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Intervention Review

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Primaquine for reducing Plasmodium falciparum transmission

  1. Patricia M Graves1,2,*,
  2. Hellen Gelband3,
  3. Paul Garner4

Editorial Group: Cochrane Infectious Diseases Group

Published Online: 12 SEP 2012

Assessed as up-to-date: 5 JUL 2012

DOI: 10.1002/14651858.CD008152.pub2


How to Cite

Graves PM, Gelband H, Garner P. Primaquine for reducing Plasmodium falciparum transmission. Cochrane Database of Systematic Reviews 2012, Issue 9. Art. No.: CD008152. DOI: 10.1002/14651858.CD008152.pub2.

Author Information

  1. 1

    EpiVec Consulting, Atlanta, USA

  2. 2

    James Cook University, School of Public Health, Tropical Medicine and Rehabilitation Sciences, Cairns, Queensland, Australia

  3. 3

    Center for Disease Dynamics, Economics & Policy, Washington, DC, USA

  4. 4

    Liverpool School of Tropical Medicine, International Health Group, Liverpool, Merseyside, UK

*Patricia M Graves, School of Public Health, Tropical Medicine and Rehabilitation Sciences, James Cook University, PO Box 6811, Cairns, Queensland, 4870, Australia. pgraves.work@gmail.com. patricia.graves@jcu.edu.au.

Publication History

  1. Publication Status: New
  2. Published Online: 12 SEP 2012

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Characteristics of included studies [ordered by study ID]
Chen 1994

MethodsPossibly individually randomized controlled trial (stated to be randomized but no information given).

Dates of study not reported.


Participants27 patients with slide positive P. falciparum including both asexual stages and gametocytes. No information given on age or sex. All dosages appear to be adult dosages.

Site: malaria endemic Hainan Island, China.

Exclusion criteria: history of antimalarial treatment for present attack.


Interventions1. Artemisinin: 1200 mg per day for 5 days (not included in review).

2. MQ: 750 mg single dose day 1 (reported as day 0).

3. MQ + PQ:750 mg single dose + 45 mg single dose day 1 (reported as day 0).


Outcomes1. Gametocyte density: days 5, 8, 15, 22, 29 (reported in paper as days 4, 7, 14, 21, 28 since first day was day 0). Given as percent of initial density on chart only.

2. Percentage of participants infectious to An. dirus: days 5, 8, 15, 22 (reported as days 4, 7, 14, 21).

3. Percentage of mosquitoes infected: days 5, 8, 15, 22 (reported as days 4, 7, 14, 21).


NotesFor gametocyte density, graph only of percentages; no raw numbers given except range of asexuals and gametocyte numbers reported for each group on day 1 (reported as day 0).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo information on sequence generation. Describes process as participants "divided into groups A, B, and C". Equal number in each group and lack of detail suggests randomization not done adequately.

Allocation concealment (selection bias)High riskNo data to suggest any measures to conceal allocation.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing participants in intervention groups 2 and 3.

Selective reporting (reporting bias)Low riskNo obvious selective reporting.

Other biasLow riskNo indication of other bias.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot reported.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot reported.

El-Sayed 2007

MethodsIndividually randomized controlled trial.

Dates of study: Randomization June 2004; trial done 17 Aug 2004 to 3 Sep 2004.


Participants104 persons with asymptomatic P. falciparum positive by slide and positive for gametocytes by PCR. No information given on age and sex.

Site: Two villages in East Sudan where there is seasonal malaria, mainly P. falciparum, during Oct to Dec.

Exclusion criteria: pregnancy, history of sulfa allergy, fever or other symptoms, Plasmodium spp other than P. falciparum present.


Interventions1. AS: Children < 50 kg: 4 mg/kg; All > 50 kg: 200 mg (2 100-mg tabs) days 1, 2, 3 (reported as days 0, 1, 2).

SP: Children < 50 kg: 25 mg/kg S + 1.25 mg/kg P; All > 50 kg: 3 tablets of 500 mg S+25 mg P.

2. As for 1 above plus PQ 0.75 mg/kg day 4 (reported as day 3).


Outcomes1. Proportion of persons with P. falciparum parasites by PCR days 4, 8 and 15 (reported as days 3, 7 and 14).

2. Proportion of persons with gametocytes by RT-PCR days 8 and 15 (reported as days 7 and 14).

3. Adverse events days 2, 3, 4, 8 and 15 (reported as days 1, 2, 3, 7 and 14).

4. Packed cell volume days 1, 8 and 15 (reported as days 0, 7 and 14).


NotesThe trial was conducted about 2 months after the initial screening for positives (asymptomatic carriers).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"The list of carriers was sorted according to village and age to ensure that the treatment groups were balanced with respect to these two variables. The random allocation of this ordered list into the treatment arms was then created using restricted randomization with a block size of 12 in STATA v7..."

Allocation concealment (selection bias)Unclear riskNo information given.

Incomplete outcome data (attrition bias)
All outcomes
Low riskOnly 3 out of 104 participants did not complete the follow up.

Selective reporting (reporting bias)Low riskNo obvious selective reporting.

Other biasLow riskNo indication of other bias.

Blinding of participants and personnel (performance bias)
All outcomes
High riskPatients and health staff were not blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskLab staff doing PCR were blinded.

Kamtekar 2004

MethodsIndividually randomized controlled trial, comprising two distinct comparisons a: (CQ or [CQ+SP]) with and without PQ and b: QN with and without PQ.

Dates of study: not given.


Participants57 persons age >/= 16 years with symptomatic uncomplicated and 46 with severe (WHO criteria) P. falciparum malaria, diagnosed by thick and thin blood slides. Gametocytaemic within first 72 hrs with > 55 P. falciparum gametocytes/μL

Site: urban areas of Mumbai, India.

Exclusion criteria: Pregnant or lactating, treatment for malaria within last two weeks, co-infection with P.vivax, history of PQ allergy.


