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Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease Control and Prevention Atlanta, GA
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Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Dec 23, 2015

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Page 1: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Chagas Disease in the United States

FDA BPAC meeting, 1 April 2009

Susan P. Montgomery, DVM MPH

LCDR, USPHS

Parasitic Diseases Branch

Centers for Disease Control and Prevention

Atlanta, GA

Page 2: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Trypanosoma cruzi

• Protozoan parasite only found in the Americas, causes Chagas disease

• Vector-borne zoonosis, humans not necessary to cycle

• Infects >100 domestic and wild mammals– Typical hosts: opossums, wood rats,

raccoons, dogs, cats

• Infection of host and vector is life-long

• Enormous domestic and sylvatic reservoirs

Page 3: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Distribution of vectors and disease

• Endemic for human Chagas disease• Infected vectors,

nonhuman mammals

Page 4: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Chagas disease worldwide

• Programs in Latin America focus on controlling transmission – Vector control– Blood safety

• WHO Global Network for Chagas disease formed in 2007– Drug donation (nifurtimox) to WHO– Unique situation in the U.S.

Page 5: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Acute phase of Chagas diseaseT. cruzi infection4 - 8 weeks

Infection remains life-long if untreated

Asymptomatic: > 90% Symptomatic: <10%

Chronic phase

Clinically manifest Chagas disease Chagas heart disease Chagas gastrointestinal disease

60 - 80% remain in indeterminateform throughout life

Can reactivateif immunosuppressed

Indeterminate form(asymptomatic, normal H&P, ECG)

20 - 40% progress over years - decades

Page 6: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Clinical testing challenges

• No gold standard test for diagnosis– Serological testing limited availability and varied

sensitivity and specificity– Specific skill necessary for parasitological

diagnosis (acute infection, reactivation disease)

• No test to identify which patients will progress from indeterminate form to clinical disease

• No test to determine cure with antiparasitic treatment

Page 7: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Risk of infection in the U.S.

• Estimated 300,000 infected immigrants in U.S.*

• Who is at risk of infection in the U.S.– People exposed to infected vectors and/ or

reservoirs– Children of infected mothers– Transplant recipients – Transfusion recipients– Laboratory staff working with vectors,

reservoir species, or parasite

*Bern and Montgomery, manuscript submitted

Page 8: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

History of bugs and T. cruzi in the United States

• 1855 – Vector bugs identified in Georgia• 1860’s / 70’s – Vector bugs identified in six

more states• 1909 – Discovery of parasite and disease

(Brazil)• 1916 – Parasite first observed in California• 1930’s – Reservoir host infections studied in

U.S.• 1955 – First autochthonous cases of Chagas

disease reported

Page 9: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

States with documentedpotential T. cruzi vectors

~ 11 potential vector species in the U.S.

Page 10: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

States with documented mammalian reservoirs

> 18 infected reservoir species identified

* *

* *

* Published human vector-associated cases

Page 11: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Vector and Chagas disease in Texas*

30 mm

Female Triatoma gerstaekeri

Male Triatoma sanguisuga

*Kjos et al. VBZD 2009 Photo courtesy of Sonia Kjos

Overall, 50% of tested bugs positive for T. cruzi

Page 12: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Vector-borne transmissionin the U.S.

• Seven autochthonous human cases published

Year State Patient

1955 Texas infant

1955 Texas infant

1982 California 56 year old woman

1983 Texas infant

1998 Tennessee infant

2006 Louisiana 74 year old woman

2006 Texas infant

Page 13: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Published U.S. autochthonous cases:Acute infections

• Age range 2 weeks to 84 years, 4 male• 4 presented with acute symptoms– Non-specific febrile illness–Myocarditis, pericardial effusion

• 2 primary complaint of bug bites– Fever within 48 hours of bug identification

• 1 unclear clinical history• Triatomines on property in 5 cases;

infected reservoir animals on property in 4 cases

Page 14: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Autochthonous infections in U.S. blood donors

• 2007 Investigation of two blood donors in Mississippi

• Ongoing study to investigate potentially autochthonous cases, U.S.– Derived T. cruzi Infection Study (USTC)– Designed in collaboration with American Red

Cross and Blood Systems Laboratories– Participants will be tested with blood center and

CDC tests

Page 15: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Travel-associated infection

• 26yo Canadian woman returned from 6 months in rural Mexico with acute Chagas disease (Romana’s sign)

• 56yo Californian man asymptomatic positive blood donor, three international trips each < 2 wks– Two trips to Mexico, one to non-endemic

area of South America

Page 16: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Congenital transmission in the U.S.

