The Hidden Disparity: Lung Infections in Indigenous American Children

Aug 25, 2015 WebinarRosalyn Singleton MD, MPH

Alaska Native Tribal Health Consortium

Learning Objectives:

1. Recognize higher morbidity for respiratory infections and chronic lung disease among American Indian / Alaska Native (AI/AN) children

2. Recognize modifiable risk factors for lower respiratory tract infections in AI/AN children

Global Childhood Mortality (<1yo)

Lozano, Global Burden of Disease, Gates Foundation, Lancet 2012

Background• High rates of mortality from pneumonia and

influenza (P+I)have been documented in indigenous populations around the world.

• Persistently higher rates of pneumonia in American Indian/Alaska Native children

• From 1999-2001, P+I was one of the 5 leading causes of mortality for AI/AN infants accounting for 2.5% of all infant deaths

IHS Regional Differences in Indian Health, 2002-2003 edition. http://www.ihs.gov/ihs_stats/files/RD_entirebook.pdf IHS Trends 2002-2003 Edition http://www.ihs.gov/ihs_stats/files/Trends%20Part%203-Nat&Inf%20Mort.pdfSingleton RJ et al. Trends in LRTI hospitalizations among AI/AN children ... J Pediatr 2012

Risk factors for the development of pneumonia worldwide

• Malnutrition (weight-for-age z-score < –2)• Low birth weight (< 2500 g)• Non-exclusive breastfeeding (first 4 mo of life)• Lack of measles immunization• Indoor air pollution• Household crowding

Rudan I, et al. Epidemiology and etiology of childhood pneumonia. Bulletin of the World Health Organization 2008

AI/AN Demographics

AI/AN US average

Median Income 35000 50000

Poverty 28% 15%

Completed High School 77% 86%

Completed College 13% 28%Crowding

(>1 person per room) 19% 6%

No safe water or sanitation 12% 0.6%

US Census data from 2000 and 2010

Indian Health Service Regions

*Texas is administered by Nashville, Oklahoma City and Albuquerque Areas.**Included for outpatient visits only.

MA

East

OklahomaNorthern Plains

SouthwestAlaska

West**

IHS Regions*

California

Alaska

Oklahoma City

Phoenix

Navajo

Tucson

Albuquerque

PortlandBillings

AberdeenBemidji

Nashville

Household Crowding in the U.S.2000 Census Data

8Structural and Occupancy Characteristics of Housing: 2000. Census 2000 brief. US Census Bureau,

Alaska Native Villages

American Indian Reservations

Tobacco smoke exposure in AI/AN children

• 21% AI/AN prenatal exposure vs. 9-17% for general US population

• 75% AI/AN children exposed to passive tobacco smoke vs. 40% for general US population

• 21-38% of AI/AN youth smoke tobacco vs. 23% for general US youth

Redding GJ et al. Chronic respiratory symptoms .. among indigenous children. Pediatric Clinics of North America 2009.MMWR September 2010

Indoor Air Pollution and AI/AN Children

• High rates of indoor smoke exposure due to wood burning stoves

• Any wood burning stove in the home increased odds of childhood LRTI by 4.9 times in Navajo children

• Household particulate matter concentration >65 μg/m3 resulted in an increase of odds of childhood LRTI by 7 times in Navajo children

Robin LF et al. Wood-burning stoves and lower respiratory illness in Navajo children. Pediatr Infect Dis J 1996.Morris K, et al. Wood-burning stoves and LRTI in American Indian children. Am J Dis Child 1990.

Indoor air pollution and childhood pneumonia

Smith KR et al. Effect of reduction in household air pollution on childhood pneumonia in Guatemala (RESPIRE): a randomized controlled trial. The Lancet 2011

Rural Alaska Household Characteristics

• Household crowding• 20% have no piped water• Many use outhouses or “honeybuckets” for sanitation• High rates of tobacco smoke exposure• Many use wood burning stoves• Poor ventilation

Hennessy TW et al. The relationship between in-home water service and the risk of respiratory tract, skin, and gastrointestinal tract infections among rural Alaska Natives. AJPH 2008.

