Transcript Hanford - Texas Department of State Health Services

Chagas Disease:
Clues to the Magnitude of
the Problem in Texas
“EJ” Hanford, ABD
Dr. F. Ben Zhan
Dr. Yongmei Lu
Dr. Alberto Giordano
Research Support & Funding
 Texas State University
Center for Geographic Information Science
 Border Health Initiative Project
Effort sponsored in part by the
311th Human Systems Wing
PIA FA8909-04-3-5000
Brooks City-Base Foundation, Inc.
New World Disease
Dr. Joseph Reinhardt Cooper
• 1850s – Brazil "mal de engasgo"
• Clinical presentation, natural history &
epidemiology  first written record
Historical Timeline
1909 Dr. Carlos Chagas
Dr. Carlos Chagas
1936 Southern Mexico –
first recognized case
1955 First indigenous cases
in U.S. = 2 in Texas
1970s Central Mexico
2006 1st FDA approved
blood-screening test
Protozoan Agent
Trypanosoma cruzi
Life Cycle
Diagnostic Techniques
• Clinical Evaluations & …
• Demonstration of Parasite
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Direct microscopic examination
Xenodiagnosis
Lab animal inoculation
Hemoculture (less sensitive)
PCR
• Serologic Testing
– CF, IH, DA, IIF
– ELISA (Cross reactions can occur to Leishmaniasis,
Blastomycosis, and Toxoplasmosis)
Transmission to Humans
• Fecal contamination
• enters Triatomid bite
• through mucosal tissue (eye)
• through open wound
• within consumed food or water
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Blood transfusion from infected person
Organ donation from infected person
Vertical transmission (Congenital  multigen.)
Laboratory-acquired
(?) Oral transmission
Other ?
Acute Chagas Disease
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Initial infection
Incubation 1 to 2 weeks
May be NO symptoms (98-99%)
May be incorrectly diagnosed
Symptoms:
Chagoma or Romaña's sign
mild fever and/or malaise
enlarged lymph nodes, liver, spleen, heart
high fever, convulsions & meningoencephalitis
• Mortality rate: up to 50% in the young, overall ~ 10%
• Diagnosis after incubation:
by serodiagnosis or xenodiagnosis
• Duration: acute stage may last up to several months
Latent Stage Chagas Disease
• Outwardly asymptomatic
• May have subtle changes in
– sympathetic & parasympathetic nervous system
– internal organs
• Duration: decades till death from other cause
or till evolution to chronic stage
• Diagnosis by serological testing
(15% prevalence DNA in sero-neg endemic pop.)
Chronic Chagas Disease
• Evolves in 20 to 40 % of infected persons
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–
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Repeated re-infections
Genetic polymorphism of T. cruzi
Variation in host susceptibility
Immuno-compromised by disease / drugs
• Cardiomyopathy or Congestive Heart Failure
– typically involves right bundle branch block
– arrhythmias
• Enlarged colon or esophagus
• Ischemic stroke
• Diagnosis by serological testing & clinical evaluation
Active T. cruzi
Parasitemia
in Blood &
Tissue Sample
Chagasic Heart
Disease
Megacolon
Vector-borne Disease
Vinchuca … Kissing bug…
Cone-nose….by any other name…
Triatomid species
Eggs
In-star nymph stages
Adult (winged)
Disease Vectors:
Nymphs & Adults
1 cm
1 inch
Complex Ecological Cycles
Synanthropic vs. Sylvatic
Depends on:
• Genotype
• Adaptation/Domestication
• Other factors ?
Chagas Disease in Humans
• Become infected for life
• Potentially progresses through 3 stages
Acute  Latent/Indeterminate  Chronic
• Fatal in acute and/or chronic stages & debilitating
• Higher risk for immuno-compromised persons
