Epidemiology ofInfectious Tropical DiseasesInfectious Tropical Diseases
François BRICAIRE
Pitié-Salpêtrière Hospital
Pierre et Marie Curie UniversityPierre et Marie Curie UniversityParis - France
Carthagena June 2008
« Plan »« Plan »
1) Epidemiology of the main infectious tropical diseases 1) Epidemiology of the main infectious tropical diseases- WHO priorities : HIV / TB / Malaria
Parasitic infections : Schistosomasis Leishmaniasis- Parasitic infections : Schistosomasis,LeishmaniasisTrypanosomiasis (Chagas +),Amoebiasis ,OthersOthers…
- Viral infections : Arbovirosis (Dengue, YF…)Bacterial infections : Cholera others- Bacterial infections : Cholera ,others…
2) Impacting factors : Natural , Human , Technical…ExampleExample
3) Vaccine capacity = Conclusion
2007HIV infected population Worldwide (2007)2007
800 000
1,6 M
800 000
230 000
380 000
33 2
22,5 M
Total Worldwide: 33.2Total Worldwide:
About 14000 new HIV infectionscases per daycases per day
More 95 % cases in poor developing countries (DC)- Women ≈ 60%- 16-24 years old ≈ 50%
Prevalence in Africa = 6 % - Senegal – Benin = 1-2%- Austral Africa = 17 % - 35 % (Bostwana)
Prevalence in pregnant women = - Cameroun – Benin = < 5 %- Zambia – Kenya = > 15 %
Life expectancy in Bostwana = 65 y 1990 - 199556 y 1995 - 2000Life expectancy in Africa 1995-2000
40 y 2007
HIV infections observed are predominent in
non B areas
BB
CRF03
CB
CRF02 CRF01
CRF08-BC
CRF07-BC
B F1
A,C,D,F,
G,H,J,K
CRF02 CRF01CRF06 CRF11
570 000
550 000
1.2 million
6 illi
980 000
440 000
1.2 million
CBCRF10CRF05
CRF1229.4 million
6 million
15 0001.5 million
M. Peeters, Rome, 2004
Discrepancies in availability of first line i ld idregimens worldwide
No. of regimens used to treat 90% of patientsNo. of regimens used to treat 90% of patients
North America 59
Western Europe 47
Western, Central & Eastern Africa
3
Asia3
South America11
Southern Africa3
3
Egger, 2007
Tuberculosis WorldwideTuberculosis Worldwide
88--10 million cases of TB / year10 million cases of TB / year
3 million deaths / year3 million deaths / year3 million deaths / year3 million deaths / year
7% = cause of death in DC7% = cause of death in DC7% cause of death in DC7% cause of death in DC
2 Billion people at risk of TB and HIV 2 Billion people at risk of TB and HIV infection +++infection +++
«« RR » : BMR ; XDR +++ (South Africa…)» : BMR ; XDR +++ (South Africa…)500 000 ?500 000 ?500 000 ?500 000 ?
Malaria infected population
•• 2 billion exposed people2 billion exposed people
•• 350350--550 million : clinical cases550 million : clinical cases
•• 50% children50% children
•• 1 51 5--2 million death cases2 million death cases1.51.5--2 million death cases2 million death casesR. Snow 2005R. Snow 2005
« Yet recently malaria has been dramatically reduced in some parts of Africa by increasing deployment of anti
mosquito measures and new artemisinin combined treatment »
BM Greenwood The J. of Clinical Investigation 2008 118-4,1266-1278G ee ood e J o C ca est gat o 008 8 , 66 8
PaludismePaludismeMALARIA
Same in 2007 !
Risk ofEntomologic inoculation
Malaria transmission :Malaria transmission :Number of monthly Number of monthly Entomologic inoculation
In Rodgers DJ & al, Nature, 2002, 415(Feb7): 710-15 transmission cases over transmission cases over one year periodone year period
HAY SI, GUERRA CA, TATEM AJ, NOOR AM, SNOW RW. Lancet Infect Dis. 2004;4:327-336.
