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 UniversityCenter 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

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

Dr. Carlos Chagas

Protozoan Agent

Trypanosoma cruzi

Life Cycle

Diagnostic Techniques

• Clinical Evaluations & …

• Demonstration of Parasite– 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)

• Fecal contamination • enters Triatomid bite • through mucosal tissue (eye)• through open wound• within consumed food or water

• Blood transfusion from infected person• Organ donation from infected person• Vertical transmission (Congenital multigen.) • Laboratory-acquired• (?) Oral transmission• Other ?

Transmission to Humans

Acute Chagas Disease• Initial infection • Incubation 1 to 2 weeks• May be NO symptoms (98-99%)• May be incorrectly diagnosed• Symptoms:

Chagoma or Romaña's signmild fever and/or malaiseenlarged lymph nodes, liver, spleen, hearthigh 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

– 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

1 cm

1 inch

Eggs

In-star nymph stages

Adult (winged)

Disease Vectors:

Nymphs & Adults

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 stagesAcute 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 TempleLocations:• 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 CaseWoody & 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• 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”Location:

• Fort Worth, Tarrant Co.

2nd Indigenous CaseTDH 1955• 6-mo. old male born

June 16 in Bryan• November: hospitalized

obstructive hydrocephalus

• Hospitalizations for Salmonella enteritis & meningitis

Yaeger 1961• Pediatrician: ? case of

transmission by transfusion

Location:• Brazos Co.

Lathrop & Ominsky ‘65• 63-yr old male

• Compliment Fixation & Hemagglutination

• 48 (of 108) children & adults bitten

• Rural area 20 miles NE of San Antonio: Shertz & Randolph AFB

Location:• Bexar Co.

Woody et al. 1965• 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 positiveLocation:• Nueces Co.

Faust 1978• 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 1x-ray: cardiomegaly, ECG poor L ventricle function Diagnosis: cardiomyopathy, origin undetermined

• Died at home, July 5• CF & HA tests confirmed

on July 25, 1977

Location:• Potter Co.

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.

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

3rd Indigenous Case

Locations:• San Patricio or Jim Wells Co.

Infection Attributed to Transfusion

Cimo et al. 1993• 59-yr old female fatality

• Acute Chagas

• T. cruzi in peripheral blood & bone marrow

• >500 units transfusion – not identified among 40 Hispanic surnamed donors testedLocation:

• Houston, Harris Co.

Cross-Section Study in HoustonDiPentima et al. 1999• 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

Location:• Harris Co.

Serologic Tests & Look-back

Leiby et al. 1999• 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)

Location:• McClennan Co.

Cardiac Surgery PatientsLeiby et al. 2000• 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

Location:• Harris Co.

ElMunzer et al. 2004

• 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

Location:• Dallas Co.

T. Cruzi Reactivation by AIDSRivera et al. 2004• 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

Location:• Dallas Co.

Hosts & Reservoirs in TX Woodrats (Neotoma)

Opossums (Didelphis)

Armadillos (Dasypus)

Coyotes (Canis)

Others (+ humans)

Host Species(sample population)

Percent Range of Infection(as reported)

Armadillo (< 20)Badger (< 10)Cattle (< 45)Coyotes (< 200)Dogs (~ 600)Horses (< 10)Lynx (< 5)Mice (< 50)Opossum (< 10)Sheep (~ 30)Wood rats (~ 600)

0 - 10025.013.3

2.8 - 14.28.8 – 15.6

40.050.0

9 - 66.76.7 - 100

13.313.3 - 46.1

Infection in Host Species in TX

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. recurva

T. rubida

T. sanguisuga

T. protracta

Historical Biogeographical

Analysis77 Counties with Triatomids

64 Counties with infected vectors/hosts

Documented Reports in Humans

Bitten: 1200+

Seropositive/ diagnosed cases = 55

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+ chronicTEXAS:

~ 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

• 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”

Research & Development

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

What is needed…