univariate analysis were
lethargy, grunting, nasal flaring, cyanosis, and complaint of inability to
breastfeed or drink. Chest indrawing with 68.9% sensitivity and 82.6%
specificity was the best predictor of hypoxemia. An older prospective
Kenyan study [69] described the prevalence of hypoxemia in children
admitted to hospital as 977 of 15289 (6.4%) admissions (5-19% depending on
age group) and was strongly associated with inpatient mortality. Only 215
of 693 (31%) hypoxemic children had a final diagnosis of lower respiratory
tract infection (LRTI). The most predictive signs for hypoxemia included
shock, heart rate <80/minute, irregular breathing, respiratory rate >60/
minute and impaired consciousness. However, 5-15% of the children who had
hypoxemia on admission were missed, and 18% of the children were
incorrectly identified as hypoxemic, suggesting that clinical signs are
poor predictors of hypoxemia.
Clinical markers of hypoxemia: A recent
Cochrane review [70] reported that cyanosis, grunting, difficulty in
feeding and mental alertness have better specificity in predicting
hypoxemia; however there is no single clinical sign or symptom that
accurately identifies hypoxemia. Another review [71] reported that very
fast breathing (>60-70 breaths per minute), cyanosis, grunting, nasal
flaring, chest retractions, head nodding and auscultatory signs, as well
as inability to feed or lethargy; all correlated with hypoxemia to varying
degrees. The sensitivity and specificity of these signs are highly
variable, but can be taught to mothers and care-givers to predict
hypoxemia with reasonable accuracy.
Although cyanosis, head nodding and drowsiness are good
predictors of hypoxia, they lack sensitivity. Decisions based on these
signs result in oxygen under-use. Pulse oximetry is the best indicator of
hypoxemia and, although relatively expensive, its use might be
cost-effective in controlling oxygen requirements [72]. In Zambia [73], of
158 under-five ALRI children, 55 (35%) were hypoxemic. For children under
1 year of age, respiratory rate of > 70 was the only significant predictor
of hypoxemia (P <0.001, sensitivity 63%, specificity 89%).
Delivery of oxygen: A Cochrane review [70]
comparing oxygen delivery methods (3 studies); showed no differences in
treatment failure (OR 0.96; 95% CI 0.48-1.93) between nasal prongs (NP)
vs nasopharyngeal catheters (NPC). A detailed review summarizing
methods of oxygen delivery concluded that all low-flow methods, i.e., NPC,
NC, NP are effective in severe pneumonia or bronchiolitis. Nasal prongs
are the safest and most preferred method in small hospitals in developing
countries [74].
In Papua New Guinea [75], an improved oxygen system
(oxygen concentrators, pulse oximeters, and management protocol) led to a
drop in pneumonia case fatality from 4.97% (95% CI 4.5-5.5%) to 3.22% (95%
CI 2.7-3.8%). The estimated costs of this system were US$51 per patient
treated, US$1673 per life saved, and US$50 per disability-adjusted
life-year (DALY) averted. In Malawi [76] five key steps enabled
introduction of concentrators: (1) develop a curriculum and training
materials; (2) train staff on use and maintenance; (3) retrain
electromedical departments on maintenance and repair; (4) conduct training
once concentrators arrived in the country; and (5) distribute
concentrators once staff had been trained.
Conclusions and Comments
• Hypoxemia is a relatively common occurrence in
pneumonia, especially severe and very severe pneumonia.
• Clinical signs often do not accurately predict
presence and/or absence of hypoxemia.
• Pulse oximetry is the only reliable, non-invasive
method to confirm hypoxemia.
• Oxygen delivery improves outcome and all low-flow
methods are safe and effective.
• Use of oxygen concentrators improves oxygenation in
small hospitals.
Zinc supplements
A systematic review published in early 2010 [77]
included 11 community-based RCTs of zinc supplementation for preventing
pneumonia in children Although pneumonia and lower respiratory tract
infection were defined differently in different trials, the study
definitions were consistent with the WHO criteria. The balance of evidence
(8 trials, 11701 participants) suggested that zinc supplementation does
not prevent the occurrence of pneumonia. A more recent systematic review
[78] (10 trials, 49450 children) also reported a similar finding that zinc
supplementation had no effect on preventing pneumonia defined by the WHO
criteria (incidence rate ratio 0.96, 95% CI 0.86-1.08) or ALRI defined by
less specific criteria or reports by caregivers (incidence rate ratio
1.01, 95% CI 0.91-1.12). However, when trials with specific definitions of
pneumonia (tachypnea plus one or more of retractions, bronchial breathing,
crackles, nasal flaring, danger signs were considered), zinc
supplementation reduced the incidence of ALRI (incidence rate ratio 0.65,
95% CI 0.52-0.82).
As recently as December 2010; a Cochrane review [79]
with 6 trials (7850 children) reported that zinc supplementation reduced
the incidence of pneumonia (RR) 0.87; 95% CI 0.81-0.94). One trial
included in the review reported that supplementation reduces the
prevalence of pneumonia (RR 0.59; 95% CI 0.35-0.99). In this review also,
the authors reported that zinc supplementation was effective when
pneumonia was defined by specific criteria (i.e clinical with radiological
confirmation) and not in trials using the lower specificity WHO case
definition. One randomized trial [80] was published after the inclusion
date in the Cochrane review; it reported that zinc supplementation did not
reduce the incidence of pneumonia or severe pneumonia.
