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Leading research at: Actualizació sobre la Malaltia de Chagas Joaquim Gascon Centre de Recerca en Salut Internacional de Barcelona (CRESIB)- Hospital Clinic Institut de Salut Global de Barcelona (ISGlobal)

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Page 1: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

Actualizació sobre la Malaltia de Chagas

Joaquim GasconCentre de Recerca en Salut Internacional de Barcelona (CRESIB)-Hospital ClinicInstitut de Salut Global de Barcelona (ISGlobal)

Page 2: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

Índex

1. Qué es la Malaltia de Chagas

2. Que hi ha de nou en…

a. Epidemiología i control: Europa es desperta lentament

b. Noves eines

• Avenços i retrocessos en el tractament parasitari

Page 3: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

Hotez, PLoSNTD, 2008

Page 4: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

LYFE CYCLEChagas is a zoonotic disease

Endemic to LatinAmerica

Page 5: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

AMASTIGOT TRYPOMASTIGOT

- In the insect digestive tract.- Host blood

- Non replicative form- EXTRACELLULAR

- Mobile (flagelate)

-Replicative form in the vertebrates.

- INTRACELLULAR.

- Not mobile.

Low and intermitent parasitaemia in chronic forms

Page 6: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

The vector and the parasite

The parasite. Six lineages: (All of them associated with cardiac damage)T.cruzi I (widespread but the only form in the north of the Amazon region)

T.cruzi II, V i VI (Southamerica). (also associated to digestive tract lesions)T,cruzi III i IV (Amazonia).

From: Carlomagno M, et al. 1989

The triatomine.Domestic and peridomestic environments in rural

dwellings and domestic animals

Page 7: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

Vectorial

Oral. Outbreaks due to contaminated food or drinks

Blood transfusion

Organ Transplants

Vertical Transmission

Lab accidents

Transmission

Page 8: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:Phases of Chagas Disease

Acute Phase

Digestive ChronicForm (10-20%)

Cardiac Chronic Form (25-35%)

Deaths (2-3%)Subacute cases(5-10%)

(<50% symptomatic)

Chronic Forms

Indeterminate Form

(no symptoms, and no pathologic changes

detected by ECG, Rx, esofagogram or barium

enema)

~60% of infected people

Chronic Phase

Neurological ChronicForm (< 5%)

Page 9: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:CLINICAL SYMPTOMS

Acute form (4-8 weeks): Symptoms in <5% of infected people.

. Fever . Diarrhea

. Hepato-splenomegaly . Vomiting

. Chagoma

. Weakness

. Limphadenopathies

. Cutaneous Rash

Usually self-limited, except in cases ofMeningitis or carditis

Oral Transmission: More severe.

Page 10: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

CHRONIC FORMS OF CHAGAS

Cardiac Chronic Form(fibrosing cardiopathy and

inflammatory lesions)

Dilated miocardiopathycongestive failure

Rhythm disturbancesThromboembolism.

Digestive Chronic Form(loss of neurons in the gut and

inflammatory lesions)

MegaesophagusMegacolon

Other megaviscera

Page 11: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

DIAGNOSIS OF CHAGAS DISEASE

Acute cases:Parasitological tests

Thick blood filmStroutMicrohematocrit (newborns)Hemoculture

Molecular testPCR

Chronic / Indeterminate forms:

Serology (two tests with different antigens)ELISA, IHA, IFI

Page 12: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

TREATMENTBenznidazol and Nifurtimox

are the only drugs currentlyavailable for Chagas disease

treatment.

Both have a poor profile for side effects (~ 10% severe)

- cutaneous (rash, urticaria, pruritis)- polineuritis

- gastrointestinal disturbances

High efficacy in acute cases, but the efficacy declines with the duration

of infection 100%

Page 13: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

Epidemiologia i control: Europa es desperta lentament

Page 14: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

NEGLECTED DISEASES AND GLOBAL HEALTH, 31 MAY – 1 JUNE 2012, VENICE, ITALY

Page 15: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

0100000200000300000400000500000600000700000

MarruecosArgentinaBoliviaColombiaEcuadorUruguayVenezuelaChinaFilipinasPakistán

Recent demographic changes in Spain.

Page 16: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:Latinamerican immigration by country

in Spain 2008

COUNTRIESESTIMATED Nº of

MIGRANTSESTIMATED T.cruzi

PREVALENCEESTIMATED INFECTED

MIGRANTS

ARGENTINA 287,760 4,13% 11,882

BOLIVIA 238,605 6,75% - 15% 16,106 – 35,791

BRASIL 140,942 1,02% 1,436

CHILE 66,270 0,99% 653

COLOMBIA 326,459 0,96% 3,121

ECUADOR 451,072 1,74% 7,844

MEXICO 42,413 1,03% 436

PARAGUAY 68,234 2,54% 1,735

PERU 160.603 0,69% 1,102

URUGUAY 86,601 0,66% 568

VENEZUELA 142,709 1,16% 1,654

TOTAL 2,090,000 47,738 – 67,423

Page 17: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

Avenços i retrocessos en el tractament parasitari

Page 18: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

Viotti, PLoS NTD, Sept 2011

Page 19: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

SEMTSI

Ahora que habíamos decidido tratar a los adultos

con benznidazol

Page 20: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

• Tabletas de 12,5 mg adaptadas para su uso en bebés y niños menores de 2 años (<20Kg), de fácil disolución en líquido para facilitar la administración

• Contribuye a mejorar la seguridad y adherencia al tratamiento, ya que permite la administración de la dosis correcta para la edad / peso del niño.

• No es necesario el fraccionamiento (a excepción de los niños prematuros nacidos con menos de 2,5 kg de peso corporal)

Page 21: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

Page 22: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

Nature Reviews Cardiology, 2012

Page 23: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

¿Com avaluar l’eficàcia del tractament?

Page 24: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

Mètodes actuals

• Disminució dels títols en la serología convencional

• PCR– Detecció precoç dels casos amb fallida terapeútica*

*Schijman A. et al. 2003

Page 25: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

Assajos Clínics

Avaluació de la

resposta terapeútica ?

CARRERA EN LA RECERCA DE NOUS TRACTAMENTS ANTIPARASITARIS

Page 26: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

1. ¿Com avaluar l’eficàcia del tractament?2. ¿Quina és la importancia dels diferents llinatges

del paràsit en la malaltia humana, i en els mecanismes de resistència?

Page 27: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

Zingales, Inf Gen Evol, 2012

Page 28: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

1. ¿Com avaluar l’eficàcia del tractament?2. ¿Quina és la importancia dels diferents llinatges

del paràsit en la malaltia humana, i en els mecanismes de resistència?

3. Podem predir el desenvolupament de la miocardiopatía?

Page 29: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at:

1. ¿Com avaluar l’eficàcia del tractament?2. ¿Quina és la importancia dels diferents llinatges

del paràsit en la malaltia humana, i en els mecanismes de resistència?

3. Podem predir el desenvolupament de la miocardiopatía?

4. Quant de temps ha de durar el tractament?

Page 30: Actualizació sobre la Malaltia de Chagas · 2014. 12. 5. · are the only drugs currently available for Chagas disease treatment. Both have a poor profile for side effects (~ 10%

Leading research at: