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Malaria Journal Jan 2021Malaria and HIV are two important public health issues. However, evidence on HIV-Plasmodium vivax co-infection (HIV/PvCo) is scarce, with most of the available...
BACKGROUND
Malaria and HIV are two important public health issues. However, evidence on HIV-Plasmodium vivax co-infection (HIV/PvCo) is scarce, with most of the available information related to Plasmodium falciparum on the African continent. It is unclear whether HIV can change the clinical course of vivax malaria and increase the risk of complications. In this study, a systematic review of HIV/PvCo studies was performed, and recent cases from the Brazilian Amazon were included.
METHODS
Medical records from a tertiary care centre in the Western Brazilian Amazon (2009-2018) were reviewed to identify HIV/PvCo hospitalized patients. Demographic, clinical and laboratory characteristics and outcomes are reported. Also, a systematic review of published studies on HIV/PvCo was conducted. Metadata, number of HIV/PvCo cases, demographic, clinical, and outcome data were extracted.
RESULTS
A total of 1,048 vivax malaria patients were hospitalized in the 10-year period; 21 (2.0%) were HIV/PvCo cases, of which 9 (42.9%) had AIDS-defining illnesses. This was the first malaria episode in 11 (52.4%) patients. Seven (33.3%) patients were unaware of their HIV status and were diagnosed on hospitalization. Severe malaria was diagnosed in 5 (23.8%) patients. One patient died. The systematic review search provided 17 articles (12 cross-sectional or longitudinal studies and 5 case report studies). A higher prevalence of studies involved cases in African and Asian countries (35.3 and 29.4%, respectively), and the prevalence of reported co-infections ranged from 0.1 to 60%.
CONCLUSION
Reports of HIV/PvCo are scarce in the literature, with only a few studies describing clinical and laboratory outcomes. Systematic screening for both co-infections is not routinely performed, and therefore the real prevalence of HIV/PvCo is unknown. This study showed a low prevalence of HIV/PvCo despite the high prevalence of malaria and HIV locally. Even though relatively small, this is the largest case series to describe HIV/PvCo.
Topics: Adolescent; Adult; Aged; Brazil; Child; Coinfection; Female; HIV Infections; HIV-1; Humans; Incidence; Malaria, Vivax; Male; Middle Aged; Plasmodium vivax; Prevalence; Young Adult
PubMed: 33407474
DOI: 10.1186/s12936-020-03518-9 -
Scientific Reports Dec 2020Plasmodium ovale is a benign tertian malaria parasite that morphologically resembles Plasmodium vivax. P. ovale also shares similar tertian periodicity and can cause... (Meta-Analysis)
Meta-Analysis
Plasmodium ovale is a benign tertian malaria parasite that morphologically resembles Plasmodium vivax. P. ovale also shares similar tertian periodicity and can cause relapse in patients without a radical cure, making it easily misidentified as P. vivax in routine diagnosis. Therefore, its prevalence might be underreported worldwide. The present study aimed to quantify the prevalence of P. ovale misidentified as P. vivax malaria using data from studies reporting confirmed P. ovale cases by molecular methods. Studies reporting the misidentification of P. ovale as P. vivax malaria were identified from three databases, MEDLINE, Web of Science, and Scopus, without language restrictions, but the publication date was restricted to 1993 and 2020. