Drug Resistance in P. falciparum in Sangkhlaburi District ?????????????????????????????????????????

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Drug Resistance in P. falciparumin Sangkhlaburi
District?????????????????????????????????????????

• Dr. Chansuda Wongsrichanalai, MD, DrPH
• Dr. R. Scott Miller, MD
• Dr. Harald Noedl, MD, PhD

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Malaria as a Re-emerging Disease Development of
Resistance in SE Asia????????????????????????????
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Wongsrichanalai 2000
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Drug-Resistant Falciparum MalariaAn Emerging
Infectious Disease in SE Asia

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  ?????????????????????? ????????????
  65,000????????
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  ???????
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Wongsrichanalai 2000
4

• Mefloquine resistance rose
• markedly in Tak Province with
• no other anti-malarials available.
• Oct 1995 artesunate/mefloquine
• combination started with a
• monitoring program for toxicity
• No resistance as yet reported
• with this regimen
• Now MQ resistance spread along
• Thai-Myanmar border and across
• Myanmar

Mekong Malaria, SE Asian J Trop Med Pub Health
30 Supp 4, 1999
5
AFRIMS Malaria Surveillance Field Sites in
1998-03


Bhutan
China
12
Hong Kong
6
India
Bangladesh
7
Vietnam
9
10
Myanmar
Laos
13
Bay of Bengal
1
Thailand
8
2
11
5
Cambodia
9
3
Andaman Sea
South China Sea
4
Malaysia
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IN VITRO DRUG SENSITIVITY
A considerable decrease in the sensitivity of
falciparum malaria parasites to MEFLOQUINE and
ARTESUNATE was seen between 1995/1996 and
2001/2002 reflecting the lower clinical efficacy
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IN VITRO DRUG SENSITIVITY
At the same time the susceptibility of P.
falciparum to CHLOROQUINE and QUININE showed
little change.
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Efficacy of Antimalarials and Genetics of
Resistance in Sangkhlaburi, Thailand

• In vivo study of mefloquine resistance in
  coordination with the Malaria Division to assess
  anecdotes of MQ failure in Sangkhlaburi in
  2001-2002
• Enrolled adult volunteers at Malaria Clinic and
  KRCH
• Uncomplicated PF
• First line PF treatment as per local guidelines
• ท         Mefloquine (Lariam?) 750 mg
  Primaquine 30mg once OR
• Mefloquine (Mephaquin?) 1250 mg once
  Artesunate 600 mg divided
• over 3-5 days (by weight)
• return for scheduled visits for repeat blood
  smear on
• days 3, 7, 21, 28, 35, and 42

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Results

• Enrolled
• 52 persons to MQ monotherapy 750 mg (MC regimen)
• 46 persons completed 42 days follow-up
• 26 of 46 (57) cured
• 20 of 46 (43) had malaria return with 42 days
• 25 had early treatment failure (recurrence
  within 1 week)
• 22 persons to MQ and AS regimens
• 18 persons completed 42 days follow-up
• 100 cured
• Malaria Division changed to this regimen for
• Sangkhlaburi district in 2002
• 2nd line treatment Artesunate 700 mg over 5 days
  Primaquine 30 mg
• 11 enrolled all cured

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IN VITRO DRUG SENSITIVITY
In 2002 the new HRP2 Field In Vitro Drug
Sensitivity Assay for Plasmodium falciparum was
first tested and validated at the KRCH against
traditional in vitro techniques. Preliminary
results suggested high sensitivity,
reproducibility, and that it is particularly
simple to establish and perform. In the meantime
the HRP2 field assay has been validated
extensively and may soon be established as the
standard methodology for testing of field samples
in Thailand.
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  ?? ??????????????????????????? ???????????????????
  ??????????????
• ??Chloroquine and SMX/PYR ????????????????
• ?????????????????????????????? (gt40 ????????)
• Artesunate ??????? MQ ??????????????????
• ????????????????? Artesunate 700mg for 7 days
• Quinine doxycycline for 7 days
• (100 effective at KRCH in 2000)

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