• MYTH = a disease only of the rural poor
• NO vaccine
• NO cure
• US FDA approved ELISA blood-screening test
But NOT in Texas ??
• Lower virulence
• Lower vector density
• Different vector habits
– Less frequent domestication
– Significantly longer feed-defecation response
• Lack of ‘trypanosomiasis consciousness’
– Fail to diagnose nondescript acute infections
Packchanian 1939
• Oct ’37 & Sept ’38
• 500 persons bitten
• Found by personal
inquiries
Packchanian 1940
• 50 infected Triatoma
in Temple
Locations:
• Austin, Dallas, Galveston, Houston, San Antonio
• Bell, DeWitt, Duval, Live Oak & Jim Wells Co.
Wood 1941 & 1942
• Bug ‘epidemic’ in
Quemado Valley
• Residents bitten
• House infested in
Sanderson (Terrell)
“these suckers have
sure dealt them
misery”
Locations:
• Maverick, Terrell & Bandera Co.
Davis & Sullivan 1946
• 8-yr old male in Blewett
tested positive
• Compliment Fixation in
significant dilution
• T. gerstaeckeri in home
Location:
• Uvalde Co.
1st Indigenous Case
Woody & Woody 1955
• 10-mo. old white
female born Oct 5,
1954 in Corpus Christi
• Parasites in blood
• Triatomids in home
• Father bitten
Location:
• Nueces Co.
Shields & Walsh 1956
Location:
• Fort Worth, Tarrant Co.
• 45 persons bitten over
prior 2 years
• Lesions by bite of
T. sanguisuga
• “from all parts of the
city, from all types of
dwellings, and from all
economic levels”
nd
2
Indigenous Case
TDH 1955
• 6-mo. old male born
June 16 in Bryan
• November: hospitalized
obstructive
hydrocephalus
• Hospitalizations for
Salmonella enteritis &
meningitis
Yaeger 1961
Location:
• Brazos Co.
• Pediatrician: ? case of
transmission by
transfusion
Lathrop & Ominsky ‘65
Location:
• Bexar Co.
• 63-yr old male
• Compliment Fixation &
Hemagglutination
• 48 (of 108) children &
adults bitten
• Rural area 20 miles NE
of San Antonio: Shertz
& Randolph AFB
Woody et al. 1965
Location:
• Nueces Co.
• 117 bitten in Coastal
Bend & Corpus Christi
• 7 weakly positive to
positive titers (ages 5.5
– 72) but no clinical
evidence
• 2 infection chagomas
(no positive test)
• T. cruzi not isolated
• 1st indigenous case still
tested positive
Faust 1978
Location:
• Potter Co.
• 38-yr old male fatality
• Oct ’76 vacation in
Caracas, Venezuela &
Caribbean
• 2 Amarillo Hospitals:
1st Admit = May 11-13, ’77
2nd Admit = May 26-July 1
x-ray: cardiomegaly, ECG
poor L ventricle function
 Diagnosis:
cardiomyopathy, origin
undetermined
• Died at home, July 5
• CF & HA tests confirmed
on July 25, 1977
Burkholder et al. 1980
• 12 of 500 long-term
residents positive
titers
• 1 being treated for
unexplained
myocardial disease &
enlarged heart
Locations:
• Cameron & Hidalgo Co.
rd
3
Indigenous Case
Betz 1984
• 7-mo old Hispanic male
fatality July 30, 1983
• April 1984 pathology
diagnosis: acute
Chagas myocarditis
• Likely infected Mathis
(SP) or Alice (JW)
• Family all seronegative
in 1984
Locations:
• San Patricio or Jim Wells Co.
Infection Attributed to Transfusion
Cimo et al. 1993
Location:
• Houston, Harris Co.
• 59-yr old female fatality
• Acute Chagas
• T. cruzi in peripheral
blood & bone marrow
• >500 units transfusion
– not identified among
40 Hispanic surnamed
donors tested
Cross-Section Study in Houston
DiPentima et al. 1999
Location:
• Harris Co.
• Pregnant women (’93’96) ages 13 - 44
• 2107 Hispanic, 1658 non
• 22 positive (18 >age 20)
13 (0.6%) Hispanic &
9 (0.5%) White & Black
• Risk factors & points of
exposure unknown
• Congenital not reported
Serologic Tests & Look-back
Leiby et al. 1999
Location:
• McClennan Co.
• 3 EIA repeatably
reactive and RIPA
