Pneumonia in Developing Countries:
Still Unresolved Problem
Dr. Pushpa Raj Sharma
Professor, Department of Child Health
Institute of Medicine
Kathmandu, Nepal
This Presentation
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Epidemiology
Risk factors
Aetiological agents
Clinical syndromes
Investigations
Treatment
Future implications
A case:
• 4 months old
• One day history of
excessive crying
• Sent home with the
diagnosis of windy
colic with antispasmodics
• Next day:
– Grunting, respiratory
distress, fever.
– Admitted, IV
ceftriaxone.
Case (contd)
• Second day:
– Mother felt child is
better but continues to
be tachypnoeic, chest
indrawing, fever
persisting.
– Vancomycin added
with oxygen
Case (contd)
• Third day
– Severe respiratory
distress
– Pus drained through water
seal drainage
– Antibiotics contd.
– Discharged after 2 wk.
Strepto.pneumoniae isolated
Total live births and surviving
infants in South East Asia
1800000
1600000
1400000
1200000
Live births
Surviving infants
Total populaliton
Measles cases
1000000
800000
600000
400000
200000
0
1980 1990 2000 2001 2002 2003 2004
Worlds population prospects. 2004 Revision. New York, United Nations, 2005
Leading infectious causes of
mortality, 2000 estimates
4
> 5 years old
< 5 years old
3.5
3
2.5
2
1.5
1
0.5
0
Pneumonia
Source WHO
AIDS
Diarrhoea
TB
Malaria
Measles
Burden of Pneumonia
South Asia
60240
18240
135600
82320
576480
,1000
• Population of
approximately
667 million
• Approximately
170 million
infants and
children, (about
one-third of all
the children in
developing
countries).
Unicef (www.childinfo.org) and Hyder et al ; Extrapolated from Black et al
DISTRIBUTION OF DISEASE
RESPIRATORY - 32
CNS - 9
2.4%
6.1%
16%
CVS - 1
6.1%
DIGESTIVE -5
HEMATOLOGY - 2
56.8%
3.7%
NEPHROLOGY - 3
RHEUMATOLOGY -2
1.2%
7.4%
MONTH OF Feb. 2006
MISCELLAN - 8
Hospital Admissions Then and Now
60%
50%
40%
30%
Admission of ARI
cases
20%
10%
0%
1982
NEPAS J 1988; 7; 1-8
2006
Age distribution of pneumonia in
hospital
80
Percentage
70
60
50
40
30
20
10
0
1 -12
months
1 - 5 years
5 - 10
years
> 10 years
Burden of Disease
• ARI episodes/child/year in U5:
5-9
• Pneumonia in ARI: 1:30-50 (2-3% of all
ARI).
• Most of these pneumonia are bacterial in
developing countries.
• Deaths in ARI are mostly due to
pneumonia
• Duration of illness who died from
pneumonia: 3.5 days (Jumla Nepal)
Acute respiratory infection prevalence in under 5
children by socioeconomic status in selected countries
30%
25%
20%
Poorest 20%
Richest 20%
15%
10%
5%
0%
Bangladesh
Vietnam
Benin
Based on World Bank data 2000.
Tanzania
Risk Factors
• In a multivariate analysis, the variables found to
be most closely associated with mortality were
breastfeeding, education of the father,
the number of under-fives, family
income and birth weight. Having a low
weight-for-age was also strongly associated
with mortality but the retrospective nature of the
study makes this finding difficult to interpret.
Int J Epidemiol. 1989 Dec;18(4):918-25.
Risk Factors contd.
• Current and past malnutrition were
associated with acute lower respiratory
infection (ALRI), even after adjusting for
potential confounders (odds ratio: 2.03; 95%
confidence interval: 1.202.43). Decreasing
malnutrition along with timely and proper
treatment of ARI may improve children's health
in developing countries.
Acta Paediatr. 2000 May;89(5):608-9.
Risk Factors: Too many …………..
A study conducted by the World Bank found
that the share of brick kilns in the valley's
air pollution was 28 per cent
while that of domestic fuel burning was
25 per cent, cement factory 17 per cent,
vehicle emission 12 per cent and
road dust 9 per cent.
The study estimated that dust particles
in the air cause 18,863 cases of asthma and
4,847 cases of bronchitis in Kathmandu
every year.
