-
Travel Medicine and Infectious Disease 2022To elucidate the relationship between CYP2D6 polymorphisms and Plasmodium vivax recurrence in patients receiving primaquine-based treatment through systematic review and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To elucidate the relationship between CYP2D6 polymorphisms and Plasmodium vivax recurrence in patients receiving primaquine-based treatment through systematic review and meta-analysis.
METHODS
We searched the PubMed, EMBASE, Cochrane Library, and Web of Science databases for eligible studies published up to August of 2021. We included studies investigating the associations between CYP2D6 polymorphisms and P. vivax recurrence. We evaluated the pooled odds ratio (OR) and 95% confidence interval (CI).
RESULTS
Data from nine studies, including 970 patients, were analyzed. We found that CYP2D6 poor metabolizers (PMs), intermediate metabolizers (IMs), or normal metabolizers slow (NM-Ss) were associated with a 1.8-fold (95% CI, 1.34-2.45; P = 0.0001) higher recurrence of P. vivax than normal metabolizers fast (NM-Fs), extensive metabolizers (EMs), or ultrarapid metabolizer (UMs). Subgroup analysis showed that studies on both Brazilian and Southeast or East Asian individuals had similar results to the main results. Sensitivity analysis by sequentially excluding individual studies also showed robust results (OR range: 1.63-2.01).
CONCLUSIONS
This meta-analysis confirmed that CYP2D6 PMs, IMs, or NM-Ss increased the risk of P. vivax recurrence compared to NM-Fs, EMs, or UMs. The results of this study could be used to predict P. vivax recurrence and suggest CYP2D6 genotype-based primaquine dosing.
Topics: Antimalarials; Cytochrome P-450 CYP2D6; Genotype; Humans; Malaria, Vivax; Plasmodium vivax; Primaquine; Recurrence
PubMed: 35452835
DOI: 10.1016/j.tmaid.2022.102333 -
Infectious Diseases of Poverty Feb 2018Plasmodium vivax is the most geographically widespread species among human malaria parasites. Immunopathological studies have shown that platelets are an important... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Plasmodium vivax is the most geographically widespread species among human malaria parasites. Immunopathological studies have shown that platelets are an important component of the host innate immune response against malaria infections. The objectives of this study were to quantify thrombocytopaenia in P. vivax malaria patients and to determine the associated risks of severe thrombocytopaenia in patients with vivax malaria compared to patients with P. falciparum malaria.
MAIN BODY
A systematic review and meta-analysis of the available literature on thrombocytopaenia in P. vivax malaria patients was undertaken. Relevant studies in health-related electronic databases were identified and reviewed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Fifty-eight observational studies (n = 29 664) were included in the current review. Severe thrombocytopaenia (< 50 000/mm) to very severe thrombocytopaenia (< 20 000/mm) was observed in 10.1% of patients with P. vivax infection. A meta-analysis of 11 observational studies showed an equal risk of developing severe/very severe thrombocytopaenia between the patients with P. vivax malaria and those with P. falciparum malaria (OR: 1.98, 95% CI: 0.92-4.25). This indicates that thrombocytopaenia is as equally a common manifestation in P. vivax and P. falciparum malaria patients. One study showed a higher risk of developing very severe thrombocytopaenia in children with severe P. vivax malaria than with severe P. falciparum malaria (OR: 2.80, 95% CI: 1.48-5.29). However, a pooled analysis of two studies showed an equal risk among adult severe cases (OR: 1.19, 95% CI: 0.51-2.77). This indicates that the risk of developing thrombocytopaenia in P. vivax malaria can vary with immune status in both children and adults. One study reported higher levels of urea and serum bilirubin in patients with P. vivax malaria and severe thrombocytopaenia compared with patients mild thrombocytopaenia or no thrombocytopaenia, (P < 0.001 in all comparisons). A pooled analysis of two other studies showed a similar proportion of bleeding episodes with thrombocytopaenia in severe P. vivax patients and severe P. falciparum patients (P = 0.09). This implied that both P. vivax and P. falciparum infections could present with bleeding episodes, if there had been a change in platelet counts in the infected patients. A pooled analysis of another two studies showed an equal risk of mortality with severe thrombocytopaenia in both P. vivax and P. falciparum malaria patients (OR: 1.16, 95% CI: 0.30-4.60). However, due to the low number of studies with small sample sizes within the subset of studies that provided clinically relevant information, our confidence in the estimates is limited.