Schistosomiasis
S d d i it i d Second endemic parasitosis : dam … > 70 countries ; >200 Million infected people Mortality : 700 000 - 800 000 / y S haematobium = Africa – Middle-East S.haematobium = Africa Middle-East S mansoni = Africa – SouthAmerica S.intercalatum = Central Africa S.japonicum ; S.mekongi = Asiaj p ; g
SchistosomiasisSchistosomiasis in the World
Leishmaniasis
Leishmania : L.donovani-infantumLeishmania : L.donovani infantummexicana-guyanensis…
• Population at risk = 350 Million• Population at risk = 350 Million• N cases = 12 Million
88 countries : 66 Old World 22 New World• 88 countries : 66 Old World – 22 New World Phlebotomes
Vi l K l / Visceral = Kala-azar = 500 000 / y Cutaneous = 1-1,5 Million / y Tt = Antimoniate – Pentamidine –
Ampho B – Itraconazole..
Leishmaniasis
Leishmaniasis
Trypanosomiasisyp
Africa : « sleeping sickness » 36 countries T bi T h d i T.gambiense – T.rhodesiense
« Tsé-Tsé fly » - Glossina 250 000/y ? Forest Arsenic derivatives-Pentamidine-
Eflornithine
Trypanosomiasis America (Central - South); Chagas T cruzi T.cruzi Arthropodes :Triatomines 16 – 18 million 300 000 new cases / Y
Initiative of « south cone » countriesEradication of the transmission by Eradication of the transmission by
Decrease in prevalences in argentin soldiers (18 y)Decrease in prevalences in argentin soldiers (18 y)transmission by
Triatoma infestanstransmission by Triatoma infestans
argentin soldiers (18 y)argentin soldiers (18 y)
Uruguay 1997Chili 1999Chili 1999Brasil 20066/20 Argentina’s provinces6/20 Argentina s provinces 1/12 Paraguay region Just a few Just a few
bolivian areas
(Segura E. Am J Trop Med Hyg 2000; 62(3): 353-362 ; Lorca M. Am J Trop Med Hyg 2001; 65(6): 861-864)
Inter-countries Initiatives
Central America CountriesInitiative, (IPCA)
Central America CountriesInitiative, (IPCA)
Andin Countries Initiative(IPA)
Andin Countries Initiative(IPA)
G d l Rh d i Di i ti lt f • Good results on Rhodnius prolixus,
• Less good on Triatoma
Disappointing results of the anticarrier fight
Infections rate : not very • Less good on Triatoma dimidiata
• Cover for blood screening =
Infections rate : not very high among childrens (1 à 4%)Cover for blood screening
>90% • Except : Mexico, Panama
Cover for blood screening = >99%
Costa Rica (< 35%)
(Guhl F. Mem Inst Oswaldo Cruz 2007; 102(Suppl. 1): 29-37 ; Ponce C. Mem Inst Oswaldo Cruz 2007; 102(Suppl. 1): 41-44)
Persistence of congenital tractg Dominating Transmission tract : important human source Issue : birth diagnostic
Countries Samples Mother’s Congenital Incidence
Issue : birth diagnostic Treatement long, expansive; no pédiatric presentations
pPrévalences Transmission
raterate
/ 1 000
Argentina (Blanco, 2000) 16842 5,5% 6,7% 3Bolivia (Torrico, 2004) 19921994
1999-200116063879
27,6%17,3%
4,9%5,9%
1410
Bolivia (Salas, 2007) 2712 42,2% 6,0% 26
