INTERRUPTION OF TRANSMISSION OF CHAGAS … OF TRANSMISSION OF CHAGAS DISEASE IN LATIN ... known in the jargon of the international ... Interruption of Transmission of Chagas disease,

INTERRUPTION OF TRANSMISSION OF CHAGAS DISEASE IN LATIN

AMERICA

Álvaro Moncayo, MDCIMPAT

Bogotá, Colombia, 2007

NEGLECTED DISEASES

• Chagas disease is classified in a group of diseasesknown in the jargon of the international publichealth as the “NEGLECTED DISEASES”

A.Moncayo, CIMPAT, 2007

NEGLECTED DISEASES

• The “Neglected diseases” affect two thirds of the human population who live in poverty

• Main “neglected diseases”: Dengue, Leishmaniasis, Malaria, Schistosomiasis, Tuberculosis, African Trypanosomiasis(Sleeping sickness) andAmerican Trypanosomiasis (Chagasdisease)


CLASSIFICATION CRITERIA

• Diseases that are prevalent in poorpopulations in developing countries and in poor people in developed countries.

• They cause high economic loss in the affected countries.

• They do not have any market appeal for the pharmaceutical industry as the affected populations have low purchasing power.


CLASSIFICATION CRITERIA

• They accumulate a disproportionately high disease burden measured in DALYs and in deaths.

• A DALY is an estimate of the economic loss in the productive life of an individual and is a function of age.


DISABILITY-ADJUSTED LIFE YEARS LOST (DALYs)

Source: World Bank 1993, World Development Report 1993: Investing in Health, World Bank,Oxford University Press, Washington DC, p. 26

DISABILITY-ADJUSTED LIFE YEARS LOST (DALYs)

• A DALY represents one lost year of “healthy”life due to premature mortality and disability of the incident cases of a disease.

• The “burden of disease” is the gap between an ideal situation where every individual in a population lives into old age in full health and the current health of a population affected by the disease.

Source: World Bank 1993, World Development Report 1993: Investing in Health, World Bank, Oxford University Press, Washington DC, p. 26and WHO, World Health Report 2004, Geneva, p.95-96

Mortality and Burden of disease due to the main “Neglected diseases” (2002)

DISEASE DEATHS DALYs (000)

Dengue 19 000 616

Leishmaniasis 51 000 2 090

Malaria 1 272 000 46 486

Schistosomiasis 15 000 1 702

Tuberculosis 1 566 000 34 736

AfricanTrypanosomiasis

48 000 1 525

Chagas disease 15 000 667

TOTAL 2 967 000 (5.3%) 87 822 (5.9%)

Source : World Health Organization, The World Health Report 2004

Image adapted from: http://www.lib.utexas.edu/maps/world_maps/world_rel_803005AI_2003.jpg


NEGLECTED DISEASESDISEASE AGENT COUNTRIES LOCATION TREATMENT

DENGUE Virus 100 Tropics No

SCHISTO. Parasite 74 Tropics + 40 years

LEISHM. Parasite 88 TropicsSub-tropical

+ 30 years

MALARIA Parasite 100 Tropics + 10 yearsResistance

SLEEPINGSICKNESS

Parasite 36 Tropical Africa

+ 50 years

CHAGASDISEASE

Parasite 15 LatinAmerica

+ 50 years

TB Bacteria 1% of theglobal

population

Cosmopolitan + 40 years

NEW MOLECULES APPROVED FOR THERAPEUTIC USE BETWEEN 1975 AND 1999

(SELECTED DISEASES)

Disease ApprovedMolecules

% of world sales

Nervous System 211 (15.1%) 15.0%

Cardiovascular 179 (12.8%) 19.8%

Cytostatics 111 (8.0%) 3.7%

HIV/AIDS 26 (1.9%) 1.5%

Tropical diseases (All)

13 (0.9%) 0.2%

Source: Drug development for neglected diseases, The Lancet, 359, p.2189,22 June 2002

DOCTOR CARLOS CHAGAS (1879 – 1934)


Source: Memorias do Instituto Oswaldo Cruz 1909, Rio de Janeiro, Brasil, Vol. 1, No. 1

CAUSAL AGENT: Trypanosoma cruzi


THE TRIATOMINE VECTOR


TRANSMISSIONCYCLE

Source: American trypanosomiasis (Chagas’ disease) and the role of molecular epidemiology in guiding control strategies, BMJ, 326:1445, 28 JUNE 2003.

HUMAN CYCLE: POOR RURAL HOUSES

CHAGAS DISEASE:ACUTE PHASE


CHAGAS DISEASE: CHRONIC PHASE


CONTROL PROGRAMS: INSECTICIDE SPRAYING

www.cdc.gov/.../features/20050126_sprayman.jpg


WORLD HEALTH ORGANIZATION PROGRAMME ON RESEARCH AND CONTROL OF TROPICAL DISEASES

launched in 1979 with two interrelated objectives

1. To develop new control methods of diseases prevalent in the tropics: Malaria, Schistosomiasis, Filariasis, Onchocerciasis, Sleeping sickness, Chagas disease,Leishmaniasis and Leprosy

2. To strengthen the research capacity of laboratories in the tropical countries

www.who.int/tdr

Research and control of Chagasdisease

• Research phase: 1980-1989• Industrial production and validation of new

tools: 1990-1993• Policy development phase/ interruption of

transmission: 1991-2007


Research phase• 1980-1985: Prevalence of T.cruzi infection

surveys in nine endemic countries

• 1980-1982: Continental standardization of serological tecniques

• 1984-1990: Prospective studies on morbidyevolution

• 1987-1989: Cloning of T.cruzi genome


Industrial Production

• 1990: Production of diagnostic kits forblood banks screening (Argentina)

• 1988-1993: Development and validation of new tools for vector control (fumigant

canisters, insecticidal paints)• 1993: Industrial production of canisters and

paints in Argentina and Brazil


Policy development phase

• 1991: Southern cone Initiative – Health programs in Mercosur– Implementation of vector control through house spraying– Annual evaluation made by Intergovernment Technical

Commission

• 1997: Andean countries and Central America Initiatives

– Health Programs of the Andean Community– Health Programs of Central American Market



ARGENTINA: Interruption of Transmission ofChagas disease, 1982-2002, Rates x 100

11.0

1.04.0

24.0

4.8

1.2 1.0 0.9

0.0

0.0

0.1

1.0

10.0

100.0

1982 1986 1990 1992 1994 1998 2002

Rat

es x

100

Infestation rates

Incidence of infection(males 18 yrs)

Linear (Infestationrates)

Linear (Incidence ofinfection (males 18yrs))

Source: WHO, Weekly Epidemiological Record, Geneva, 1996, 71:2, 12-15 and Informe Ministerio de Salud 2002

BRAZIL: Interruption of Transmission of Chagas disease, Rates x 100

1982-2007

26.0

2.7 1.90.3

0.0

0.4

4.8

0.0

4.8

0.30.1 0.1

0.0

0.0

0.0

0.0

0.1

1.0

10.0

100.0

1982 1986 1990 1994 1997 1999 2002 2004 2006

Rat

es x

100

Infestation rates

Incidence ofinfection (0-7 yrs)

Log. (Infestationrates)

Log. (Incidence ofinfection (0-7 yrs))

Source: Weekly Epidemiological Record, 1997, WHO, Geneva,72:1/2, p.1-5 and Informe Comisión Intergubernamental 2004

CHILE: Interruption of Transmission of Chagas disease, 1982- 2004, Rates x 100

28.8

0.7

0.2

3.0

1.01.8

1.9

0.9

0.2

5.4

0.0

0.1

1.0

10.0

100.0

1982 1986 1990 1992 1996 1999 2003

Rat

es x

100

Infestation rates

Incidence ofinfection (0-4 yrs)



Source: WHO, Weekly Epidemiological Record, Geneva, 1999, 74:2, 9-11 and Informe Comisión Intergubernamental, 2004

PARAGUAY: Interruption of Transmission of Chagas disease, Rates x 100

1980-2003

10.0

1.8

3.9

14.0

9.76.6

1.0

10.0

100.0

1980 1986 1990 1994 1998 2003

Rat

es x

100

Infestation rates

Incidence of infection(males 18 yrs)

Log. (Infestation rates)

Linear (Incidence ofinfection (males 18 yrs))