Risk Factors contd
Indoor Air
Pollution
Emissions Along The Household Fuel Ladder
Smith et al.98
Aetiology:
• N. America and Europle
(nine studies /range: 4380%)
• Aetiology of pneumonia
established in 62%:
– S. pneumoniae 22%
– RSV
20%
– H. influenzae
7%
– M. pneumoniae 15%
• Africa and S. America
(eight studies/ range: 3268%)
• Aetiology of pneumonia
established in 56%:
–
–
–
–
S. pneumoniae 33%
H. influenzae
21%
RSV
M. pneumoniae
Aetiology: Viruses isolated from
children with ARI (n=287)
60
50
40
PIV
INF
RSV
MPV
ADENO
30
20
10
0
Feb
Apr
Unpublished report: CHRP; IOM
June
Aug
Oct
Aetiology based on lung aspirates
Study
Age:yrs
Total C
S.Pneu
H.Infl
S.Aur
other
Schuster, Chile
1966
<10
67/125
(54%)
26/125
(21%)
19/125
(15%)
15/125
(12%)
13/125
(10%)
Rozov
1974
Brazil
<7
20/37
(54%)
15/37
(41%)
3/37
(8%)
1/37
(3%0
1/37
(3%)
Silverma
n 1977
Nigeria
<8
54/88
(61%)
31/88
(35%)
9/88
(10%)
8/88
(9%)
20/88
(23%)
Shan
1984
Papua
NG
<5
48/71
(68%)
27/71
(38%)
41/71
(58%)
1/71
(1%)
23/71
(32%)
Wall
1986
Gambia
<9
29/51
(57%)
26/51
(51%)
12/51
(24%)
1/51
(2%)
2/51
(4%)
Ikeogu
1988
Zimbabe
<11
13/40
(32%
7/40
(18%)
3/40
(8%)
4/40
(10%)
1/40
(2%)
231/412
(56%)
132/312
(42%)
96/312
(31%)
29/312
(9%)
60/312
(19%)
Total
Country
Aetiology: Yield from cultures of lung puncture on
755 neonates who were stillborn or died in the first 72
hours of life
Bacteria
Number
Escherichia coli
71
Aerobacter aerogenes
45
Streptococcus beta haemolytic
29
Pseudomonas aeruginosa
27
Streptococcus viridans
21
Staphylococcus aureus
17
Proteus vulgaris
11
Streptococcus non haemolytic (Group D)
Naeye RL, Dellinger WS, Blanc WA. Fetal and maternal features of antenatal bacterial
infections. J Pediatr 1971;79:733–9.
8
Aetiology: Burden of Hib disease in Nepal
(Based on Hib Rapid Assessment Tool of WHO)
Eastern region
Western region
Under 5 mortality
rate
5.4
13.7
84
Annual number of
196
Hib meningitis cases
497
3,048
Annual number of
Hib Meningitis death
59
50
914
Annual number of
Hib pneumonia
cases
980
2,486
15,241
Annual number of
Hib pneumonia
deaths
147
373
2,286
Annual Hib
meningitis
incidence*
*per 100,000 U5s
Paper presented at the WHO dissemination seminar by Dr. Fiona Russeli et al
50
45
40
35
30
25
20
15
10
5
0
1800
1600
1400
1200
1000
800
600
400
200
0
1st
2nd
3rd
4th
1st
2nd
3rd
4th
1st
2nd
3rd
4th
1st
2nd
3rd
4th
1st
2nd
3rd
4th
1st
2nd
3rd
4th
1st
2nd
3rd
4th
1st
2nd
3rd
4th
1st
2nd
3rd
4th
1st
2nd
3rd
4th
1st
2nd
3rd
4th
1st
2nd
3rd
4th
1st
2nd
3rd
4th
1st
2nd
3rd
4th
1st
2nd
3rd
Total Pneumococci cultured and
identified
SAPNA:Distribution of patients with Pneumococci cultured and identified
in Nepal KCH from Nov04-Feb06
Dec-04 Jan
Feb March April May
CSF Culture Isolate
Blood Culture Isolate
June
July
Aug
Sep
Cumulative no. of Blood Collection
Oct
Nov Dec-05 Jan-06 Feb
Cumulative no. of CSF Collected
Bacterial
or
Viral?
LOOKS SICK
•
•
•
•
Fever > 38.50C
Respiratory rate >50/min
Chest recession
Wheeze is not a sign of
primary bacterial LRTI
(except in mycoplasma)
• Other viruses may be
concurrent
• Clinical and radiological
signs of consolidation
rather than collapse.
