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Table 5 Clinical studies of uncomplicated P. falciparum malaria in Cambodia, 2001–2018

From: Efficacy of three anti-malarial regimens for uncomplicated Plasmodium falciparum malaria in Cambodia, 2009–2011: a randomized controlled trial and brief review

Study Date Province Regimen, n Baseline gametocyte Day 3 positive Clearance (h) PfK13 PfMdr1 PfPlasmepsin PCR-ACPR (days)
Denis et al. 2006a 2001 Battambang AS/MQ, 50        96% PP (28)
2003 Battambang AS/MQ, 55        92% PP (28)
2002 Pailin AS/MQ, 81        86% PP (28)
2004 Pailin AS/MQ, 90   10%    1.5 copies Overall   79% PP (42)
2002 Pursat AS/MQ, 83        93% PP (28)
2004 Pursat AS/MQ, 85        93% PP (28)
2003 Oddar Meanchey AS/MQ, 92        98% PP (28)
2002 Preah Vihear AS/MQ, 36        97% PP (28)
2004 Preah Vihear AS/MQ, 85        100% PP (42)
2001 Kratie AS/MQ, 50        100% PP (28)
2003 Kratie AS/MQ, 66        100% PP (28)
2002 Ratanakiri AS/MQ, 75        100% PP (28)
2004 Ratanakiri AS/MQ, 80        100% PP (42)
2003 Kampong Speu AS/MQ, 97        97% PP (28)
Rogers et al. 2009b 2006–2008 Kampot AS/MQ, 151   11%    2.7 copies fail
1.9 copies ACPR
  81% KM (42)
Noedl et al. 2008
Noedl et al. 2010c
2006–2007 Battambang AS, 74   22% PCT = 58   1.1 copies overall   94% KM (28)
QN + TET, 37   34% PCT = 78    100% KM (28)
Rueangweerayut et al. 2012d 2007–2008 Pailin AS/PYR, 140   37% PCT = 64     90% KM (42)
AS/MQ, 71   38% PCT = 64     100% KM (42)
Dondorp et al. 2009e 2007–2008 Pailin AS/MQ, 20 30% 55% PCT = 72   5% amplified   95% ITT (63)
AS, 20 25% PCT = 84    70% ITT (63)
Leang et al. 2013f 2008–2009 Pailin DHA/PPQ, 59   26%    17% amplified   90% KM (42)
2009–2010 Pailin DHA/PPQ, 41   33%    24% amplified   92% KM (42)
2010–2011 Pailin DHA/PPQ, 30   45%    16% amplified   76% KM (42)
2008 Pursat DHA/PPQ, 86   8%    32% amplified   99% KM (42)
2010 Pursat DHA/PPQ, 64   10%    25% amplified   90% KM (42)
2009 Preah Vihear DHA/PPQ, 60   5%      100% KM (42)
2009–2010 Ratanakiri DHA/PPQ, 59   0%      100% KM (42)
2010 Ratanakiri DHA/PPQ, 61   0%      100% KM (42)
Bethell et al. 2011g 2008–2009 Battambang AS2, 75 13% 49% PCT = 74     88% PP (42)
AS4, 40 10% 46% PCT = 78     90% PP (42)
AS6, 28 21% 48% PCT = 78     79% PP (42)
Amaratunga et al. 2012h 2009–2010 Pursat AS/MQ, 180 16%   PC1/2 = 5.9
PCT = 78
    