Linear (Infestation rates)

Source: Control of Chagas disease, Report of the ExpertCommittee,WHO, TRS 905, Geneva 2002, p.68-69 and Informe ComisiónIntergubernamental, 2004

URUGUAY: Interruption of Transmission Chagas disease, Rates x 100

1982-2004

0.6 0.5

6.0

0.6

0.10.10.1

2.4

0.0

0.0

0.1

1.0

10.0

1982 1986 1990 1994 1997 2004

Rat

es x

100

Infestation rates

Incidence of infection(6-12 yrs)



Source: WHO, Weekly Epidemiological Record, Geneva, 1998, 73:1/2 1-4, and Informe Ministerio de Salud, 2004

Distribution of main vectors, 1990

Source: Control of Chagas disease, Report of a WHO Expert Committee, TRS No. 811, Geneva 1991, p. 16

Distribution of main vectors, 2000

Source: Control of Chagas disease, Second Report of the WHO Expert Committee, TRS No. 905, Geneva 2002, p. 44

INTERRUPTION OF TRANSMISSION OF CHAGASDISEASE, INFECTION RATES X 100

SOUTHERN CONE, 1982-2007

AGEYears

1982 86 90 92 94 98 02 04 06

ARG 18 4.8 1.2 1.0

BRA 0-7 4.8 0.4 0.28 0.1 0.1 0.00

CHI 0-4 5.4 1.9 0.9 0.0 0.00

PAR 18 9.7 3.9 2.0

URU 6-12 2.4 0.1 0.1 0.00 0.00

Source: WHO, 2002; Reports INCOSUR, 1993-2007

INTERRUPTION OF TRANSMISSION OF CHAGASDISEASE, INFECTION RATES X 100

SOUTHERN CONE, 1982-20076.5

0.4 0.30.1 0.1

0.0

5.40.9

0.1

2.4

0.1 0.10.0

1.0

1.24.8

0.2

1.9

0.00

0.00

0.00

0.00

0.01

0.10

1.00

10.00

ARG(18 yrs)

BRA (0-7)

CHI (0-4)

URU(6-12)ARG (18 yrs) 6.5 1.2 1.0

BRA (0-7) 4.8 0.4 0.3 0.1 0.1 0.0CHI (0-4) 5.4 1.9 0.9 0.2 0.1URU (6-12) 2.4 0.1 0.1 0.0

1982 1990 1992 1994 1998 2002 2004 2006

Source: WHO, 2002; Reports INCOSUR, 1993-2007

Southern Cone Initiative

• 1997: Uruguay certified free of transmission• 1999: Chile certified free of transmission• 2006: Brazil certified free of transmission• ----------------------------------------------------------• Source:WHO (1998) Chagas disease, Interruption of transmission in

Uruguay, Weekly Epidemiological Record, 1/2:1-4• WHO (2000) Chagas disease, Certification of interruption of

transmission in Chile, Weekly Epidemiological Record, 2:10-12• WHO (2000) Chagas disease, Interruption of transmission in Brazil,

Weekly Epidemiological Record, 19:153-155 and Informe do Ministerio da Saúde, 2006




Serological evidence of the interruption of transmission in Brazil, Instituto de Patología

Tropical, Universidad Federal de Goias, June 2006

• Serological survey in 94 500 serum samples in children 0 – 5 years, in all endemic States of Brazil

• No positive samples were found in this surveywhich demonstrates the interruption of transmission of Trypanosoma cruzi in Brazil

Source: Luquetti A, Personal Communication, Instituto de Patología Tropical, Universidade Federal de Goiás, Brasil, June 2006

Changes in epidemiologic parameters as a consequence of the interruption of transmission and the decrease of

incidence, Latin America, 1990 - 2006

Parameters 1990 2006

Annual deaths 40 000 21 000

Infected cases 18 million 10 million

Annual Incidence 700 000 cases 200 000 cases

Population at risk 100 million 40 million

Distribution 18 countries 15 countries (Transmission interrupted in Uruguay, Chile and Brazil)

BURDEN OF DISEASE DUE TO CHAGAS DISEASE IN LATIN AMERICA, (DALYs IN MILLIONS) 1993-2002

6.5

3.3

5.9

2.4

4.4

3.2 2.7

0.6

2.6

0.9

01234567

DALYS (Millions)