InterventionsComparison a: for uncomplicated malaria

1. CQ or (CQ+SP)
CQ 10 mg/kg on days 1 and 2; 5 mg/kg on day 3;

SP 1500 mg S, 75 mg P on day 1;

Placebo for PQ on day 4.

2. [CQ or (CQ+SP)] + PQ

As above in 1, substituting PQ 45 mg for placebo on day 4

Comparison b: (for severe malaria)

3. QN

QN 10 mg/kg every 8 hrs for 24-48 hrs and orally for total of 7 days

Placebo for PQ on day 8.

4. QN +PQ

As above in 3, substituting PQ 45 mg for placebo on day 8.


Outcomes1. Proportion of persons with gametocytes, days 1, 4, 8, 15, 22, 29.

2. Proportion of persons with viable gametocytes (exflagellation), days 1, 4, 8, 15, 22, 29.

3. Gametocyte density (given as range) days 1, 4, 8, 15, 22, 29.


NotesNo screening for G6PD deficiency. It is not stated how many got SP in addition to CQ or why.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High risk'simple computer generated randomization code'.

Not all patients had gametocytes on day 1. Inclusion criteria were that the person had to have gametocytes in the first 72 hours (from day 1?). This suggests some post randomization inclusions or exclusions.

Allocation concealment (selection bias)Unclear riskNo information.

Incomplete outcome data (attrition bias)
All outcomes
High riskOriginally there were 57 persons included in uncomplicated comparison (a), of whom 2 were lost to follow up and 9 were not evaluated as they showed CQ resistance.

There were 46 in severe comparison (b), of whom 3 were lost to follow up.

The final numbers evaluated in each group were (a) 22 and 24 (b) 22 and 21.

Selective reporting (reporting bias)Unclear riskNo obvious selective reporting.

Other biasHigh riskIt was not clear why some patients got SP and others did not, and the numbers in each group are not given.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskStudy used a placebo for PQ. Patients and health workers were blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskSlide readers were blinded.

Khoo 1981

MethodsIndividually randomized controlled trial.

Dates of study: between June 1976 and March 1978.


Participants69 persons (adults and children of both sexes, no ages specified) with G6PD deficiency (full or partial by Brewer's methaemoglobin reduction test) who were slide positive for malaria (P. falciparum, P. vivax or mixed).

Site: Sabah, Malaysia.

Exclusion criteria:other associated clinical conditions.


Interventions1. CQ

1.5 g CQ over 3 days for P. falciparum, P. vivax or mixed, less for children

2. CQ + PQ

CQ as above plus 75 mg PQ over 3 days for P. falciparum; 201 mg PQ over 14 days for P. vivax and mixed infections; less for children

3. SP (not included in this review)

1.5 g S and 75 mg P, single dose


Outcomes1. Hemolysis

2. Proportion cleared parasites by 72 hours

3. Need for blood transfusion

4. Renal failure


NotesThe participants are not divided by P. falciparum, P. vivax or mixed, so it is not possible to use the data.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"those found G6PD deficient were randomly assigned."

Allocation concealment (selection bias)Unclear riskNo information given.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNo information given.

Selective reporting (reporting bias)Low riskNo apparent selective reporting.

Other biasLow riskNo indication of other bias.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot reported.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot reported.

Kolaczinski 2012

MethodsIndividually randomized controlled trial.

Dates of study: between July and January, from 2000 to 2003.


Participants237 individuals aged from 3 to 70 years, in 5 villages for Afghan refugees in Pakistan.

Inclusion: > 2 years of age, P. falciparum mono-infection, confirmed by slide, will be resident during entire follow-up period.

Exclusions: pregnancy, signs of severe malaria, report of antimalarial drug in past 21 days, other serious disease


Interventions1. CQ

3 days 25 mg/kg.

2. CQ+PQ

CQ as in 1; PQ on day 3 (0.5 mg/kg).

3. SP

25:1.25 mg/kg in single dose.

4. SP+PQ

SP as in 3; PQ on same day (0.5 mg/kg).


Outcomes1. Clinical treatment failure (PCR non-adjusted and adjusted).

2. Gametocytes on day 8.

3. Gametocyte density on days 1 to 8 of follow-up.

4. Genotyping of resistant strains for CQ and SP-specific mutations.


NotesAlso included CQ + AS and SP + AS arms, compared with CQ +/- PQ and SP +/- PQ arms, respectively.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskPatients numbered sequentially at enrolment. Random numbers with treatment assignment from Excel-generated lists, then paired with patient numbers.

Allocation concealment (selection bias)Low riskPatient number concealed until after enrolment.

Incomplete outcome data (attrition bias)
All outcomes
Low risk209 of 237 randomized completed treatment and at least one follow-up test. 47 (13%) of those randomized did not contribute data. Variable numbers tested during follow-up (see analyses).

Selective reporting (reporting bias)Low riskNone detected.

Other biasLow riskNone noted.

Blinding of participants and personnel (performance bias)
All outcomes
High riskIdentified in report as 'single-blind'. Manager (gave Rx) not blinded; patients, microscopists and health workers ‘partially blinded’ due to different drug appearance and times of follow-up. No placebos used, but vitamin given to those in non-PQ arms.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskImplied only.

Ledermann 2006

MethodsIndividually randomized controlled trial.

Date of study July-Oct 2001.


Participants117 malaria cases with P. falciparum >/= 400 asexual stages/μL (thick film) recruited by mass blood survey and passive case detection. Symptoms not required.

Age: >/=15 years

Site: Central Java, Indonesia, an area with high CQ resistance and resurgent malaria approximately equal P. falciparum and P. vivax.

Exclusion criteria: Pregnancy, breast feeding, body weight < 40kg, G6PD deficiency, history of antimalarial or antibiotic in last 7 days, severe or complicated malaria, history or allergy or adverse reaction to study medications, Pv or mixed infection.


Interventions1. CQ only (not included in this review).

2. CQ+SP.

CQ 150 mg base, 10, 10 and 5 mg/kg on days 1, 2, 3 (reported as days 0, 1, 2).