Brasil (Bittencourt, 1985) 2651 8,5% 1,1%* 1*Chili (Garcia 2001) hyperendemic 938 7 8% 1 4%* 1*Chili (Garcia, 2001) hyperendemic
hypoendémic938
54957,8%1,4%
1,4%3,9%*
10,5*
Paraguay (Russomando, 1998) 1862 9,1% 3,0% 3
Uruguay (Sarasua 1986) 2303 8 3% 1 6% 1Uruguay (Sarasua, 1986) 2303 8,3% 1,6% 1Peru (Mendoza, 2005) 3139 0,7% 0% -
(Gürtler R. Emerg Infect Dis 2003; 9(1): 29-32 ; Carlier Y. Rev Soc Bras Med Trop 2003; 36(6): 767-771) (* xénodiagnostic)
Countries Risk to receive Risk to becomeCountries Risk to receive a infected unit /
10 000 d ti
Risk to become infected / 10 000
donations
Transfusional
donations
TransfusionalTransmission
Peru 0 0
Bolivia 138 28
Brasil 0 0
Chili 2 5 0 5Chili 2,5 0,5
Paraguay 4 0,7
Argentina 0 0
Uruguay 0 0
(Schmunis G & Cruz J. Clin Microbiol Rev 2005; 18(1): 12-29)
g y
A difficult EradicationA resisting areaA resisting area Ecological area of ChacoEcological area of Chaco
CHACO :
Bad results of anticarriersfi hfight
Residual Resistance Resistance New infestation
(Gürtler R. PNAS 2007; 104(41): 16194-16199)
Mortality at 10 y = Mortality at 10 y =
PrognosisDeaths / y = 50 000Deaths / y = 50 000
Mortality at 10 y High CV risk =84%Low CV risk = 10%
Mortality at 10 y High CV risk =84%Low CV risk = 10%
Cardiac annual Cardiac annual progression rate = 2 à 5%
Annual rate sudden death
6 à 9/1000= 6 à 9/1000
(Rassi A. Arq Bras Cardiol 2001; 76(1): 86-96 ; Rassi A. Circulation 2007; 115(9): 1101-1108)
Treatment EfficacyBen nida ole vs placeboBenznidazole vs placebo
14%
4%
(Andrade A. Am J Trop Med Hyg 2004; 71(5): 594-597 ; Viotti R. Ann Intern Med 2006; 144(10): 724-734)
Spreading ++
Spain: 300 000 immigrantsSpain: 300.000 immigrants from 8 countries in 2002. Minimum prevalence: 0.87%240.000 immigrants in 2003 from mainly Bolivia and Paraguay. Minimum prevalence: 2.7%
Illegal immigration:2002: 550 000 tourists2002: 550.000 tourists entered from 17 L.A: countries and 86.000 left. 101.432 tourists from101.432 tourists from Ecuador entered and only 8 left.
Amaebiasis
P i l S d iti i f tiPreviously = Second parasitic infectionafter malaria
= 10% world populationToday : E histolytica ≠ E disparToday : E.histolytica ≠ E.disparPrevalence Africa – Asia- S.America
E.histolytica = 2%E dispar = 10%E.dispar = 10%
Epidemiology: Other Parasitic Diseasesp gy
Ascaridiosis = 1.5 Billion5 Ankylostomiasis = 1.3 Billion Onchocercosis = 18 M (Africa ++ Central America) Onchocercosis = 18 M (Africa ++ - Central America) Lymphatic filariosis = 120 M Cysticercosis = ++ , N = 20 M ? , 50 000 deaths
Asia- Africa - Central - South America
Cerebral Cysticercosis
ArbovirosisArbovirosis
DENGUES DENGUES : +++
Flavivirus : 1 to 4 Aedes Aedes Endemo-epidemic intertropical area
6 Milli / S i f- 60-100 Million/y ; 500 000 Serious forms- West Indies (2007) –South America- Pacific area (Tahiti…)
Minor ++ but hemorragic forms Minor ++ but hemorragic forms Chikungunya = India , Malaisia…
