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Parasitology Nov 2022From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease... (Review)
Review
From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease (ChD) treatment. The research protocol was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and patient, intervention, comparison and outcome strategy. Only randomized controlled trials (RCT) were retrieved from Embase, Medline, Scopus and Web of Science databases. Diagnostic tools, treatment protocols, seroconversion rates and adverse events were investigated. Fifteen RCT mainly concentrated in endemic countries were identified. ChD diagnosis was mainly based on haemagglutination, immunofluorescence, enzyme-linked immunosorbent assay and polymerase chain reaction. Benznidazole (BNZ), nifurtimox, fosravuconazole, posaconazole, allopurinol and thioctic acid were the identified drugs. The best negative seroconversion results (100, 96, 94 and 91.3%) were, respectively, based on BNZ (5 mg kg day, 200 mg day, 150 mg day and 2.5 mg kg) administration for 60 days. Negative seroconversion was not achieved with allopurinol (300 mg day for 60 days). Adverse reactions ranged from 5 to 73% in patients receiving antiparasitic chemotherapy. Treatment discontinuation (1.5–57%) was mainly associated with gastrointestinal, cutaneous and neurological manifestations. Current RCT-based evidence indicates that BNZ is the most viable option for ChD treatment. However, new protocols need to be developed to mitigate side effects and increase patient adherence to antiparasitic chemotherapy. Therefore, shorter regimens, lower concentrations and treatments combining BNZ with posaconazole, fosravuconazole or ravuconazole may be viable to ensure comparable efficacy to BZN-based monotherapy, contributing to reduce dose- and time-dependent toxicity reactions.
Topics: Humans; Trypanosoma cruzi; Trypanocidal Agents; Allopurinol; Randomized Controlled Trials as Topic; Chagas Disease; Nitroimidazoles; Drug Therapy, Combination; Treatment Outcome
PubMed: 35957576
DOI: 10.1017/S0031182022001081 -
The Cochrane Database of Systematic... May 2011Vaginitis due to Trichomonas vaginalis is one of the most common of sexually transmitted diseases. Trichomoniasis affects women during pregnancy as well but it is not... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vaginitis due to Trichomonas vaginalis is one of the most common of sexually transmitted diseases. Trichomoniasis affects women during pregnancy as well but it is not clearly established whether it causes preterm birth and other pregnancy complications.
OBJECTIVES
The objective of this review was to assess the effects of various treatments for trichomoniasis during pregnancy.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (14 January 2011).
SELECTION CRITERIA
Randomized trials comparing anti-trichomonas agents during pregnancy. Trials including symptomatic or asymptomatic women with trichomoniasis were eligible.
DATA COLLECTION AND ANALYSIS
Two review authors assessed eligibility and trial quality.
MAIN RESULTS
We included two trials with 842 pregnant women. In both trials around 90% of women were cleared of trichomonas in the vagina after treatment. In the US trial, women with asymptomatic trichomoniasis between 16 and 23 weeks were treated with metronidazole on two occasions at least two weeks apart. The trial was stopped before reaching its target recruitment because metronidazole was not effective in reducing preterm birth and there was a likelihood of harm (risk ratio 1.78; 95% confidence interval 1.19 to 2.66). The South African trial recruited women later in pregnancy and did not have the design and power to address adverse clinical outcomes. We excluded two recent studies, identified for the current update, because they did not address the primary question.
AUTHORS' CONCLUSIONS
Metronidazole, given as a single dose, is likely to provide parasitological cure for trichomoniasis, but it is not known whether this treatment will have any effect on pregnancy outcomes. The cure rate could probably be higher if more partners used the treatment.
Topics: Antiprotozoal Agents; Female; Humans; Metronidazole; Pregnancy; Pregnancy Complications, Parasitic; Randomized Controlled Trials as Topic; Trichomonas Vaginitis
PubMed: 21563127
DOI: 10.1002/14651858.CD000220.pub2 -
Travel Medicine and Infectious Disease 2017Mefloquine is recommended in international health guidelines for preventing malaria in travellers. Reports of psychosis and suicide are often alluded to but are not... (Review)
Review
BACKGROUND
Mefloquine is recommended in international health guidelines for preventing malaria in travellers. Reports of psychosis and suicide are often alluded to but are not clearly established.
