Malaria trends in a Afghan refugee health programme, b Pakistan MOHMCP

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Malaria trends in a) Afghan refugee health
programme, b) Pakistan MOH/MCP
2

• While the malaria burden reported by the Afghan
  refugee health system fell during the 1990s, the
  burden reported by the Pakistan govt. health
  system continued to rise.
• Slide Positivity Rate (next slide) shows the same
  pattern as malaria burden, therefore these trends
  are consistent and likely to be real .

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Trend in SPR in a) Afghan refugee MCP, and b)
Pakistan MOH/MCP
4

• While it is true the burden reported among 3.5
  million refugees was higher than that reported
  for the 120 million Pakistan population (!), is
  it fair to say that refugees have made malaria
  worse in the local Pakistani population?
• Some critics claim that it has been made worse,
  and to make their point examined the malaria
  burden at district level (using Pakistan MCP
  data).
• We repeated the exercise using Afghan refugee MCP
  data to see if refugee data was consistent with
  Pakistan data
• We produced maps of malaria burden by district
  ..

5
NWFP malaria trends by district for a) Refugee
health programme b) Pakistan health programme

• Malaria burden in Refugee and Pakistan programmes
  show inverse relationship at district level.
• So no evidence that refugees are increasing the
  malaria burden in the Pakistani population

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• So what is the explanation for the
• observed trends over time?
• During the 1990s, as half the refugee
• population returned to Afghanistan and
• the refugee health services were
• scaled down, those that remained
• turned to the Pakistani health services
• for free health care.
• So where refugee health services are inadequate,
  refugees now use the Pakistani health services -
  and this produces the observed inverse
  relationship in malaria burden between parallel
  health services.
• With partial data sets (i.e. when many people use
  a parallel service whose data is inaccessible)
  it is easy to make wrong inferences.
• The same may be true for Pakistan, since an
  estimated 80 are treated through the private
  sector

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Trends in falciparum malaria over last 25 years
Malaria showed an upward trend in Pakistan during
the 1980s. What was the reason?

• Slide positivity rate of falciparum malaria (PF
  / TSE) increased 6-fold during the 1980s in the
  data reported by Pakistan MoH and Afghan Refugee
  Health Programme.
• According to the Pakistan MoH data, SPR trends
  remained stable during the 1990s in the refugee
  population SPR declined mainly due to intensive
  vector control campaigns.
• Malaria species ratio, PF/ (PFPV), shows PF to
  be increasing relative to PV.

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In vivo chloroquine resistance surveys in
Pakistan 1977-1995 (NIMRT/NIH)
CQ resistance emerges around 1982, and spreads
rapidly
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In vivo resistance surveys in refugee camps
confirm the spread of CQ resistance and the low
frequency of SP resistance
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Resistance in Afghan refugee campsRecurrent
clinical attacks in chloroquine treated cases due
to resistance
Natural relapse in vivax cases

• Repeated visits to the clinic for re-treatment
  lead to increase in reported malaria and inflates
  true incidence
• But resistance does also increases the parasite
  reservoir, and this contributes to the increased
  year-to-year transmission of PF

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In-vivo chloroquine tests in Eastern Afghanistan
Location Total Sensitive R I R II Nangarhar
80 31 65 4 Kunar 50 40 34 26 Laghm
an 12 17 83 0
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Drug efficacy trials in Jalalabad and NWFP,
Pakistan
Plasmodium falciparum drug efficacy trials in
Jalalabad, Afghanistan, and NWFP, Pakistan
Principal Investigators Mark Rowland
LSHTM Kate Graham LSHTM and HNI Naeem
Durrani HNI Funded by WHO Special
Programme for Research and Training in Tropical
Diseases (TDR)
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Drug efficacy trials in Jalalabad and NWFP,
Pakistan

• Objectives
• To examine the in vivo resistance levels to the
  current 1st and 2nd line drug regimens
• To examine potential drug combination regimens,
  in terms of their
• efficacy
• potential for transmission reduction
• impact on selection for drug resistance

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Drug efficacy trials in Jalalabad and NWFP,
Pakistan

• Treatment Arms
• Single drug regimens
• CQ Chloroquine (Jalalabad and
  NWFP)
• SP Sulphadoxine-pyrimethamine (Jalalabad
  and NWFP)
• AQ Amodiaquine (Jalalabad only)
• Combination drug regimens
• CQPQ Chloroquine and primaquine (NWFP
  only)
• CQAS Chloroquine and artesunate (NWFP
  only)
• SPPQ Sulphadoxine-pyrimethamine and primaquine
  (NWFP only)
• SPAS Sulphadoxine-pyrimethamine and artesunate
  (NWFP only)
• AQAS Amodiaquine and artesunate
  (Jalalabad only)