Risk Factors for LRTI and RSV Hospitalizations, Rural Alaska

• Medically high-risk status (<35 weeks gestation, congenital heart disease, or chronic lung disease)

• Absence of breastfeeding• Household crowding• <2 rooms with sinks • No piped water• Woodstove in the house• Vomiting after feeding

Bulkow LR et al. Risk Factors for Hospitalization With LRTIs in Children in Rural Alaska. Pediatrics 2012Bulkow LR et al. Risk factors for severe RSV infection among Alaska native children. Pediatrics 2002

Hospitalization rate among infants by percentage of rural Alaska village homes with

water service, 1999–2004

Lower Resp. Tract Infection

Pneumonia Resp. Syncytial Virus

0

50

100

150

200

250

300

350

400

< 10%

10 - 79%

>= 80%

Town

All USRa

te p

er

10

00

Hennessy TW et al. The relationship between in-home water service and the risk of respiratory tract, …. infections among rural Alaska Natives. AJPH 2008.

Rates of infectious disease in 4 rural Alaska villages 3 years before and after introduction of water

service adjusted for age

Respira

tory infecti

ons

Skin Infecti

ons

Gastrointesti

nal Infecti

ons0

200

400

600

800

1000

1200

1400

1600 1520

310

50

1370

250

30

Pre-piped waterPost-piped water

Clin

ic e

ncou

nter

s an

d ho

spita

l-iz

ation

s pe

r 100

0/yr

Thomas T. Impact of In-home Water Service on the Rates of Infectious Diseases. In: The 20th IEA World Congress of Epidemiology 2014.

Pneumonia and influenza-associated childhood death rate by race and age

group, 1999-2009

<1 year 1-4 years 5-19 years0

5

10

15

20

25 23.5

1.90.8

4.8

0.7 0.3

AI/ANWhite

Dea

th R

ate

per 1

00,0

00/y

ear

5-fold higher

Groom AV et al. Pneumonia and Influenza Mortality Among American Indian and Alaska Native People, 1990-2009. AJPH 2014

Influenza-associated hospitalizations in infants <1 year of age from April 2008-

March 2011

US AI/AN AN0

5

10

15

20

25

30

35

40

45

1.5

9.8

38.9Apr08-Mar09

APR09-MAR10

APR10-MAR11

Influ

enza

-ass

ocia

ted

Hos

pita

liza-

tions

/100

0 pe

r yea

r

Unpublished data from KIDS and NIPRS datasets, Arctic Investigations Program- CDC, Indian Health Service

Influenza Hospitalizations AI/AN and comparison US population

Indian Health Service hospital discharge data (2001–2011) for AI/AN people and 13 State Inpatient Databases for the general U.S. population.

Gounder PP et al. Influenza hospitalizations among AI/AN .OpenForumID 2014

All ages Infants0

200

400

600

800

1000

1200

98

1070

58

210

AI/ANU.S. population

Hos

pita

lizati

ons/

1000

00

Annual influenza-associated hospitalization rate, AI/AN and US child population <5 years, 1998-2011

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 20110

2

4

6

8

10

12

AI/AN < 1 Year AI/AN 1-4 Years US < 1 Year US 1-4 Years

Year of Discharge

Influ

enza

-ass

ocia

ted

Hosp

italiz

ation

s(p

er 1

000)

2009 H1N1 pandemic

Foote E, et al. Unpublished data from IHS and Nationwide Inpatient Survey

20

Influenza Prevention & Treatment

Vaccination• IHS Influenza Vaccination 2013-14 season

– 38% of children 6 months – 17 years – 38% of adults 18 years and older

Treatment• Hospitalized patients and all high-risk patients

(hospitalized or outpatient) with suspected influenza should be treated with timely anti-virals.