CONCLUSION
The current review has provided some evidence of the clinical relevance of severe thrombocytopaenia in P. vivax malaria. To substantiate these findings, there is a need for well designed, large-scale, prospective studies among patients infected with P. vivax. These should include patients from different countries and epidemiological settings with various age and gender groups represented.
Topics: Adult; Child; Female; Humans; Malaria, Falciparum; Malaria, Vivax; Male; Observational Studies as Topic; Plasmodium falciparum; Plasmodium vivax; Severity of Illness Index; Thrombocytopenia
PubMed: 29427995
DOI: 10.1186/s40249-018-0392-9 -
Memorias Do Instituto Oswaldo Cruz Aug 2014Plasmodium vivax radical cure requires the use of primaquine (PQ), a drug that induces haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals,... (Review)
Review
Plasmodium vivax radical cure requires the use of primaquine (PQ), a drug that induces haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals, which further hampers malaria control efforts. The aim of this work was to study the G6PDd prevalence and variants in Latin America (LA) and the Caribbean region. A systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Low prevalence rates of G6PDd were documented in Argentina, Bolivia, Mexico, Peru and Uruguay, but studies from Curaçao, Ecuador, Jamaica, Saint Lucia, Suriname and Trinidad, as well as some surveys carried out in areas of Brazil, Colombia and Cuba, have shown a high prevalence (> 10%) of G6PDd. The G6PD A-202A mutation was the variant most broadly distributed across LA and was identified in 81.1% of the deficient individuals surveyed. G6PDd is a frequent phenomenon in LA, although certain Amerindian populations may not be affected, suggesting that PQ could be safely used in these specific populations. Population-wide use of PQ as part of malaria elimination strategies in LA cannot be supported unless a rapid, accurate and field-deployable G6PDd diagnostic test is made available.
Topics: Antimalarials; Caribbean Region; Contraindications; Female; Geographic Mapping; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Hemolysis; Humans; Latin America; Malaria, Vivax; Male; Prevalence; Primaquine
PubMed: 25141282
DOI: 10.1590/0074-0276140123 -
Colombia Medica (Cali, Colombia) Dec 2015To compare efficacy and safety of primaquine regimens currently used to prevent relapses by P. vivax. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare efficacy and safety of primaquine regimens currently used to prevent relapses by P. vivax.
METHODS
A systematic review was carried out to identify clinical trials evaluating efficacy and safety to prevent malaria recurrences by P. vivax of primaquine regimen 0.5 mg/kg/ day for 7 or 14 days compared to standard regimen of 0.25 mg/kg/day for 14 days. Efficacy of primaquine according to cumulative incidence of recurrences after 28 days was determined. The overall relative risk with fixed-effects meta-analysis was estimated.
RESULTS
For the regimen 0.5 mg/kg/day/7 days were identified 7 studies, which showed an incidence of recurrence between 0% and 20% with follow-up 60-210 days; only 4 studies comparing with the standard regimen 0.25 mg/kg/day/14 days and no difference in recurrences between both regimens (RR= 0.977, 95% CI= 0.670 to 1.423) were found. 3 clinical trials using regimen 0.5 mg/kg/day/14 days with an incidence of recurrences between 1.8% and 18.0% during 330-365 days were identified; only one study comparing with the standard regimen (RR= 0.846, 95% CI= 0.484 to 1.477). High risk of bias and differences in handling of included studies were found.
CONCLUSION
Available evidence is insufficient to determine whether currently PQ regimens used as alternative rather than standard treatment have better efficacy and safety in preventing relapse of P. vivax. Clinical trials are required to guide changes in treatment regimen of malaria vivax.