SP 500 mg S 25 mg P on day 1 (reported as day 0).

3. CQ+SP as for group 2 above plus PQ 45 mg on day 1 (reported as day 0).

4. CQ+SP as for group 2 above plus PQ 45 mg on day 3 (reported as day 2).


Outcomes1. Parasite clearance time assessed at days 1, 3, 8, 15, 22, 29 or day of recurrent parasitaemia (reported as days 0, 2, 7, 14, 21, 28).

2. Fever clearance time at days 2, 3, 4, 5, 8, 12, 15, 19, 22, 29.

3. Proportion of persons with gametocytes (from chart) days 1 to 29.

4. Adverse events.


NotesSome comparisons in the results reported include the CQ only group.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskStudy subject codes were assigned to treatment arms by a random process (not specified).

Allocation concealment (selection bias)High riskEligibles were assigned a sequential participant number by the screening physician. Pre-packaged treatment but not stated whether allocation was concealed.

Incomplete outcome data (attrition bias)
All outcomes
Low risk7% of participants withdrew before day 28.

Selective reporting (reporting bias)Unclear riskAbstract states that drugs were well tolerated and safe but no evidence is given in report.

Other biasLow riskNo indication of other bias.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskBlinding was implied only.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskBlinding was implied only.

Pukrittayakamee 2004

MethodsIndividually randomized controlled trial.

Time of study not stated.


Participants176 patients with acute uncomplicated P. falciparum. After exclusion of QN+tetracycline group: 146.

Age 14 to 62.

All male.

Site: Hospital for Tropical Diseases, Bangkok, Thailand.

Exclusion criteria: Severe malaria, mixed malaria infection, history of drug hypersensitivity, any antimalarial within last 48 hrs, urine positive for sulfonamide or 4-aminoquinoline.

Persons with G6PD deficient phenotype were excluded from receiving PQ.


Interventions1. QN
QN sulfate (300 mg salt/tab) at 10 mg salt/kg, 3x per day for 7 days.

2. QN+tetracycline (excluded from this review).

3. QN+PQ low dose

QN as above in 1 plus PQ 15 mg base/tab, 0.25 mg/kg base (adult dose 15 mg base) daily for 7 days.

4. QN+PQ high dose

QN as above in 1 plus PQ 0.50 mg/kg base (adult dose 30 mg base) daily for 7 days.

5. AS
AS 50 mg salt/tab 3.3 mg/kg (adult dose 200 mg) on day 1 and 1.65 mg/kg (adult dose 100 mg) daily on days 2 to 7.

6. AS+PQ (high dose)

AS as above plus PQ 0.5 mg/kg base daily on days 1 to 7.


Outcomes1. Parasite clearance time: measured at 12 hrs until clearance.

2. Gametocyte clearance time: median, 12 hrs until clearance.

3. Fever clearance time (measured every 4 hr at first and then every 6-12 hrs until resolution of fever.

4. Parasite reduction ration at 48 hrs.

5. Reappearance of infection P. falciparum/P. vivax up to 28 days.

6. Prevalence of gametocytes on admission/after treatment/total.

7. Gametocyte carriage: total number of hours for which gametocytes were detectable.


NotesPatients with recrudescence of P. falciparum or relapse of P. vivax were re-treated with 7 day QN+tetracycline or 'standard doses' of CQ+PQ respectively; not clear if they were excluded from further study.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskMethod not stated. Patients with G6PD deficiency were excluded from getting PQ which suggests randomization was biased.

Allocation concealment (selection bias)Unclear riskNo information given.

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk122/142 of the original participants in the 5 groups studied here completed follow up. Patients with recrudescences of P. falciparum or relapse of P. vivax were re-treated with QN+tetracycline or CQ+PQ respectively; not clear if they were excluded from further study.

Selective reporting (reporting bias)Unclear riskNot detected.

Other biasUnclear riskThose who were unable to stay in hospital until clearance of both fever and parasites were excluded from study of fever clearance time.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot reported.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot reported.

Shekalaghe 2007

MethodsIndividually randomized controlled trial.

Time of study Jun to Sept 2006.


Participants108 children with fever > 37.5 °C or history of fever in last 48 hours and P. falciparum mono-infection 500 - 100,000/μL.

Age 3 to 15 years.

Both sexes.

Site: Mynuzi health center, NE Tanzania, a hyperendemic area with rainy seasons in Mar-June and Oct-Dec.

Exclusion criteria: Hb < 8, inability to take drugs orally, known hypersensitivity to meds, reported anti-malarial treatment in last 2 weeks, evidence of chronic disease or acute infection other than malaria, domicile outside study area, signs of severe malaria, eligible for other malaria studies.


Interventions1. AS+SP

AS: 4 mg/kg once daily for 3 days

SP: S 25 mg/kg and P: 1.125 mg/kg

2. AS+SP+PQ

As above for AS and SP plus PQ base 0.75 mg/kg on the third day.


Outcomes1. Proportion of persons with gametocytes (by microscopy) days 1, 4, 8, 15, 29, 43 (reported as 0, 3, 7, 14, 28, 42).

2. Proportion with gametocytes (by PCR), same time points.

3. Gametocyte density by PCR.

4. AUC for gametocyte presence.

5. Adverse events.

6. Adequate clinical and parasitological response.

7. Haemoglobin.


NotesHb outcome assessed with respect to G6PD variant.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskGenerated in STATA 8.0 using restricted randomization with block size of 20.

Allocation concealment (selection bias)Unclear riskPre-prepared envelopes (but person who opened envelope administered treatment).

Incomplete outcome data (attrition bias)
All outcomes
Low riskOnly 2 out of 108 failed to complete follow-up.

Selective reporting (reporting bias)Low riskWhy no day 22 results?

Other biasLow riskNo indication of other bias.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskStudy physician evaluated patients, opened envelopes, and administered treatment. Other staff were blinded. Not clear of participants were blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated.

Singhasivanon 1994

MethodsStudy design: Individually randomized controlled trial.

