Chaga s s Disease Disease Chaga Terry L Dwelle Dwelle MD MPHTM - - PowerPoint PPT Presentation

Chaga Chaga’ ’s s Disease Disease

Terry L Terry L Dwelle Dwelle MD MPHTM MD MPHTM

Trypanosomiasis Trypanosomiasis

► ►African

African trypanosomiasis trypanosomiasis

• Trypanosoma

Trypanosoma brucei brucei gambiense gambiense

• Trypanosoma

Trypanosoma brucei brucei rhodesiense rhodesiense ► ►American

American trypanosomiasis trypanosomiasis

• Trypanosoma

Trypanosoma cruzi cruzi

• Trypanosoma

Trypanosoma rangeli rangeli

Basic Basic Hemoflaggelatology Hemoflaggelatology

► ►Found in the blood

Found in the blood

► ►They are also called

They are also called kinitoplastida kinitoplastida (contain (contain kinetoplasts kinetoplasts or modified mitochondria)

• r modified mitochondria)

► ►Basic forms

Basic forms

• Amastigotes

Amastigotes

• Promastigotes

Promastigotes

• Epimastigotes

Epimastigotes

• Trypomastigotes

Trypomastigotes

• Metacyclic

Metacyclic trypomastigotes trypomastigotes

Amastigote Amastigote (old (old Leishmania Leishmania stage) stage)

► ► Slightly oval (2

Slightly oval (2-

• 3 X 3

3 X 3-

• 4 microns)

4 microns)

► ► Axonemes

Axonemes are like microtubules that are are like microtubules that are associated with future flagellate motility associated with future flagellate motility

► ► Found inside

Found inside reticuloendothelial reticuloendothelial cells cells

► ► Multiplies by longitudinal binary fission

Multiplies by longitudinal binary fission

► ► There is generally a small zone between the K and

There is generally a small zone between the K and A A

Nucleus (N) Kinetoplast (K) Axoneme (A)

Promastigote Promastigote (old (old leptomonas leptomonas stage) stage)

► ►May have various shapes from short and fat

May have various shapes from short and fat to long and thin to long and thin

► ►Occasionally see

Occasionally see volutin volutin granules (VG) that granules (VG) that represent waste products in the cytoplasm represent waste products in the cytoplasm

N K A Flagellum (F) Flagellar pocket (FP) Volution Granules (VG)

Epimastigote Epimastigote (old (old crithidia crithidia stage) stage)

► ►

Varies in length (12 Varies in length (12-

• 75 microns)

75 microns)

► ►

K is always anterior to the nucleus K is always anterior to the nucleus

► ►

F pulls the body through tissues F pulls the body through tissues

► ►

Epimastigote Epimastigote has an undulating membrane where the has an undulating membrane where the promastigote promastigote doesn doesn’ ’t t

► ►

The undulating membrane causes the body to undulate The undulating membrane causes the body to undulate

N K A F Undulating membrane (UM) Anterior End Posterior End

Trypomastigote Trypomastigote and and Metacyclic Metacyclic Trypomastigote Trypomastigote

► ►

This is the Trypanosome This is the Trypanosome

► ►

The K is posterior to the N The K is posterior to the N vs vs the the Epimastigote Epimastigote with the N with the N posterior to the K posterior to the K

► ►

Binary fission of the Binary fission of the Promastigote Promastigote, , Epimastigote Epimastigote and and Trymastigote Trymastigote are the same (K first followed by the A, F, are the same (K first followed by the A, F, the N and then the cell) the N and then the cell)

► ►

Metacyclic Metacyclic Tryposmastigote Tryposmastigote is the same as the is the same as the tryposmastigote tryposmastigote but is the infectious stage in the vector but is the infectious stage in the vector

K A F N UM Anterior Posterior

American American Trypanosomiasis Trypanosomiasis

From Manson’s Tropical Diseases, pp 1200, Saunder’s 1996.

