informal consultation to consolidate the regional response to address artemisinin resistance and...

Informal Consultation to Consolidate the Regional Response to Address Artemisinin Resistance and

Substandard Antimalarial Medicines in the GMS, Bangkok, Thailand, 24-26 April 2012

Regional Framework for Artemisinin Resistance

Containment

A Working Document

Charles Delacollette



Roll Back Malaria Objectives Proposed in 1999 in the GMS

- to reduce malaria mortality (50% reduction in 2010 as compared to 1998)

- to significantly reduce malaria morbidity(no suggested % of reduction)

- to attain or maintain acceptable level of parasite resistance to antimalarial medicines in all endemic falciparum malaria

areas(ACPR of first line antimalarial medicines above 90%)

Ho Chi Minh City, Viet Nam, 3-4 March 1999



Malaria Mortality Trends(From MOH through WHO)

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Myanmar 3182 3648 2756 2814 2634 2476 1982 1707 1647 1265 1088 972 788

Cambodia 621 891 608 476 457 492 382 296 396 241 209 279 151

Thailand 688 740 625 424 361 325 230 71 113 97 101 70 80

Viet Nam 183 190 148 91 50 50 24 18 41 20 25 28 21

Lao PDR 427 338 350 244 195 187 105 77 21 14 13 5 24

China 24 67 39 28 42 52 31 48 38 18 23 12 3

5125 5874 4526 4077 3739 3582 2754 2217 2256 1655 1459 1364 1067



1998 Pf (%) 2010 Pf (%)

Myanmar 104,753 >80 420,808 >90

Cambodia 58,874 >90 49,356 >80

Thailand 131,055 >50 32,502 >50

Viet Nam 72,091 >70 17,515 >80

Lao PDR 39,031 >95 20,800 >95

China (Yunnan) 27,090 <20 13,055 <20

Confirmed malaria cases in the Greater Mekong Subregion in 1998 and 2010 [MOH data through WHO]



Confirmed malaria cases in the GMS, 2010

Lao PDR, 20,800 4%

Cambodia, 49,356 9%

China-Yunnan, 2,277 0%

Viet Nam, 17,515 3%

Thailand, 32,502 , 6%

Myanmar, 420,808 78%

Cambodia

China-Yunnan

Lao PDR

Myanmar

Thailand

Viet Nam



Malaria deaths in the GMS, 2010

Myanmar, 788 75%

Thailand, 80 7%

Viet Nam, 21 2%

China-Yunnan, 3 0%

Cambodia, 151 14%

Lao PDR, 24 2%

Cambodia

China-Yunnan

Lao PDR

Myanmar

Thailand

Viet Nam



control pre-elimination elimination prevention of reintroduction

cases country-wide area-wide

transmission foci clusters of cases imported cases only

Reduce transmission intensity

Halt local transmission nationwide Reduce onward

transmission

Control to elimination continuumControl to elimination continuum



Yunnan China- Confirmed Malaria cases and Malaria deaths(1998-2010)

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

16,000

18,000

Year

No.o

f con

firm

ed m

alar

ia c

ases

-

10

20

30

40

50

60

no.o

f mal

aria

dea

ths

Confirmed malaria cases 13,055 16,307 8,775 11,302 12,218 15,314 11,416 8,359 11,064 6,085 4,027 2,237 2,277

malaria deaths 18 50 29 21 33 43 25 38 32 9 6 3 3

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Cambodia- Malaria confirmed cases and Malaria Deaths (1998-2010)

0

10,000

20,000

30,000

40,000

50,000

60,000

70,000

80,000

90,000

Year

No. o

f con

firmed

mala

ria ca

ses

-

100

200

300

400

500

600

700

800

900

1,000

No. o

f Mala

ria De

aths


malaria deaths 621 891 608 476 457 492 382 296 396 241 209 279 151

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Lao- Confirmed malaria cases and Malaria Deaths (1998-2010)

-

5,000

10,000

15,000

20,000

25,000

30,000

35,000

40,000

45,000

Year

No. o

f con

firmed

mala

ria ca

ses

-

50

100

150

200

250

300

350

400

450

No. o

f mala

ria de

aths


malaria deaths 427 338 350 242 195 187 105 77 21 14 11 5 24

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Myanmar-Confirmed malaria cases and Malaria deaths (1998-2010)

-

50,000

100,000

150,000

200,000

250,000

300,000

350,000

400,000

450,000

500,000

Year

No.of

confi

rmed

mala

ria ca

ses

-

500

1,000

1,500

2,000

2,500

3,000

3,500

4,000

no.of

mala

ria de

aths


malaria deaths 3,182 3,648 2,756 2,814 2,634 2,476 1,982 1,707 1,647 1,647 1088 972 788

