Pneumonia in children

challenges to highlight
Steve Graham
Centre for International Child Health
University of Melbourne Department of Paediatrics
Murdoch Childrens Research Institute
Royal Childrens Hospital
Melbourne, Australia
International Union Against Tuberculosis and Lung
Disease
Paris, France

1993:
Pneumonia causes 4.1 million child
deaths per year or 34% under 5
mortality

2010:
Pneumonia causes 1.3 million child
deaths per year or 18% under 5
mortality

Child Health Epidemiology Reference Group: WHO/Unicef data

Consider morbidity and mortality

Most cases occur in SE Asia
Most deaths occur in sub-Saharan Africa (50%)
and SE Asia (20%)

Rudan I et al. Bull WHO 2008

Risk factors for child pneumonia

Young age incidence and
outcome
Poor immunisation coverage

Pertussis
Measles
Hib
PCV

Socioeconomic

Indoor air pollution

Crowding
Hygiene
Access to health
services

Nutrition

Low birth weight

Malnutrition
Not breast fed
Vitamin A deficiency
Zinc deficiency

Underlying disease
HIV
Cardiac
Neurological

Causes of childhood pneumonia

Category

Pathogen

Bacterial 45%

Streptococcus pneumoniae

20%

Haemophilus influenzae

15%

Staphylococcus aureus

5%

Other Gram negatives

5%

Mixed

5-10%

Viral

40%

RSV
Influenza A and B

Proportion

15-20%
5%

Parainfluenza

7-10%

Adenovirus

2-4%

Data from 14 lung aspiration studies Berman S. Rev Infect Dis 1991

Causes of child pneumonia: changing spectrum

increasing proportion of pneumonia is due to viruses
socioeconomic development
improved nutrition
vaccine introduction e.g. measles, Hib, pneumococcal
frequency and pathogenicity of viral/bacterial co-infection

limited aetiological data from Asian settings: challenges

inappropriate hospitalization
inappropriate use of antibiotics
uncertainty of vaccine effectiveness to reduce burden

Radiologically confirmed pneumonia reduced by 39% after

introduction of Hib vaccine in Viet Nam
Viruses from nasopharynx in 60% of 3,039 cases

Fast breathing and chest indrawing but no danger

signs can be managed as
outpatient with oral
amoxicillin

Severe pneumonia with

danger signs: ampicillin (or
penicillin) plus gentamicin
Ceftriaxone as second-line

Aetiology in other high-risk groups:

severely malnourished and neonates
High incidence and risk of death
Clinical diagnosis more challenging
Limited aetiological data
Gram negatives Klebsiella pneumoniae,
Acinetobacter and staphylococcus
Community-acquired or hospital-acquired
MDR isolates common

Tuberculosis in acute severe pneumonia in TB

endemic settings
Oliwa J, et al Lancet Resp Med

11 clinical studies heterogeneity but mainly HIV

endemic Africa, central hospital-based studies
6,504 severe pneumonia cases: 11% clinical or
confirmed tuberculosis
3,644 samples for culture or Xpert: 7.5%
bacteriologically confirmed Mycobacterium
tuberculosis
Majority had acute (<2 weeks) symptoms
Supports evidence from autopsy studies

Causes of bacterial pneumonia in

tropical Africa

Bacteraemia studies in Kilifi District, rural Kenya Berkley JA et al, BMJ 2005
Non-severe
pneumonia

Severe
pneumonia

Very severe
pneumonia

Total

29 (43%)

28 (31%)

14 (44%)

71

H.influenzae

6 (9%)

18 (20%)

5 (16%)

29

Salmonellae

16 (24%)

18 (20%)

2 (6%)

36

E.coli

3 (4%)

11 (12%)

2 (6%)

16

Other

4 (5%)

8 (9%)

3 (9%)

15

Total

68

89

32

S. pneumoniae

50% of blood isolates from children with pneumonia in rural Gambia were
non-typhoidal Salmonellae ODempsey TJ, et al Pediatr Infect Dis J 1994

The future point of care diagnosis?

Hypoxia is associated with an increased

risk of death in children
Increased risk of death if hypoxic in Kenyan children:
age-adjusted risk ratio 4.5 (95% CI 3.8-5.5)
Malawian children with severe pneumonia
SpO2 < 80% 33%
SpO2 80-90% 12%
SpO2 > 90% 4%
2 for trend: p<0.001

Mwaniki MK et al Bull WHO 2009 ; Graham SM et al. Pediatr Infect Dis J 2011

Clinical detection of
hypoxia can be difficult
Oxygen saturation
SpO2

Percentage of children
(n=1116) detected
to have cyanosis

70-84%

44%

50-69%

81%

<50%

88%

Duke T, Int J Tuberc Lung Dis 2001

Oxygen system:
oxygen therapy and pulse
oximetry

Oxygen concentrators and pulse

oximetry reduce pneumonia
deaths
Duke T, et al. Lancet 2008

11,000 children with pneumonia

Risk reduction 0.65 (0.52-0.78): 35% reduction in the risk of
pneumonia mortality post-intervention
$1673 per additional life saved, $51 per DALY averted
Cf. Pneumococcal conjugate vaccine: $4,500 per life saved
Sinha et al, Lancet 2007

Scaling up is possible

2005: 5 provincial and district hospitals

Scaling up is possible

2010: 17 provincial and district hospitals

Costs of concentrators versus

cylinders
The Gambia: costed 8 years of oxygen
concentrator plus UPS back-up
Conservative estimate: 49% of cost of
cylinders
Savings of USD 46,000
Bradley B, et al. IJTLD 2015

Comparison in rural Gambia Schneider G. IJTLD 2001

Oxygen concentrator with solar power cost
effective if hospital needs more than 6
treatment days at 1 litre/min of oxygen therapy
per month

CPAP in children with severe

pneumonia
Chisti MJ, et al. Lancet 2015

Median (IQR) age: 7 (3.8-13.0) months

Nutritional state: severe wasted 22% and 8% nutritional oedema
All hypoxaemic: median (IQR) SpO2 at enrolment 86% (82-88)
Bacteraemia 12%
225 enrolled and study stopped at interim analysis

BCPAP
N=79

HFNC
N=79

LFNC
N=67

Treatment
failure

5 (6%)

10 (13%)

16 (24%)

Death

3 (4%)

10 (13%)

10 (15%)

Compared to children LFNC, receiving BCPAP had a lower rate of:

treatment failure (RR 0.27 99.7% CI 0.07-0.99), and
death (RR 0.25 95% CI 0.07-0.89)