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BMJ Clinical Evidence Jul 2010Malaria transmission occurs most frequently in environments with humidity greater than 60% and ambient temperature of 25 °C to 30 °C. Risks increase with longer... (Review)
Review
INTRODUCTION
Malaria transmission occurs most frequently in environments with humidity greater than 60% and ambient temperature of 25 °C to 30 °C. Risks increase with longer visits and depend on activity. Infection can follow a single mosquito bite. Incubation is usually 10 to 14 days but can be up to 18 months depending on the strain of parasite.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug preventive interventions in non-pregnant adult travellers? What are the effects of drug prophylaxis in non-pregnant adult travellers? What are the effects of antimalaria vaccines in adult and child travellers? What are the effects of antimalaria interventions in child travellers, pregnant travellers, and in airline pilots? We searched: Medline, Embase, The Cochrane Library, and other important databases up to November 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 79 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: aerosol insecticides, amodiaquine, air conditioning and electric fans, atovaquone-proguanil, biological control measures, chloroquine (alone or with proguanil), diethyltoluamide (DEET), dietary supplementation, doxycycline, electronic mosquito repellents, full-length and light-coloured clothing, insecticide-treated clothing/nets, mefloquine, mosquito coils and vapourising mats, primaquine, pyrimethamine-dapsone, pyrimethamine-sulfadoxine, smoke, topical (skin-applied) insect repellents, and vaccines.
Topics: Antimalarials; Bedding and Linens; Chloroquine; Humans; Malaria; Mefloquine; Primaquine; Travel
PubMed: 21418669
DOI: No ID Found -
BMJ Global Health Dec 2023The optimal dosing of primaquine to prevent relapsing malaria in South Asia remains unclear. We investigated the efficacy and safety of different primaquine regimens to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The optimal dosing of primaquine to prevent relapsing malaria in South Asia remains unclear. We investigated the efficacy and safety of different primaquine regimens to prevent relapse.
METHODS
A systematic review identified efficacy studies from South Asia published between 1 January 2000 and 23 August 2021. In a one-stage meta-analysis of available individual patient data, the cumulative risks of recurrence at day 42 and 180 were assessed by primaquine total mg/kg dose and duration. The risk of recurrence by day 180 was also determined in a two-stage meta-analysis. Patients with a >25% drop in haemoglobin to <70 g/L, or an absolute drop of >50 g/L between days 1 and 14 were categorised by daily mg/kg primaquine dose.
RESULTS
In 791 patients from 7 studies in the one-stage meta-analysis, the day 180 cumulative risk of recurrence was 61.1% (95% CI 42.2% to 80.4%; 201 patients; 25 recurrences) after treatment without primaquine, 28.8% (95% CI 8.2% to 74.1%; 398 patients; 4 recurrences) following low total (2 to <5 mg/kg) and 0% (96 patients; 0 recurrences) following high total dose primaquine (≥5 mg/kg). In the subsequent two-stage meta-analysis of nine studies (3529 patients), the pooled proportions of recurrences by day 180 were 12.1% (95% CI 7.7% to 17.2%), 2.3% (95% CI 0.3% to 5.4%) and 0.7% (95% CI 0% to 6.1%), respectively. No patients had a >25% drop in haemoglobin to <70 g/L.
CONCLUSIONS
Primaquine treatment led to a marked decrease in recurrences following low (~3.5 mg/kg) and high (~7 mg/kg) total doses, with no reported severe haemolytic events.
PROSPERO REGISTRATION NUMBER
CRD42022313730.