Cases of dengue reported in 8 Asian countries1991-2007
Dengue : Mortality in Cambodia ; 1991 - 2004
Monthly cases of Dengue in Thailand 2003-2006
Yellow Fever
Africa – South-AmericaA d ti Aedes aegypti
2005 Africa (12 Contries) : 206 000 cases ; 52 000 † 2008 :America :Brasil , Paraguay , Argentina..
Africa :Liberia , Central african Rep., Ivory Coast, p , y Just after Monkeys
epizootye ++epizootye ++ Mortality : 20-30%
V i Vaccine +++
CholeraCholera2008
Bacterial Infections Cholera : -
- Africa ++ : Senegal – Ivory Coast (2007)Africa ++ : Senegal Ivory Coast (2007)Somalia-Zambia-AngolaKenya (2008)
• Salmonellosis : Δ «R » FQ +++
• Cerebrospinal Meningitis : Africa +++: Equatorial Africa
Burkina Fasso Mali NigerBurkina Fasso , Mali , Niger…
• « Buruli »ulcer : M.ulcerans ; 3rd mycobacteriosis infection;Emergence : WHO 1998 ++Intertropical areasStagnant water contacts ; Short clothes ;Stagnant water contacts ; Short clothes ;Neglected wounds
• …/…
« Summary »y
Recurring outbreak : Yellow fever Extending :- Cholera (Africa)
- Cerebrospinal meningitis- Tuberculosis- Buruli ulcer
Declining : - Filariosis , Onchocercosis- Tetanos- Leprosis
P li li i- Poliomyelitis
E i HCV Emerging : - HCV - Arbovirosis
Impacting Factorsp g Natural factors: - Climate (global warming) , Disasters… Human factors : Actions : Ecologic: Deforestation Urbanization ++ Human factors : - Actions : Ecologic: Deforestation,Urbanization ++
Dam construction- Breeding, Food manufacturing- Wars …/…
- Host’s predisposition : ID , Malnutrition- Political willo t ca w
• Survey• Diagnosis means , Screening • Means to fight :• Means to fight :
- Hygiene measures- Vectors : Larval spots , old tyres…- Antiinfectious drugs : Antibiotics ;
Antiparasitics (praziquantelalbendazolnitroimidazol)…
Arbovirosis - Climate
Malaria TransmissionMalaria TransmissionSeasonalSeasonal -- PermanentPermanentSeasonal Seasonal PermanentPermanent
Reaching the people left behindReaching the people left behind
Bangkok – 1 February 2007Bangkok 1 February 2007
“The fight againstThe fight against neglected tropical
diseases is an initiativediseases is an initiative aimed at the poorest
people . A strategy againstpeople . A strategy against poverty.”
Dr Margaret Chan
N l t d T i l DiNeglected Tropical Diseases
Preventive ChemotherapyInnovative and Intensified Preventive Chemotherapy and Transmission control
Innovative and Intensified Disease Management
African trypanosomiasisChagas diseaseBuruli UlcerL i h i i
DracunculiasisLymphatic filariasisOnchocerciasisShi t i iLeishmaniasis ShistosomiasisSoil transmitted helminthiasis
Integrated Vector Management
DDengueOthers
Inter-Country I iti ti
INCOSUR was created in Brasilia in 1991 by the Ministers of Health of Argentina BoliviaInitiatives the Ministers of Health of Argentina, Bolivia, Brazil, Chile ,Paraguay and Uruguay.
IPA was created in Bogota in 1997 by theIPA was created in Bogota in 1997 by the Ministers of Health of Colombia, Ecuador, Peru and Venezuela,
IPCA was created in Tegucigalpa in 1997 by the Ministers of Health of Belize, Costa Rica, El Salvador, Guatemala, Honduras, Nicaragua and
AMCHA was created in 2005 by the Ministers
Panama.,
AMCHA was created in 2005 by the Ministers of Health of Bolivia, Brazil, Colombia, Equator, French Guyana, Guyana, Peru, Surinam, Venezuela
MEXICO
Chagas DiseaseChagas Disease
Intensive Actions
Fight against Take care of acute MonitoringFightsA i t Blood transmission
MTCTand chonic cases
gAgainstVectors
Key to success : +++
Paris, underground, April 2004 and 2007Paris, underground, April 2004 and 2007
« Here is a massive destruction weapon« Here is a massive destruction weaponthat nobody cares about »
CambodiaCa bod a
Available Vaccines
Vi P li liti Virus ++ : PoliomyelitisYellow Fever Dengue (1-4)But : HIV !!!
• Bacteria : more complex = BCG , Cholera , Typhoid
• Parasitic diseases = Highly complex M l i !- Malaria !...
- Others = 0
Vaccine against malaria ?
Anti sporozoïtes, anti hépatic stages ?CS bi hé i 8 -CSP recombinant or synthétic 1987: no
-RTS, S/AS02: 1997-2004 (P. Alonso) :study ongoing-LSA33
Anti mérozoïtes ?-SPf66 (M. Patarroyo) 1988-1996: no-MSP3 LSP (P Druilhe) 1994-2005: study2 ongoing-MSP3 LSP (P. Druilhe) 1994-2005: study ongoing
Anti gamétocytes ? Altruist...-Pfs25 (R. Carter) 2001
In 5 years ? In 10 years ? …?
But : « Mosquirix »Phase II : study ongoing
1: Alonso PL et al. Lancet 2004; 364: 1411-202: Druilhe P et al. PLOS Medicine 2005: 2: e344
AcknowledgmentsAcknowledgments
Pr Martin DANIS PhD Pr. Martin DANIS PhD Pierre BUFFET MD
Parasitology – Mycology UnitPitié-Salpetrière Hospital-Paris-France
