Child lung health in resource-limited settings

Steve Graham
Centre for International Child Health University of Melbourne Department of Paediatrics Royal Childrens Hospital Melbourne

Child Lung Health International Union Against Tuberculosis and Lung Disease Paris

Balance and perspective

Patient care focus
Resource rich Benefit Expecting best possible outcome Often complicated from 95% to 99.9% Relevant to local priorities Social determinants

Public health focus

Resource poor Cost best can be the enemy of the good Keep it simple from 85% to 95% Relevant to local priorities Social determinants

Global mortality among children (< 5 years) has fallen by 40% in past 20 years Estimates of 12.2 million child deaths from preventable causes in 1993 falling to less than 7 million in 2011 Pattern of causes has changed slightly but pneumonia remains major single cause

Lancet Child Survival series

Female illiteracy is a more important determinant of high child mortality than low income per capita, and both are more important than low public expenditure on health

Schell C, et al. Scand J Pub Health, 2007;35:288-97

Female illiteracy is a more important determinant of high child mortality than low income per capita, and both are more important than low public expenditure on health

Schell C, et al. Scand J Pub Health, 2007;35:288-97

Female literacy and child mortality: examples from south Asia

Country Afghanistan Bangladesh India Nepal

Year 1998 1998 1997 1997

Male 46.0 63.1 70.5 62.5

Female 16.0 48.1 43.9 27.7

Pakistan
Sri Lanka

1997
1998

55.3
92.0

29.1
88.0

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

Age Poor immunisation coverage
Pertussis Measles Hib

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

Risk for death for Malawian children with severe pneumonia Risk factor Category Death/ numbers Casefatality rate Test of significance

66/477
Age
< 6 months 6-12 months 1-4 years 5 -14 years 47/175 16/110 3/153 0/39

14 %
27 % 15 % 2% 0% Chi-square for trend P<0.0001

Severity

Very severe pneumonia Severe pneumonia

SpO2 <80% SpO2 80-89% SpO2 90% HIV-infected HIV-uninfected

19/87 14/239
42/102 15/104 9/271 42/227 6/187

22 % 6%
41 % 14 % 3% 19 % 3%

Fishers exact P<0.001

Chi-square for trend P<0.0001 Fishers exact P<0.001

Hypoxia

HIV status

Graham SM, et al. Lancet 2000; Graham SM, et al Pediatr Infect Dis J 2011

Causes of childhood pneumonia

Category
Bacterial 45%

Pathogen
Streptococcus pneumoniae Haemophilus influenzae type B Staphylococcus aureus Other Gram negatives 20% 15% 5% 5%

Mixed
Viral

5-10%
40% RSV Influenza A and B Parainfluenza adenovirus 15-20% 5% 7-10% 2-4%
Berman S. Rev Infect Dis 1991

Data from 14 lung aspiration studies

Changing spectrum of aetiology /prevalence of specific causes Poor diagnostic techniques

Did not investigate for tuberculosis

Limited data from HIV endemic setting

Disease burden
Very severe pneumonia

Severe pneumonia

Non-severe pneumonia

WHO pneumonia case definitions

Disease burden
Very severe pneumonia

Cause of death

Severe pneumonia

Non-severe pneumonia

Lung aspiration studies in early 1980s identified that most fatal cases were due to bacteria especially pneumococcus and Hib
Shann F, et al Lancet 1981

Disease burden

WHO case definitions

Very severe pneumonia

Presence of danger signs

Severe pneumonia

Chest indrawing

Non-severe pneumonia

Fast breathing

Disease burden

WHO case definitions

Very severe pneumonia

Parenteral antibiotics +/oxygen Antibiotics +/- hospitalise

Severe pneumonia

Non-severe pneumonia

Home oral antibiotics

Management of child pneumonia

Case-management strategy
Focus on reducing mortality Reduce unnecessary antibiotic use

Antibiotics
Recent changes to recommendations: amoxicillin Availability Community-based care and improved access

Hypoxia management

Implementation a major challenge

Cost-effective

Malawi Child Lung Health Project 2000-2005

All deaths 20% 18% 16% 14% 12% 10% 8% 6% 4% 2% 0% 0 2 4 6 8 10 12 14 16 18 20 22 24 26

Stepped implementation design 25 district government hospitals >47,000 severe or vey severe pneumonia cases

Training, antibiotics and oxygen

Cost-effective

How common is the need for oxygen?