Topics: Antimalarials; Artemisinins; Artesunate; Chloroquine; Drug Administration Schedule; Humans; Malaria, Vivax; Plasmodium vivax; Primaquine; Recurrence; Secondary Prevention
PubMed: 26848199
DOI: No ID Found -
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 -
Parasitology Nov 2023Of the 5 human malarial parasites, and are the most prevalent species globally, while and are less prevalent and typically occur as mixed-infections. , previously... (Review)
Review
Of the 5 human malarial parasites, and are the most prevalent species globally, while and are less prevalent and typically occur as mixed-infections. , previously considered a non-human primate (NHP) infecting species, is now a cause of human malaria in Malaysia. The other NHP species, , , , , and cause malaria in primates, which are mainly reported in southeast Asia and South America. The non- NHP species also emerged and were found to cross-transmit from their natural hosts (NHP) – to human hosts in natural settings. Here we have reviewed and collated data from the literature on the NHPs-to-human-transmitting species. It was observed that the natural transmission of these NHP parasites to humans had been reported from 2010 onwards. This study shows that: (1) the majority of the non- NHP mixed species infecting human cases were from Yala province of Thailand; (2) mono/mixed infections with other human-infecting species were prevalent in Malaysia and Thailand and (3) and were found in Central and South America.
Topics: Animals; Humans; Malaria; Plasmodium knowlesi; Primates; Asia, Southeastern; Plasmodium vivax
PubMed: 37929579
DOI: 10.1017/S003118202300077X -
Travel Medicine and Infectious Disease 2021In 2018, tafenoquine was approved for malaria chemoprophylaxis. We evaluated all available data on the safety and efficacy of tafenoquine chemoprophylaxis. (Meta-Analysis)
Meta-Analysis
BACKGROUND
In 2018, tafenoquine was approved for malaria chemoprophylaxis. We evaluated all available data on the safety and efficacy of tafenoquine chemoprophylaxis.
METHODS
This systematic review followed the PRISMA guidelines and was registered on PROSPERO (CRD42019123839). We searched PubMed, Embase, Scopus, CINAHL and Cochrane databases. Two authors (JDM, PS) screened all papers.
RESULTS
We included 44 papers in the qualitative and 9 in the quantitative analyses. These 9 randomized, controlled trials included 2495 participants, aged 12-60 years with 27.3% women. Six studies were conducted in Plasmodium spp.-endemic regions; two were human infection studies. 200 mg weekly tafenoquine and higher dosages lead to a significant reduction of Plasmodium spp. infection compared to placebo and were comparable to 250 mg mefloquine weekly with a protective efficacy between 77.9 and 100% or a total risk ratio of 0.22 (95%-CI: 0.07-0.73; p = 0.013) in favour of tafenoquine. Adverse events (AE) were comparable in frequency and severity between tafenoquine and comparator arms. One study reported significantly more gastrointestinal events in tafenoquine users (p ≤ 0.001). Evidence of increased, reversible, asymptomatic vortex keratopathy in subjects with prolonged tafenoquine exposures was found. A single, serious event of decreased macular sensitivity occurred.
CONCLUSION
This systematic review and meta-analysis of trials of G6PD-normal adults show that weekly tafenoquine 200 mg is well tolerated and effective as malaria chemoprophylaxis focusing primarily on Plasmodium falciparum but also on Plasmodium vivax. Our safety analysis is limited by heterogenous methods of adverse events reporting. Further research is indicated on the use of tafenoquine in diverse traveller populations.
Topics: Adult; Aminoquinolines; Antimalarials; Chemoprevention; Female; Humans; Malaria; Male
PubMed: 33227500
DOI: 10.1016/j.tmaid.2020.101908 -
Malaria Journal Nov 2014Artemisinin combination therapy (ACT) is recommended as first-line treatment for uncomplicated Plasmodium falciparum malaria, whereas chloroquine is still commonly used... (Review)
Review
BACKGROUND
Artemisinin combination therapy (ACT) is recommended as first-line treatment for uncomplicated Plasmodium falciparum malaria, whereas chloroquine is still commonly used for the treatment of non-falciparum species (Plasmodium vivax, Plasmodium ovale and Plasmodium malariae). A more simplified, more uniform treatment approach across all malaria species is worthwhile to be considered both in endemic areas and for malaria as an imported condition alike.
METHODS
A PROSPERO-registered systematic review to determine the efficacy and safety of ACT for the treatment of non-falciparum malaria was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to November 2014.