Topics: Humans; Primaquine; Malaria, Vivax; Antimalarials; Plasmodium vivax; Recurrence; Asia, Southern; Hemoglobins
PubMed: 38123228
DOI: 10.1136/bmjgh-2023-012675 -
BMJ Clinical Evidence Nov 2007Malaria transmission occurs most frequently in environments with humidity over 60% and ambient temperature of 25-30 degrees C. Risks increase with longer visits and... (Review)
Review
INTRODUCTION
Malaria transmission occurs most frequently in environments with humidity over 60% and ambient temperature of 25-30 degrees C. Risks increase with longer visits and depend on activity. Infection can follow a single mosquito bite. Incubation is usually 10-14 days but can be up to 18 months depending on the strain of parasite.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug preventive interventions in adult travellers? What are the effects of drug prophylaxis in adult travellers? What are the effects of antimalaria vaccines in travellers? What are the effects of antimalaria interventions in child travellers, pregnant travellers, and in airline pilots? We searched: Medline, Embase, The Cochrane Library and other important databases up to February 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 69 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: acoustic buzzers, aerosol insecticides, amodiaquine, air conditioning and electric fans, atovaquone-proguanil, biological control measures, chloroquine (alone or with proguanil), diethyltoluamide (DEET), doxycycline, full-length and light-coloured clothing, insecticide-treated clothing/nets, mefloquine, mosquito coils and vaporising mats, primaquine, pyrimethamine-dapsone, pyrimethamine-sulfadoxine, smoke, topical (skin-applied) insect repellents, and vaccines.
Topics: Administration, Oral; Animals; Antimalarials; Bedding and Linens; Chloroquine; Humans; Insect Repellents; Insecticides; Malaria; Travel
PubMed: 19450348
DOI: No ID Found -
BMC Medicine Sep 2022In 2012, the World Health Organization (WHO) recommended single low-dose (SLD, 0.25 mg/kg) primaquine to be added as a Plasmodium (P.) falciparum gametocytocide to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In 2012, the World Health Organization (WHO) recommended single low-dose (SLD, 0.25 mg/kg) primaquine to be added as a Plasmodium (P.) falciparum gametocytocide to artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing, to accelerate malaria elimination efforts and avoid the spread of artemisinin resistance. Uptake of this recommendation has been relatively slow primarily due to safety concerns.
METHODS
A systematic review and individual patient data (IPD) meta-analysis of single-dose (SD) primaquine studies for P. falciparum malaria were performed. Absolute and fractional changes in haemoglobin concentration within a week and adverse effects within 28 days of treatment initiation were characterised and compared between primaquine and no primaquine arms using random intercept models.
RESULTS
Data comprised 20 studies that enrolled 6406 participants, of whom 5129 (80.1%) had received a single target dose of primaquine ranging between 0.0625 and 0.75 mg/kg. There was no effect of primaquine in G6PD-normal participants on haemoglobin concentrations. However, among 194 G6PD-deficient African participants, a 0.25 mg/kg primaquine target dose resulted in an additional 0.53 g/dL (95% CI 0.17-0.89) reduction in haemoglobin concentration by day 7, with a 0.27 (95% CI 0.19-0.34) g/dL haemoglobin drop estimated for every 0.1 mg/kg increase in primaquine dose. Baseline haemoglobin, young age, and hyperparasitaemia were the main determinants of becoming anaemic (Hb < 10 g/dL), with the nadir observed on ACT day 2 or 3, regardless of G6PD status and exposure to primaquine. Time to recovery from anaemia took longer in young children and those with baseline anaemia or hyperparasitaemia. Serious adverse haematological events after primaquine were few (9/3, 113, 0.3%) and transitory. One blood transfusion was reported in the primaquine arms, and there were no primaquine-related deaths. In controlled studies, the proportions with either haematological or any serious adverse event were similar between primaquine and no primaquine arms.
CONCLUSIONS
Our results support the WHO recommendation to use 0.25 mg/kg of primaquine as a P. falciparum gametocytocide, including in G6PD-deficient individuals. Although primaquine is associated with a transient reduction in haemoglobin levels in G6PD-deficient individuals, haemoglobin levels at clinical presentation are the major determinants of anaemia in these patients.
TRIAL REGISTRATION
PROSPERO, CRD42019128185.
Topics: Antimalarials; Artemisinins; Child; Child, Preschool; Glucosephosphate Dehydrogenase; Hemoglobins; Humans; Malaria, Falciparum; Plasmodium falciparum; Primaquine
PubMed: 36109733
DOI: 10.1186/s12916-022-02504-z -
Malaria Journal Jul 2017Ethiopia is among countries with a high malaria burden. There are several studies that assessed the efficacy of anti-malarial agents in the country and this systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ethiopia is among countries with a high malaria burden. There are several studies that assessed the efficacy of anti-malarial agents in the country and this systematic review and meta-analysis was performed to obtain stronger evidence on treatment outcomes of malaria from the existing literature in Ethiopia.