Time of study: not stated.


Participants23 persons with uncomplicated P. falciparum malaria, parasitaemia between 1-5 per 1000 rbc.

Age 5 to 12 years, sex not stated.

Exclusion criteria: antimalarial drugs, urine with quinoline and sulfonamide drugs, other diseases, hematocrit </=20%, inability to take oral medication.


Interventions1. MSP

MQ 20 mg/kg; S 40 mg base/kg; P 2 mg/kg; single dose.

2. MSP + PQ

As above plus PQ 0.75 mg/kg single dose.

MSP+PQ crushed and mixed with 30 ml syrup (83% dextrose).


Outcomes1. Gametocyte clearance time (days) (assessed twice daily until negative, then once daily, by blood slide).

2. Adverse drug reactions, assessed once daily in first week then once a week.

3. Parasite clearance time (hrs).

4. Fever clearance time (hrs).

5. Cure rate.


NotesThose who vomited within 3 hr of Rx were excluded - this is a post randomization exclusion.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo information given.

Allocation concealment (selection bias)Unclear riskNo information given.

Incomplete outcome data (attrition bias)
All outcomes
High riskOutcomes only reported for 18 of the 23 participants.

Selective reporting (reporting bias)Unclear riskNo information given.

Other biasHigh riskThose who vomited within 3 hr of Rx were excluded- this is a post randomization exclusion.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot stated.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated.

Smithuis 2010

MethodsStudy design: Individually randomized controlled trial (5 comparisons - 10 arms).

Follow up: Patients were asked to return weekly for 9 weeks for assessment and at any other time they were unwell.

Dates: Dec 2008 to March 2009.


ParticipantsNumber: 808 persons attending clinics in Myanmar.

Inclusion criteria: Age > 6 months, weight > 5kg, P. falciparum mono-infection 500 to 200,000 parasites/µL or co-infection with P. vivax, informed consent.

Exclusion criteria: Pregnancy, signs of severe malaria, severe malnutrition, history of hypersensitivity to any of the study drugs, severe malnutrition, concomitant febrile illness, history of psychiatric disorder, a full course of MQ in the previous 9 weeks or any other antimalarial in the previous 48 hrs.


InterventionsEach of the five study arms was divided into two where one half also received a one-off dose of 0.75 mg/kg PQ on day 1.

Groups:

1+2. AS plus amodiaquine, fixed dose combination: 25 mg/67.5 mg or 50 mg/135 mg or 100 mg/270 mg tablets.

  • AS 4 mg/kg once daily for 3 days
  • AQ 10.8 mg base/kg once daily for 3 days


3+4. Artemether-lumefantrine, fixed dose combination: 20 mg/120 mg tablets.

  • A 3.3 mg/kg in two divided doses each day for 3 days
  • L 19.8 mg/kg in two divided doses each day for 3 days
  • Advised to consume fatty food or breast feed before each dose


5+6. ASplus MQ, fixed dose combination: 25 mg/55 mg or 100 mg/220 mg tablets (artesunate: Guilin, Lariam: Hoffman-La Roche)

  • AS 4 mg/kg once daily for 3 days
  • MQ 8.8 mg/kg once daily for 3 days


7+8. Artesunate plus MQ, loose combination (artesunate: Guilin, Lariam: Hoffman-La Roche)

  • AS 4 mg/kg once daily for 3 days
  • MQ 25 mg base/kg as a single dose on day 1 (reported as day 0)


9+10. Dihydroartemisinin-piperaquine, fixed-dose combination: 40 mg/320 mg or 20 mg/160 mg tablets (Artekin: Holleykin)

  • DHA 2.5 mg/kg once daily for 3 days
  • P 20 mg/kg once daily for 3 days


First dose supervised, all others unsupervised.


Outcomes
  1. Recurrent parasitaemia at day 15, 29, 43 and 64 (reported as days 14, 28, 42 and 63).
  2. Treatment failure due to P. falciparum.
  3. Gametocytaemia prevalence.
  4. Person-gametocyte weeks.
  5. Haemoglobin on days 1 and 64.
  6. Adverse events (monitoring not described).


NotesFunding: Médecins sans Frontières (Holland).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk'After patients were screened and enrolled in the study, they were stratified prospectively into three age groups (1-4 years, 5-14 years and older than 14 years). Patients were randomly assigned in equal numbers to receive one of the five different treatments. They were then randomly assigned either a single dose of PQ ... or not.'

Allocation concealment (selection bias)Low risk'Treatment allocations were put in sealed envelopes in blocks of 50 for each age group, and random assignment was achieved by patients drawing an envelope from a box after enrollment. When the box was empty, another 50 envelopes were added.'

Incomplete outcome data (attrition bias)
All outcomes
Low riskAttrition is low in absolute numbers and unlikely to have introduced significant bias.

Selective reporting (reporting bias)Low riskNo evidence of selective reporting.

Other biasLow riskNo indication of other bias.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial for patients and medical staff.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskMicroscopists were blinded.

Vasquez 2009

MethodsIndividually randomized controlled trial.

Time of study: Apr 2007 to Feb 2008.


Participants50 persons with uncomplicated P. falciparum diagnosis by thick blood slide, 150-50,000 parasites per μL

Age 1 yr and over, both sexes.

Exclusion criteria: pregnant, mixed infection, danger signs and complications, allergy to antimalarials, serious illness at time or presentation, antimalaria treatment in last 72 hrs, MQ in last 4 weeks.


Interventions1. AS+MQ

Age 1-6: AS 50 mg on days 1, 2, 3 (reported as 0, 1, 2); MQ 250 mg on day 2.

Age 7-13: AS 100 mg on days 1, 2, 3, MQ 250 mg on days 1, 2, 3.

Age > 13: AS 200 mg on days 1, 2, 3, MQ 500 mg on days 1, 2, 3.

2. AS+MQ+PQ

As above plus PQ:

Age 1-6: 0.3-0.6 mg/kg day 3 (reported as day 2).