A systematic review [77] evaluated whether zinc has a
possible therapeutic role when given with antibiotics in children with
severe pneumonia . The 4 included trials used various definitions for
pneumonia, but all were consistent with the WHO criteria. The balance of
evidence suggests that there is no therapeutic benefit of adding zinc to
antibiotic therapy. Since then, two more trials [81,82] have confirmed the
absence of benefit in pneumonia as well as severe pneumonia.
Conclusions and Comments
• Zinc supplementation for at least three months
duration could be useful to prevent pneumonia (defined by specific
criteria).
• Zinc does not have therapeutic value in childhood
pneumonia.
Knowledge gap
• It is not clear if zinc supplementation would be
useful if it is used only in a sub-group of children with clinical
deficiency.
Vitamin A supplementation
A recent systematic review [83] on vitamin A identified
11 trials exploring prophylactic role of vitamin A, and 9 trials examining
therapeutic role. There was no difference between vitamin A and placebo
for any of the outcomes in the prophylaxis trials. In the therapy trials,
five outcomes viz. mortality, duration of hospitalization, duration of
illness, complications, and side effects; were not significantly different
with vitamin A or placebo. An even more recent Cochrane review [84]
confirmed these findings. Vitamin A supplementation did not have
beneficial effect on lower respiratory tract infection mortality (RR 0.78;
95% CI 0.54-1.14), LRTI incidence (RR 1.14, 95% CI 0.95-1.37), LRTI
prevalence (RR 0.46, 95% CI 0.21-1.03) or hospitalization (RR 0.11, 95% CI
0.01-2.06).
An older Cochrane review on vitamin A in measles [85]
showed that there was no significant reduction in mortality with 1 dose
(RR 0.70; 95% CI 0.42-1.15; but mortality declined with two doses (RR
0.18; 95% CI 0.03-0.61). Likewise with two doses, pneumonia-specific
mortality (RR 0.33; 95% CI 0.08-0.92), incidence of pneumonia (RR 0.92,
95% CI 0.69-1.22) and diarrhea (RR 0.80; 95% CI 0.27-2.34) declined
significantly.
Conclusions and Comments
• Vitamin A has neither therapeutic nor prophylactic
value in childhood pneumonia.
• Two doses of vitamin A appear to be beneficial in
children who develop measles.
Knowledge gap
• It is not clear if vitamin A supplementation would
be useful in a sub-group of children with clinical deficiency.
Routine immunization and pneumonia
A detailed review of observational studies [86]
examined the mortality reduction with childhood vaccines. A total of 24
studies on measles vaccine were included; the authors reported that
relative risk of mortality was reduced by 62-86%. Even when
methodologically lower quality data was eliminated, there was a 31-46%
relative reduction in mortality. This reduction is a consequence of
reduction of measles disease and attendant complications (among which
pneumonia is the most significant). Another systematic review [87]
identified 10 cohort and 2 case-control studies reported a similar 38-86%
reduction in mortality with measles vaccine when children from the same
community were compared. When immunized children were compared with
unimmunized children from different communities, mortality reduction was
estimated to be 30%-67%. In this review, vaccine efficacy was reportedly
far greater than could be attributed to reduction in measles deaths;
confirming that the benefit extended to reduced complications.
A systematic review [88] of published RCTs and
quasi-experimental studies identified three measles vaccine RCTs and two
studies with data on prevention of measles disease. Meta-analysis showed
85% (CI 83-87%) efficacy in preventing measles disease. The review also
suggested that 95% effect estimate is reasonable when vaccinating at 1
year or later and 98% for two doses of vaccine based on serology reviews.
Conclusion and Comment
• Measles immunization leads to significant decline
in child mortality, at least partly mediated by its impact on reduction
of complications, including pneumonia.
Hib vaccine
A systematic review [89] on Hib vaccine efficacy showed
that there was decline in invasive Hib disease (OR 0.16; 95% CI
0.08-0.30), meningitis (OR 0.25; 95% CI 0.08-0.84) and pneumonia (OR 0.31;
95% CI 0.10-0.97). Another systematic review of RCTs [90] in developing
countries reported the effect of Hib conjugate vaccines as follows:
pneumonia mortality RR 0.93 (95% CI 0.81-1.07), all-cause mortality RR
0.95 (95% CI 0.86-1.04), radiologically confirmed pneumonia RR 0.82 (95%
CI 0.67-1.02), clinically defined severe pneumonia RR 0.94 (95% CI
0.89-0.99) and clinical pneumonia RR 0.96 (95% CI 0.94-0.97). This
corresponds to effect on all clinical severe pneumonia as 6% reduction
(95% CI 1-11%) and clinical pneumonia as 4% reduction (95% CI 3-6%). These
findings suggest a marginal unequivocal benefit on clinical pneumonia and
clinical severe pneumonia. A Cochrane review on Hib vaccine published in
October 2009 [91] has since been withdrawn; hence is not discussed
further.
Yet another systematic review of the effectiveness of
Hib vaccine reported that conjugate vaccines are highly effective in
reducing the incidence of invasive Hib disease, with similar efficacy
across geographical regions and different levels of socioeconomic
development [92]. Indirect benefits of vaccination even in countries with
poor immunization coverage due to reported herd effect [93] has also been
reported. However, some recent publications from India have challenged the
data regarding Hib incidence, prevalence and beneficial effect of routine
Hib vaccine in Indian children [94,95].
