Spectrophotometric Method for Determination of Primaquine ...
When did we surrender to relapse, and why take it on now? · 04/03/15 17 Where feasible all...
Transcript of When did we surrender to relapse, and why take it on now? · 04/03/15 17 Where feasible all...
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When did we surrender to relapse, and why take it on now?
Head of UnitEijkman‐Oxford Clinical Research Unit
Jakarta, Indonesia&
Centre for Tropical MedicineNuffield Department of Medicine
University of OxfordOxford, United Kingdom
J. Kevin Baird, Ph.D.
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The history of primaquine‐G6PD answers that question
• Primaquine hemolytic toxicity in G6PD deficient patients only recently acknowledged as a serious access issue for all patients
• Lack of access only recently acknowledged as a serious clinical and public health problem.
• What took so long to recognize the “primaquine‐G6PD dilemma”?
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The primaquine‐G6PD dilemma
• If I treat this patient without G6PD screening, the primaquine may kill him
• If I don’t treat the patient without G6PD screening, the parasite may kill him
If you do If you do notDAMNED
Primaquine and the parasite being dangerous is new understanding
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Plasmodium vivax 1960
• On verge of elimination everywhere outside of Africa, and virtually absent from there
• A benign and non‐threatening infection• Primaquine therapy in endemic setting thought to be unnecessary
• Primaquine therapy without G6PD screening considered safe
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Primaquine therapy 1960 to 2010
If you do If you do not
NO HARM DONE NO HARM DONE
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Plasmodium vivax 1960
Sri Lanka
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Plasmodium vivax 1960
Brazil Mem. Inst. Oswaldo Cruz vol.109 no.5 Rio de Janeiro Aug. 2014
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Plasmodium vivax 1960
India
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Before the Primaquine‐G6PD Dilemma
• Primaquine used against relapse since 1952• G6PD deficiency discovered in 1956• US Army invented primaquine and used it before G6PD
deficiency was even known – so who needs screening? • US Army experience based on mild, self‐limiting A‐
variant, and they had very few poor outcomes• WHO adopted that view in recommending PQ therapy
without G6PD screening• WHO viewed both relapse and treatment against it as
not threatening
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The US experience with primaquine seemed universally applicable
PRACTICE
WHO
US ARMY
Primaquine Policy Since 1952
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Mild G6PD Deficiency
Alving et al., Bull WHO 1960
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Variable G6PD Deficiency
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But rationalizations continued• “Reports on large numbers of patients treated with this
regimen, even where G6PD deficiency is quite common, indicate this regimen is generally well tolerated and that hemolyisis, when it occurs, is mild and self‐limiting.” WHO TGM 1981
“no harm if you do”• “It is doubtful if radical treatment of vivax malaria is
necessary if the patient lives in an endemic area where transmission of the infection continues and reinfection likely.” WHO TGM 1981
“no harm if you do not”
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Wising Up
• “In patients with the African variant of G6PD deficiency, the standard course of primaquine therapy produces a benign and self‐limiting anemia. In the Mediterranean and Asian variants, hemolysis may be much more severe.” WHO TGM 2010
“harm if you do”
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Wising Up
WHO Technical Brief on Control & Elimination of P. vivax, 2015
Odds of death when hospitalized with PV vs. PF
“harm if you do not”
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Plasmodium vivax causes significant morbidity and mortality and poses unique challenges for malaria control and elimination.
Severe cases and deaths due to P. vivaxmalaria have been reported from all endemic regions
Testing for G6PD deficiency is currently technically challenging and relatively expensive; hence, many clinicians fear prescribing primaquine to patients of unknown G6PD status. Weighing that risk against the possibility of repeated clinical attacks with attendant risk of debilitating or threatening illness and onward transmission to others is very difficult.
The primaquine‐G6PD dilemmaat last acknowledged and expressed
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Where feasible all patients should be tested for G6PD deficiency before administering primaquine. Testing for G6PD deficiency in vivax malaria cases should be seen as an integral part of ensuring universal access to diagnosis and treatment.
G6PD testing should be incorporated into treatment guidelines, and services made available, as tools become available (possibly with referral of patients from lower to higher level health facilities).
Solving primaquine‐G6PD dilemmaacknowledged as screening for G6PDd
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Evidence Review Group
• ERG formation expresses the will and ability to resolve the primaquine‐G6PD dilemma with point‐of‐care G6PD screening
• ERG formation acknowledges the necessity of attacking the hypnozoite reservoir and the caution needed in doing so
Held at WHO Geneva, 8‐9 October 2014
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What next?• ERG report goes to the WHO Malaria Policy Advisory Committee first week of March
• MPAC decides upon their recommendation to make to WHO policy board
• WHO may make strong recommendations regarding the necessity of therapy against relapse in vivax malaria, and the necessity for testing for G6PD deficiency before doing so.