Hypoxaemia in >16,000 child pneumonia cases in 21 studies: median prevalence of 13.3% (IQR 9.3-37.5)
Varies widely between settings

11-20 million children admitted to hospitals with pneumonia each year

At least 15 to 27 million annual cases of hypoxaemic pneumonia presenting to hospitals

Subhi R, et al. Lancet Infect Dis 2009

Clinical detection of hypoxia can be difficult

Oxygen saturation SpO2
70-84% 50-69% <50%

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

44% 81% 88%

Duke T, Int J Tuberc Lung Dis 2001

Oxygen availability
Papua New Guinea: oxygen not available for 22% of 1300 children in 5 hospitals 1 of 20 hospitals had pulse oximetry Sierra Leone: 40% of hospitals no oxygen
South Africa health clinics: 39% no oxygen Lao: some central hospitals, few district hospitals have oxygen

Wandi F, et al. Ann Trop Paediatr 2006; English M, et al. Lancet 2004; Kingham T P, et al. Arch Surg 2009;

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 Cost-effective intervention: $1673 per additional life saved, $51 per DALY averted

Scaling up is possible

2010: 17 provincial and district hospitals

Oxygen concentrators and the role of bubble CPAP

Causes of respiratory disease in autopsy studies in African children

Causes of pneumonia
Bacterial PcP CMV Tuberculosis Co-infection

HIV-infected N=473
238 (50%) 145 (31%) 121 (26%) 50 (11%) 98 (21%)

HIV-uninfected N=338
132 (39%) 11 (3%) 7 (2%) 27 (8%) 5 (1.5%)

Total N=811
370 (46%) 156 (19%) 128 (16%) 77 (9%) 103 (13%)

Pneumocystis jirovecii pneumonia (PcP)

PcP is commonest cause of death in HIV-infected infants Presents in early infancy: 2-6 months of age PcP is often associated with CMV disease PcP is preventable by cotrimoxazole prophylaxis in HIV exposed infants

Treatment of severe and very severe pneumonia and HIV

Site and year
Zambia Rural hospital 1995 Malawi Urban hospital 1996 South Africa Urban hospital 1998 South Africa Urban hospital 1998 South Africa Urban hospital 1999-2001 South Africa Urban hospital 2001-2 Mozambique Rural hospital 2004-2006 Malawi Urban hospital 2006

Number in study

HIV-infected (%)

Case-fatality rate HIV uninfected HIV infected

132 150 250 1165 366 358 195 264

14 (11%) 93 (62%) 151 (60%) 548 (47%) 82 (22%) 242 (68%) 49 (25%) 134 (51%)

14% 9% 8% 2% 0.7% 2.5% 2% 3%

36% 30% 20% 13% 3.6% 21% 27% 13%

Overall in-hospital CFR was 16.8% in 1313 HIV-infected children compared to 3.4% in 1567 HIV-uninfected children: OR 5.67 [95%CI 4.17-7.71] HIV-related increased mortality is in infants: PcP major contributor

Chronic lung disease extremely common among adolescents with vertically-acquired HIV infection Severely restrictive lung disease with marked exercise intolerance

Pulmonary hypertension common

Ferrand R, et al. CROI 2010

Notification Rates of Sputum Smear-Positive Tuberculosis, by Age, Tanzania Mainland, 1984 and 1995
200 1995

Notifications per 100,000

150

100

1984

50

0 0 15 25 35 45 55 65

Age group (years)

Tanzania NTLP / IUATLD. Progress Report 1996;No. 36

Childhood TB and TB control programmes

Public health approach: Proper identification and treatment of infectious cases will prevent childhood TB Child TB historically afforded a low priority by NTPs:
Diagnostic difficulties Usually not infectious Limited resources Lack of recording and reporting

But - this disregards the impact of TB on childhood morbidity and mortality - relevant MDGs 4 and 5 as well as MDG 6 - child TB reflects recent TB control

Signed by more than 1000 individuals/organisations

Child TB is common wherever TB is common but how common?