A Cochrane review [96] compared the efficacy of DTP-HBV-Hib
combination versus DTP-HBV and Hib separately. However, none of the
included trials reported clinical outcomes; all reported surrogate
outcomes, especially immunogenicity. Children receiving the combination
achieved lower antibody responses than the separate vaccines for Hib and
HBV. Serious and minor adverse events were comparable.
Conclusion and Comment
• The exact burden of Hib pneumonia in India is not
clear. The vaccine is efficacious in reducing invasive Hib disease and
Hib pneumonia and meningitis in research trials; however the overall
effectiveness depends on the proportion of childhood pneumonia caused by
Hib.
Knowledge gap
• Public health impact and cost-effectiveness of Hib
vaccination in India.
Role of Pneumococcal conjugate vaccine
An updated Cochrane review [97] included 11
publications from six RCTs conducted in Africa, US, Philippines and
Finland where 57015 children received PCV and 56029 received placebo or
another vaccine. Pooled vaccine efficacy (VE) for invasive pneumocococcal
disease (IPD) caused by vaccine serotypes was 80% (95% CI 58%-90%); for
IPD caused by any serotype 58% (95% CI 29%-75%); for radiological
pneumonia (defined as per WHO criteria) 27% (95% CI 15%-36%); for clinical
pneumonia 6% (95% CI 2%-9%); and for all-cause mortality 11% (95% CI
-1%-21%). Another systematic review of RCTs (in developing countries) [90]
evaluated 9 and 11 valent Pneumococcal conjugate vaccines (PCV) and
reported the effect of vaccination on various outcomes as follows:
clinical pneumonia 7% (95% CI –2 to, 15%), clinical severe pneumonia 7%
(95% CI –1 to 14%), radiologically confirmed pneumonia 26% (95% CI
12-37%), and all-cause mortality 15% (95% CI 2-26%). This suggests that
the vaccine has limited efficacy against pneumonia identified by less
specific definitions.
A 2009 systematic review [98] included trials of PCV in
children and reported the vaccine efficacy as 89% for vaccine-serotype
invasive pneumococcal disease (IPD); and 63% to 74% for all serotypes.
Vaccine efficacy to prevent clinical pneumonia was 6% and 29% for
radiologically confirmed pneumonia. In yet another systematic review [99],
42 studies were included to review safety of PCV. Reacto-genicity data
from some trials suggested that PCV-7 may result in more mild,
self-limiting local reactions and fever than control vaccines; although
severe adverse events were not increased. Two of the largest trials
reported a statistically significant increased risk of hospitalization for
reactive airway disease, including asthma; this was true for 7 as well as
9 valent vaccine. However, a third trial did not substantiate this
observation.
A Cochrane review of pneumococcal vaccination during
pregnancy [100] to prevent pneumococcal disease during the first months of
life, included three trials and reported the absence of benefit for
reducing neonatal infection (RR 0.51; 95% CI 0.18-1.41). However, there
was reduction in neonatal coloni-zation (RR 0.33; 95% CI 0.11-0.98),
though this was not sustained at 2 months (RR 0.28; 95% CI 0.02-5.11) or 7
months of age (RR 0.32; 95% CI 0.08-1.29).
In India, limited data [31,32] suggests that the
7-valent PCV covers a little over 50% of the serotypes responsible for
invasive disease; based on this a recent analysis [8] reported that the
limited efficacy of the vaccine is further diminished in the Indian
context. The recently introduced 13-valent PCV is expected to cover about
three quarters of the serotypes responsible for invasive disease in India,
and is expected to be slightly more efficacious than PCV-7.
Conclusions and Comments
• The exact burden of Pneumococcal pneumonia and the
serotypes responsible for invasive disease in India are not clear. PCV
are efficacious in reducing disease caused by vaccine-serotypes, however
the overall effectiveness against childhood pneumonia is dependent on
the relative burden of Pneumococcal pneumonia and the serotype coverage
of the vaccine.
Knowledge gaps
• Serotypes of Pneumococci responsible for
significant clinical disease in India need further exploration.
• Public health impact and cost-effectiveness of
Pneumococcal vaccination in India are not known.
Current guidelines for treatment of childhood pneumonia
The current treatment guidelines of the national
program (RCH-II) are concordant with the guidelines of Integrated
Management of Newborn and Childhood Illnesses (IMNCI) for children under
five years [101]. According to IMNCI, all children classified as pneumonia
(based on rapid breathing and absence of danger signs) should receive oral
antibiotics. Cotrimoxazole is proposed as the drug of first choice, and
amoxicillin is proposed as the second line drug if there is no
improvement. Children with danger signs or those with chest indrawing
and/or stridor are classified as severe pneumonia; they require referral
for admission and management after an initial dose of chloramphenicol.
Where referral is not possible, continued intramuscular chloramphenicol is
recommended.
The recent IAP-IndiaCLEN 2010 paper [102] further
reviewed the evidence on antibiotic treatment of pneumonia and made the
following additional observations and recommendations:
(i) Assessment of need for antibiotics:
Although fast breathing is used for identifying children requiring
antibiotics at the community level, at the facility level auscultation
should be used to identify and exclude other causes of fast breathing. It
is especially important to identify wheezing, which may improve with
bronchodilators without requiring antibiotics.
(ii) Selection of appropriate antibiotic:
In view of increasing resistance of S. pneumoniae and H.
influenzae to cotrimoxazole, amoxicillin is recommended as the first
line antibiotic for non-severe pneumonia, at both community level
and in clinic settings.