Lower respiratory tract infection hospitalization rates, AI/AN and US children,

2009-2011

AI/AN US AI/AN US<1 Year 1-4 Years

0

10

20

30

40

50

60

70

80

Other

Bronchiolitis without pneumonia

Any pneumonia

Ann

ual r

ates

per

1,0

00

Foote E, et al. Unpublished data from IHS and Nationwide Inpatient Survey

Pneumonia-associated hospitalizations in AI/AN and US infants, 1998-2011

1998 2000 2002 2004 2006 2008 20100

10

20

30

40

50

60

AI/AN <1 year

US <1 year

Pneu

mon

ia-a

ssoc

iate

d ho

spita

liza-

tions

/100

0 pe

r yea

r

PCV7 PCV13

Foote E, et al. Unpublished data from IHS and Nationwide Inpatient Survey

Pneumonia-associated hospitalization rate in AI/AN and general US infants,

1998-99 to 2009-11

1998-1999 2009-2011 1998-1999 2009-2011AI/AN US

0.0

10.0

20.0

30.0

40.0

50.0

60.0 55.7

36.9

18.7

11.7

Infa

nt p

neum

onia

-ass

ocia

ted

hosp

italiz

ation

s pe

r 100

0/ye

ar

34% decline

37% decline

Pneumonia-associated Hospitalization rate by IHS region, 1999-2011

Alaska Northern Plains West

Southwest East Northern Plains East

Southern Plains

U.S.0

10

20

30

40

50

60

70

80

Hosp

italiz

ation

s per

100

0 pe

r yea

r

Foote E, et al. Unpublished data from IHS and Nationwide Inpatient Survey

Pneumonia-associated hospitalizations in Alaska Native infants <1 year, 2009-2011

YK Delta Maniilaq A B C D Anchorage US0

20

40

60

80

100

120

140

160

180

200

117.4

172.5

110.299.1

42.3

13.9 16.1 11.7

Pneu

mon

ia-a

ssoc

iate

d H

ospi

tal-

izati

ons/

1000

per

yea

r

Two rural sub-regions with high crowding, poverty, decreased water access

Foote, E. Alaska Native Research Conference, 2014, Anchorage, AK

Invasive Pneumococcal Disease (IPD) in AI/AN and general US Children less than 2 years prior to PCV7 introduction

AN White Mountain Apache

Navajo US0

200

400

600

800

1000

1200

1400

1600

1800

2000

403

1820

537

167

Rate

per

100

,000

AN = Alaska Native

Invasive Pneumococcal Disease rates, Children <5 years, YK Delta, AK, 2001-2007, by water

service level and socioeconomic factors

Wenger JD et al. Invasive pneumococcal disease in Alaskan children. Pediatr Infect Dis J 2009

Summary Impact of PCV7 and PCV13 Introduction, 1998-2012

Invasive Pneumococcal Disease,Alaska, Children <5 years of age

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 20140

20

40

60

80

100

120

140

160

180

Rate

per

100

,000

Arctic Investigations Program – Centers for Disease Control and Prevention, unpublished

IPD Rates Pre- and Post PCV13 Introduction Children < 5 Years of Age, Alaska

Alaska Native, PCV13 Alaska Native, Non-PCV13 Non-Native, PCV13 Non-Native, Non-PCV130

10

20

30

40

50

60

70

80

90

100

Pre (2005-2008)

Post (4/2010-2014)

Rate

per

100

,000

* P<0.05Number of Cases shown at top of bars

Arctic Investigations Program – Centers for Disease Control and Prevention, unpublished

RSV

RSV hospitalization rates around the globe RSV hospitalization rates in AI/AN and Alaska Native

children Risk factors for RSV hospitalization Changes in RSV hospitalization rates over time

Global estimates of severe RSV: Rate of Severe or Hospitalized RSV/1000 infants/yr

Baffin Isl

and

YK Delta

Navajo

Kenya

All AI/A

N

United St

ates

Indonesia

Thailan

d UK

German

ySp

ain

South

Africa

IndiaKenya

0

50

100

150

200

250

300

350

289

11391

1334 27 30 30 28 28 26 15 14 13H

osp

rat

e/10

00/y

r

Nair H et al. Global burden of RSV…Lancet 2010;375:1545-55; Banerji. PIDJ 2009.

RSV Follow-up Study:Wheezing visits / year, Cases vs. Controls

0

1

2

2 3 4 5 6

Age (Years)

Mea

n #

of w

heez

ing

visi

ts

Cases Controls

p<.004

p=.07p=.024

p=.140 p=.287

Compared to control children, RSV hospitalized children had more clinic visits for wheezing until 5 years of age.

