Study · Randomized controlled trial · n = 40 · 2018

3 results

Efficacy and safety of primaquine and methylene blue for prevention of Plasmodium falciparum transmission in Mali: a phase 2, single-blind, randomised controlled trial.

Dicko A, Roh ME, Diawara H, Mahamar A, Soumare HM, Lanke K, Bradley J, Sanogo K, Kone DT, Diarra K, Keita S, Issiaka D and 11 more

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Traore SF, McCulloch C, Stone WJR, Hwang J, Müller O, Brown JM, Srinivasan V, Drakeley C, Gosling R, Chen I, Bousema T

The Lancet. Infectious diseases6 Feb 2018Cited by 88 (Europe PMC)

PMID29422384PMCIDPMC5968371DOI10.1016/s1473-3099(18)30044-6PepBankPUB-29422384

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Summary

BackgroundPrimaquine and methylene blue are gametocytocidal compounds that could prevent Plasmodium falciparum transmission to mosquitoes. We aimed to assess the efficacy and safety of primaquine and methylene blue in preventing human to mosquito transmission of P falciparum among glucose-6-phosphate dehydrogenase (G6PD)-normal, gametocytaemic male participants.MethodsThis was a phase 2, single-blind, randomised controlled trial done at the Clinical Research Centre of the Malaria Research and Training Centre (MRTC) of the University of Bamako (Bamako, Mali). We enrolled male participants aged 5-50 years with asymptomatic P falciparum malaria. G6PD-normal participants with gametocytes detected by blood smear were randomised 1:1:1:1 in block sizes of eight, using a sealed-envelope design, to receive either sulfadoxine-pyrimethamine and amodiaquine, sulfadoxine-pyrimethamine and amodiaquine plus a single dose of 0·25 mg/kg primaquine, dihydroartemisinin-piperaquine, or dihydroartemisinin-piperaquine plus 15 mg/kg per day methylene blue for 3 days. Laboratory staff, investigators, and insectary technicians were masked to the treatment group and gametocyte density of study participants. The study pharmacist and treating physician were not masked. Participants could request unmasking. The primary efficacy endpoint, analysed in all infected patients with at least one infectivity measure before and after treatment, was median within-person percentage change in mosquito infectivity 2 and 7 days after treatment, assessed by membrane feeding. This study is registered with ClinicalTrials.gov, number NCT02831023.FindingsBetween June 27, 2016, and Nov 1, 2016, 80 participants were enrolled and assigned to the sulfadoxine-pyrimethamine and amodiaquine (n=20), sulfadoxine-pyrimethamine and amodiaquine plus primaquine (n=20), dihydroartemisinin-piperaquine (n=20), or dihydroartemisinin-piperaquine plus methylene blue (n=20) groups. Among participants infectious at baseline (54 [68%] of 80), those in the sulfadoxine-pyrimethamine and amodiaquine plus primaquine group (n=19) had a median 100% (IQR 100 to 100) within-person reduction in mosquito infectivity on day 2, a larger reduction than was noted with sulfadoxine-pyrimethamine and amodiaquine alone (n=12; -10·2%, IQR -143·9 to 56·6; p<0·0001). The dihydroartemisinin-piperaquine plus methylene blue (n=11) group had a median 100% (IQR 100 to 100) within-person reduction in mosquito infectivity on day 2, a larger reduction than was noted with dihydroartemisinin-piperaquine alone (n=12; -6·0%, IQR -126·1 to 86·9; p<0·0001). Haemoglobin changes were similar between gametocytocidal arms and their respective controls. After exclusion of blue urine, adverse events were similar across all groups (59 [74%] of 80 participants had 162 adverse events overall, 145 [90%] of which were mild).InterpretationAdding a single dose of 0·25 mg/kg primaquine to sulfadoxine-pyrimethamine and amodiaquine or 3 days of 15 mg/kg per day methylene blue to dihydroartemisinin-piperaquine was highly efficacious for preventing P falciparum transmission. Both primaquine and methylene blue were well tolerated.FundingBill & Melinda Gates Foundation, European Research Council.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

2 results from studies that gave the peptide. 2 results from people.