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Thailand- Confirmed malaria cases and Malaria deaths )1998-2010)

-

20,000

40,000

60,000

80,000

100,000

120,000

140,000

Year

No.o

f con

firm

ed m

alar

ia c

ases

0

100

200

300

400

500

600

700

800

no.o

f mal

aria

dea

ths


malaria deaths 688 740 625 424 361 325 204 161 113 97 101 70 80

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

Vietnam-Confirmed malaria casesand Malaria deaths (1998-2012)

0

10,000

20,000

30,000

40,000

50,000

60,000

70,000

80,000

Year

No. o

f con

firmed

mala

ria

case

s

-

20

40

60

80

100

120

140

160

180

200

No.of

mala

ria de

aths


malaria deaths 183 190 148 91 50 50 34 18 41 20 25 26 21

1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010



PailinTrat

Ninh Thuan

Preah Vihear

Quang Tri

Dak Nong

Binh Phuoc

Ranong

Tak

Luang Prabang

Bago

Menglian

Kanchanaburi

Kawthaung

Kyaing Tone

Yingjiang

Mae Hong Son

Kalay

Sentinel Sites (2008-2011)

1. Cambodia 1.1 Rattanakiri 1.2 Preah Vihear 1.3 Pailin 1.4 Pursat 1.5. Snoul 2. China 2.1 (Menglian, Yunnan) 2.2 Yingjiang, Yunnan 2.3 Tengchong, Yunnan 3. Lao PDR 3.1 Khammoune 3.2 Attapeu / Champassak 3.3 (Luang Namtha / L Prabang) 4. Myanmar 4.1 Myit Kin Nar, Kachin 4.2 Shwe Kyin, Bago 4.3 Kawthaung, Thanintharyi 4.4 Kalay, Sagaing 4.5 Myawaddy, Kayin 4.6 Tanphyuzayat, Mon 4.7 Kyauk Taw, Rakhine 4.8 Kyaing Tone, Eastern Shan 5. Thailand 5.1 Tak 5.2 Kanchanaburi 5.3 Mae Hong Son 5.4 Ranong 5.5 Chanthaburi 5.6 Yala 5.7 Ubon Ratchathani 5.8 Trat 6. Viet Nam 6.1 Quang Tri 6.2 Dak Nong 6.3 Binh Phuoc 6.4 Ninh Thuan 6.5 Gia Lai

Rattanakiri

Chantaburi

Yala

Attapeu

Khammoune

MEKONG TES NETWORK

Pursat

Myit Kin Nar

Mon

Myawaddy

Rakhine

Ubon Ratchathani

Gia Lai

Jiangsu

New sites for 2011-2012- Surin, Thailand- Bhamo, Kachin, MMR- Kayah, MMR

Tengchong



Definition of Early Treatment Failure (ETF) : Day 1-3

danger signs or severe malaria on day 1, 2 or 3 in the presence of parasitaemia;

parasitaemia on day 2 higher than on day 0, irrespective of axillary temperature;

parasitaemia on day 3 with axillary temperature ≥ 37.5 ºC;

parasitaemia on day 3 ≥ 25% of count on day 0.

WHO. Susceptibility of Plasmodium falciparum to antimalarial drugs. Report on global monitoring 1996–2004. Geneva, World Health Organization, 2005 (WHO/HTM/MAL/2005.110) (http://www.who.int/malaria/resistance).



Definition of Late Treatment Failure (LTF) : Day 7-28/42

Late clinical failure

danger signs or severe malaria in the presence of parasitaemia on any day between day 4 and day 28 (day 42) in patients who did not previously meet any of the criteria of early treatment failure;

presence of parasitaemia on any day between day 4 and day 28 (day 42) with axillary temperature ≥ 37.5 ºC (or history of fever) in patients who did not previously meet any of the criteria of early treatment failure

Late parasitological failure

presence of parasitaemia on any day between day 7 and day 28 (day 42) with axillary temperature < 37.5 ºC in patients who did not previously meet any of the criteria of early treatment failure or late clinical failure




Definition of Adequate Clinical and Parasitological Response (ACPR)

absence of parasitaemia on day 28 (day 42), irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure




Working definition of As R

The working definition of artemisinin resistance is based on clinical and parasitological outcomes observed during routine therapeutic efficacy studies of ACTs and clinical trials of artesunate monotherapy:

an increase in parasite clearance time, as evidenced by 10% of cases with parasites detectable on day 3 after treatment with an ACT (suspected resistance) Or

treatment failure after treatment with an oral artemisinin-based monotherapy with adequate antimalarial blood concentration, as evidenced by the persistence of parasites for 7 days, or the presence of parasites at day 3 and recrudescence within 28/42 days (confirmed resistance).