Singleton RJ, Redding GJ, Lewis TC, et al. Pediatrics 2003;112:285-290

RSV Hospitalization Rates in the YK Delta, Alaska

285

223177

65

RSV hospitalization rates fell by 3-fold, despite stable overall ARI rates

Village-level factors associated with LRTI and RSV rates in children <1 year of age in YK Delta villages during 1995-2005 and 2005-2012

LRTI Multivariate RR P-value Time Period (2005-2012 vs. 1995-2005) 0.88 [0.81, 0.95] 0.001

Large Community (>500 persons) 1.18 [1.09, 1.28] <0.0001

% of Families Below Poverty Line 1.15 [1.05, 1.26] 0.003

% of Households > 1.5 persons/room 1.20 [1.13, 1.28] <0.0001

Lack Plumbing 1.25 [1.05, 1.26] <0.0001

36Bruden et al, 18 years of RSV Surveillance. Ped Infect Dis J, 2015, In press.

RSV Multivariate RR P-value Time Period (2005-2012 vs. 1995-2005) 0.51 [0.45, 0.59] <0.0001

Large Community (>500 persons) 1.14 [1.01, 1.30] 0.04

% of Families Below Poverty Line 1.25 [1.08, 1.45] 0.003

% of Households > 1.5 persons/room 1.17 [1.07, 1.28] 0.0005

Lack Plumbing 1.45 [1.19, 1.78] 0.0003

RSV Rate and Household Crowding(< 1 Year Olds)

37

1995-2005 2005-20120

20

40

60

80

100

120

140

160

180

200

More Crowded CommunitiesLess Crowded Communities

Time Period

Hos

pita

lizati

on R

ate/

1000

Bir

ths

RSV Hospitalization Rate, YK Delta infants, before and after Synagis

High-risk premies Non-premature0

50100150200250300350400450500

439

148150 142

Before Synagis (1993-1996)

After Synagis (1998-2001)

Rat

e pe

r 1,

000

infa

nts

Singleton R et al. Pediatr Infect Dis J, 2003;22:540-545

In 1997, Synagis prophylaxis was implemented in high risk infants, including premature infants.From 1993-1996 to 1998-2001 RSV hospitalization rates decreased 3-fold in premature infants ,But remained stable in non-premature infants.

The Present and Future of RSV Prevention

• Palivizumab (Synagis®) prophylaxis for high risk children– 2014 Redbook Statement severely restricts AAP recommendations.

• Palivizumab prophylaxis recommended for infants born <29 weeks gestation.• Other indications: Chronic Lung Disease, Congenital Heart, Neuromuscular.

– Redbook recognizes special consideration for Alaska Native children

• Future maternal vaccination?

Conclusions

• Rates of RSV hospitalization in Alaska’s YK Delta have declined but remain > 3-fold higher than the US national average.

• Average length of RSV season has decreased by > 4 months and season onset is most recently not until January.

• We did not find that colder winters were associated with more severe seasons.

• Household factors, especially crowding, are associated with higher RSV and LRTI hospitalization rates.

We are not Alone….

Respiratory Infections in Indigenous children from Canada, Australia,

New ZealandGina Rempel, MD and Kent Saylor MD, CanadaAnne Chang MD and Kerry O’Grady, Australia ;

Elizabeth Edwards and Cass Byrnes, New Zealand.

Indigenous Canadians: Housing

• 67% people report their houses are in need of repair

• 18% have no phone• 3.5% have no flush toilets• 3.7% have no hot running water• 118 First Nations communities in Canada need

to boil their water

http://www.hc-sc.gc.ca/fniah-spnia/promotion/public-publique/water-eau.php#how_many

Indigenous Canadians: Air Quality

• Reduced ventilation, tobacco smoke exposure and crowding may contribute to observed excess of LRTI