• Infants and young
children
• Wheeze
• Fever< 38.50C
• Marked recession
• Hyperinflation
• Respiratory rate normal
or raised
• Hyperinflation and patchy
collapse in 25%
• Lobar collapse when
severe
Atypical Pneumonia
• Clark J, Archives Disease Childhood 2003
Mean age of children with M pneumoniae
3.5 yrs
• Block S, Paediatric Infectious Disease
Journal 1995
23% of 3-4 year old children had M
pneumoniae
Signs of Pneumonia
Symptoms and Signs in Pneumonia
100
90
80
70
60
50
40
30
20
10
0
Cough
Indrawing
Convulsion
Cyanosis
Abdominal pain
crepitations
Fast breathing
Comparison of Methods for the
Detection of Pneumonia in Children
Method
Sensitivity
Specificity
53%
59%
77%
58%
Stethoscope
(crepetations)
Simple clinical signs
(fast breathing or
chest indrawing)
Note: Pneumonia diagnosis confirmed by Chest X-ray
Comparison of total leucocyte counts in
different age group with clinically diagnosed
as pneumonia
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
<15000/cmm
>15000/cmm
2-5 m 6-11 m 12-23 >24 m
m
Diagnostic value of total leucocyte count in
radiologically positive cases:
sensitivity: 33.7% and specificity: 71.8%
True negative
False negative
False positive
True positive
0%
10%
20%
30%
40%
Indications for CXR in either
primary care or hospital
• • For diagnosis of child <5 years with fever
of 39°C of unknown origin
• • If complication (for example, pleural
effusion) suspected
• • Atypical symptoms or unresponsive to
treatment
• • For follow up of children with lobar
collapse or ongoing symptoms
Laboratory studies*
• Complete blood count Not helpful in distinguishing
etiology
• Erythrocyte sedimentation rate Not helpful in
distinguishing etiology
• C-reactive protein level Not helpful in distinguishing
etiology
• Gram stain and culture Helpful if specimen is
adequate
• Polymerase chain reaction Helpful with Mycoplasma
and Chlamydia infections
• Rapid viral antigen testing Useful if available
• Serologies Not helpful in acute settings
• Imaging Chest radiograph*Not helpful in distinguishing
etiology*-Not routinely recommended.
*Pediatr Infect Dis J 2002;21:592-8, 613-4.
Clinical Diagnosis
• Tachypnoea according to the usual
WHO criteria:
<2 months: 60
2-12 months: 50
!-5 years: 40
Is Co-trimoxazole still the first line
of drug for IMCI
Pneumococcal isolates and their sensitivity to
different antibiotics
75
80
60
% Resistance
40
20
8
0
8
8
0
Penicillin
Chloramphenicol Erythromucin
cefotaxime
Name of antibiotics tested
cotrimoxazole
Antibiotics for OPD treatment in
4months to 5 year old children
• Amoxicillin, 90 mg per kg per day orally in
divided doses every 8 hours for 7 to 10
days
• A 10 Kg child will need one and half tablet
per dose of 250mg/ disp.tab or three tea
spoon per dose of 125mg/5ml
concentration.
N Engl J Med 2002;346:429-37.
Three days versus five days treatment
with amoxicillin for nonsevere
community acquired pneumonia
• Three day courses of amoxicillin are as
effective as five days without increasing risk of
relapse or worsened disease.
• 15 mg/kg amoxicillin every 8 hourly.
Lancet, July 23, 2002 (MASCOT Group)
BMJ 2004;328:791 (3 April), (ISCAP Group)
Time for temperature to settle in the oral and IV groups
Probability that the child meets the primary
outcome measure after time t
1.0
=IV treatment
--------- = oral treatment
.8
.6
Wellek logrank
test for equivalence
P=0.0013
.4
ITT
P=0.0001
.2
0.0
0
2
4
6
8
10
12
14
Time for temperature to be less than 380C for 24 continuous hours (days)
Arch Dis Child Edu Pract 2004; 29-34
Time to resolution of symptoms
IV group
Time to resolution of symptoms
oral group
25
30
25
20
Number of children
Number of children
20
15
10
5
15
10
5
0
0
0
10
20
30
40
50
Time to resolution of symptoms in days
0
10
20
30
40
50
Time to resolution of symptoms in days
Median of 9 days to full recovery in both arms of the study
Arch Dis Child Edu Pract 2004; 29-34
Length of stay in hospital in the
IV group
Length of stay in hospital in the
oral group
Length of hospital stay in days
50
40
40
Number of children
50
30
30
20
20
10
10
0
0
0
5
10
15
0
5
10
15
Length of hospitalOral
stay in
days - median 1.77 days (1-2.2)
IV Group - median 2.1 days (1.8-2.9)
Group
P=<0.001
IV Group - median 2.1 days (1.8-2.9)
Oral
Group
median
1.77
days (1-2.2)
P=<0.001
Arch Dis
Child
Edu- Pract
2004;
29-34
Indications for admission to
hospital
Older children
•
•
•
•
•
Oxygen saturation <92%
Respiratory rate > 50
Difficulty breathing
Grunting
Signs of dehydration Family not able to support
at home
> 1 year 120/182 (66%) met 1 or more criteria
Thorax. 2002;57;1-24
SWT Therapy
• No RCT’s in children
• 2 prospective observational studies
• Both demonstrate that IV therapy for CAP
can be successfully be decreased to 2-4
days Al-Eidan F, Journal Antimicrobial
Chemotherapy 1999
Ciommo V, Journal of evaluation in clinical practice 2002
Previous studies comparing
macrolides with other groups of
antibiotics
Only 1 study in children comparing betalactams with macrolides
Divided children clinically into “atypical”
(randomised to azithromycin or erythromycin)
or “classic” pneumonia (randomised to
amoxicillin or azithromycin)
Results – no difference between the 2 groups
Kogan et al Pediatric Pulmonology 2003
Indication of macrolide in infant
• 3 weeks to 3 months If patient is afebrile:
Azithromycin, 10 mg per kg orally on day
1, then 5 mg per kg per day on days 2
through 5or
• Erythromycin, 30 to 40 mg per kg per day
orally in divided doses every 6 hours for
10 days
• Admit if patient is febrile or hypoxic
Vitamin A and pneumonia
The evidence did not suggest a significant
reduction with vitamin A adjunctive treatment in
mortality, measures of morbidity, nor an effect on
the clinical course of pneumonia in children with
non-measles pneumonia. However, not all studies
measured all outcomes, limiting the number of
studies that could be incorporate into the metaanalyses, so that there may have been a lack of
statistical power to detect statistically significant
differences.