(iii) Treatment of severe or very severe
pneumonia: All children with severe pneumonia should be admitted and
given injectable antibiotics and supportive care including oxygen,
intravenous fluids and close monitoring.
While there is some evidence of efficacy of oral
amoxicillin for children with severe pneumonia [103], application in
program guidelines does not appear justified at this moment. The research
trial excluded children with very severe disease (cyanosis, lethargy,
recurrent vomiting, unable to feed), severe malnutrition, and those who
received prior antibiotic therapy.
For hospital treatment, a combination of injectable
ampicillin and gentamicin is superior to Injection chloramphenicol, in
view of equal efficacy and lower adverse effects. Parenteral third
generation cephalosporins (cefotaxime, ceftriaxone) should not be used
routinely but serve as reserve drugs for those who fail to respond to
first-line therapy or have associated complications (septicemia and
meningitis). Staphylococcal infection should be suspected in children with
skin boils, abscesses or having rapid progression/ deterioration; and
Cloxacillin added.
Subsequently, the above recommendations have been
included in the Facility based IMNCI training modules (F-IMNCI) [104].
In India, under the RCH-II program, community based
workers (ANM and Anganwadi workers; and in some states ASHA) are trained
in IMNCI, including management of pneumonia. However, there are several
gaps in the current policy regarding community based management of
pneumonia in India. Firstly, there is no clear policy on whether the
community health workers (especially ASHAs and AWWs) can use antibiotics
for treatment of childhood pneumonia. Secondly, antibiotics are not
included in the drug kits of either ASHAs or AWWs [105]. Thirdly, drug
kits for ANMs that do include antibiotics have had erratic supply for many
years, though is more streamlined now [106].
No treatment guidelines applicable to older children
and adolescents were found. The WHO IMCI strategy is also designed for
under-five children, hence not applicable to older children.
Conclusions and Comments
• The existing guidelines and programs for management
of childhood pneumonia are widely applicable.
• The mandate of the community health workers to
manage childhood pneumonia is unclear; deficiencies in antibiotic
supplies can adversely affect the scale-up of community based management
of pneumonia in India.
• The applicability of individual (even
multi-centric) research studies on alternative treatment strategies,
such as community management of severe pneumonia, requires careful
evaluation in non-research settings, before considering universal
implementation.
Knowledge gap
The individual and community impact of empiric
antibiotic therapy to all children with WHO-defined pneumonia, in terms of
increased antibiotic resistance is not known.
Adherence to clinical guidelines
A systematic review of interventions [107] to encourage
adherence to community-acquired pneumonia guidelines showed that they are
safe and improve patient and process outcomes. The review included 6
studies (31618 children) including 2 cluster RCTs (n=2351), 2
before-and-after studies with concurrent controls (n=28840) and 2 time
series (n=427). One cluster RCT, 1 before-and-after study and 1
time series reported statistically significant reductions in length of
stay and 1 before-and-after study reported statistically significant
reductions in mortality with CAP treatment according to the guidelines;
other studies reported no significant differences. All 6 studies reported
significant improvements in at least one process measure with guideline
adherence.
Conclusions and Knowledge gaps
• Adhering to guidelines appears to improve clinical
and process outcomes.
• Effectiveness in the Indian context is not known.
Case-finding and/or community-based management
A systematic review of 9 studies [108] (7 of which were
controlled trials) on the mortality impact of WHO case-management showed
reduction in total mortality of 27% (95% CI 18-35%), 20% (95% CI 11-28%),
and 24% (95% CI 14-33%) among neonates, infants, and children 0-4 years of
age, respectively. In the same three groups, pneumonia mortality was
reduced by 42% (95% CI 22-57%), 36% (95% CI 20-48%), and 36% (95% CI
20-49%). Meta-analysis of community-based trials of case management of
pneumonia included seven concurrent trials from Bangladesh, India
(2 trials), Nepal, Pakistan, Philippines and Tanzania. Mortality
surveillance and verbal autopsy reported odds ratio for mortality as 0.70
(95% CI 0.59-0.84), 0.74 (95% CI 0.63-0.87) and 0.74 (95% CI 0.64-0.86)
among children <1 month, <1 year and 0 to 4 years. The odds ratio for
pneumonia-specific mortality, was 0.56 (95% CI 0.37-0.83), 0.63 (95% CI
0.46-0.86) and 0.63 (95% CI 0.47-0.86) among children <1 month, <1 year
and 0 to 4 years respectively. This translates to child mortality
reduction of 26% and a 37% reduction in pneumonia mortality.
The Gadchiroli field trial [109] involved training of
paramedical workers, village health workers and traditional birth
attendants to diagnose and treat childhood pneumonia. Over 3.5 years, a
total of 2568 episodes of childhood pneumonia were managed. The case
fatality rate in the area of active intervention was far lower than the
control areas (0.9% vs 13.5%) [110]. The case fatality rates for
the three types of worker were similar.
A systematic review [90] of the effect of pneumonia
case management on mortality from childhood pneumonia estimated that
community-based management could result in 70% mortality reduction among
under-5 children. However, there is insufficient evidence for quantitative
estimates of the effect of hospital case management pneumonia mortality. A
2009 review [111] reported that community management of neonatal
infections, including pneumonia in neonates in a developing country
setting resulted in significant reduction in mortality.