Trypomastigote Trypomastigote of

• f Trypanosoma

Trypanosoma Cruzi Cruzi

► ► 20 micrometers long

20 micrometers long

► ► Larger

Larger kinetoplast kinetoplast than than Trypanosoma Trypanosoma Rhodesiense Rhodesiense

• r
• r Gambiense

Gambiense

► ► 3

3 zymodeme zymodeme profiles profiles – – all produce human all produce human infections infections

• Z1 and Z2

Z1 and Z2 – – arboreal and terrestrial mammalian arboreal and terrestrial mammalian transmission transmission

• Z3

Z3 – – domiciliary parasites domiciliary parasites

K A F N UM Anterior Posterior

Large Kinetoplast Nucleus

Life Cycle Life Cycle

Bug (bite site, mucous membrane, GI) Metacyclic Trypomastigote Macrophages Amastigotes

• M. Trypomastigote

Trypomastigote

4-5 days

• f binary

fission

Blood Stream Other cells (heart, skeletal muscle, neuroglia, etc) Amastigotes Trypomastigote Trypomastigote Pseudocyst ruptures Bug bite Insect Vector Binary Fission of Amastigotes and Epimastigotes

• M. Trypomastigotes

(30 days) (5-12 days) Acute Symptoms 2-3 weeks

Amastigotes

Transmission Factors Transmission Factors

► ►Vector exposure

Vector exposure

► ►Blood transfusions

Blood transfusions

► ►Vertical transmission

Vertical transmission

► ►Trans

Trans-

• mammary transmission

mammary transmission

► ►Infected food or meat

Infected food or meat

► ►Laboratory accidents

Laboratory accidents

► ►Land colonization

Land colonization

► ►Quality of human dwellings

Quality of human dwellings

Vector Vector

► ►Adult insects can fly.

Adult insects can fly.

► ►Feed at night

Feed at night

► ►Live in holes, like dark, humid sites

Live in holes, like dark, humid sites

Before feeding After feeding

Chagas Chagas’ ’ Disease Disease

Acute Acute

Entry site lesions Entry site lesions Systemic signs and symptoms Systemic signs and symptoms Organ involvement Organ involvement

Chronic Chronic

Dilation of hollow viscera including the heart Dilation of hollow viscera including the heart

Acute phase Acute phase

► ►95% have no acute phase

95% have no acute phase

► ►Children have more symptoms

Children have more symptoms

► ►Acute phase is often followed by a life

Acute phase is often followed by a life-

• long

long asymptomatic period (70 asymptomatic period (70-

• 90% of those

90% of those infected) infected)

► ►Some patients experience a

Some patients experience a subacute subacute progression of illness that can result in a progression of illness that can result in a rapid demise. rapid demise.

► ►10% fatality rate in the acute phase

10% fatality rate in the acute phase

Portals of Entry Portals of Entry

► ►Ocular

Ocular – – 48% 48%

► ►Skin

Skin – – 24% 24%

► ►Other /

Other / Inapparent Inapparent – – 28% 28%

Entry site lesions Entry site lesions

► ► Romana

Romana’ ’s s sign sign

• Unilateral, painless,

Unilateral, painless, erythematous erythematous palpebral palpebral edema edema

• Occasional swelling of the entire side of the face

Occasional swelling of the entire side of the face

• Preauricular

Preauricular or

• r submaxillary

submaxillary adenopathy adenopathy

• Conjunctivitis

Conjunctivitis

• Dacroadenitis

Dacroadenitis

► ► Chagoma

Chagoma

• Erythema

Erythema, , prurritus prurritus, painless infiltration of the dermis , painless infiltration of the dermis

• Central desquamation with rare ulceration

Central desquamation with rare ulceration

• Exposed parts of a sleeping person

Exposed parts of a sleeping person

• Last for weeks

Last for weeks

Organ Involvement Organ Involvement

► ► Hepatosplenomegaly

Hepatosplenomegaly

► ► Lymphadenopathy

Lymphadenopathy

► ► Muscles

Muscles

► ► GI

GI

► ► Pulmonary

Pulmonary

► ► Heart

Heart

► ► CNS

CNS – – meningoencephalitis meningoencephalitis

► ► Bone marrow

Bone marrow

► ► Skin

Skin

Congenital Congenital Chagas Chagas’ ’ Disease Disease

► ►Low birth weight

Low birth weight

► ►Hepatomegaly

Hepatomegaly

► ►Meningoencepalitis

Meningoencepalitis with seizures and with seizures and tremors tremors

Chronic Chronic Chagas Chagas Disease Disease

► ►

Often seen at 30 Often seen at 30-

• 40 years old

40 years old

► ►

Occurs in 10 Occurs in 10-

• 30% of those infected

30% of those infected

► ►

Chronic Chronic myocarditis myocarditis is most common is most common

• Diffuse

Diffuse multifocal multifocal myocarditis myocarditis with edema and fibrosis with edema and fibrosis

• Increased thrombosis seen in the heart wall

Increased thrombosis seen in the heart wall

• Apical

Apical aneuryms aneuryms occasionally seen

• ccasionally seen
• EKG is the 1

EKG is the 1st

st manifestation (RBBB, PVC

manifestation (RBBB, PVC’ ’s) s)

• Sudden death is common

Sudden death is common

• May present with CHF, embolism, ruptured aneurysm, vent.