This studyi 2009–2011 Oddar Meanchey AS/MQ, 63 44% 52%    3.5 copies fail
1.8 copies ACPR
  81% KM (42)
DHA/PPQ, 77 47% 62%    3.9 copies fail
2.2 copies ACPR
  97% KM (42)
ATQ/PG, 71 51% 62%    2.1 copies fail
2.2 copies ACPR
  94% KM (42)
Lon et al. 2014j 2010–2011 Oddar Meanchey DHA/PPQ × 2, 8 13% 50% PCT = 80 82% C580Y 1.2 copies fail
1.1 copies ACPR
  75% PP (42)
DHA/PPQ × 3, 12 42% 42% PCT = 68   82% PP (42)
Leang et al. 2015k 2011–2013 West DHA/PPQ, 147   31%   87% C580Y 16% amplified   85% PP (42)
East DHA/PPQ, 278   17%   23% C580Y 21% amplified   98% PP (42)
Ashley et al. 2014l 2011–2013 Pailin AS4 + DHA/PPQ, 100 19% 66% PC1/2 = 6.1 ~ 75% C580Y   ~ 50% 98% PP (42)
Pursat AS4 + DHA/PPQ, 120 18% 60% PC1/2 = 5.6  
Preah Vihear AS2/4 + DHA/PPQ, 120 5% 18% PC1/2 = 3.0 Diverse   Mostly WT  
Ratanakiri AS2/4 + DHA/PPQ, 120 6% 7% PC1/2 = 3.0 Mostly WT   100% WT  
Amaratunga et al. 2016m 2012–2013 Pursat DHA/PPQ, 110 17% 61% PC1/2 = 6.1 77% Mutant 0% amplified fail
11% amplified ACPR
  63% KM (63)
Preah Vihear DHA/PPQ, 65 9% 26% PC1/2 = 3.0 34% mutant   85% KM (63)
Ratanakiri DHA/PPQ, 66 2% 3% PC1/2 = 2.4 11% mutant   98% KM (63)
Saunders et al. 2014
Spring et al. 2015n
2012–2014 Oddar Meanchey DHA/PPQ, 51 10% 65% PC1/2 = 6.4
PCT = 80
65% C580Y
31% R539T
   58% mITT (42)
DHA/PPQ + PQ, 50 8% 42%    50% mITT (42)
Leang et al. 2016o 2014–2015 Pailin AS/PYR, 55 0% 13%   96% C580Y    84% KM (42)
Pursat AS/PYR, 60 8% 44%     90% KM (42)
Battambang AS/PYR, 8 0% 25%     100% KM (42)
Wojnarski et al. 2019p 2014–2015 Oddar Meanchey ATQ/PG + PQ, 79 21% 42% PC1/2 = 5.6 100% C580Y    88% KM (42)
AS + ATQ/PG + PQ, 78 42% PC1/2 = 5.9 99% C580Y    91% KM (42)
Kratie ATQ/PG + PQ, 24 19% 17% PC1/2 = 5.6 91% C580Y    100% KM (42)
AS + ATQ/PG + PQ, 24 4% PC1/2 = 5.3 86% C580Y    94% KM (42)
Van der Pluijm et al. 2019
Van der Pluijm et al. 2020q
2015–2018 Pailin DHA/PPQ + PQ, 9 41% 72% PC1/2 = 7.2 97% C580Y 0% amplified 69% 52% KM (42)
DHA/PPQ + MQ + PQ, 11 100% KM (42)
AS/MQ + PQ, 22 100% KM (42)
DHA/PPQ + MQ + PQ, 22 100% KM (42)
Pursat DHA/PPQ + PQ, 8 46% PC1/2 = 6.3 89% C580Y 79% 25% KM (42)
DHA/PPQ + MQ + PQ, 11 100% KM (42)
AS/MQ + PQ, 48 100% KM (42)
DHA/PPQ + MQ + PQ, 45 100% KM (42)
Preah Vihear AS/MQ + PQ, 3   14% PC1/2 = 5.2 100% C580Y 100% 100% KM (42)
DHA/PPQ + MQ + PQ, 4 100% KM (42)
Ratanakiri DHA/PPQ + PQ, 44 16% 52% PC1/2 = 7.0 85% C580Y 71% 73% KM (42)
DHA/PPQ + MQ + PQ, 46 100% KM (42)
  1. PP per-protocol, QN quinine, TET tetracycline, PYR pyronaridine, PQ primaquine, PCT parasite clearance time, PC1/2 parasite clearance half-life, WT wild-type, ITT intention-to-treat, mITT modified intention-to-treat, KM Kaplan–Meier
  2. aReport of 14 therapeutic efficacy studies [9]; Day 3 Positive and median Pfmdr1 copies from Alker et al. [40]
  3. bTherapeutic efficacy study reporting mean Pfmdr1 copies; failures had 3.6 copies at recrudescence [10]
  4. cRandomized controlled trial reporting median PCT and Pfmdr1 copies [64, 65]
  5. dPhase 3, randomized controlled trial reporting median PCT [66]
  6. eRandomized controlled trial with another site in Wang Pha, Thailand; reporting median PCT [41]
  7. fReport of 8 therapeutic efficacy studies [42]
  8. gRandomized controlled trial comparing 2, 4, and 6 mg/kg AS; reporting median PCT [67]
  9. hParasite clearance rate study reporting geometric mean PC1/2 [33]
  10. iRandomized controlled trial; mean Pfmdr1 copies at recrudescence were 3.6, 1.0, and 1.6 for AS/MQ, DHA/PPQ, and ATQ/PG, respectively
  11. jRandomized controlled trial comparing 2- versus 3-day regimens of DHA/PPQ, reporting median PCT and Pfmdr1 [47]; PfK13 mutations were essentially at fixation [35]
  12. kTherapeutic efficacy study; Western refers to Battambang, Pursat, Kampot, and Kampong Speu; Eastern refers to Kratie, Preah Vihear, Ratanakiri, and Kampong Thom [13]
  13. lTRACI: parasite clearance rate study of AS 2 or 4 mg/kg with DHA/PPQ, reporting median PC1/2 [36]; PfK13 and Pfplasmepsin status reported in van der Pluijm et al. [43]
  14. mTherapeutic efficacy study reporting median PC1/2 [37]
  15. nRandomized controlled trial reporting median PC1/2 and PCT [12, 35]; Gametocytemia reported in Lin et al. [61]
  16. oTherapeutic efficacy study [68]
  17. pRandomized controlled trial reporting median PC1/2 [51]
  18. qTRACII: randomized controlled trial; gametocytemia for Pailin and Pursat refer to the 17 subjects receiving DHA/PPQ [43, 44]