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). The random-effects model was used to estimate the pooled prevalence of the misidentification of P. ovale as P. vivax malaria by the microscopic method when compared to those with the reference polymerase chain reaction method. Subgroup analysis of participants was also performed to demonstrate the difference between imported and indigenous P. ovale cases. The heterogeneity of the included studies was assessed using Cochran's Q and I statistics. Publication bias across the included studies was assessed using the funnel plot and Egger's test, and if required, contour-enhanced funnel plots were used to identify the source(s) of funnel plot asymmetry. Of 641 articles retrieved from databases, 22 articles met the eligibility criteria and were included in the present study. Of the 8,297 malaria-positive cases identified by the PCR method, 453 P. ovale cases were confirmed. The pooled prevalence of misidentification of P. ovale as P. vivax malaria by the microscopic method was 11% (95% CI: 7-14%, I: 25.46%). Subgroup analysis of the participants demonstrated a higher prevalence of misidentification in indigenous cases (13%, 95% CI: 6-21%, I: 27.8%) than in imported cases (10%, 95% CI: 6-14%, I: 24.1%). The pooled prevalence of misidentification of P. vivax as P. ovale malaria by the microscopic method was 1%, without heterogeneity (95% CI: 0-3%, I: 16.8%). PCR was more sensitive in identifying P. ovale cases than the microscopic method (p < 0.00001, OR: 2.76, 95% CI: 1.83-4.15, I: 65%). Subgroup analysis of participants demonstrated the better performance of PCR in detecting P. ovale malaria in indigenous cases (p: 0.0009, OR: 6.92, 95% CI: 2.21-21.7%, I: 68%) than in imported cases (p: 0.0004, OR: 2.15, 95% CI: 1.41-3.29%, I: 63%). P. ovale infections misidentified as P. vivax malaria by the microscopic method were frequent and led to underreported P. ovale cases. The molecular identification of P. ovale malaria in endemic areas is needed because a higher rate of P. ovale misidentification was found in endemic or indigenous cases than in imported cases. In addition, updated courses, enhanced training, and refreshers for microscopic examinations, particularly for P. ovale identification, are necessary to improve the microscopic identification of Plasmodium species in rural health centres where PCR is unavailable.
Topics: Diagnostic Errors; Humans; Malaria, Vivax; Microscopy; Plasmodium ovale; Plasmodium vivax
PubMed: 33311528
DOI: 10.1038/s41598-020-78691-7 -
Expert Opinion on Drug Safety Mar 2021: A century-long history in 8-aminoquinolines, the only anti-malaria drug class preventing malaria relapse, has resulted in the approval of tafenoquine by the U.S. Food... (Meta-Analysis)
Meta-Analysis
: A century-long history in 8-aminoquinolines, the only anti-malaria drug class preventing malaria relapse, has resulted in the approval of tafenoquine by the U.S. Food and Drug Administration (FDA) and the Australian Therapeutic Goods Administration (TGA) and to date registration in Brazil and Thailand. Tafenoquine is an alternative anti-relapse treatment for vivax malaria and malaria prophylaxis. It should not be given in pregnancy, during lactation of infants with glucose-6-phosphate dehydrogenase (G6PD) unknown or deficient status, and in those with G6PD deficiency or psychiatric illness.: This systematic review assesses tafenoquine associated adverse events in English-language, human clinical trials. Meta-analysis of commonly reported adverse events was conducted and grouped by comparison arms.: Tafenoquine, either for radical cure or prophylaxis, is generally well tolerated in adults. There is no convincing evidence for neurologic, ophthalmic, and cardiac toxicities. Psychotic disorder which has been attributed to higher doses is a contraindication for the chemoprophylaxis indication and psychiatric illness is a warning for the radical cure indication. Pregnancy assessment and quantitative G6PD testing are required. The optimal radical curative regimen including the tafenoquine dose along with its safety for parts of Southeast Asia, South America, and Oceania needs further assessment.
Topics: Adult; Aminoquinolines; Animals; Antimalarials; Dose-Response Relationship, Drug; Glucosephosphate Dehydrogenase Deficiency; Humans; Malaria, Vivax; Mental Disorders
PubMed: 33306921
DOI: 10.1080/14740338.2021.1859476 -
Tropical Biomedicine Jun 2020After a centenary fight against malaria, Brazil has seen an opportunity for change with the proposal of the malaria elimination policy set by the Brazilian government,...
