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)
A.Moncayo, CIMPAT, 2007
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.
A.Moncayo, CIMPAT, 2007
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.
A.Moncayo, CIMPAT, 2007
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
A.Moncayo, CIMPAT, 2007
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)
A.Moncayo, CIMPAT, 2007
Source: Memorias do Instituto Oswaldo Cruz 1909, Rio de Janeiro, Brasil, Vol. 1, No. 1
CAUSAL AGENT: Trypanosoma cruzi
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THE TRIATOMINE VECTOR
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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
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CHAGAS DISEASE: CHRONIC PHASE
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CONTROL PROGRAMS: INSECTICIDE SPRAYING
www.cdc.gov/.../features/20050126_sprayman.jpg
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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
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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
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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
A.Moncayo, CIMPAT, 2007
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
A.Moncayo, CIMPAT, 2007
A.Moncayo, CIMPAT, 2007
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)
Log. (Infestationrates)
Log. (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)
Log. (Infestationrates)
Log. (Incidence ofinfection (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
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A.Moncayo, CIMPAT, 2007
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)
BURDEN OF DISEASE DUE TO CHAGAS DISEASE IN LATIN AMERICA, (DALYs IN MILLIONS) 1993-2002
2.6
0.60.8
0.10.3
0.09 0.1 0.040
0.5
1
1.5
2
2.5
3
DALYS (Millions)
CHD MAL SCH LEI
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)
BURDEN OF DISEASE DUE TO CHAGAS DISEASE IN LATIN AMERICA, (DALYs IN MILLIONS) 1993-2004
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
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)
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
INTERRUPTION OF TRANSMISSION OF CHAGAS DISEASE IN LATIN AMERICANEGLECTED DISEASESNEGLECTED DISEASESCLASSIFICATION CRITERIACLASSIFICATION CRITERIADISABILITY-ADJUSTED LIFE YEARS LOST (DALYs)Mortality and Burden of disease due to the main “Neglected diseases” (2002)NEGLECTED DISEASESNEW MOLECULES APPROVED FOR THERAPEUTIC USE BETWEEN 1975 AND 1999 (SELECTED DISEASES)THE TRIATOMINE VECTORCHAGAS DISEASE: ACUTE PHASEResearch and control of Chagas diseaseResearch phaseIndustrial ProductionPolicy development phaseARGENTINA: Interruption of Transmission of Chagas disease, 1982-2002, Rates x 100BRAZIL: Interruption of Transmission of Chagas disease, Rates x 100 1982-2007CHILE: Interruption of Transmission of Chagas disease, 1982- 2004, Rates x 100PARAGUAY: Interruption of Transmission of Chagas disease, Rates x 100 1980-2003URUGUAY: Interruption of Transmission Chagas disease, Rates x 1001982-2004Distribution of main vectors, 1990Distribution of main vectors, 2000INTERRUPTION OF TRANSMISSION OF CHAGASDISEASE, INFECTION RATES X 100SOUTHERN CONE, 1982-2007INTERRUPTION OF TRANSMISSION OF CHAGASDISEASE, INFECTION RATES X 100SOUTHERN CONE, 1982-2007Southern Cone InitiativeSerological evidence of the interruption of transmission in Brazil, Instituto de Patología Tropical, Universidad Federal de GChanges in epidemiologic parameters as a consequence of the interruption of transmission and the decrease of incidence, LatinBURDEN OF DISEASE DUE TO CHAGAS DISEASE IN LATIN AMERICA, (DALYs IN MILLIONS) 1993-2002BURDEN OF DISEASE DUE TO CHAGAS DISEASE IN LATIN AMERICA, (DALYs IN MILLIONS) 1993-2002BURDEN OF DISEASE DUE TO CHAGAS DISEASE IN LATIN AMERICA, (DALYs IN MILLIONS) 1993-2004COST-EFFECTIVENESS OF THE CHAGAS DISEASE CONTROL PROGRAM, BRAZIL, 1975-1999THE FUTURE: ENTOMOLOGICAL SURVEILLANCEFUNDS INVESTED IN THE INTERRUPTION OF TRANSMISSION OF CHAGAS DISEASE IN THE SOUTHERN CONE COUNTRIES 1991 – 1999(US THOUSANDS)FUNDS INVESTED IN THE INTERRUPTION OF TRANSMISSION OF CHAGAS DISEASE IN THE SOUTHERN CONE COUNTRIES 1991 – 1999(US THOUSANDSCOSTS AND BENEFITS OF SURVEILLANCE PROGRAMS