• No confirmed cases in U.S.– 3 possible cases reported– Case reports from other non-endemic areas

• Congenital transmission 1 – 10% in endemic areas• Usually asymptomatic or non-specific findings

– Low birth weight, hepatosplenogmegaly, respiratory distress, anemia, fever

• Estimate 63 – 315 infected infants per year in U.S.*

*Bern and Montgomery, manuscript submitted

Page 17: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Transplant transmission in the U.S.

• Five published cases• 24 recipients of solid organs from

seropositive donors in U.S.– Heart– Liver– Kidney– Pancreas/ kidney, liver/ kidney, pancreatic

islet

• 7 (41 %) of 19 recipients became infected

Page 18: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Transfusion transmission in the U.S. and Canada

• 7 transfusion transmission cases reported in U.S. and Canada

• Likely under-recognized and under-reported

Year Recipient residence Country of donor

1987 California Mexico

1989 New York City Bolivia

1989 Manitoba Paraguay

1993 Houston unknown

1999 Miami Chile

2000 Manitoba Paraguay

2002 Rhode Island Bolivia

Page 19: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Laboratory-associated transmission in the U.S.

• Possible exposures– Feces of infected triatomenes– Handling cultures from infected persons or animals– Routes of entry

• Needlesticks• Existing micro-abrasions on skin• Mucus membranes• Inhaling aerosolized organisms?

• 8 cases reported in the U.S.– 3 needlesticks– 3 contact with infectious material and break in skin– 2 unknown

Page 20: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Chagas disease may not be recognized in the U.S.

• Most physicians not familiar with Chagas disease– Recent ACOG survey–Medscape surveys– Community-based organization focus

groups

• Even clinical Chagas disease is not diagnosed– Up to 14% of Hispanic cardiac patients

found to be positive for Chagas disease (screened for typical EKG changes)

Page 21: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

U.S. public health and Chagas disease

• Not nationally notifiable– Reportable only in AZ, soon in MA

• No systematic public health surveillance– AABB Biovigilance system

• Competing priorities at public health departments

• Lack of public health testing capacity for Chagas disease

Page 22: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

2007 – 2008 CDC consultations and drug releases for Chagas-positive

blood donors

45 drug releases

115 consultations (19 suspected autochthonous infections)

Total of 765 RIPA-positive blood donors*

* AABB Chagas Biovigilance reporting system

Page 23: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

0

10

20

30

40

50

60

1997 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

Year

Nu

mb

er o

f re

leas

es

Clinical patient releases

Blood donor releases

Blood donor screening starts

* as of March 25, 2009

CDC Nifurtimox releases by year1997 – 2009*

*

Page 24: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Challenges to be addressed

• Improve healthcare provider awareness of Chagas disease– Diagnose clinical disease – Recognize transfusion transmission – Screen for transplant transmission risk

• Quantify burden of clinical disease in U.S.– Cardiac disease burden– Gastrointestinal disease burden

Page 25: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Risk of Trypanosoma cruzi infection in the U.S.

• No estimates because insufficient data

• Requires studies to investigate risk of T. cruzi infection by mode of transmission– Autochthonously– During travel – Transfusion-associated– Congenitally

Page 26: Chagas Disease in the United States FDA BPAC meeting, 1 April 2009 Susan P. Montgomery, DVM MPH LCDR, USPHS Parasitic Diseases Branch Centers for Disease.

Thanks to

• Sonia Kjos, CDC and TX DSHS

• Paul Cantey, CDC

• Caryn Bern, CDC

The findings and conclusions in this presentation are those of the author(s) and do not necessarily

represent the views of the Centers for Disease Control and Prevention.