May present with CHF, embolism, ruptured aneurysm, vent. fibrillation fibrillation ► ►

Can see dilation of other hollow viscera Can see dilation of other hollow viscera

• Esophagus

Esophagus

• Colon with

Colon with megacolon megacolon

• Ureter

Ureter

Aneurysmal dilatation Parasites Parasitized Giant Cell

Laboratory Diagnosis Laboratory Diagnosis

► ►Acute phase

Acute phase

• Giemsa

Giemsa stained stained buffy buffy coat blood smear coat blood smear

• Biopsy specimen

Biopsy specimen – – find find Trypomastigotes Trypomastigotes and and Amastigotes Amastigotes ► ►Chronic phase

Chronic phase

• Culture on NNN media

Culture on NNN media

• Xenodiagnosis

Xenodiagnosis

• Serology

Serology – – CF, IHA, IFAT, ELISA, RIPA, Latex CF, IHA, IFAT, ELISA, RIPA, Latex Agglutination, Direct Agglutination Tests Agglutination, Direct Agglutination Tests

Clinical Diagnosis Clinical Diagnosis

► ►No single laboratory test is adequately

No single laboratory test is adequately sensitive and specific to diagnose sensitive and specific to diagnose Chaga Chaga’ ’s s disease disease

► ►Generally the diagnosis is made by at least

Generally the diagnosis is made by at least 2 different serologic tests (ELISA, 2 different serologic tests (ELISA, immunoflourescence immunoflourescence, indirect , indirect hemagglutination hemagglutination) along with clinical and ) along with clinical and exposure history. exposure history.

Terminal Kinetoplast Nucleus Large Parasitized Cell

Treatment Treatment

Drug Drug Adult Adult Child Child Benznidazole Benznidazole (not (not available in the US) available in the US) 5 5-

• 7 mg/kg/day in 2

7 mg/kg/day in 2 div doses X 30 div doses X 30-

• 90

90 days days < < 12 12 yo yo: 10 : 10 mg/kg/day div in 2 mg/kg/day div in 2 doses X 30 doses X 30-

• 90 days

90 days Nifurtimox Nifurtimox* (consider * (consider with gamma with gamma interferon X 20 days) interferon X 20 days) 8 8-

• 10 mg/kg/day div in

10 mg/kg/day div in 3 3-

• 4 doses X 90

4 doses X 90-

• 120

120 days days 1 1-

• 10

10 yo yo: 15 : 15-

• 20

20 mg/kg/day div in 4 mg/kg/day div in 4 doses X 90 days doses X 90 days 11 11-

• 16

16 yo yo: 12.5 : 12.5-

• 15

15 mg/kg/day div in 4 mg/kg/day div in 4 doses X 90 days doses X 90 days

*Nifurtimox (Lampit, Bayer, Germany). It is only available under the Investigational New Drug (IND) protocol from CDC Drug Service, CDC, 404-639-3670 (evenings, weekends, or holidays: 404-639-2888).

Control Measures Control Measures

► ►

Avoid habitation in buildings infested with Avoid habitation in buildings infested with reduviid reduviid bugs (constructed bugs (constructed

• f mud, palm thatch, adobe brick especially those with cracks in
• f mud, palm thatch, adobe brick especially those with cracks in walls

walls

• r roofs
• r roofs

► ►

Use insecticide impregnated bed nets Use insecticide impregnated bed nets

► ►

Don Don’ ’t sleep or camp outdoors in highly endemic areas t sleep or camp outdoors in highly endemic areas

► ►

Blood and serologic screening of household members of infected Blood and serologic screening of household members of infected patients with common exposure histories patients with common exposure histories

► ►

Serologic screening before and after travel if exposure to the v Serologic screening before and after travel if exposure to the vector is ector is unavoidable unavoidable

► ►

Eliminate vectors in homes Eliminate vectors in homes

► ►

Blood and organ donor screening by serology Blood and organ donor screening by serology

► ►

Treat donated blood in endemic areas with gentian violet (dilute Treat donated blood in endemic areas with gentian violet (diluted d 1:4000) 1:4000)

► ►

Treat infected (acute and chronic) to prevent progression to car Treat infected (acute and chronic) to prevent progression to cardiac diac morbidity and congenital infection morbidity and congenital infection

Blood Donor Screening for Blood Donor Screening for Chagas Chagas in in the US, 2006 the US, 2006-

• 2007

2007

► ►

American Red Cross screened 148,969 blood samples at three American Red Cross screened 148,969 blood samples at three collection centers, Los Angeles, Oakland, and Tucson. collection centers, Los Angeles, Oakland, and Tucson.