Age 7-13: 22.5 mg/kg day 3.

Age > 13: 45 mg day 3.


OutcomesAssessed on days 2, 3, 4, 8, 15, 22, 29, 36, 43.

1. Clinical recurrence.

2. Parasitemia prevalence.

3. Parasite density.

4. Fever resolution.

5. Prevalence of gametocytes.

6. Density of gametocytes.

7. Adverse effects.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskSeems to be alternate allocation following order of arrival ("segun el orden de llegada").

Allocation concealment (selection bias)Unclear riskNot clear.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo dropouts noted.

Selective reporting (reporting bias)Low riskNo evidence of bias.

Other biasLow riskNo suggestion of other bias.

Blinding of participants and personnel (performance bias)
All outcomes
High riskSeems not be blinded ("con determination no ciega del efecto en grupos iguales").

Blinding of outcome assessment (detection bias)
All outcomes
High risk

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Arango 2012Not randomized.

Baird 2002Outcome is cure of asexual infection. No gametocyte outcomes.

Bunnag 1980Comparison of SP plus either 5 day PQ 15 mg, single dose PQ 30 mg or single dose PQ 45 mg in patients with and without gametocytes at presentation. No regimen without PQ. Authors state they will do further studies, including transmission. No difference in gametocyte outcomes between regimens and gametocytes persisted for up to 21 days.

Che 1987No mention of randomization. No valid comparison group (pyronaridine phosphate plus sulfadoxine plus PQ versus pyronaridine phosphate only).

Clyde 1971Prophylactic efficacy trial of drug regimens, some including PQ, against sporozoite challenge. Gametocyticidal effect of single dose 45 mg PQ tested in 7 P. falciparum gametocyte carriers but no comparison group. Gametocytes cleared in 4 to 9 days in these persons. Inhibition of oocyst development despite presence of gametocytes after PQ treatment also demonstrated in 2 persons but with no controls.

da Silva 1984Trial of treatment regimens, some including PQ, for P. vivax and P. falciparum.

Doi 1989Non-randomized community observational study.

Giao 2004No gametocyte outcomes.

Gogtay 1999Compares QN+PQ against QN+bulaquine. Not a relevant comparison.

Gogtay 2004Compares QN+Doxycyline+PQ against QN+doxycycline+bulaquine. Not a relevant comparison.

Gogtay 2006No appropriate control group. Seems to be part of a CQ+PQ versus CoArtem trial but only reports results from one arm.

Hii 1987Controlled before and after study comparing SP+PQ+ITN versus SP+PQ only. Only one cluster per arm and no group without PQ.

Huang 2001No gametocyte outcomes.

Kaneko 1989Non-randomized community trial comparing SP+PQ in one village with SP only in another. Only one cluster per arm.

Karbwang 1992Pharmacokinetic study; no gametocyte outcomes or control group.

Santana 2007Study of 14 day regimen of 15 mg PQ. Some P. falciparum cases were included but study did not distinguish between the patients with P. falciparum and P. vivax . Study was a comparison of association between methaemoglobinaemia after 14 day PQ in persons with and without G6PD deficiency.

Shekalaghe 2010Randomized comparison of anaemia after SP+AS+PQ versus placebo. Children with haemoglobin < 8g were excluded from receiving PQ.

Shekalaghe 2011Trial was a comparison of SP+AS+PQ versus placebo. No comparison of groups with and without PQ.

Suputtamongkol 2003Comparison of MQ+AS versus MQ+PQ. No appropriate control group.

Tangpukdee 2008Comparison of Artequick (contains PQ) with MQ+AS. No appropriate control group and no gametocyte outcomes.

 
Characteristics of studies awaiting assessment [ordered by study ID]
Ishii 2009

MethodsUnclear

ParticipantsResidents of trial villages in Solomon Islands (number not given)

InterventionsTesting of clinical malaria patients for G6PD and addition of single dose PQ to a partner drug if appropriate

OutcomesVillage prevalence of malaria

Notes

 
Characteristics of ongoing studies [ordered by study ID]
Eziefula ongoing

Trial name or titleEvaluation of the efficacy and safety of PQ in uncomplicated falciparum malaria in Uganda

MethodsIndividually randomized trial

ParticipantsInclusion criteria: >/= 1 yr-10 years; both genders; 38 ° C (tympanic) or history of fever in last 24 hours; P. falciparum parasitaemia < 500,000/µL; normal G6PD enzyme function

Exclusion criteria: enrolled in another study; evidence of severe illness/danger signs; known allergy to medications; haemoglobin < 8 g/dL; started menstruation; pregnant or breastfeeding; PQ taken in last 4 weeks; blood transfusion in last 90 days; Non-falciparum malaria co-infection.

InterventionsPQ

OutcomesPrimary:

1. Fall in Hb from enrollment to day 28.

2. Mean days to gametocyte clearance.

Secondary:

1. Follow-up day of Hb nadir.

2. GI symptoms.

3. Serious adverse events.

4. AUC of gametocyte density during 14 days of follow-up.

5. Need for blood transfusion.

Starting dateDecember 2011

Contact informationAlice Eziefula; chi.eziefula@gmail.com

Notes

 
Comparison 1. GIVEN WITH CQ, OR CQ+SP

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Participants with gametocytes3Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Day 4
1139Risk Ratio (M-H, Fixed, 95% CI)0.99 [0.69, 1.42]

    1.2 Day 8
3303Risk Ratio (M-H, Fixed, 95% CI)0.45 [0.34, 0.60]

    1.3 Day 12
1120Risk Ratio (M-H, Fixed, 95% CI)0.07 [0.01, 0.49]

    1.4 Day 15
3270Risk Ratio (M-H, Fixed, 95% CI)0.12 [0.05, 0.26]

    1.5 Day 22
3227Risk Ratio (M-H, Fixed, 95% CI)0.09 [0.03, 0.31]

    1.6 Day 29
3201Risk Ratio (M-H, Fixed, 95% CI)0.29 [0.10, 0.86]

    1.7 Day 36
119Risk Ratio (M-H, Fixed, 95% CI)0.6 [0.13, 2.82]

    1.8 Day 43
112Risk Ratio (M-H, Fixed, 95% CI)0.71 [0.06, 8.90]

 2 Participants with asexual parasites (treatment failure day 29)1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 Not PCR adjusted
1135Risk Ratio (M-H, Fixed, 95% CI)0.90 [0.75, 1.09]