seropositive – all from
Waco
• 1 from Durango MX
• 2 TX natives (17 & 40)
• All 3 families: history of
heart ailments &
complications (enlarged
heart & arrhythmias)
Cardiac Surgery Patients
Leiby et al. 2000
Location:
• Harris Co.
• 23 repeatably reactive
 6 confirmed at 3
hospitals, including:
Methodist Hospital &
St. Luke’s Episcopal in
Houston
• Original source of
infection unknown; all
had received blood
transfusions
ElMunzer et al. 2004
Location:
• Dallas Co.
• 70-yr old Hispanic male
• Immigrated to TX 20 yrs
• Oct 2002 presented to
ER Parkland Memorial
• History of acute MI, with
right bundle branch
block on ECG,
ventricular arrythmia
• Diagnosis confirmed by
Complement Fixation
T. Cruzi Reactivation by AIDS
Rivera et al. 2004
Location:
• Dallas Co.
• 29-yr old male Honduran
fatality
• 5-yr Immigrant was
diagnosed 5-mo. with HIV
• Developed acute
congestive heart failure
secondary to cardiac
Chagas Disease
• Necropsy showed T.cruzi
amastigotes in
myocardium – no
atherosclerosis
Hosts & Reservoirs in TX
 Woodrats (Neotoma)
 Opossums (Didelphis)
 Armadillos (Dasypus)
 Coyotes (Canis)
 Others (+ humans)
Infection in Host Species in TX
Host Species
(sample population)
Armadillo (< 20)
Badger (< 10)
Cattle (< 45)
Coyotes (< 200)
Dogs (~ 600)
Horses (< 10)
Lynx (< 5)
Mice (< 50)
Opossum (< 10)
Sheep (~ 30)
Wood rats (~ 600)
Percent Range of Infection
(as reported)
0 - 100
25.0
13.3
2.8 - 14.2
8.8 – 15.6
40.0
50.0
9 - 66.7
6.7 - 100
13.3
13.3 - 46.1
Human Reservoirs
• Canada (1%)
• Berlin, Germany (2%)
• Spain, Romania, Japan …
Chagas Disease in the U.S.
• Blood Transfusion
Immuno-compromised individuals
? Immuno-competent
• Organ Transplants
2002 = 3 from 1 donor
2006 = 2 cases, 6 monitor from 2 donors
• 6 Autochthonous cases: TX, CA, TN, LA
• Unrecognized ????
Triatomid Species in Texas
T. gerstaeckeri
T. rubida
T. recurva
T. sanguisuga
T. protracta
77 Counties with
Triatomids
64 Counties with
infected
vectors/hosts
Historical
Biogeographical
Analysis
Bitten: 1200+
Seropositive/
diagnosed
cases = 55
Documented
Reports in Humans
Demographics & Estimates
• Latin America: DALY 2.7m ~ U.S.$6.5b
United States:
16 m (incl 6.2 undoc) Latin Am immigrants
~ 7% infection rate
 1m + infected
 150,000+ chronic
TEXAS:
 ~ 300,000 - 600,000 infected
 ~ 50,000 - 100,000 chronic
Under-Estimation ??


Actual infection rate
Number of undocumented immigrants

Number of congenital cases

Multi-generational transmission

Infected immuno-competent


Sero-negative but still infected
More aggressive genotype
Significance = Emerging Disease
More is needed in Texas:
• Education & Prevention
• Research & Development
• Awareness / Recognition
And in other states
• Endemic regions
• Introduced
Research & Development
• Improved understanding of environmental
ecology of vectors & hosts (adaptability)
• Field studies to determine infection rates and
ranges of endemic vector and host species
• Field studies to monitor introduced/migrating
vectors and hosts & interactions with native
species
• FDA-approved tests for diagnosis & screening of
blood supply & donor organs
• Preventative vaccine
• Pharmaceuticals to control disease progression
or to produce a “cure”
What is needed…
Recognition as
– endemic zoonotic risk for humans
– introduced disease associated with changing human
demographics & genotypes
Education  Prevention & Awareness
– public health, physicians & cardiologists
– veterinary & animal care workers
Recommendations
– Inclusion as Communicable / Reportable to TDSHS
– Serologic screening test