► ►

Initial screen with ELISA. If positive it is repeated twice. I Initial screen with ELISA. If positive it is repeated twice. I f the second f the second

• r third test is positive a RIPA (
• r third test is positive a RIPA (radioimmunoprecitation

radioimmunoprecitation assay) is assay) is

• completed. If the RIPA is positive the specimen is considered p
• completed. If the RIPA is positive the specimen is considered positive.
• sitive.

► ►

63 specimens from 61 donors were ELISA repeat positive. 32 were 63 specimens from 61 donors were ELISA repeat positive. 32 were RIPA positive (51%). RIPA positive (51%).

► ►

Prevalence 1/4655. Prevalence 1/4655.

► ►

On December 13, 2006 the FDA licensed the Ortho T On December 13, 2006 the FDA licensed the Ortho T cruzi cruzi ELISA test ELISA test to screen blood donors in the US. It is labeled for testing pla to screen blood donors in the US. It is labeled for testing plasma and sma and serum samples from living cell and tissue donors and from heart serum samples from living cell and tissue donors and from heart beating organ donors but not labeled for general clinical diagno beating organ donors but not labeled for general clinical diagnostic stic use. use.

► ►

US blood supply began screening all donations for T US blood supply began screening all donations for T cruzi cruzi on January

• n January

29, 2007 and providing testing services for smaller blood collec 29, 2007 and providing testing services for smaller blood collection tion centers and hospitals that request testing. centers and hospitals that request testing.

MMWR;56:7,pp141-143, Feb 23, 2007

American Association of Blood Banks American Association of Blood Banks

► ►

All components from blood donations that are repeat All components from blood donations that are repeat reactive by ELISA should be quarantined and removed reactive by ELISA should be quarantined and removed from distribution from distribution

► ►

Donor should be deferred from making donations Donor should be deferred from making donations indefinately indefinately

► ►

Recipient tracing should be done on those specimens Recipient tracing should be done on those specimens repeat positive by ELISA and confirmed with RIPA repeat positive by ELISA and confirmed with RIPA

► ►

Test at risk family members of confirmed positives with a Test at risk family members of confirmed positives with a similar history of exposure to similar history of exposure to Chaga Chaga vectors in an endemic vectors in an endemic area area

► ►

Deferred donors, at risk family members, and potentially Deferred donors, at risk family members, and potentially infected recipients should be referred to health care infected recipients should be referred to health care providers providers

Trypansome Trypansome Rangeli Rangeli

► ►

Historically known as T. Historically known as T. Ariari Ariari

► ►

Seen in Uruguay, Chile, Seen in Uruguay, Chile, Hondura Hondura, Guatemala, Southern Mexico to , Guatemala, Southern Mexico to Brazil where Brazil where Rhodnius Rhodnius is present is present

► ►

Larger and more slender than T. Larger and more slender than T. Cruzi Cruzi (26 (26-

• 34 micrometers)

34 micrometers)

► ►

Has a Has a subterminal subterminal kinetoplast kinetoplast

► ►

Host Host – – animals and occasionally man animals and occasionally man

► ►

Does not cause disease Does not cause disease

► ►

Life cycle Life cycle – – similar to T. similar to T. Cruzi Cruzi except for method of transmission to except for method of transmission to humans humans

► ►

Transmitted by bug bite (anterior Transmitted by bug bite (anterior innoculative innoculative transmission) not from transmission) not from bug feces bug feces

► ►

Diagnosis Diagnosis – – Blood smear, Culture of blood Blood smear, Culture of blood

► ►

Problem Problem – – may be confused with T. may be confused with T. Cruzi Cruzi

Trypomastigote Trypomastigote of

• f Trypanosoma

Trypanosoma Rangeli Rangeli ► ►26

26-

• 34 micrometers long

34 micrometers long

► ►Subterminal

Subterminal kinetoplast kinetoplast vs vs T.

• T. Cruzi

Cruzi, T. , T. Rhodesiense Rhodesiense or T.

• r T. Gambiense

Gambiense

Subterminal K A F N UM Anterior Posterior Terminal K position

Subterminal Kinetoplast