METHODS
We carried out a systematic review of the literature to identify and critically appraise any reported death or parasuicide associated with mefloquine prophylaxis. We developed a comprehensive search that included publications up to 11 July 2017. We included case studies but excluded newspaper reports. Two authors independently appraised each death or parasuicide against a standardised causality assessment tool. The protocol was registered on PROSPERO (CRD42016041988).
RESULTS
We identified 527 articles that required full-text retrieval; of these 17 were unique publications that reported deaths or parasuicide. Eight unique publications had sufficient detail to be included in causality assessment. We identified 2 deaths with a probable association that appeared to be idiosyncratic drug reactions; we categorised the remaining 8 deaths as "unlikely" to be related to mefloquine, or "unclassifiable". There was one parasuicide with a possible causal association. There were 9 additional publications that searched spontaneous drug reporting databases; none provided sufficient detail to perform a causality assessment.
CONCLUSIONS
Overall, the number of deaths that we could reliably attribute to the prophylactic use of mefloquine is very low.
Topics: Antimalarials; Cause of Death; Chemoprevention; Humans; Malaria; Mefloquine; Self-Injurious Behavior; Travel Medicine
PubMed: 29107173
DOI: 10.1016/j.tmaid.2017.10.011 -
Journal of Hazardous Materials Aug 2022Increasing usage of antimicrobials is a significant contributor to the emergence and dissemination of antimicrobial resistance. Wastewater-based epidemiology is a useful...
Increasing usage of antimicrobials is a significant contributor to the emergence and dissemination of antimicrobial resistance. Wastewater-based epidemiology is a useful tool for evaluating public health, via the monitoring of chemical and biological markers in wastewater influent, such as antibiotics. Sixteen antimicrobials and their metabolites were studied: sulfonamides, trimethoprim, metronidazole, quinolones, nitrofurantoin, cyclines, and antiretrovirals. Correction factors (CFs) for human drug excretion, for various drug forms, were determined via a systematic literature review of pharmacokinetic research. Analyte stability was examined over a 24 h study. The estimation of community-wide drug intake was evaluated using the corresponding catchment prescription data. Overall, antimicrobials excreted in an unchanged form were often observed to over-estimate daily intake. This could be attributed to biotransformation, e.g., via glucuronide cleavage, or direct disposal of unused drugs. Acetyl-sulfonamides, trimethoprim, hydroxy-metronidazole, clarithromycin, ciprofloxacin, ofloxacin, tetracycline, and oxytetracycline generally performed well in the estimation of drug intake, relative to prescription records. The low prevalence of quinolone and trimethoprim metabolites, and the low stability of nitrofurantoin, limited the ability to evaluate these metabolites and their respective CFs.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Humans; Metronidazole; Nitrofurantoin; Quinolones; Sulfonamides; Trimethoprim; Wastewater-Based Epidemiological Monitoring; Water Pollutants, Chemical
PubMed: 35594673
DOI: 10.1016/j.jhazmat.2022.129001 -
The Cochrane Database of Systematic... Dec 2012Giardiasis infection may be asymptomatic, or can cause diarrhoea (sometimes severe), weight loss, malabsorption, and, in children, failure to thrive. It is usually... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Giardiasis infection may be asymptomatic, or can cause diarrhoea (sometimes severe), weight loss, malabsorption, and, in children, failure to thrive. It is usually treated with metronidazole given three times daily for five to 10 days.
OBJECTIVES
To evaluate the relative effectiveness of alternative antibiotic regimens for treating adults or children with symptomatic giardiasis.
SEARCH METHODS
We searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6 2012); MEDLINE, EMBASE, LILACS and the International Clinical Trials Registry Platform Search Portal (3 July 2012).