Although case finding and management are reported to be
immensly beneficial, there is controversy about the most appropriate tools
for detecting cases accurately. A recent review [112] enumerating clinical
signs predictive of pneumonia listed fever, tachypnea, nasal flaring and
reduced oxygen saturation to have high specificity in infants suspected to
have pneumonia. However, the negative predictive value of all of them is
low; hence absence of these features does not rule out pneumonia. An older
review [113] identified fever, decreased breath sounds, crackles, and
tachypnea as independent predictors of pneumonia in children 1-16 years of
age. Fever plus diminished breath sounds, crackles, or tachypnea; or
fever, crackles, and tachypnea had high sensitivity (93-97%) but poor
specificity (11-19%). Another study [114] confirmed that the absence of
fever and presence of hypoxemia in children with cough was highly
predictive of pneumonia.
Conclusions and Comments
• Research studies and real-world experiences show
that community based case detection and management can lead to
significant improvements in pneumonia specific mortality and overall
child mortality.
• The reduction in mortality depends on the rigour
with which community workers are trained, supervised and monitored.
• In India, the policies and programs lack adequate
clarity and emphasis on involvement of community health workers for
management of childhood pneumonia.
Knowledge gaps
• It is not clear as to what systemic factors affect
performance of the community health workers in management of childhood
pneumonia. It is not clear as to what content of training, supervision
structure and monitoring protocol are required for optimal performance
and at what cost.
• There is need to evaluate the effectiveness,
feasibility and cost of delivering single interventions (such as
management of childhood pneumonia) compared to delivering integrated
interventions.
4. Wheezing in ARI
The WHO strategy focuses on reducing mortality due to
pneumonia and hence includes a very sensitive but less specific
definition. This has resulted in many children without pneumonia (but
another diagnosis) being treated for pneumonia, with consequent overuse of
antibiotics and underuse of bronchodilator therapy in children with
wheezing.
Frequency of wheezing
There is no systematic review reporting the prevalence
of wheezing among children with WHO-defined pneumonia. The recent review
[115] on the subject quoted older reports [116] and estimated that up to
75% of children with ‘pneumonia’ or ‘severe pneumonia’ classified on the
basis of WHO criteria have associated wheezing in hospital-based studies.
Likewise these studies generally report asthma to be a more frequent
diagnosis among children with cough or difficult breathing than pneumonia
[117,118].
The multicentric ISCAP trial [30] reported wheezing in
287 of 2188 (13%) children 2-59 months of age enrolled with non-severe
pneumonia, despite excluding children with recurrent respiratory distress,
and those responding to bronchodilators. Similarly, a cluster randomized
multicentric study [49] with over 2000 children (2-59 months) with WHO
defined non-severe pneumonia reported wheezing in 22%, despite excluding
recurrent respiratory distress. The CATCHUP multicentric RCT [119] in
Pakistan recorded wheezing in 10.9% children (2-59 months) with non-severe
pneumonia. The investigators analyzed children less than 1 year and older
than one year separately and reported comparable wheezing frequency (11.4%
vs 10.3%) in both age groups. However, the COMET trial [60] in 2-59
month old children with non severe pneumonia reported wheezing to be far
more prevalent among infants less than 12 months than older children
(31.5% vs 19.9%). A multicentric trial in Pakistan [103] in
children (3-59 months) with severe pneumonia documented wheezing at
enrolment in 499 of 2100 (23.8%), despite excluding known asthmatics
(those with >3 episodes of wheezing in 1 year) and those with lower chest
indrawing that responded to bronchodilators alone. Wheezing was much more
common in infants than those over one year.
Diagnosing wheeze in ARI
Although a large proportion of children have wheeze, it
is audible without aid in less than one-third, making it difficult to
diagnose in a field setting [115]. Therefore the standard case management
of ARI (two doses of rapid acting inhaled bronchodilator at 15 minute
intervals to children with audible wheeze and fast breathing and/or lower
chest indrawing) misses a number of children with treatable wheeze. In a
significant proportion of children, the respiratory rate comes back to
normal and the chest indrawing disappear after two to three cycles of
inhaled bronchodilator medications.
Distinguishing pneumonia and wheezing disorders in children
A study in children 2-59 months old with radiologic
pneumonia and wheezing [120] re-examined the validity of the WHO criteria
for diagnosis. The WHO criteria used alone had sensitivity 84% (95% CI
73-92%) and specificity 14% (95% CI 8-24%); WHO criteria plus fever had
sensitivity 81% (95% CI 70-90%) and specificity 33% (95% CI 23-45%). The
higher specificity of including fever with the WHO criteria was valid in
infants below as well as above 2 years of age.
A history of previous episode(s) of wheezing in the
setting of WHO pneumonia appears to be a strong predictor of the diagnosis
being non-pneumonia. A prospective study in India [117] reported that
history of previous episode of cough and difficult breathing, and history
of fever in the WHO case management algorithm can identify more specific
diagnoses. A way out could be to assess the response to inhaled
bronchodilator before assigning the diagnosis of pneumonia or severe
pneumonia in all children with ‘fast breathing’ or ‘chest indrawing.’
However, such a strategy would result in considerable overuse of
bronchodilators and potentially delay the management/referral of children.
Perhaps the ideal approach would be the appropriate assessment by
auscultation [115]. It may be possible to train health workers to do this
efficiently in the field itself.