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Drug efficacy trials in Jalalabad and NWFP,
Pakistan
Outcomes Drug efficacy Parasitological cure
with no recrudescence Clinical cure
rates Potential for transmission
reduction Gametocyte carriage Gametocyte
viability in feeding studies (NWFP arms
only) Potential impact on selection for drug
resistance Ratio of resistant to susceptible
alleles present pre- and post- treatment,
detected by PCR (NWFP arms only) Side
effects Liver function tests (AQ in comparison
with CQ in Jalalabad) Haematological effects
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Drug efficacy trials in Jalalabad and NWFP,
Pakistan
Drug efficacy in Jalalabad Patients recruited
throughout the most recent Pf season (August 2002
- March 2003)
N116
N24
N 69
cure rate (follow-up to day 42)
N78
N 75

• Resistance to both chloroquine and amodiaquine
  is greater than 80
• SP efficacy is still high
• when given as 1st line treatment it has a 92
  cure rate
• when given as 2nd line treatment to patients
  failing in CQ or AQ arms it also achieves over
  90 cure
• Amodiaquine and artesunate combination has a
  cure rate of less than 80, resistance to
  amodiaquine is already too high to make a
  combination including AQ a feasible option

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Drug efficacy trials in Jalalabad and NWFP,
Pakistan
Drug efficacy in NWFP Patients recruited over the
previous 3 Pf seasons (August 2000 January 2003)
N41
N41
N33
N66
cure rate (follow-up to day 28)
N64
N64

• Resistance to chloroquine is almost 80
• SP efficacy is still high at over 90 cure rate
• Resistance to chloroquine is already too high to
  make a combination of CQ with artesunate a
  feasible alternative
• Treatment arms that were replicated in Jalalabad
  (CQ and SP) gave similar results in both NWFP and
  Jalalabad

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Drug efficacy trials in Jalalabad and NWFP,
Pakistan
Gametocyte carriage in NWFP Patients recruited
over the previous 3 Pf seasons (August 2000
January 2003)
N41
N64
N33
gametocytaemic on or after day 7 post-treatment
N64
N66
N41

• Both CQ mono-therapy and SP mono-therapy result
  in a high rate of gametocyte carriage after
  treatment. This is slightly, but significantly,
  higher after SP treatment than CQ treatment
• The addition of primaquine to CQ greatly reduces
  gametocyte carriage but has a negligible effect
  when added to a SP regimen
• Both artesunate combination regimens result in
  low gametocyte carriage rates

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Drug efficacy trials in Jalalabad and NWFP,
Pakistan

• In Conclusion
• Chloroquine mono-therapy for falciparum malaria
  in this region is no longer acceptable
• In addition
• Chloroquine resistance levels are too high to
  make a policy of chloroquine in combination with
  artesunate a feasible option
• Amodiaquine resistance is also high. Despite no
  use of this drug in treatment guidelines,
  resistance may have developed either through
  significant use of the drug through private
  outlets, or through selection by chloroquine to
  which it shows cross resistance
• SP mono-therapy is highly effective
• Resistance to SP may develop quickly it has an
  extended trophozoite clearance time and high
  levels of persisting gametocyte carriage
• Recommendation
• SP in combination with artesunate is the most
  attractive drug regimen it has good efficacy,
  fast gametocyte clearance rates, and may prevent
  further selection of resistance to SP

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Drug efficacy trials in Jalalabad and NWFP,
Pakistan
Why is drug resistant falciparum malaria going
unnoticed
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Drug efficacy trials in Jalalabad and NWFP,
Pakistan
Why is drug resistant falciparum malaria going
unnoticed
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Drug efficacy trials in Jalalabad and NWFP,
Pakistan

• Acknowledgements
• HealthNet International Abdur Rab, Jan
  Kolaczinski, Fayaz Ahmed, Dr Hayat and staff of
  Jalalabad and Adizai
• WHO Piero Olliaro, Bob Taylor, Nadine Ezard,
  Kamal Mustafa
• DOMC/NIH (Pakistan) Arif Munir, Imtiaz Shah,
  Ch. Mujahid
• IMPD/MOH (Afghanistan) Dr Abdul Wasi Asha (Dir.
  IMPD), Dr Ferouz (Dep. Dir. MoH)