    2.2 PCR adjusted
1135Risk Ratio (M-H, Fixed, 95% CI)0.87 [0.65, 1.16]

 
Comparison 2. GIVEN WITH SP

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Participants with gametocytes1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Day 2
184Risk Ratio (M-H, Fixed, 95% CI)0.61 [0.32, 1.16]

    1.2 Day 3
183Risk Ratio (M-H, Fixed, 95% CI)0.75 [0.45, 1.27]

    1.3 Day 4
182Risk Ratio (M-H, Fixed, 95% CI)0.60 [0.35, 1.04]

    1.4 Day 8
179Risk Ratio (M-H, Fixed, 95% CI)0.77 [0.60, 1.01]

    1.5 Day 15
173Risk Ratio (M-H, Fixed, 95% CI)0.68 [0.48, 0.95]

    1.6 Day 22
173Risk Ratio (M-H, Fixed, 95% CI)0.51 [0.34, 0.78]

    1.7 Day 29
166Risk Ratio (M-H, Fixed, 95% CI)0.37 [0.19, 0.72]

    1.8 Day 36
162Risk Ratio (M-H, Fixed, 95% CI)0.30 [0.09, 0.97]

    1.9 Day 43
161Risk Ratio (M-H, Fixed, 95% CI)0.14 [0.01, 2.47]

 2 Participants with asexual parasites (treatment failure day 29)1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 Not PCR adjusted
174Risk Ratio (M-H, Fixed, 95% CI)1.55 [0.45, 5.33]

    2.2 PCR adjusted
174Risk Ratio (M-H, Fixed, 95% CI)1.55 [0.45, 5.33]

 
Comparison 3. GIVEN WITH MQ, OR MQ+SP

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Participants infectious1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Day 5
118Risk Ratio (M-H, Fixed, 95% CI)0.05 [0.00, 0.79]

    1.2 Day 8
118Risk Ratio (M-H, Fixed, 95% CI)0.06 [0.00, 0.89]

    1.3 Day 15
118Risk Ratio (M-H, Fixed, 95% CI)0.11 [0.01, 1.80]

    1.4 Day 22
118Risk Ratio (M-H, Fixed, 95% CI)0.33 [0.02, 7.24]

 2 Mosquitoes infected1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 Day 5
1161Risk Ratio (M-H, Fixed, 95% CI)0.01 [5.49, 0.14]

    2.2 Day 8
1152Risk Ratio (M-H, Fixed, 95% CI)0.01 [9.17, 0.23]

    2.3 Day 15
1168Risk Ratio (M-H, Fixed, 95% CI)0.04 [0.00, 0.71]

    2.4 Day 22
1152Risk Ratio (M-H, Fixed, 95% CI)0.07 [0.00, 1.18]

 3 Gametocyte clearance time (days)118Mean Difference (IV, Fixed, 95% CI)-14.90 [-18.18, -11.62]

 4 Asexual parasite clearance time (hrs)118Mean Difference (IV, Fixed, 95% CI)-4.0 [-30.07, 22.07]

 
Comparison 4. GIVEN WITH QN

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Participants with gametocytes2Risk Ratio (M-H, Random, 95% CI)Subtotals only

    1.1 Day 8
1126Risk Ratio (M-H, Random, 95% CI)1.17 [0.49, 2.78]

    1.2 Day 15
143Risk Ratio (M-H, Random, 95% CI)0.30 [0.07, 1.28]

    1.3 Day 22
143Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    1.4 Day 29
143Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 2 Asexual parasite clearance time (hours)1126Mean Difference (IV, Fixed, 95% CI)-1.44 [-9.76, 6.88]

 
Comparison 5. GIVEN WITH AS, OR WITH ACTs

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Participants with gametocytes (microscopy)4Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Day 4
149Risk Ratio (M-H, Fixed, 95% CI)0.48 [0.10, 2.38]

    1.2 Day 8
41006Risk Ratio (M-H, Fixed, 95% CI)0.15 [0.09, 0.24]

    1.3 Day 15
3923Risk Ratio (M-H, Fixed, 95% CI)0.10 [0.04, 0.22]

    1.4 Day 22
2776Risk Ratio (M-H, Fixed, 95% CI)0.06 [0.01, 0.24]

    1.5 Day 29
3873Risk Ratio (M-H, Fixed, 95% CI)0.15 [0.05, 0.51]

    1.6 Day 36
2766Risk Ratio (M-H, Fixed, 95% CI)0.21 [0.01, 4.32]

    1.7 Day 43
3847Risk Ratio (M-H, Fixed, 95% CI)0.41 [0.04, 3.85]

 2 Participants with gametocytes (PCR)2Risk Ratio (M-H, Random, 95% CI)Totals not selected

    2.1 Day 8
2Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    2.2 Day 15
2Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    2.3 Day 29
1Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    2.4 Day 43
1Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

 3 Log(10) AUC of gametocyte density over time d1-431106Mean Difference (IV, Fixed, 95% CI)-0.88 [-1.32, -0.43]

 4 Participants with asexual parasites (PCR)2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    4.1 Day 8
194Risk Ratio (M-H, Fixed, 95% CI)1.28 [0.30, 5.40]