METHODS
A systematic literature search using the preferred reporting items for systematic review and meta-analysis (PRISMA) statement was conducted on studies from Pubmed, Google Scholar, and ScienceDirect databases to identify published and unpublished literature. Comprehensive meta-analysis software was used to perform all meta-analyses. The Cochrane Q and the I were used to evaluate heterogeneity of studies. Random effects model was used to combine studies showing heterogeneity of Cochrane Q p < 0.10 and I > 50.
RESULTS
Twenty-one studies were included in the final analysis with a total number of 3123 study participants. Treatment outcomes were assessed clinically and parasitologically using World Health Organization guidelines. Adequate clinical and parasitological response was used to assess treatment success at the 28th day. Overall, a significant high treatment success of 92.9% (95% CI 89.1-96.6), p < 0.001, I = 98.39% was noticed. However, treatment success was higher in falciparum malaria patients treated with artemether-lumefantrine than chloroquine for Plasmodium vivax patients [98.1% (97.0-99.2), p < 0.001, I = 72.55 vs 94.7% (92.6-96.2), p < 0.001, I = 53.62%]. Seven studies reported the adverse drug reactions to anti-malarial treatment; of 822 participants, 344 of them were exposed to adverse drug reactions with a pooled event rate of 39.8% (14.1-65.5), p = 0.002.
CONCLUSIONS
On the basis of this review, anti-malarial treatment success was high (92.9%) and standard regimens showed good efficacy against Plasmodium falciparum (98.1%) and P. vivax (94.7%) infections in Ethiopia, but associated with high rates of adverse drug reactions (ADRs). However, these ADRs were not serious enough to discontinue anti-malarial treatment. The results of this study suggest that the current anti-malarial medications are effective and safe; however, greater priority should be placed on the discovery of new anti-malarial drugs to achieve successful outcomes as resistance seems inevitable since cases of anti-malarial drug resistance have been reported from other areas of the world.
Topics: Antimalarials; Artemether, Lumefantrine Drug Combination; Artemisinins; Chloroquine; Drug Combinations; Ethanolamines; Ethiopia; Fluorenes; Humans; Malaria, Falciparum; Malaria, Vivax; Primaquine; Pyrimethamine; Sulfadoxine; Treatment Failure
PubMed: 28673348
DOI: 10.1186/s12936-017-1922-9 -
Malaria Journal Oct 2023Imperfect adherence is a major barrier to effective primaquine radical cure of Plasmodium vivax. This study investigated the effect of reduced adherence on the risk of... (Meta-Analysis)
Meta-Analysis
Effect of adherence to primaquine on the risk of Plasmodium vivax recurrence: a WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysis.
BACKGROUND
Imperfect adherence is a major barrier to effective primaquine radical cure of Plasmodium vivax. This study investigated the effect of reduced adherence on the risk of P. vivax recurrence.
METHODS
Efficacy studies of patients with uncomplicated P. vivax malaria, including a treatment arm with daily primaquine, published between January 1999 and March 2020 were identified. Individual patient data from eligible studies were pooled using standardized methodology. Adherence to primaquine was inferred from i) the percentage of supervised doses and ii) the total mg/kg dose received compared to the target total mg/kg dose per protocol. The effect of adherence to primaquine on the incidence of P. vivax recurrence between days 7 and 90 was investigated by Cox regression analysis.
RESULTS
Of 82 eligible studies, 32 were available including 6917 patients from 18 countries. For adherence assessed by percentage of supervised primaquine, 2790 patients (40.3%) had poor adherence (≤ 50%) and 4127 (59.7%) had complete adherence. The risk of recurrence by day 90 was 14.0% [95% confidence interval: 12.1-16.1] in patients with poor adherence compared to 5.8% [5.0-6.7] following full adherence; p = 0.014. After controlling for age, sex, baseline parasitaemia, and total primaquine dose per protocol, the rate of the first recurrence was higher following poor adherence compared to patients with full adherence (adjusted hazard ratio (AHR) = 2.3 [1.8-2.9]). When adherence was quantified by total mg/kg dose received among 3706 patients, 347 (9.4%) had poor adherence, 88 (2.4%) had moderate adherence, and 3271 (88.2%) had complete adherence to treatment. The risks of recurrence by day 90 were 8.2% [4.3-15.2] in patients with poor adherence and 4.9% [4.1-5.8] in patients with full adherence; p < 0.001.
