Pneumonia: Past and Present
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
Number of Pneumonia Episodes Per
Year in Childeren Under 5 Years
Place Annual Incidence per 100
Seattle (USA) 3.0
Gadchiorili (India) 13.0
Bankok (Thailand) 7.0
Nepal 16.5
Egypt ???
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
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.
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
Epidemiology,Clinical,and Laboratory Features of
Acute Pneumonia in Normal Infants and Children
According to Etiologic Agents
Bacteria Virus Mycoplasma
Historical clues
- Age Any,esp.infant Any School
age,adolescent
- Temp. Majority ≥ 39° C < 39° C Majority < 39° C
- Onset Abrupt Gradually
worsening URI
Gradually
worsening cough
- Others in home ill Infrequent Frequent Frequent,wk.apart
- Ass. Signs,
symptom
Meningitis,otitis,
arthritis
Myalgia,rash,co
njunctivitis
Headache, sore
throat, myalgia
- Cough Productive Nonproductive Hacking
- Pleuritic chest
pain
Frequent Infrequent Infrequent
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 þ-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 µg/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 þ-
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 02
intermediate causes tissue damage

Pneumonia in children

  • 1.
  • 2.
  • 3.
    Epidemiology •Each year, acuterespiratory 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)
  • 4.
    • Identifying thecause of community- acquired pneumonia is more difficult in children
  • 5.
    Number of PneumoniaEpisodes Per Year in Childeren Under 5 Years Place Annual Incidence per 100 Seattle (USA) 3.0 Gadchiorili (India) 13.0 Bankok (Thailand) 7.0 Nepal 16.5 Egypt ???
  • 6.
    Epidemiology •A lower respiratorytract 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
  • 7.
    Risk Factors • Significantrisk 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
  • 8.
  • 9.
    Types of Pneumonia •Currentlypneumonias 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
  • 10.
    Aetiological agents •The exactincidence 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.
  • 11.
    Diagnosis Clinical evaluation ofpneumonia •Cough, Grunting, Chest pain, •Tachypnea. Retractions, •Signs of consolidation, •Crackles Wheezing , •Cyanosis, •Abdominal pain , Drooping of shoulder.
  • 12.
  • 13.
    Symptoms and Signsin Pneumonia 0 10 20 30 40 50 60 70 80 90 100 Cough Indrawing Convulsion Cyanosis Abdominal pain crepitations Fast breathing Wheeze
  • 14.
    Comparison of Methodsfor 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
  • 15.
    Diagnosis Diagnostic evaluation oflower respiratory infections: •WBC count Blood cultures •C-reactive protein •Chest radiograph. •Bacterial antigen assays •Nasopharyngeal cultures
  • 16.
    Epidemiology,Clinical,and Laboratory Featuresof Acute Pneumonia in Normal Infants and Children According to Etiologic Agents Bacteria Virus Mycoplasma Historical clues - Age Any,esp.infant Any School age,adolescent - Temp. Majority ≥ 39° C < 39° C Majority < 39° C - Onset Abrupt Gradually worsening URI Gradually worsening cough - Others in home ill Infrequent Frequent Frequent,wk.apart - Ass. Signs, symptom Meningitis,otitis, arthritis Myalgia,rash,co njunctivitis Headache, sore throat, myalgia - Cough Productive Nonproductive Hacking - Pleuritic chest pain Frequent Infrequent Infrequent
  • 17.
    Diagnosis •Recent studies haveconcluded 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
  • 18.
    Clinical Diagnosis • Tachypnoeaaccording 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.
  • 19.
    Pneumonia and VitaminA •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.
  • 20.
    Pneumonia and Zinc Reductionin 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)
  • 21.
    Compositions of coughmixtures 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
  • 22.
    Formulations available Type ofFormulation Tablets/capsules 19 23.75% Liquid/Syrups 56 70.00% Other forms 5 6.25% TOTAL 80 100%
  • 23.
    Role of coughmixtures in pneumonia
  • 24.
    Over the countercough 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.
  • 25.
    Systematic review ofrandomised 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.
  • 26.
    •Treatment must assessthe 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 .
  • 27.
    Causative Agents • InAfrica 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
  • 28.
    Haemophilus influenzae •polyribosyl ribitolphosphate (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 þ-lactamase-producing strains
  • 29.
    Streptococcus pneumoniae •Ccapsular polysaccharideis most important virulence factor; approximately 85 capsular types •Penicillin is drug of choice for susceptible organisms (MIC = 0.06 µg/mL) . •Vaccine contains 23 most common capsular serotypes
  • 30.
    Mycoplasma pneumoniae •special attachmentorganelle; 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
  • 31.
    Integrated Management ofChildhood 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
  • 32.
    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
  • 33.
    Prevention • Within twoyears 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
  • 34.
    Summary Pneumonia in childrenin 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.
  • 35.
    Haemophilus influenzae •Strains areclassified 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.
  • 36.
    Haemophilus influenzae •Approximately 20-30%of isolates are beta-lactamse positive. •Treatment with either amoxicillin/clavulanic acid or TMP/SMX is effective against þ- lactamase-producing strains.
  • 37.
    Mycoplasma pneumoniae •Data suggestthat 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)
  • 38.
    Structure, Virulence Factorsand 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
  • 39.
    Mycoplasma pneumoniae •M. pneumoniaeacts 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.
  • 40.
    Structure, Virulence Factorsand 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 02 intermediate causes tissue damage