• Exposure to tobacco smoke was universal in homes tested

• Association between LRTI and indoor carbon dioxide levels

Kovesi (2007); CMAJ 177:155-159

LRTI in Indigenous Canadian Children

• Streptococcus pneumoniae• RSV• Often children require mechanical ventilation• High cost to health care system due to need

for medical evacuation from home communities

• Disproportionately high rates of chronic lung disease

Hemmelgarn (1997); Am J Respir Crit Care Med; 156:1870-5

LRTI in Indigenous Canadian Children

• Newfoundland & Labrador:– Hospitalization was 11.6 vs 3/1000 in the Innu/Inuit

communities– Infants 93.4/1000

Alaghehbanda (2007); Int J Infect Dis 11:23-8

• Nunavik (Northern Quebec)– LRTI 10x more frequent than in the rest of Canada– Hospitalization 198/1000 infants, 119/1000 toddlers,

31/1000 preschoolersDallaire (2006); Canadian J Public Health 97:362-369

LRTI’s in Aboriginal Australians

• Despite Australia being one of the wealthiest countries of the world, Australian Indigenous children have a health status and social circumstance comparable to developing countries.

• Indigenous infants have 10 times the mortality rate for respiratory conditions.

• The LRTI rate in Australian Indigenous children is as high as that of children in developing countries.

• The frequency of LRTI hospitalizations of Indigenous infants is triple that of non-Indigenous Australian infants (201.7 vs. 62.6/1000, respectively).

O’Grady KA. J Paediatr Child Health 2010;46:461-465

Pneumonia in New ZealandDESIGN: • A consecutive sample of children hospitalized with pneumonia at the

Starship Children’s Hospital from 1 July 1993 to 30 June 1996, by ethnicity

RESULTS: • The average annual hospitalization rate was 5.0 per 1000 children

aged 0-14 years (95% CI 4.8-5.2).• The average annual hospitalization rate for Pacific Island children was

14.0 per 1000, for Maori children 6.7 per 1000 and for European/other children was 2.7 per 1000.

• A larger percentage of Pacific Island (61%) and Maori (60%) children were aged less than 2 years compared to European/other (42%) children (P < 0.001).

Grant CC. Hospitalization for pneumonia in children in Auckland, New Zealand. J Paediatr Child Health. 1998 Aug;34(4):355-9.

Pneumonia in Childhood and Impaired Lung Function in Adults

• Prospective Tucson Children’s Respiratory Study• Early pneumonia cases had impaired lung function (FEV1:FVC

ratio) compared with those without LRI and those with other LRI at 11-26 years

• Early pneumonia associated with double the risk of asthma and wheeze up to age 29 years.

Chan J et al. Pediatrics 2015;135:607-615

FEV1:FVC ratio % P-value

No LRI ref

Pneumonia -3.9 <0.001

Other LRIs -1.1 0.010

Long-term Sequelae of Pneumonia Non-CF Bronchiectasis

• Alaska Native children and other indigenous children have high rates of non-CF bronchiectasis

• Early/Recurrent pneumonia in childhood is the major risk factor• Bronchiectasis can lead to morbidity (including COPD) and

mortality by the 3rd decade

Chang AB, Med J Aust. 2002;177:200-204; Twiss J, Arch Dis Child 2005;90:737-740Singleton R, Pediatr Pulmonol 2000;29:182-187

Bronchiectasis

Infant pneumonia

0

400

800

1200

16001600 1470

160 70 0.4

Rate

per

100

,000

Demographic features in children with bronchiectasis compared with local and national population: YK/Australia

Overcr

owding

No running w

ater

Woodburn

ing

Tobacco

exposu

re

Premature

0

20

40

60

80

100

120Bronchiec-tasisYK Delta

Overcr

owding

High Sc

hool grad LB

W

Tobacco

exposu

re

Premature

0

20

40

60

80

100

120 BronchiectasisN TerritoriesAustralia

50Singleton RJ et al. Indigenous children from three countries with non-cystic fibrosis chronic suppurative lung disease/bronchiectasis. Pediatr Pulmonol 2014

Alaska – YK Delta Australia – N. Territories

Conclusion

AI/AN children, similar to indigenous children from Canada, Australia and New Zealand, experience higher morbidity and mortality and long-term sequelae due to pneumonia.

AI/AN and US child pneumonia hospitalizations have decreased over the past decade; however, hospitalization rates remain higher.

Improving access to piped water and quality housing, reducing household crowding, maximizing breastfeeding and immunization rates, and improving parent education can help in closing this disparity