Management of children with (WHO) pneumonia and wheezing
In a large, multi-centric trial across 8 public sector
hospitals in India [121], 3487 children (2-59 months) with non-severe
pneumonia were first nebulized with salbutamol to assess response to
bronchodilator. Among them, 46% responded in terms of normalization of
respiratory rate, suggesting that a large proportion of children who have
non-severe pneumonia (by the WHO criteria) do not require antibiotic
therapy. From the remainder, those who did not have radiological signs of
pneumonia were randomized to receive either amoxicillin or placebo in
addition to bronchodilators. It was noted that treatment failure rate was
higher in those who did not receive antibiotics (risk difference of
failure 4.2%, 95% CI 0.2%-8.2%). This suggests that a cohort of non-severe
pneumonia with wheezing requires antibiotic treatment. The risk factors
predictive of treatment failure were presence of vomiting (adjusted OR
1.50, 95% CI 1.14-1.98), history of previous bronchodilator use (adjusted
OR 1.72, 95% CI 1.31-2.26) and respiratory rate >10/min over the
age-specific cut-off (adjusted OR 8.24, 95% CI 4.46-15.20).
Conclusions and Comments
• Wheezing is fairly common among children with
pneumonia diagnosed by the WHO criteria, but requires auscultation to be
properly appreciated.
• Alternate diagnoses are more likely with history of
recurrent wheezing and family history.
• Treating all children with antibiotics can result
in overuse; on the other hand treating all children with bronchodilator
results in overuse of the latter and potential delayed management of
pneumonia.
• The solution lies in trying to achieve a reasonably
accurate diagnosis for the cause of wheezing by auscultation and
assessment of the background history. While this would be feasible in
facility settings, feasibility and accuracy of detection of wheeze in
the community settings requires more research
Knowledge gap
• Effectiveness of enlarging the scope of the current
WHO definition to manage auscultable wheezing differently in the field
setting is not known in the Indian context.
5. Family Practices in Management of Pneumonia
The latest NFHS [4] reported that 64.2% children with
ARI or fever in the preceding two weeks, were taken to a health-care
facility. The care-seeking was higher among urban residents (78.1%)
compared to rural residents (59.9%). Care seeking for ARI was slightly
higher in comparison to care seeking for diarrhea (total 58.0%, urban
65.3% and rural 55.6%). Children of mothers with low or no education, and
those belonging to lower socio-economic status were much less likely to be
taken to a health facility than those born to more educated mothers, and
mothers of higher socio-economic status respectively [4] Only 13% of
children with ARI symptoms received antibiotics.
A small-scale study in neonates in Lucknow [122]
reported care seeking from unqualified providers (spiritual/traditional)
as 23.5% for pneumonia and 33.3% for persistent diarrhea; use of
traditional and/or home remedies delayed appropriate and timely
care-seeking. In a study conducted in Kerala [123], among children with
acute respiratory illness or diarrhea during a 2-week interval, 17% did
not receive medical care. Among the 83% receiving medical care, 88%
received allopathic medical care, and 12% alternative medical care. In
contrast, in rural Rajasthan [124], among 290 mothers interviewed 70%
reported at least one medical neonatal condition requiring medical care
with 37% reporting danger sign(s); however only 31% were taken to care
providers; among which half were unqualified modern or traditional care
providers. Decision to seek care outside the home almost always involved
the fathers or another male member.
A very old prospective study [125] of 200 mothers
reported that mothers’ awareness of signs of pneumonia included a
perception ‘retractions’ (pasli chalna); which correlated with
actual retractions in over 90% cases. Honey and ginger were the most
common home remedies used for relief of cough.
Reasons for prevailing client practices
A cross-sectional study in Wardha [120] noted that
although two-thirds mothers knew newborn danger signs and nearly 90%
agreed that the sick child should be immediately taken to a doctor, only
41.8% of such sick newborns actually received treatment either from
government or private facilities. Over 45% sick babies received no
treatment. The reasons for this included ignorance, financial constraint,
faith in supernatural causes, non availability of transport, home remedy,
non availability of doctor and absence of responsible person at home. An
older Gujarat study [126] reported that women’s education, income, family
structure and kinship affiliation were significant predictors of use of
service. Women seemed to be more sensitive to travel time to the health
service and its associated costs (purdah restrictions,
transportation and time costs) than to the direct costs of service.
An urban study in a RCH center and District hospital
[127] reported mean out-of-pocket expenditure on neonatal illness as Rs
547.5 and for hospitalization (for IMNCI illnesses) Rs 4993. Another
prospective study [128] found that prices and income were significant
determinants of the choice of healthcare provider in rural areas. Distance
to healthcare facilities negatively affected demand for outpatient care,
an effect that was mitigated as access to transportation improved. Age,
sex, educational status of the household members and the number of
children and adults living in the household also affected the choice of
healthcare provider in rural India. Major reasons for non-utilization of
health-care facilities include: (i) absence of nearby facility; (ii)
facility timing being inconvenient, (iii) absence of health
personnel, (iv) unacceptably long waiting time; and (v) poor
quality of care [129].
Potential solutions
Behavior change communication (BCC) inter-ventions
appear to improve care-seeking practices as demonstrated by a study in two
urban public hospitals at Lucknow [130]. A study to assess the
satisfaction of parents with the immunization services [131] reported that
although over 90% people were satisfied with immunization services,
dissatisfaction with accessibility and information provided by health
workers were responsible for lower acceptance; this could be important for
all community strategies.
A recent IMNCI evaluation survey reported that in
clusters where it was implemented, the proportions of the population
failing to (i) seek care, (ii) seek care within 24 hours of
illness, (iii) seek appropriate care, and (iv) seek care
from an appropriate care provider within 24 hours; were significantly
lower among the IMNCI clusters for severe illness and moderate illness.