SELECTION CRITERIA
We included randomized controlled trials (RCT) comparing metronidazole administered for five to 10 days with any of the following drugs: metronidazole (single dose), tinidazole, albendazole, mebendazole, and nitazoxanide. The primary outcomes were parasitological and clinical cure.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies for inclusion, performed the risk of bias assessment, and extracted data. We summarized data using risk ratios and mean differences and we presented the results in forest plots and performed meta-analyses where possible. We assessed heterogeneity using the Chi(2) test, I(2) statistic and visual inspection; and we explored this by using subgroup analyses.We assessed the quality of evidence by using the GRADE approach.
MAIN RESULTS
We included 19 trials, involving 1817 participants, of which 1441 were children. Studies were generally small, with poor methods reporting. . Most reported parasitological outcomes rather than clinical improvement.Ten trials, from India, Mexico, Peru, Iran, Cuba, and Turkey, compared albendazole (400 mg once daily for five to 10 days) with metronidazole (250 mg to 500 mg three times daily for five to 10 days). This once-daily regimen of albendazole is probably equivalent to metronidazole at achieving parasitological cure (RR 0.99, 95% CI 0.95 to 1.03; 932 participants, 10 trials; moderate quality evidence), and improving symptoms (RR 0.98, 95% confidence interval (CI) 0.93 to 1.04; 483 participants, five trials; moderate quality evidence), but the duration of follow-up was short (two to three weeks). Albendazole probably has fewer side effects than metronidazole (gastrointestinal side effects: RR 0.29, 95% CI 0.13 to 0.63; 717 participants, eight trials; moderate quality evidence; neurological side effects: RR 0.34, 95% CI 0.18 to 0.64; 453 participants, five trials; low quality evidence).Five trials from Turkey, Spain and the UK compared mebendazole (200 mg three times daily for five to 10 days) with metronidazole (5 mg/kg (or 250 mg) three times daily for five to 10 days). These trials were small in size, and at high risk of bias. Consequently, reliable conclusions on the relative effectiveness cannot be made (very low quality evidence).Five further trials, from Iran, Spain and Peru, have evaluated shortened regimens of tinidazole (single dose; 179 participants, three trials), metronidazole (single dose; 55 participants, one trial), and nitazoxanide (three days; 55 participants, one trial). Again, these trials were at high risk of bias and too small to reliably detect or exclude important differences (very low quality evidence).
AUTHORS' CONCLUSIONS
Albendazole may be of similar effectiveness to metronidazole, may have fewer side effects, and has the advantage of a simplified regimen. Large, high quality trials, assessing clinical outcomes (such as diarrhoea) will help assess further alternatives.
Topics: Adult; Albendazole; Antiparasitic Agents; Child; Giardiasis; Humans; Mebendazole; Metronidazole; Nitro Compounds; Randomized Controlled Trials as Topic; Thiazoles; Tinidazole
PubMed: 23235648
DOI: 10.1002/14651858.CD007787.pub2 -
PloS One 2012Chemotherapy based on repeated doses of praziquantel is still the most effective control strategy against Schistosomiasis, however artemisinin derivatives emerged as a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chemotherapy based on repeated doses of praziquantel is still the most effective control strategy against Schistosomiasis, however artemisinin derivatives emerged as a family of compounds with schistomicide activity. The aim of the present work is to compare the efficacy of artemisinin-based therapies in the treatment and prophylaxis of human schistosomiasis. The design of this work involved a quantitative systematic review and meta-analysis.