    4.2 Day 15
2198Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.23, 4.15]

    4.3 Day 29
1106Risk Ratio (M-H, Fixed, 95% CI)0.75 [0.35, 1.63]

    4.4 Day 43
1106Risk Ratio (M-H, Fixed, 95% CI)1.13 [0.63, 2.03]

 5 Asexual parasite clearance time150Mean Difference (IV, Fixed, 95% CI)-6.0 [-16.31, 4.31]

 6 Haemoglobin concentration1Mean Difference (IV, Fixed, 95% CI)Subtotals only

    6.1 Day 8
1105Mean Difference (IV, Fixed, 95% CI)-0.39 [1.00, 0.22]

    6.2 Day 15
1106Mean Difference (IV, Fixed, 95% CI)-0.04 [-0.53, 0.44]

    6.3 Day 29
1105Mean Difference (IV, Fixed, 95% CI)0.26 [-0.25, 0.77]

    6.4 Day 43
1103Mean Difference (IV, Fixed, 95% CI)-0.05 [-0.61, 0.52]

 7 % change in haemoglobin concentration1Mean Difference (IV, Fixed, 95% CI)Subtotals only

    7.1 Day 8
1101Mean Difference (IV, Fixed, 95% CI)-0.06 [-0.11, -0.02]

    7.2 Day 15
1102Mean Difference (IV, Fixed, 95% CI)-0.03 [-0.08, 0.02]

    7.3 Day 29
1101Mean Difference (IV, Fixed, 95% CI)0.00 [-0.06, 0.07]

    7.4 Day 43
199Mean Difference (IV, Fixed, 95% CI)-0.03 [-0.10, 0.04]

 
Comparison 6. ALL TREATMENTS COMBINED

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Participants with gametocytes at day 8 (microscopy)71322Risk Ratio (M-H, Fixed, 95% CI)0.36 [0.30, 0.43]

    1.1 Non-artemisinin-based partner drug
4446Risk Ratio (M-H, Fixed, 95% CI)0.62 [0.51, 0.76]

    1.2 Artemisinin-based partner drug
4876Risk Ratio (M-H, Fixed, 95% CI)0.12 [0.08, 0.20]

 
Summary of findings for the main comparison. Primaquine for preventing infectiousness with ACT treatments

Primaquine for preventing infectiousness with ACT treatments

Patient or population: patients with symptomatic malaria
Settings: endemic malarial areas
Intervention: primaquine

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlPrimaquine

Malaria incidence, prevalence or EIR - not measured0 studies

People infectious to mosquitoes - not measured0 studies

Gametocytaemia
Log(10) area under curve of density over time. Scale from: 0 to 100.
Follow-up: 43 days
Relative decrease ranged from 26.1 to 87.5%907
(2 studies1)
⊕⊕⊕⊝
moderate2

Participants with gametocytes
Microscopy
Follow-up: 8 days
242 per 100036 per 1000
(22 to 58)
RR 0.15
(0.09 to 0.24)
1006
(4 studies3)
⊕⊕⊕⊝
moderate4,5

Mean percent change in haemoglobin6
Follow-up: 28 days
The mean percent change in haemoglobin in the control groups was
0.03 % change
The mean percent change in haemoglobin in the intervention groups was
0.06 lower
(0.11 to 0.02 lower)
101
(1 study)
⊕⊝⊝⊝
very low7,8

*The basis for the assumed risk (eg the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Includes two trials with six comparisons. We excluded one trial as high risk of bias (Vasquez 2009) due to small sample size and large difference in baseline gametocyte count in the two groups
2 Downgraded by 1 for imprecision: wide range of estimates in two trials (six comparisons)
3 Includes four trials, with eight comparisons: one trial included five separate comparisons with AS-AQ, DHAP, AS-MQ, and AL (Smithuis 2010)
4 No serious risk of bias: two studies did not conceal allocation but these trials report smaller effect sizes.
5 Downgraded by 1 for indirectness: the reduction in gametocytes has only been demonstrated in Myanmar. In the three other studies gametocyte carriage was low in both groups on day 8, and no differences were detected.
6 Shekalaghe 2007 reported relative decrease in haemoglobin against baseline in both groups at day 8, 15, 29 and 43 in all participants irrespective of G6PD status. The comparison between those receiving primaquine and those not was significant at day 8 and these results are presented in the SOF. It was not significantly different at the other time points.
7 Downgraded by 2 for indirectness:the percentage of people with large drops in haemoglobin, not the mean change in the population, is the important safety outcome..
8 Downgraded by 1 for imprecision: only one study in 101 people to detect an adverse effect that, if present, is likely to be relatively uncommon.
 
Summary of findings 2. Primaquine for preventing infectiousness with non-ACT malaria treatment

Primaquine for preventing infectiousness with non-ACT malaria treatment

Patient or population: patients with symptomatic malaria
Settings: endemic malarial areas
Intervention: primaquine

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlPrimaquine

Malaria incidence, prevalence or EIR - not measured-

People infectious to mosquitoes (day 8)
Follow-up: 22 days
100 per 1005 per 100
(0 to 80)
RR 0.05
(0 to 0.8)
18
(1 study)
⊕⊕⊝⊝
low1,2

Gametocytaemia
Log(10) area under curve of density over time. Scale from: 0 to 100.
Follow-up: 43 days
Relative decrease ranged from 24.3 to 27.1%219
(1 study)
⊕⊕⊕⊝
moderate3

Participants with gametocytes
Microscopy
Follow-up: 8 days
Study populationRR 0.62
(0.51 to 0.76)
446
(4 studies)
⊕⊕⊕⊝
moderate4

619 per 1000384 per 1000
(315 to 470)

Evidence of haemolysis0 studies






*The basis for the assumed risk (eg the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Downgraded by 1 for risk of bias: this study did not conceal allocation, and no method of allocation is described
2 Downgraded by 1 for imprecision: this single study is underpowered which limits the confidence in the results
3 Downgraded by 1 for indirectness: one study, with two comparisons, and thus only two estimates of AUC (24.3% and 27.1% reduction)
4 Downgraded by 1 for risk of bias: one study with two comparisons is good quality, but all the other three studies have methodological deficiencies
 
Table 1. G6PD status, partner drugs, and PQ dose and treatment schedule

ComparatorTrialComparisonPlaceG6PD statusParasite speciesPartner drugPQ day(s)