Estimated TB incidence rates, 2011

Global Tuberculosis Report 2012

Reported: range 1%-40%

Important factors: Incidence of TB Demographics - age Effectiveness of case-finding and management Prevalence of risk factors in children BCG coverage

Donald PR. Curr Opin Pulm Med 2002

Risk of TB disease following infection by age

Adapted from Marais B, et al. Int J Tuberc Lung Dis 2004

Incidence by age when TB was first diagnosed

400

Average annual case rate (per 100,000)

300

Diagnostic challenges

200

100

0
0 5 10 15 20 25 30 35 40

Age (years)
Comstock GW, et al. Am J Epidemiol 1974;99:131-8

Clinical challenges are the diagnostic challenges

Young age

Acute severe pneumonia

HIV-infected

Malnourished
MDR TB

Recommended approach to diagnose TB in children

WHO Guidance for NTP on management of TB in children 2006

1. Careful history
includes history of TB contact symptoms suggestive of TB

2. Clinical examination
includes growth assessment

3. Tuberculin skin test 4. Bacteriological confirmation whenever possible 5. Investigations relevant for suspected PTB or suspected EPTB

Recommended approach to diagnose TB in children

1. Careful history
includes history of TB contact symptoms suggestive of TB
TST and culture are often unavailable. Neither is required for a decision to treat for TB in most cases.

2. Clinical examination
includes growth assessment

CXR is an important tool for 3. Tuberculin skin test diagnosis of TB in children but recognised limitations 4. Bacteriological confirmation whenever possible 5. Investigations relevant for suspected PTB or suspected EPTB 6. HIV testing routine

Revised National Guideline on Management of Tuberculosis in Children, 2012, Myanmar

Risk of TB disease following infection by age

Adapted from Marais B, et al. Int J Tuberc Lung Dis 2004

Bugs or biomarkers
Xpert MTB/RIF

from Boehme CC et al, NEJM 2010

from Tebruegge M, PhD student

Uni of Melbourne 2011

Improving management point of care diagnosis

Studies of child contacts in Asian countries

Study Andrew et al Narain et al Kumar et al Singh et al Location India India India India No. of child contacts Proportion with TB infection Proportion with TB disease

398 790 142 281

39 % 24 %
NR

5.5 %
NR

34 %*

3 %* 3 %*
NR

Rathi et al
Salazar et al Tornee et al Nguyen et al Okada et al

Pakistan
Philippines Thailand Lao PDR Cambodia

151 153 500 148 217

27 % 69 % 47 % 31 % 24 %*

3%
NR NR

9 %*

* Data only for < 5 years; NR: not recorded

From Triasih R et al, J Trop Med 2011

WHO symptom based screening

Children in close contact with a case of sputum smear-positive TB

Less than 5 years

More than 5 years

Well

Symptomatic

Symptomatic

Well

Preventive therapy

Evaluate for TB disease

No treatment

If becomes symptomatic

If becomes symptomatic

Note that contact screening has two important roles 1. Active case-finding 2. Preventive therapy for at-risk contacts without TB

The outcome of symptom based screening in Indonesian children

269 All child contacts
108 Children < 5 yrs 71 well 37 symptomatic 161 Children > 5 yrs 61 symptomatic 100 well

28

49

99

12

149

TB DISEASE AT BASELINE

TB DISEASE AT FOLLOW UP
Triasih R, Graham SM. Unpublished data

The outcome of symptom based screening in Indonesian children

269 All child contacts
108 Children < 5 yrs 71 well 37 symptomatic

IPT

No IPT
161 Children > 5 yrs

28

61 symptomatic

49

100 well

99

12

149

TB DISEASE AT BASELINE

TB DISEASE AT 12 MONTH FOLLOW UP

Triasih R, Graham SM. Unpublished data

Childhood TB and NTPs

Best Practices in Tuberculosis Control September 2010, Kigali, Rwanda

1. 2. 3. 4. 5.

Develop and adapt child TB guidelines Operationalise child TB guidelines Identify child TB champion Focal person for child TB at NTP working group Training provide child TB training and incorporate into ongoing training related to TB and TB/HIV

6. Incorporate child TB into annual plans and 5-year strategic plan 7. Incorporate child TB into budget 8. Include child TB data in routine reporting and reviews 9. Operational research to determine constraints and barriers 10.Research aimed to improve child TB and contact management

 There are many contributions which the pediatrician can make to a TB control program. First the negativism about tuberculosis so prevalent in pediatrics must be overcome
Edith Lincoln, 1961

Donald PR. Edith Lincoln, an American Pioneer of Childhood Tuberculosis. Pediatr Infect Dis J 2013

Launched 1st October 2013 Washington D.C.

Prevention of disease and deaths

Addressing social determinants

Expanded Program on Immunisation

Pneumococcal conjugate vaccine

HIV prevention and management

Lower antenatal HIV prevalence Prevention of Mother to Child Transmission Cotrimoxazole preventive therapy Early antiretroviral therapy

Improve management of hypoxia

Preventive therapy for TB contacts

Thank you