Based on analysis of District Level Household Surveys 2 and 3, it was
estimated that proportion of children seeking treatment for ARI increased
by 6.7% in IMNCI districts; whereas it declined by 11.1% in the control
areas (Mohan P, personal communication). In an earlier study [132]
conducted in Rajasthan, PHC physicians of the intervention sites were
trained on counseling families on care-seeking. While the interventions
resulted in significant improvements in knowledge of caretakers on when to
seek care, it did not result in significant improvements in actual
care-seeking.
Conclusions and Comments
• Care-seeking for ARI among children is poor: even
when families do seek care, they often do so from the private informal
providers.
• Cost of care, distance from the health facilities,
and poor quality of care (including factors such as absence of staff at
health facilities and long waiting times) are the major supply side
reasons why families do not seek care from public health facilities.
• In addition, faith in supernatural causes and in
efficacy of home remedies are other demand side factors that affect
care-seeking.
• Education and counseling by health workers appear
to improve care seeking, though the benefit is not clear.
Knowledge gap
• The effectiveness of community empowerment on
improving care-seeking for sick children, including those with ARI has
not been tested.
6. Providers’ Behavior and Practices
This section is not restricted to prescribing
practices, but also includes physician and provider behaviour and
practices. The WHO-UNICEF document [7] states that although it is
critical, globally, only 1 of every 5 caregivers knows that fast breathing
and difficult breathing are indicators of pneumonia.
A study [133] comparing physicians’ diagnosis with IMCI
algorithm diagnosis in hospitalized children (2-59 months) reported low
concordance. A UNICEF study [134] to record procedures for ARI reported
that of 228 episodes where respiratory rate counting was required, it was
done in only 76% and correctly in only 57%. A study on physician practices
showed that majority of private practitioners prescribed antibiotics
(77%), antihistaminics (47%), allopathic cough syrups (43%) for ARI. For
pneumonia, 96% prescribed antibiotics and 28% prescribed steroids. X-ray
to diagnose pneumonia was suggested by over 90% practitioners.
A study of antibiotic prescribing practices in Uttar
Pradesh [135] observed an overall prescription rate of 82%; especially in
the presence of fever, lower age of patients and higher socioeconomic
status. Government health-facilities had a lower prescribing rate. In
Sikkim [136], among 562 URTI prescriptions for children, aged 0-12 years
the average number of medications prescribed was 2.37; 59.2% were
fixed-dose combination products and two-thirds of FDCs were respiratory
medicines. Others included antimicrobials (30.7%) and
analgesic-antipyretics (18.8%). Respiratory medicines included cough and
cold preparations, nasal drops and bronchodilators. In another study
[137], among interns’ prescriptions, the average number of drugs per
prescription was 2.47. The commonest drugs prescribed were antibiotics
(33.9%), analgesics and anti-inflammatory (17.0%), vitamins (13.0%), cough
syrups (10.5%) and antihistamines (8.6%). The authors estimated that only
57.9% of the antibiotics used were appropriate. Interns often omitted to
write the diagnosis (43%), signs and symptoms (50.2%), dosages and
frequency of treatment. A study based in a village health center
[138] also reported high level of antibiotic over-prescription for common
respiratory illnesses including upper and lower respiratory tract
infection. The existing guidelines were totally ignored and cephalosporins
were the most commonly prescribed antibiotics across all age groups (cefadroxil
in <1 yr old infants and cefixime beyond 1 year of age). Azithromycin was
prescribed in only one fourth of older children.
A recent IMNCI review noted that performance of IMNCI
trained community health workers was affected by poor supervision and
inadequate essential supplies. In Nepal [139], an integrated program for
community-based ARI and diarrhea control includes trained to diagnose,
assess disease severity and danger signs, treat children and refer them to
health facilities. This program also provides nutritional and immunization
services. Training curricula and modules based on WHO’s Integrated
Management of Childhood Illness (IMCI) strategy were simplified and
adapted to make them interactive and suited to participation by these
groups. In districts without the program, facility-based care and
immunization programmes continued. The rate of reported ARI cases was
higher in intervention districts, showing that community-based
interventions enable early detection and classification of children with
ARI.
Conclusions and Comments
• About one-third families do not seek care for their
children suffering from ARI. Even when they seek care, they often
consult informal providers, especially in northern states. Education and
counseling by health workers appear to improve care seeking, though the
benefit is not clear.
• On one hand, a small proportion of those who do
seek care receive antibiotics, on the other, many modern providers
prescribe antibiotics indiscriminately.
• Performance of community health workers in
management of childhood illnesses is affected by quality and intensity
of supervision and by availability of drugs and logistics
Knowledge gaps
• There is limited understanding and/or application
of interventions that promote care-seeking for sick children including
those for ARI.
• Interventions to improve and maintain providers
practices in appropriate management of ARI/pneumonia need to be
identified and evaluated.
7. Existing Strategies/Policies/Initiatives/Programs that can Impact
ARI Control/ARI Outcomes in India
The various National programs/strategies that
include/involve ARI management are not listed/described here. Only the
current programs are mentioned.
National ARI Control Program
The National ARI control program was launched in 14
districts in 1990; initially as a pilot project. Another 10 districts were
included during 1991. Thereafter the ARI strategy became integral to the
Child Survival and Safe Motherhood (CSSM) program in 1992; and was
continued into the RCH Phase I project in 1997. Under this program,
cotrimoxazole tablets are made available at health facilities above the
level of subcenters.