RESULTS
The literature search identified 986 reports; 40 publications were found eligible for inclusion, all of them on non-falciparum malaria in endemic areas. Most evidence was available for P. vivax (n = 35). Five clinical trials in total were identified evaluating ACT for P. ovale, P. malariae and Plasmodium knowlesi. Most ACT presentations have high efficacy against P. vivax parasites; artemisinin-based combinations have shorter parasite and fever clearance times compared to chloroquine. ACT is as effective as chloroquine in preventing recurrent parasitaemia before day 28. Artemisinin-based combinations with long half-lives show significantly fewer recurrent parasitaemia up to day 63. The limited evidence available supports both the use of chloroquine and an ACT for P. ovale and P. malariae. ACT seems to be preferable for optimal treatment of P. knowlesi.
CONCLUSION
ACT is at least equivalent to chloroquine in effectively treating non-falciparum malaria. These findings may facilitate development of simplified protocols for treating all forms of malaria with ACT, including returning travellers. Obtaining comprehensive efficacy and safety data on ACT use for non-falciparum species particularly for P. ovale, P. malariae and P. knowlesi should be a research priority.
TRIAL REGISTRATION
CRD42014009103.
Topics: Antimalarials; Artemisinins; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Humans; Malaria; Treatment Outcome
PubMed: 25428624
DOI: 10.1186/1475-2875-13-463 -
Scientific Reports Sep 2023Reduced glutathione (GSH) is a crucial antioxidant with recognized roles in malaria pathogenesis and host response. Despite its importance, reports on the association of... (Meta-Analysis)
Meta-Analysis
Reduced glutathione (GSH) is a crucial antioxidant with recognized roles in malaria pathogenesis and host response. Despite its importance, reports on the association of GSH with malaria are inconsistent. Therefore, this systematic review and meta-analysis investigated the differences in GSH levels in relation to Plasmodium infection. A comprehensive literature search of six electronic databases (Embase, MEDLINE, Ovid, PubMed, Scopus, and ProQuest) was conducted. Of the 2158 initially identified records, 18 met the eligibility criteria. The majority of studies reported a significant decrease in GSH levels in malaria patients compared with uninfected controls, and this was confirmed by meta-analysis (P < 0.01, Hedges g: - 1.47, 95% confidence interval [CI] - 2.48 to - 0.46, I: 99.12%, 17 studies). Additionally, there was no significant difference in GSH levels between Plasmodium falciparum malaria and P. vivax malaria (P = 0.80, Hedges g: 0.11, 95% CI - 0.76 to 0.98, I: 93.23%, three studies). Similarly, no significant variation was observed between symptomatic and asymptomatic malaria cases (P = 0.78, Hedges g: 0.06, 95% CI - 0.34 to 0.46, I: 48.07%, two studies). In conclusion, although GSH levels appear to be generally lower in malaria patients, further detailed studies are necessary to fully elucidate this complex relationship.
Topics: Humans; Malaria, Vivax; Plasmodium falciparum; Glutathione; Plasmodium vivax; Malaria, Falciparum; Malaria
PubMed: 37777547
DOI: 10.1038/s41598-023-43583-z -
Diagnostics (Basel, Switzerland) Mar 2021Rapid diagnostic tests (RDTs) have become a mainstay of malaria diagnosis in endemic countries since their implementation in the 1990s. We conducted a 30-year systematic... (Review)
Review
Rapid diagnostic tests (RDTs) have become a mainstay of malaria diagnosis in endemic countries since their implementation in the 1990s. We conducted a 30-year systematic review and meta-analysis on malaria RDTs performance in India. Outcomes of interest were sensitivity (Se), specificity (Sp), positive/negative likelihood ratio (PLR/NLR), and diagnostic odd ratio (DOR). Among the 75 studies included, most of the studies were cross-sectional (65.3%), hospital-based (77.3%), and targeted febrile patients (90.6%). Nearly half of RDTs were designed for detecting only (47.5%) while the rest were for and (11.9%), and /Pan- except for (32.3%). When compared to light microscopy (gold standard), pooled estimates of performances were: Se = 97.0%, Sp = 96.0%, PLR = 22.4, NLR = 0.02 and DOR = 1080. In comparison to polymerase chain reaction, the RDTs showed Se = 89.0% and Sp = 99.0%. Performance outcomes (Se and Sp) were similar for RDT targeting only, but decreased for mixed and non-falciparum infections. Performances of malaria RDTs are still high India. However, there is a need for developing RDTs with regard to targeting minor malarial species, individuals carrying only mature gametocytes, and -deleted parasites.
PubMed: 33806066
DOI: 10.3390/diagnostics11040590