CONCLUSION
Reduced adherence, including less supervision, increases the risk of vivax recurrence.
Topics: Humans; Primaquine; Antimalarials; Plasmodium vivax; Recurrence; Malaria, Vivax; Folic Acid Antagonists
PubMed: 37817240
DOI: 10.1186/s12936-023-04725-w -
The Lancet. Infectious Diseases Feb 2024Primaquine radical cure is used to treat dormant liver-stage parasites and prevent relapsing Plasmodium vivax malaria but is limited by concerns of haemolysis. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Primaquine radical cure is used to treat dormant liver-stage parasites and prevent relapsing Plasmodium vivax malaria but is limited by concerns of haemolysis. We undertook a systematic review and individual patient data meta-analysis to investigate the haematological safety of different primaquine regimens for P vivax radical cure.
METHODS
For this systematic review and individual patient data meta-analysis, we searched MEDLINE, Web of Science, Embase, and Cochrane Central for prospective clinical studies of uncomplicated P vivax from endemic countries published between Jan 1, 2000, and June 8, 2023. We included studies if they had active follow-up of at least 28 days, if they included a treatment group with daily primaquine given over multiple days where primaquine was commenced within 3 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether-lumefantrine, artesunate-mefloquine, artesunate-amodiaquine, or dihydroartemisinin-piperaquine), and if they recorded haemoglobin or haematocrit concentrations on day 0. We excluded studies if they were on prevention, prophylaxis, or patients with severe malaria, or if data were extracted retrospectively from medical records outside of a planned trial. For the meta-analysis, we contacted the investigators of eligible trials to request individual patient data and we then pooled data that were made available by Aug 23, 2021. The main outcome was haemoglobin reduction of more than 25% to a concentration of less than 7 g/dL by day 14. Haemoglobin concentration changes between day 0 and days 2-3 and between day 0 and days 5-7 were assessed by mixed-effects linear regression for patients with glucose-6-phosphate dehydrogenase (G6PD) activity of (1) 30% or higher and (2) between 30% and less than 70%. The study was registered with PROSPERO, CRD42019154470 and CRD42022303680.
FINDINGS
Of 226 identified studies, 18 studies with patient-level data from 5462 patients from 15 countries were included in the analysis. A haemoglobin reduction of more than 25% to a concentration of less than 7 g/dL occurred in one (0·1%) of 1208 patients treated without primaquine, none of 893 patients treated with a low daily dose of primaquine (<0·375 mg/kg per day), five (0·3%) of 1464 patients treated with an intermediate daily dose (0·375 mg/kg per day to <0·75 mg/kg per day), and six (0·5%) of 1269 patients treated with a high daily dose (≥0·75 mg/kg per day). The covariate-adjusted mean estimated haemoglobin changes at days 2-3 were -0·6 g/dL (95% CI -0·7 to -0·5), -0·7 g/dL (-0·8 to -0·5), -0·6 g/dL (-0·7 to -0·4), and -0·5 g/dL (-0·7 to -0·4), respectively. In 51 patients with G6PD activity between 30% and less than 70%, the adjusted mean haemoglobin concentration on days 2-3 decreased as G6PD activity decreased; two patients in this group who were treated with a high daily dose of primaquine had a reduction of more than 25% to a concentration of less than 7 g/dL. 17 of 18 included studies had a low or unclear risk of bias.
INTERPRETATION
Treatment of patients with G6PD activity of 30% or higher with 0·25-0·5 mg/kg per day primaquine regimens and patients with G6PD activity of 70% or higher with 0·25-1 mg/kg per day regimens were associated with similar risks of haemolysis to those in patients treated without primaquine, supporting the safe use of primaquine radical cure at these doses.
FUNDING
Australian National Health and Medical Research Council, Bill & Melinda Gates Foundation, and Medicines for Malaria Venture.