METHODOLOGY/PRINCIPAL FINDINGS
Retrieval of published studies was carried out through an electronic search of the PubMed (MEDLINE), EMBASE, Cochrane Library and CINAHL databases. This included reports comparing the therapeutic efficacy of artesunate alone, artesunate plus sulfadoxine-pyrimethamine and a combination of artemisinin derivatives plus praziquantel against praziquantel alone on different types of schistosomiasis. Moreover, studies on artesunate and artemether used as preventive drugs were also analyzed against placebo. The primary outcome measure for schistosomiasis treatment was "parasitological cure", whereas for the prophylaxis the outcome evaluated was "infection rate". Our results show that patients treated with artesunate alone have significantly lower cure rates than those treated with praziquantel (OR = 0.27 (95% C.I. 0.13-0.53; p<0.001)) and that the combined therapy of artesunate plus sulfadoxine-pyrimethamine is also significantly less effective than praziquantel treatment (OR = 0.14 (95% C.I. 0.02-0.92; p = 0.04)). However, the combination of an artemisinin derivatives plus praziquantel showed a higher cure rate than praziquantel monotherapy with OR = 2.07 (95% C.I. 1.27-3.36; p = 0.003). Finally, chemoprophylaxis with either artesunate (RR = 0.11 (95% C.I. 0.06-0.22; p<0.001)) or artemether (RR = 0.25 (95% C.I. 0.16-0.40; p<0.001)) was significantly better than a placebo in both cases.
CONCLUSIONS/SIGNIFICANCE
This meta-analysis confirms that artemisinin derivatives used in combination with praziquantel have the potential to increase the cure rates in schistosomiasis treatment, but not artesunate alone. It is also confirmed that repeated doses of artemisinin derivatives play a prophylactic role, significantly reducing the incidence of Schistosoma japonicum infections compared with placebo.
Topics: Antiprotozoal Agents; Artemisinins; Clinical Trials as Topic; Drug Combinations; Drug Therapy, Combination; Humans; Praziquantel; Pyrimethamine; Schistosomiasis; Sulfadoxine; Treatment Outcome
PubMed: 23029285
DOI: 10.1371/journal.pone.0045867 -
PLoS Neglected Tropical Diseases Jan 2018By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits.
METHODOLOGY/PRINCIPAL FINDINGS
This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains-learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5-19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The significance of infection-associated deficits in scholastic achievement was sensitive to ROB. Schistosoma infection-related deficits in learning and memory tests were invariant by ROB and study design.
CONCLUSION/SIGNIFICANCE
Schistosoma infection/non-treatment was significantly associated with educational, learning, and memory deficits in SAC. Early treatment of children in Schistosoma-endemic regions could potentially mitigate these deficits.
TRIAL REGISTRATION
ClinicalTrials.gov CRD42016040052.
Topics: Adolescent; Animals; Anthelmintics; Child; Child, Preschool; Cognition; Cognitive Dysfunction; Humans; Intelligence; Learning Disabilities; Memory; Memory Disorders; Memory and Learning Tests; Praziquantel; Reaction Time; Schistosoma; Schistosomiasis
PubMed: 29329293
DOI: 10.1371/journal.pntd.0005524 -
Malaria Journal Mar 2017Despite increased efforts to control and ultimately eradicate human malaria, Plasmodium ovale malaria is for the most part outside the focus of research or public health... (Review)
Review
BACKGROUND
Despite increased efforts to control and ultimately eradicate human malaria, Plasmodium ovale malaria is for the most part outside the focus of research or public health programmes. Importantly, the understanding of P. ovale-nowadays regarded as the two distinct species P. ovale wallikeri and P. ovale curtisi-largely stems from case reports and case series lacking study designs providing high quality evidence. Consecutively, there is a lack of systematic evaluation of the clinical presentation, appropriate treatment and relapse characteristics of P. ovale malaria. The aim of this systematic review is to provide a systematic appraisal of the current evidence for severe manifestations, relapse characteristics and treatment options for human P. ovale malaria.
METHODS AND RESULTS
This systematic review was performed according to the PRISMA guidelines and registered in the international prospective register for systematic reviews (PROSPERO 2016:CRD42016039214). P. ovale mono-infection was a strict inclusion criterion. Of 3454 articles identified by the literature search, 33 articles published between 1922 and 2015 met the inclusion criteria. These articles did not include randomized controlled trials. Five prospective uncontrolled clinical trials were performed on a total of 58 participants. P. ovale was sensitive to all tested drugs within the follow-up periods and on interpretable in vitro assays. Since its first description in 1922, only 18 relapsing cases of P. ovale with a total of 28 relapse events were identified in the scientific literature. There was however no molecular evidence for a causal relationship between dormant liver stages and subsequent relapses. A total of 22 severe cases of P. ovale malaria were published out of which five were fatal. Additionally, two cases of congenital P. ovale malaria were reported.
