Pneumonia: Past and Present

Dr. Pushpa Raj Sharma

Professor of Child Health
Institute of Medicine
Disease Pattern
Epidemiology
Each year, acute respiratory infections
cause approximately 2-3 million deaths
among children <5 years old and are the
leading cause of death in this age group.
About 1% of pneumonia cases result in
sequelae (e.g., bronchiectasis)
Identifying the cause of community-acquired
pneumonia is more difficult in children
Children with ARI presenting in
OPD
Place % of children
London (UK) 35.0
Herston (Australia) 34
Ethiopia (Whole country) 25.5
Sau aulo (Brazil) 41.8
India 38.9
Nepal 37.6
Number of Pneumonia Episodes Per
Year in Childeren Under 5 Years
Place Annual Incidence per 100
Seattle (USA) 3.0
Gadchiorili (India) 13.0
Basse, (Gambia) 17.0
Bankok (Thailand) 7.0
Nepal 16.5

Epidemiology
A lower respiratory tract infection (LRI)
develops in one in three children in the first
year of life.
Twenty-nine percent of these children
develop pneumonia
Approximately 10-20% of all children <5
years old in developing countries develop
pneumonia each year
Risk Factors
Significant risk factors were younger
age (2-6 months), low parental
education, smoking at home,
prematurity, weaning from breast milk
at < 6 months, a negative history of
diphtheria, pertussis and tetanus
vaccination, anaemia and malnutrition.
Trop Doct 2001 Jul;31(3):139-41
Pathology
Pathology
Types of Pneumonia

Currently pneumonias are
defined as either community-
acquired (CAP) or nosocomial or
hospital-acquired .


CAP is defined as an infection
acquired in the community
setting; the definition varies and
it may or may not include
infections acquired in a nursing
home or long-term care facility

Aetiological agents

The exact incidence varies but
in a meta-analysis of 122 cases
of CAP, it accounted for 66% of
cases in which a microbiological
diagnosis was made.

Exact incidences of the
various aetiologic organisms
are not known.

Diagnosis
Clinical evaluation of pneumonia

Cough, Grunting, Chest pain,
Tachypnea. Retractions,
Signs of consolidation,
Crackles Wheezing ,
Cyanosis,
Abdominal pain , Drooping of shoulder.

Mechanism of cough
Bronchioles and Respiratory bronchiole
alveolus
Signs of Pneumonia
Symptoms and Signs in Pneumonia
0
10
20
30
40
50
60
70
80
90
100
Cough
Indrawing
Convulsion
Cyanosis
Abdominal pain
crepitations
Fast breathing
Wheeze
Comparison of Methods for the
Detection of Pneumonia in Children
Method Sensitivity Specificity
Stethoscope 53% 59%
(crepetations)

Simple clinical signs 77% 58%
(fast breathing or
chest indrawing)
Note: Pneumonia diagnosis confirmed by Chest X-ray
Diagnosis
Diagnostic evaluation of lower respiratory
infections:
WBC count Blood cultures
C-reactive protein
Chest radiograph.
Bacterial antigen assays
Nasopharyngeal cultures

Diagnosis

Recent studies have concluded
that generally radiology is not
helpful for determining the
aetiology of the infection.

The diagnosis of pneumonia is
based on a history of respiratory
tract infection and the
radiological finding of new
pulmonary infiltrates

Clinical Diagnosis
Tachypnoea according to the usual
WHO criteria.
Auscultatory signs have lower
specificity.
Acute phase reactants cannot be relied
for aetiological diagnosis.
Blood culture positivity in only <10%
Viral antigen detection not available.

Pneumonia and Vitamin A
Weekly low-dose (10 000 IU) vitamin A
supplementation in a region of
subclinical deficiency protected
underweight children

from ALRI and
paradoxically increased ALRI in
normal children

with body weight
over -1 SD in Ecuadorian Children .


Large doses of vitamin A had no
protective

effect on the course of
pneumonia in hospitalized Tanzanian
children.


Pneumonia and Zinc
Reduction in all respiratory diseases.
(Indian J Pediatr 1995; 62,181-93

2.5 fold decrease in respiratory infection.
(Am J Clin Nutr; 1996; 63; 514-9

Significant reduction in upper respiratory tract
disease.
(Am J Clin. Nutr. 1996; 63;514-9)

Reduction of 45% incidence of lower respiratory
tract infection.
(PEDIATRICS 1998; 102 ;1-5)

Compositions of cough mixtures
available
Category


A - Only Antitussive F - Expectorant + Antitussive
B - Only expectorant G - Expectorant + Bronchodilator
C - Only mucolytics H - Expectorant + Mucolytics
D - Only bronchodilator I - Expectorant + Antihistamines
E - Only Antihistamine J - Having more than 2 of the
A,B,C,D,E.
K - Bronchodilator + Antihistamine

Formulations available
Type of Formulation




Tablets/capsules

19

23.75%

Liquid/Syrups

56

70.00%

Other forms

5

6.25%

TOTAL

80

100%

Role of cough mixtures in
pneumonia
Over the counter cough mixtures
No well-controlled studies supporting the use of
codeine or dextromethorphan as antitussives for
children have been published, and indications for
their use have not been established.
Cough due to URTI can often be treated with non-
drug measures (fluids and humidity).
Pediatric dosages of antitussives are extrapolated
from adult data and thus are imprecise for children.
Significant adverse effects of their use have been
documented.
Clinicians should tell parents and patients about
these concerns.