Topics: Humans; Antimalarials; Artemether, Lumefantrine Drug Combination; Artesunate; Australia; Hemoglobins; Hemolysis; Malaria, Vivax; Plasmodium vivax; Primaquine; Prospective Studies; Retrospective Studies
PubMed: 37748497
DOI: 10.1016/S1473-3099(23)00431-0 -
Parasites & Vectors Sep 2013Among the currently used drugs in malaria case management, artemisinin derivatives and primaquine have an impact on the transmissible stages of Plasmodium falciparum.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Among the currently used drugs in malaria case management, artemisinin derivatives and primaquine have an impact on the transmissible stages of Plasmodium falciparum. Hence, they reduce the transmission of the parasite from the patient to the mosquitoes. The present study aimed to assess evidence for this hypothesis from controlled trials.
METHODS
All controlled clinical trials evaluating the transmission blocking activity of artemisinin derivatives and primaquine with or without other antimalarials were included in this systematic review. PubMed, Google Scholar, Web of Science, ScienceDirect, Medscape and the Cochrane library were systematically searched without language, publication status or date restrictions. The literature references were also scanned manually. The last search was run on July 15, 2013. Search terms included artemisinin derivatives, primaquine, malaria transmission, transmission blocking/reducing drugs and mosquito infection. The outcome measure was the mosquito infectivity rate after treatment of patients. Data were compared using odds ratio (OR), in random effects models.
RESULTS
Nine trials with a total of 13,831 mosquitoes were included in the meta-analysis. After combining the trials, the transmission of P. falciparum to Anopheles mosquitoes were lower in artesunate, artemether-lumefantrine and primaquine groups as compared with their control counterparts with OR of 0.36 (95% confidence interval (CI), 0.14-0.90), 0.49 (95% CI, 0.31-0.79) and 0.09 (95% CI, 0.01-0.73); respectively. In non-comparative longitudinal studies, the use of a single-dose of primaquine was shown to deter the transmission of malaria briefly.
CONCLUSION
Evidence on the transmission blocking effect of artemisinin derivatives and primaquine is conclusive. Trials evaluating the combined impact of artemisinin derivatives and primaquine on malaria transmission is urgently needed.
Topics: Animals; Anopheles; Antimalarials; Artemisinins; Humans; Malaria, Falciparum; Plasmodium falciparum; Primaquine
PubMed: 24499628
DOI: 10.1186/1756-3305-6-278 -
International Journal For Parasitology.... Aug 2017Recurrent P. vivax infections are associated with significant morbidity and mortality. Although radical cure can reduce recurrent infection, it is confounded by... (Review)
Review
INTRODUCTION
Recurrent P. vivax infections are associated with significant morbidity and mortality. Although radical cure can reduce recurrent infection, it is confounded by antimalarial resistance and the lack of safe and effective hypnozoitocidal treatment. This study documents the available literature of published clinical trials of P. vivax, providing an up to date, online, open access tool to view and download available information.
METHODS
A systematic review was conducted according to PRISMA guidelines to identify prospective P. vivax therapeutic clinical trials with at least 28 days follow-up published between 1st January 1960 and 12th October 2016. Treatment arms and evidence of chloroquine resistance were mapped to trial sites.
RESULTS
Since 1960, a total of 1152 antimalarial clinical trials with a minimum 28 days follow-up have been published, of which 230 (20.0%) enrolled patients with P. vivax and were included. Trials were conducted in 38 countries: 168 (73.0%) in the Asia-Pacific, 13 (5.7%) in Africa and 43 (18.7%) in the Americas. The proportion of antimalarial trials assessing P. vivax rose from 10.7% (12/112) in 1991-1995, to 24.9% (56/225) in 2011-2015. Overall, 188 (81.7%) P. vivax trials included a chloroquine treatment arm, either alone or in combination with primaquine, and 107 (46.5%) trials included a chloroquine treatment arm with early primaquine to assess radical cure. There has been a recent increase in treatment arms with artemisinin derivatives. Of the 131 sites in which chloroquine resistance could be quantified, resistance was present in 59 (45.0%) sites in 15 endemic countries.
CONCLUSIONS
Over the last 20 years there has been a substantial increase in clinical research on the treatment of P. vivax, which has generated a greater awareness of the global extent of chloroquine resistance. The WWARN open access, online interactive map provides up to date information of areas where drug resistant P. vivax is emerging.