*
PQ dose per day

Non-artemisinin (CQ or

CQ+SP)
Kamtekar 2004aIndia (Mumbai)Not screenedPf only CQ days 1-3 or

CQ days 1-3 + SP day 1 
day 445 mg (˜0.75 mg/kg)

Khoo 1981Malaysia (Sabah)Only deficient

(method: Brewer's methaemoglobin

reduction test)
Pf, Pv or mixedCQ days 1-3days 1-325 mg (˜0.42 mg/kg)

Kolaczinski 2012aPakistanNot reportedPf onlyCQ days 1-3day 30.5 mg/kg

Ledermann 2006aIndonesia (Central Java)Only non-deficient

(method: semiquantitative glucose-6-phosphate dehydrogenase (G6PD) assay)
Pf only CQ days 1-3 + SP day 1day 145 mg (˜0.75 mg/kg)

Ledermann 2006bIndonesia (Central Java)Only non-deficient

(method: semiquantitative glucose-6-phosphate dehydrogenase (G6PD) assay)
Pf only CQ days 1-3 + SP day 1day 345 mg

(˜0.75 mg/kg)

Non-artemisinin (SP)Kolaczinski 2012bPakistanNot reportedPf onlySP day 1day 10.5 mg/kg

Non-artemisinin (MQ or MQ+SP)Chen 1994China (Hainan province)Not reportedPf only MQ day 1day 145 mg (˜0.75 mg/kg)

Singhasivanon 1994Thailand (Bangkok)Not reportedPf only MQ+SP fixed day 1day 10.75 mg/kg

Non-artemisinin (QN)Kamtekar 2004bIndia (Mumbai)Not screenedPf onlyQN iv days 1-2 and orally days 1-7day 845 mg (˜0.75 mg/kg)

Pukrittayakamee 2004aThailandPatients with G6PD deficiency were excluded from getting PQ

(method not reported)
Pf only QN days 1-7days 1-70.25 mg base/kg

Pukrittayakamee 2004bThailandPatients with G6PD deficiency were excluded from getting PQ

(method not reported)
Pf only QN days 1-7days 1-70.5 mg base/kg

Artemisinin-

based

AS or ACT
El-Sayed 2007Sudan

(east)
Not reportedPf only AS+SP days 1-3day 40.75 mg/kg

Pukrittayakamee 2004cThailandPatients with G6PD deficiency were excluded from getting PQ

(method not reported)
Pf only AS days 1-7days 1-70.5 mg base/kg

Shekalaghe 2007Tanzania (North east)Screened and all included

(method: detection of single nucleotide polymorphisms in the human G6PD gene (G202A, A376G) by a simple high throughput PCR using sequence specific oligonucleotide probes (SSOPs) and ELISA testing)
Pf only AS+SP days 1-3day 40.75 mg/kg

Smithuis 2010aMyanmar (3 states) Not screenedPf or mixedAS+AQ days 1-3day 10.75 mg/kg

Smithuis 2010bMyanmar (3 states)Not screenedPf or mixedAL days 1-3day 10.75 mg/kg

Smithuis 2010cMyanmar (3 states)Not screenedPf or mixedAS+MQ fixed dose days 1-3day 10.75 mg/kg

Smithuis 2010dMyanmar (3 states)Not screenedPf or mixedAS days 1-3 + MQ day 1 looseday 10.75 mg/kg

Smithuis 2010eMyanmar (3 states)Not screenedPf or mixedDHAP days 1-3day 10.75 mg/kg

Vasquez 2009Colombia (Antioquia)Not reportedPf only AS+MQ days 1-3  (MQ only on day 2 for children < 6)day 345 mg (˜0.75 mg/kg)

 * first day of any treatment = day 1
Pf = P. falciparum; Pv = P. vivax
 
Table 2. AUC of gametocyte density over time, days 1 to 29 after treatment

Partner

drug

type
TrialPartner drugAUC

with PQ

days

1-29
AUC

without PQ

days

1-29
% reduction

AUC

days

1-29
log(10)

AUC

with PQ

days

1-29
log(10)

AUC

without PQ

days

1-29
% reduction

log(10)

AUC

days

1-29

Non-artemisinin-

based
Kolaczinski 2012CQ 732.988777.2491.7 2.873.9427.3

Kolaczinski 2012SP 2111.5512847.3783.6 3.324.1119.1

Artemisinin-

based
Shekalaghe 2007AS+SP40.3087.6954.01.611.9417.4

Smithuis 2010AS+AQ141.08649.4678.32.152.8123.6

Smithuis 2010AL197.57318.2337.92.32.58.3

Smithuis 2010AS+MQ fixed240.79535.4055.02.382.7312.7

Smithuis 2010AS+MQ loose183.51321.9643.02.262.519.7

Smithuis 2010DHAP307.14952.9367.82.492.9816.5

Vasquez 2009AS+MQ526.40349.04-50.82.722.54-7.0

 
Table 3. AUC of gametocyte density over time, days 1 to 43 after treatment

Partner

drug

type
TrialPartner drugAUC

with PQ

days

1-43
AUC

without PQ

days

1-43
% reduction

AUC

days

1-43
log(10)

AUC

with PQ

days

1-43
log(10)

AUC

without PQ

days

1-43
% reduction

log(10)

AUC

days

1-43

Non-artemisinin-

based
Kolaczinski 2012CQ 71.02279.1374.6 1.852.4524.3

Kolaczinski 2012SP 85.47445.6580.8 1.932.6527.1

Artemisinin-

based
Shekalaghe 2007AS+SP1.163.2264.10.060.5187.5

Smithuis 2010AS+AQ3.3619.2982.60.531.2959.1

Smithuis 2010AL4.708.1242.10.670.9126.1

Smithuis 2010AS+MQ fixed5.7312.7555.00.761.1131.4

Smithuis 2010AS+MQ loose4.377.7443.50.640.8927.9

Smithuis 2010DHAP7.3825.4971.10.871.4138.3

Vasquez 2009AS+MQ12.538.87-41.31.100.95-15.8