01HumanRandomized controlled trialEfficacy outcome
In infectious male malaria participants, adding methylene blue reduced mosquito infectivity more than dihydroartemisinin-piperaquine alone on day 2.
In plain wordsIn infectious male malaria participants, adding methylene blue reduced mosquito infectivity more than dihydroartemisinin-piperaquine alone on day 2.
Peptide
Methylene blue
Outcome
DecreaseMosquito infectivity reduction at day 2
Study
n = 23
Comparator
Dihydroartemisinin-piperaquine alone
Analysis
Primary
Outcome group
Infection and antimicrobial activity · Infection
Studied dose
15 mg/kg per day · 3 daysAs given in this study (human).
Measurements
Median within-person infectivity reduction
100%
MB combination
Median within-person infectivity reduction
−6%
control
Source sentences
Summary
The dihydroartemisinin-piperaquine plus methylene blue (n=11) group had a median 100% (IQR 100 to 100) within-person reduction in mosquito infectivity on day 2, a larger reduction than was noted with dihydroartemisinin-piperaquine alone (n=12; -6·0%, IQR -126·1 to 86·9; p<0·0001).
2 context sentences(design, population, supporting numbers)
Summary · context
We enrolled male participants aged 5-50 years with asymptomatic P falciparum malaria.
Summary · context
dihydroartemisinin-piperaquine, or dihydroartemisinin-piperaquine plus 15 mg/kg per day methylene blue for 3 days.
Show in the study text Report a problemFND-2942238401
02HumanRandomized controlled trialSafety outcome
Haemoglobin changes were similar with dihydroartemisinin-piperaquine plus methylene blue and dihydroartemisinin-piperaquine alone in male malaria participants.
In plain wordsIn male malaria participants, haemoglobin changes were similar with dihydroartemisinin-piperaquine plus methylene blue and dihydroartemisinin-piperaquine alone.
Peptide
Methylene blue
Outcome
No significant changeHaemoglobin change
Study
n = 40
Comparator
Dihydroartemisinin-piperaquine alone
Outcome group
Adverse events · Whole body
Studied dose
15 mg/kg per day · 3 daysAs given in this study (human).
Source sentences
Summary
Haemoglobin changes were similar between gametocytocidal arms and their respective controls.
2 context sentences(design, population, supporting numbers)
Summary · context
We enrolled male participants aged 5-50 years with asymptomatic P falciparum malaria.
Summary · context
dihydroartemisinin-piperaquine, or dihydroartemisinin-piperaquine plus 15 mg/kg per day methylene blue for 3 days.
Show in the study text Report a problemFND-2942238402

Studies that did not test the peptide alone1

In this study, Methylene blue was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Methylene blue.

03HumanNot a test of Methylene blue aloneRandomized controlled trialSafety outcome
After excluding blue urine, adverse events were similar across all malaria treatment groups, including dihydroartemisinin-piperaquine plus methylene blue.
In plain wordsExcluding blue urine, adverse events were similar across all malaria treatment groups, including dihydroartemisinin-piperaquine plus methylene blue.
Peptide
Methylene blue
Outcome
No significant changeAdverse events excluding blue urine
Study
n = 80
Comparator
Other trial regimens
Outcome group
Adverse events · Whole body
Measurements
Participants with adverse events
59 participants
All treatment groups, excluding blue urine
Adverse events
162 events
All treatment groups, excluding blue urine
Mild adverse events
145 events
All treatment groups, excluding blue urine
Source sentences
Summary
After exclusion of blue urine, adverse events were similar across all groups (59 [74%] of 80 participants had 162 adverse events overall, 145 [90%] of which were mild).
2 context sentences(design, population, supporting numbers)
Summary · context
We enrolled male participants aged 5-50 years with asymptomatic P falciparum malaria.
Summary · context
dihydroartemisinin-piperaquine, or dihydroartemisinin-piperaquine plus 15 mg/kg per day methylene blue for 3 days.
In this study, Methylene blue was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Methylene blue.
Show in the study text Report a problemFND-2942238403

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 2NCT02831023

Phase 2 Efficacy Study of Primaquine and Methylene Blue

University of California, San Franciscon = 80Jul 2016 to Jan 2017

Malaria

Trial page ClinicalTrials.govUpdated 11 Jan 2017

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:46 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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