Topics: Africa; Americas; Antimalarials; Asia; Chloroquine; Clinical Trials as Topic; Databases, Factual; Drug Resistance; Humans; Malaria, Vivax; Online Systems
PubMed: 28384505
DOI: 10.1016/j.ijpddr.2017.03.003 -
The Lancet. Infectious Diseases Feb 2024Primaquine is used to eliminate Plasmodium vivax hypnozoites, but its optimal dosing regimen remains unclear. We undertook a systematic review and individual patient... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Primaquine is used to eliminate Plasmodium vivax hypnozoites, but its optimal dosing regimen remains unclear. We undertook a systematic review and individual patient data meta-analysis to investigate the efficacy and tolerability of different primaquine dosing regimens to prevent P vivax recurrence.
METHODS
For this systematic review and individual patient data meta-analysis, we searched MEDLINE, Web of Science, Embase, and Cochrane Central for prospective clinical studies of uncomplicated P vivax from endemic countries published between Jan 1, 2000, and June 8, 2023. We included studies if they had active follow-up of at least 28 days, and if they included a treatment group with daily primaquine given over multiple days, where primaquine was commenced within 7 days of schizontocidal treatment and was given alone or coadministered with chloroquine or one of four artemisinin-based combination therapies (ie, artemether-lumefantrine, artesunate-mefloquine, artesunate-amodiaquine, or dihydroartemisinin-piperaquine). We excluded studies if they were on prevention, prophylaxis, or patients with severe malaria, or if data were extracted retrospectively from medical records outside of a planned trial. For the meta-analysis, we contacted the investigators of eligible trials to request individual patient data and we then pooled data that were made available by Aug 23, 2021. We assessed the effects of total dose and duration of primaquine regimens on the rate of first P vivax recurrence between day 7 and day 180 by Cox's proportional hazards regression (efficacy analysis). The effect of primaquine daily dose on gastrointestinal symptoms on days 5-7 was assessed by modified Poisson regression (tolerability analysis). The study was registered with PROSPERO, CRD42019154470.
FINDINGS
Of 226 identified studies, 23 studies with patient-level data from 6879 patients from 16 countries were included in the efficacy analysis. At day 180, the risk of recurrence was 51·0% (95% CI 48·2-53·9) in 1470 patients treated without primaquine, 19·3% (16·9-21·9) in 2569 patients treated with a low total dose of primaquine (approximately 3·5 mg/kg), and 8·1% (7·0-9·4) in 2811 patients treated with a high total dose of primaquine (approximately 7 mg/kg), regardless of primaquine treatment duration. Compared with treatment without primaquine, the rate of P vivax recurrence was lower after treatment with low-dose primaquine (adjusted hazard ratio 0·21, 95% CI 0·17-0·27; p<0·0001) and high-dose primaquine (0·10, 0·08-0·12; p<0·0001). High-dose primaquine had greater efficacy than low-dose primaquine in regions with high and low relapse periodicity (ie, the time from initial infection to vivax relapse). 16 studies with patient-level data from 5609 patients from ten countries were included in the tolerability analysis. Gastrointestinal symptoms on days 5-7 were reported by 4·0% (95% CI 0·0-8·7) of 893 patients treated without primaquine, 6·2% (0·5-12·0) of 737 patients treated with a low daily dose of primaquine (approximately 0·25 mg/kg per day), 5·9% (1·8-10·1) of 1123 patients treated with an intermediate daily dose (approximately 0·5 mg/kg per day) and 10·9% (5·7-16·1) of 1178 patients treated with a high daily dose (approximately 1 mg/kg per day). 20 of 23 studies included in the efficacy analysis and 15 of 16 in the tolerability analysis had a low or unclear risk of bias.
INTERPRETATION
Increasing the total dose of primaquine from 3·5 mg/kg to 7 mg/kg can reduce P vivax recurrences by more than 50% in most endemic regions, with a small associated increase in gastrointestinal symptoms.
FUNDING
Australian National Health and Medical Research Council, Bill & Melinda Gates Foundation, and Medicines for Malaria Venture.
Topics: Humans; Antimalarials; Artemether; Artemether, Lumefantrine Drug Combination; Artesunate; Malaria; Malaria, Vivax; Plasmodium vivax; Primaquine; Prospective Studies; Recurrence; Retrospective Studies
PubMed: 37748496
DOI: 10.1016/S1473-3099(23)00430-9