CONCLUSIONS
Current knowledge of P. ovale malaria is based on small trials with minor impact, case reports and clinical observations. This systematic review highlights that P. ovale is capable of causing severe disease, severe congenital malaria and may even lead to death. Evidence for relapses in patients with P. ovale malaria adds up to only a handful of cases. Nearly 100 years after P. ovale's first description by Stephens the evidence for the clinical characteristics, relapse potential and optimal treatments for P. ovale malaria is still scarce.
Topics: Antimalarials; Humans; Malaria; Plasmodium ovale; Recurrence
PubMed: 28284211
DOI: 10.1186/s12936-017-1759-2 -
Clinical Microbiology and Infection :... Jul 2024Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several... (Meta-Analysis)
Meta-Analysis Comparative Study Review
Comparative efficacy and safety of Pneumocystis jirovecii pneumonia prophylaxis regimens for people living with HIV: a systematic review and network meta-analysis of randomized controlled trials.
BACKGROUND
Pneumocystis jirovecii pneumonia (PCP) is a common opportunistic infection among people living with HIV (PWH), particularly among new and untreated cases. Several regimens are available for the prophylaxis of PCP, including trimethoprim-sulfamethoxazole (TMP-SMX), dapsone-based regimens (DBRs), aerosolized pentamidine (AP), and atovaquone.
OBJECTIVES
To compare the efficacy and safety of PCP prophylaxis regimens in PWH by network meta-analysis.
METHODS
DATA SOURCES: Embase, MEDLINE, and CENTRAL from inception to June 21, 2023.
STUDY ELIGIBILITY CRITERIA
Comparative randomized controlled trials (RCTs).
PARTICIPANTS
PWH.
INTERVENTIONS
Regimens for PCP prophylaxis either compared head-to-head or versus no treatment/placebo.
ASSESSMENT OF RISK OF BIAS
Cochrane risk-of-bias tool for RCTs 2.
METHODS OF DATA SYNTHESIS
Title or abstract and full-text screening and data extraction were performed in duplicate by two independent reviewers. Data on PCP incidence, all-cause mortality, and discontinuation due to toxicity were pooled and ranked by network meta-analysis. Subgroup analyses of primary versus secondary prophylaxis, by year, and by dosage were performed.
RESULTS
A total of 26 RCTs, comprising 55 treatment arms involving 7516 PWH were included. For the prevention of PCP, TMP-SMX was ranked the most favourable agent and was superior to DBRs (risk ratio [RR] = 0.54; 95% CI, 0.36-0.83) and AP (RR = 0.53; 95% CI, 0.36-0.77). TMP-SMX was also the only agent with a mortality benefit compared with no treatment/placebo (RR = 0.79; 95% CI, 0.64-0.98). However, TMP-SMX was also ranked as the most toxic agent with a greater risk of discontinuation than DBRs (RR = 1.25; 95% CI, 1.01-1.54) and AP (7.20; 95% CI, 5.37-9.66). No significant differences in PCP prevention or mortality were detected among the other regimens. The findings remained consistent within subgroups.
CONCLUSIONS
TMP-SMX is the most effective agent for PCP prophylaxis in PWH and the only agent to confer a mortality benefit; consequently, it should continue to be recommended as the first-line agent. Further studies are necessary to determine the optimal dosing of TMP-SMX to maximize efficacy and minimize toxicity.
Topics: Humans; Pneumonia, Pneumocystis; Randomized Controlled Trials as Topic; Network Meta-Analysis; Trimethoprim, Sulfamethoxazole Drug Combination; Pneumocystis carinii; HIV Infections; AIDS-Related Opportunistic Infections; Dapsone; Pentamidine; Atovaquone; Antifungal Agents; Treatment Outcome
PubMed: 38583518
DOI: 10.1016/j.cmi.2024.03.037 -
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