Systematic review of randomised controlled trials of over the
counter cough medicines for acute cough in adults
BMJ 2002;324:329 ( 9 February )

Conclusion: Over the counter cough
medicines for acute cough cannot be
recommended because there is no good
evidence for their effectiveness. Even
when trials had significant results, the
effect sizes were small and of doubtful
clinical relevance. Because of the small
number of trials in each category, the
results have to be interpreted cautiously.

Treatment must assess the severity of the
illness, appropriate setting for treatment
(outpatient vs. inpatient), socioeconomic
conditions, and local susceptibility
patterns of common pathogens.

Treatment


Various guidelines have been developed.

Once treatment has begun, no change
in medication is indicated within the 1st
72 hours unless a specific organism is
identified and is not covered by the
current medication .

Causative Agents
In Africa and South America (8 studies),
bacteria were recovered from 56% (range
32%-68%) of severely ill children studied
by lung aspirate. The most often isolated
bacteria were Streptococcus pneumoniae
(33%) and Haemophilus influenzae (21%)

Braz J Infect Dis 2001 Apr;5(2):87-97
Haemophilus influenzae

polyribosyl ribitol phosphate (PRP) capsule
is an important virulence factor which
renders type b H. influenzae resistant to
phagocytosis by PMNs in the absence of
specific anticapsular antibody .

produce IgA protease which may
facilitate attachment to mucosal surfaces

treatment with a combination of
amoxicillin and clavulanic acid
(Augmentin) or TMP/SMX is effective
against -lactamase-producing strains

Streptococcus pneumoniae

Ccapsular polysaccharide is most
important virulence factor;
approximately 85 capsular types

Penicillin is drug of choice for
susceptible organisms (MIC =
0.06 g/mL) .

Vaccine contains 23 most
common capsular serotypes


Mycoplasma pneumoniae

special attachment organelle; attach to
epithelium via protein adhesins on the
attachment organelle; major adhesin is a
170-kilodalton (kDa) protein, named P1

bacteria injure mucosa by producing
oxidants (hydrogen peroxide &
superoxide radicals) which cause
ciliostasis and epithelial necrosis thus
inhibiting normal clearance mechanisms

Integrated Management of
Childhood Illnesses
Does the child have cough or difficulty in breathing?
If Yes Ask: Signs Clsssify as
For How Long? Any general danger sign or Severe
Chest indrawing or pneumonia
Stridor
Look, Listen Fast breathing Pneumonia
Count the breaths
Chest indrawing No signs of pneumonia No Pneumonia:
Stridor or very severe disease cough or cold



Suggested Drug Treatment
Birth to 20 days:
Admission
3 weeks to 3 months:
Afebrile: oral
erythromycin
Febrile: add
cefotaxime


4 months to 5 years:
Amoxycillin
80mg/kg/dose
6-14 years:
Erythromycin
NEJM
Volume 346:429-437
Prevention
Within two years of the introduction of routine
Hib vaccination of infants in the UK, the risk of
serious Hib infection had fallen from 1:600 to
1:30,000 by 5 years of age
Eur J Clin Microbiol Infect Dis 1995
Nov;14(11):935-48

It is important that these highly effective
vaccines should be made available to children in
the developing countries.
Acta Paediatr 2001 May;90(5):473-6

Summary
Pneumonia in children in the age
group of 2 months to 5 years
Pneumonia is the commonest cause of mortality
Fast breathing in a child with cough or difficulty
breathing is highly sensitive and specific for diagnosis
Co-trimoxazole is the effective treatment for
community pneumonia in children
Cough mixtures are not useful but harmful.
Cough persists for few weeks.
Haemophilus influenzae

Strains are classified as either
serotypable (if they display a capsular
polysaccharide antigen) or nontypable
(no capsule); seven generally
recognized serotypes: a, b, c, d, e, e'
and f; H. influenzae type b (Hib) is the
most virulent

Nontypable H. influenzae strains
colonize the nasopharynx of most
normal children.

Haemophilus influenzae

Approximately 20-30% of isolates
are beta-lactamse positive.

Treatment with either
amoxicillin/clavulanic acid or
TMP/SMX is effective against -
lactamase-producing strains.

Mycoplasma pneumoniae
Data suggest that repeated infections
are required before symptomatic
disease occurs - antibodies to M.
pneumoniae can be found in most
children age 2 - 5 years while illness
occurs with greater frequency among
older children and young adults .

Resistant to antibiotics that inhibit
bacterial cell wall synthesis (e.g.,
penicillin, cephalosporins, vancomycin)

Structure, Virulence Factors and
Pathogenesis

encapsulated organisms can
penetrate the epithelium of the
nasopharynx and invade blood
capillaries directly; nontypable strains
are less invasive, but they, as well as
typable strains, induce an
inflammatory response that causes
disease

Mycoplasma pneumoniae

M. pneumoniae acts as a superantigen
(macrophage activation, cytokine
induction) and stimulates inflammation;
pneumonia is induced largely by local
immunologic and phagocytic responses
to the parasites.

some children may develop cold
agglutinins as a result of infection.


Structure, Virulence Factors and
Pathogenesis

Secretory IgA protease - inhibits
function of secretory IgA which
normally binds bacteria to mucin to
facilitate clearance from the
respiratory tract
Pneumolysin - creates pores in and
destroys ciliated epithelial cells
Hydrogen peroxide - reactive 0
2

intermediate causes tissue damage