RI

DD

HIV

/AID

S

CH

D TB

19932002

Source: - World Bank 1993, World Development Report 1993: Investing in Health,World Bank, Oxford University Press, Washington DC, p. 216-218- WORLD HEALTH ORGANIZATION, WHOSIS, (www.who.int, may 2007)


2.6

0.60.8

0.10.3

0.09 0.10.04

0

0.5

1

1.5

2

2.5

3

DALYS (Millions)

CHD MAL SCH LEI

19932002



DISEASE 1993 2004 % Decrease

Respiratory Infections 6.4 3.3

2.35

3.2

0.6

0.9

0.12

0.07

0.04

Diarrheal diseases 5.9

48.0

40.0

28.0

78.0

65.0

26.0

65.0

HIV/AIDS 4.4

Chagas disease 2.7

Tuberculosis 2.6

Malaria 0.5

Schistosomiasis 0.2

Leishmaniasis 0.04 0.0


COST-EFFECTIVENESS OF THE CHAGAS DISEASE CONTROL PROGRAM, BRAZIL,

1975-1999

Avertedcases

Averteddeaths

Avertedexpenses

(67% Medical

care, 33% Incapacity)

Return perUS$

invested in control

2 399 000 337 000 7 500 000 000 17.oo

Source: Akhavan D (2000) Análise de Custo-efetividade do Programa de Controle da Doença de Chagas no Brasil, Organizaçao Pan-Americana da Saúde, Brasilia 271pp.

THE FUTURE: ENTOMOLOGICAL SURVEILLANCE

• As Chagas disease becomes less a public healthproblem, its continued surveillance and control can be decreased in view of other pressingpriorities such as Dengue Fever control

• Risk of re-establishment of active vector foci, house re-infestation and disease transmission

• Surveillance programs should be continued on a permanent basis

Source: Dias JCP et al. 2002, The impact of Chagas Disease Control in Latin America,A Review, Mem Inst Oswaldo Cruz, Rio de Janeiro, 97(5), 603-612

FUNDS INVESTED IN THE INTERRUPTION OF TRANSMISSION OF CHAGAS DISEASE IN THE

SOUTHERN CONE COUNTRIES 1991 – 1999(US THOUSANDS)

Country 1991-94 1995 1996 1997 1998 1999 Total

ARG 52 000 18 000 18 000 14 000 16 000 13 000 131 000

BOL 83 430 706 2 940 4 410 4 500 13 069

BRA 38 420 48 00 28 000 35 000 15 000 20 000 184 420

CHI 1 200 300 1 000 600 500 500 4 100

PAR 2 224 1 250 1 252 2 019 2 400 1 200 10 345

URU 179 74 74 74 75 100 676

Total 94 106 68 054 49 039 54 633 38 385 39 300 343 517

Source: Reports by the Ministries of Health to the Intergovernment Commission INCOSUR, 1991-2000

FUNDS INVESTED IN THE INTERRUPTION OF TRANSMISSION OF CHAGAS DISEASE IN THE SOUTHERN CONE COUNTRIES

1991 – 1999(US THOUSANDS)

39 30038 38554 633

211 199

0

50000

100000

150000

200000

250000

1991-96 1997 1998 1999

US

Dol

lars

(tho

usan

ds)

Source: Reports by the Ministries of Health to the Intergovernment Commission

INCOSUR, 1991-2000

COSTS AND BENEFITS OF SURVEILLANCE PROGRAMS

0102030405060708090

100

1 2 3 4 5 6 7 8 9 10 11 12 13

Years

Perc

enta

ge

Costs

Benefits withSurveillanceBenefits withoutSurveillance

Source: (Adapted from) Dias JCP et al. 2002, The impact of Chagas DiseaseControl in Latin America, A Review, Mem Inst Oswaldo Cruz, Rio de Janeiro, 97(5), 603-612

$53 Millions/year

Total cost in 10 years:$350 Millions

Documents

INTERRUPTION OF TRANSMISSION OF CHAGAS … OF TRANSMISSION OF CHAGAS DISEASE IN LATIN ... known in the jargon of the international ... Interruption of Transmission of Chagas disease,