Integrated Management of Neonatal and Childhood Illness
(IMNCI)
The Government of India adapted the WHO-UNICEF
Integrated Management of Childhood Illness [140] strategy to the
Integrated Management of Neonatal and Childhood Illness (IMNCI) [101]. The
generic IMCI strategy targets 5 important childhood healthcare issues
viz pneumonia, diarrhea, measles, malaria and malnutrition. The main
components of the IMCI strategy are improved case management, health
system strengthening and improved household practices. One of the
limitations of IMCI was that it excluded the vulnerable early neonatal
period (<7 days); this lacuna was taken care of in India’s IMNCI strategy
along with other innovations such as a Basic health worker module, Home
visit module by provider for care of newborn and young infant, and Home
based training. The training duration was shortened from 11 to 8 days;
with 50% of the training time devoted to newborn and young infants. The
current focus is to scale up further with ‘IMNCI Plus’ that includes a
comprehensive range of interlinked interventions which is the backbone of
the newborn and child health component of the RCH Phase II program. IMNCI
is currently being implemented in 323 districts. The National Rural Health
Mission (NRHM) [141] has incorporated the Facility Based Integrated
Management of Neonatal and Childhood Illness (F- IMNCI) package to empower
the health personnel with skills to manage new born and childhood illness
at the community as well as facility level. F-IMNCI focuses on appropriate
inpatient management of birth asphyxia, sepsis and low birth weight among
neonates and pneumonia, diarrhea, malaria, meningitis, and severe
malnutrition in children.
No data were available on state level actions to manage
the burden of childhood ARI/pneumonia in India.
International experiences relevant in Indian context
UNICEF Accelerated Child Survival and Development (ACSD)
program [142] in 11 West African countries showed decline in mortality in
children in ACSD areas by 13% in Benin, 20% in Ghana and 24% in Mali. ACSD
districts showed significantly greater increases in coverage for
preventive interventions delivered through outreach and campaign
strategies in Ghana and Mali, but not Benin. Although the project did not
accelerate child survival in Benin and Mali focus districts relative to
comparison areas, this could be due to coverage for effective treatment
interventions for malaria and pneumonia not being accelerated, and causes
of neonatal deaths and undernutrition not being addressed.
An evaluation of IMCI in Peru and Honduras [143]
documented increase in mothers’ knowledge of exclusive breastfeeding,
vaccination coverage, recognition of danger signs for pneumonia and
diarrhea and antenatal check-ups. There was associated reduction in
malaria. In Pakistan [144], community-based Lady Health Worker (LHW)
Program and IMCI are used for improving nutrition, reducing indoor
pollution, improving mass vaccination, and introducing newer vaccines
effective against important respiratory pathogens. An old report from
three counties in China and Fiji [145] noted that factors important in the
success of a community program included improved recognition of the signs
of childhood pneumonia by parents, earlier presentation to health-care
facilities, availability of antimicrobials at the primary health-care
level, and rational usage decisions by health-care workers. An even older
report showed that in Nepal, pneumonia case management by female
community-based workers decreased under-five mortality by 28% [139].
Discussion
To the best of our knowledge, this is the first
systematic review that has meticulously collected and collated evidence
from a variety of sources (including but not restricted to peer reviewed
publications), to guide the initiating and/or scaling up of advocacy and
actions for tackling the burden of childhood pneumonia in India. This is a
critical first-step in today’s era of evidence-informed decision-making.
Previous reviews tended to have methodological limitations such as
incorporation of outdated data; or selective inclusion (or omission) of
evidence supporting a particular viewpoint. Another strength of this
review is that we could access current data relevant to India from
multiple sources including Health Ministry documents, NFHS series etc.
Therefore, this systematic review can be regarded as current,
comprehensive and oriented to facilitating informed decision making,
especially at a programmatic level.
Nevertheless, some limitations of this review must also
be recognized. We did not undertake critical appraisal of the included
publications, except for Methodology. Therefore we have not presented
insights into the applicability, transferability or appropriateness of
cited evidence; with specific reference to the Indian context. Owing to
constraints of resources (manpower and finances), we could not undertake
secondary analysis of the data presented in the included publications.
Therefore, we are unable to present a weighted average for numerical data
or other meta-analyses. We have reported data as presented in the original
publications, without filtering or treating them to fit a common reporting
format. This can make it slightly difficult to compare (for example) odds
ratios for one outcome in a systematic review with risk ratios for another
outcome. Although we have accorded highest priority to recent systematic
reviews, some conclusions presented in systematic reviews could stem from
a limited number of trials (in some cases, even one RCT) and participants.
It must also be noted that we have not undertaken literature search for
some relevant issues like need (or otherwise) of chest radiographs in
childhood CAP, potential role of vitamin C in preventing ARI, subgroup
analysis in malnourished children, the effect of HIV on childhood
pneumonia etc; since these were not identified a priori.
Contributors: JLM undertook the systematic review,
drafted the manuscript and finalized it. AKP, PG and PM provided critical
inputs. All authors participated in formulating the methodology, reviewing
the manuscript and finalizing it.
Conflict of interest: PM is a staff member of
UNICEF that supports community based management of pneumonia. All other
authors: None stated.
Funding: UNICEF.
Disclaimer: The views expressed in the paper are
the authors’ own and do not necessarily reflect the decisions or stated
policies of the institutions/organizations they work in/with.
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