Percentage of treatment failure of different ACTs in Greater Mekong Sub-region, 2006-2010

Global Malaria Report 2010

Trat

Updates: June 2011

Pailin DHA-PIP

Trat A+M (containment zone)



Percentage of positive cases on Day 3 after ACT in the Greater Mekong Sub-region, 2006-2010

Global Malaria Report 2010

Binh Phuoc

Updates, June 2011

Viet Nam Binh Phuoc: DHA-PIP

Myanmar Mon DHA-PIP Tanintharyi DHA-PIP

Cambodia Pailin DHA-PIP

Thailand Trat A+M

Trat

Updates: Dec 2011

Pailin A+M

* Surin/Sisaket A+M (containment Zone 2)



Phuoc Long

Eastern Shan



Qinghaosu - Artemisinins

Rapid action, broad stage specificity, safe, gametocytocidal



Limited access to (and use of) quality diagnosis and quality medicines including adherence to Treatment by vulnerable population (mobile pop and migrants, ethnic groups … ) or due to occupational risk situations (development projects, forest, …)

Marketing and Use of Monotherapies, Counterfeits and Substandard Medicines

Private Sector Engagement to adhere to best practices

Lack of direction and coordination to boost harmonized activities

Lack of support to operational research (alongside with programmes)

Declining interest of Governments and Donors (competing priorities)

Potential Contributing Factors to As resistance and impacting on Malaria Elimination

Possibly better addressed through a Regional Response



Cross-border Migration in GMS

India

Bangladesh

Malaysia

Cambodia

China

Vietnam

Indonesia

Myanmar

Thailand

Laos



Definition of tiers

Tier I: Areas for which there is credible evidence of artemisinin resistance

Tier II: Areas with significant inflows of mobile and migrant populations from tier I areas or shared borders with tier I areas

Tier III: P. falciparum endemic areas which have no evidence of artemisinin resistance and limited contact with tier I areas



What to do? Summary of recommendations by Tier.

Tier IIITier III

Good Control

More routine monitoring

Eliminate monotherapies & poor-quality drugs

Tier IITier II

Intensified & accelerated control

Intensified monitoring, esp. on border near foci

Actively eliminate monotherapies

& poor-quality drugs

Lower transmission; focus on mobile & migrant

populations

Tier ITier I

Intensified & accelerated control to universal

coverage

Intensified monitoring, esp. around foci

Aggressively eliminate monotherapies

& poor-quality drugs

Lower transmission; focus on mobile & migrant

populations

Consider ACD, MSAT, FSAT or MDA



Contain or eliminate artemisinin resistance where it already exists

Prevent artemisinin resistance where it has not yet appeared

Motivate action and mobilize resources

Invest in artemisinin resistance-

related research

5

Stop the spread of resistant parasites

1 4

Improve access to

diagnostics and rational

treatment with ACTs

3

Increase monitoring and surveillance to

evaluate the artemisinin resistance

threat

2

Contain or eliminate artemisinin resistance where it already exists

Prevent artemisinin resistance where it has not yet appeared

Motivate action and mobilize resources

Invest in artemisinin resistance-

related research

5


1


1 4

Improve access to


treatment with ACTs

3

Improve access to


treatment with ACTs

3



threat

2



threat

2



Goal of the Regional Framework

The goal of the Regional Framework is to contribute to the global effort to protect ACTs

as an effective treatment for falciparum malaria and contribute to the health of the

population in the Greater Mekong Subregion.



Objectives

DRAFT



1. Coordination of an intensified containment effort2. Raise awareness at every level, build political support and

secure adequate financial resources3. Support mapping of the extent of the artemisinin resistance

problem, and expand and strengthen monitoring and evaluation

4. Promote access to and rational use of quality assured, safe, effective antimalarials and diagnostics, including support for intensive action against oral artemisinin-based monotherapies and substandard and counterfeit antimalarial medicines

5. Increase the use of appropriate vector control measures6. Support rapid implementation of special measures for high-

risk occupational groups and migrant/mobile populations7. Support and coordinate containment specific research and

development of new tools



•Main activities by regional objective

•Indicators

•M&E plan

•Budget



Group work

a)to endorse the joint strategic assessment of the Response to AR in the GMS and

b)to provide with inputs in the draft Regional Framework for Artemisinin Resistance Containment.

informal consultation to consolidate the regional response to address artemisinin resistance and...

Documents

malaria objectives

malaria morbidityno

confirmedincidence rate

viet nam

line antimalarial medicines

clinical symptoms

endemic areas

moh data