Cochrane Database Syst Rev. 2005 Jul 20;(3): CD003700.
ZINC AND PNEUMONIA
• FINDINGS: In a pooled analysis of trials, zinc
supplementation reduced the incidence of
pneumonia infection by 41% and daily zinc
supplementation reduced the incidence of
pneumonia in Delhi children ages 6 to 30 months
given vitamin A
• IMPLICATION: Zinc reduces the incidence of
pneumonia but zinc in combination with vitamin A
may be more effective than the administration of
either micronutrient alone.
Sources: 1Bhutta ZA, et al. Prevention of diarrhea and pneumonia by zinc supplementation in
children in developing countries: pooled analysis of randomized controlled trials. J Pediatr.
1999 Dec;135(6):689-97. 2Bhandari N, et al. Effect of routine zinc supplementation on
pneumonia in children aged 6 months to 3 years: randomised controlled trial in an urban slum.
BMJ. 2002 Jun 8;324(7350):1358.
Pneumonia with associated diseases
• Most children in developing countries with
recurrent pneumonia diagnosed by WHO
criteria do not have evidence of
tuberculosis, HIV infection or pulmonary
anomalies, but they may be more likely to
have asthma, and this should be
considered as an alternative diagnosis.
Pediatr Infect Dis J. 2002 Feb;21(2):108-12
Hib Vaccination schedule
Recommended vaccination schedule
from 2 months old: same schedule as DTP
Act-HIB™
6, 10, 14 weeks
booster at 18 months
of age
ACIP
Recommendation
Plotkin S, Vacccine, 3rd ed. 1999
2- 4- 6 months
12-15 months
Pneumococcal Vaccination
schedule??
Recommended vaccination schedule
from 2 months old: same schedule as DTP
PCV
2- 4- 6 months
PPV
12-15 months
Recommended in addition to the PCV for
certain high risk group after two years.
Immunization for common serotypes
(pneumococcus)
Serotype of S. pneumoniae From Nepal KCH
7
6
5
5
4
No. of Isolates
3
2
2
1
1
1
1
1
1
0
1
39
5
7F
18F
23F
SEROTYPES
PCV7 (Wyeth)
*
PCV12 (Wyeth)
*
*
*
PCV10 (GSK)
*
*
*
*
Nontypable
Areas of continuing uncertainty
• • The most useful clinical signs and symptoms that help
to predict a diagnosis of pneumonia
• • Which children require a chest x ray before treatment
• • Which test to detect the causative organism will be
sensitive, specific, affordable, and quick and easy to use
• • Which antibiotic should be prescribed
• • Which route should be used for administering the
antibiotic prescribed
• • If the intravenous route is used when should a switch to
oral antibiotics occur
Areas of continuing uncertainty
• • All children under 2 years should be
given the new conjugate pneumococcal
vaccine routinely or not
• • Variation in individual host response to
the disease: the reason.
• The aetiology of pneumonia.
• Long term follow-up and effects of
pneumonia
SAARS and now The Avian Flue!!!!!
•
2 Mar 06 – Medical News Today
Authorities in Germany have today announced
detection of H5N1 avian influenza in a domestic
cat. The cat was found dead over the weekend
on the northern island of Ruegen. Since midFebruary, more than 100 wild birds have died
on the island, and tests have confirmed H5N1
infection in several.
• Formation of bulla in the lung parenchyma:
difficult to ventilate.
The Avian Flu