After a centenary fight against malaria, Brazil has seen an opportunity for change with the proposal of the malaria elimination policy set by the Brazilian government, in line with malaria elimination policies in other Latin American countries. Brazilian malaria experts regard eliminating malaria by 2030 to be within reach. Herein we evaluated the likelihood that malaria elimination can be accomplished in Brazil through systematic review of the literature on malaria elimination in Brazil and epidemiological analysis. Fifty-two articles referring to malaria eradication/elimination in Brazil were analyzed to identify challenges and technological breakthroughs for controlling malaria. Monthly deaths (1979-2016) and monthly severe malaria cases (1998-2018) were analyzed according to age groups, geographic region and parasite species. As a result, we observed that the declining malaria burden was mostly attributable to a decline in At the same time, the proportional increase of -malaria in comparison with -malaria was notable. This niche replacement mechanism was discussed in the reviewed literature. In addition, the challenges to -malaria elimination outnumbered the available technological breakthroughs. Although accumulated and basic information exists on mosquito vector biology, the lack of specific knowledge about mosquito vector taxonomy and ecology may hamper current attempts at stopping malaria in the country. An impressive reduction in malaria hospitalizations and mortality was seen in Brazil in the past 3 decades. Eliminating malaria deaths in children less than 5 years and severe cases may be achievable goals under the current malaria policy until 2030. However, eliminating malaria transmission and morbidity seems unattainable with the available tools. Therefore, complete malaria elimination in Brazil in the near future is unlikely.
Topics: Antimalarials; Brazil; Disease Eradication; Humans; Malaria; Malaria, Falciparum; Malaria, Vivax; Policy
PubMed: 33235398
DOI: No ID Found -
Malaria Journal Nov 2020Malaria still represents a major health threat, in terms of both morbidity and mortality. Complications of malaria present a diversified clinical spectrum, with...
BACKGROUND
Malaria still represents a major health threat, in terms of both morbidity and mortality. Complications of malaria present a diversified clinical spectrum, with neurological involvement leading to the most serious related-conditions. The authors recently encountered a case of a 60-year old Italian man presenting with confusion, language disturbances and Parkinson-like syndrome 3 weeks after complete remission from severe Plasmodium falciparum cerebral malaria. Chemical and microbiological analysis revealed aseptic meningitis, diffuse encephalitis and abnormal immune-activation. Re-infection and recrudescence of infection were excluded. Further analysis excluded paraneoplastic and autoimmune causes of encephalitis. A diagnosis of Post-Malaria Neurological Syndrome (PMNS) was finally formulated and successfully treated with high dose of steroids.
METHODS
A systematic research of current literature related to PMNS was performed.
RESULTS
151 cases of PMNS were included, the majority of which occurred after severe P. falciparum infections. Four main clinical pattern were identified: 37% of the cases presented as "classical" PMNS, 36% presented as delayed cerebellar ataxia (DCA), 18% resembled acute inflammatory demyelinating polyneuropathy (AIDP), and 8% presented as acute disseminated encephalomyelitis (ADEM)-like form. Differentiation between different forms was not always simple, as clinical and radiological findings frequently overlap. Overall, in almost all of the tested cases, cerebrospinal fluid was found pathological; EEG revealed nonspecific encephalopathy in 30% of classical PMNS and 67% ADEM; imaging tests were found abnormal in 92% of ADEM-like forms. Pathogenesis remains unclear. An autoimmune mechanism is the most corroborated pathogenic hypothesis. Overall, the majority of PMNS cases revert without specific treatment. In most severe forms, high dose steroids, intravenous immunoglobulins, and plasmapheresis have been shown to improve symptoms.
CONCLUSIONS
PMNS is a disabling complication of malaria. The overall incidence is not known, due to frequent misdiagnosis and under-reporting. Pathogenesis is not also fully understood, but rapid response to immune-modulating treatment along with similarities to auto-immune neurological disease, strongly support a dysregulated immunological genesis of this condition. The lack of randomized controlled studies regarding therapeutic approaches is a major unmet need in this setting. A systematic collection of all the PMNS cases would be desirable, in order to increase awareness of this rare condition and to prospectively investigate the most appropriate management.
Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Female; Humans; Infant; Italy; Malaria, Falciparum; Malaria, Vivax; Male; Middle Aged; Nervous System Diseases; Syndrome; Young Adult
PubMed: 33228672
DOI: 10.1186/s12936-020-03476-2 -
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 -
The Cochrane Database of Systematic... Nov 2020Plasmodium vivax (P vivax) is a focus of malaria elimination. It is important because P vivax and Plasmodium falciparum infection are co-endemic in some areas. There are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Plasmodium vivax (P vivax) is a focus of malaria elimination. It is important because P vivax and Plasmodium falciparum infection are co-endemic in some areas. There are asymptomatic carriers of P vivax, and the treatment for P vivax and Plasmodium ovale malaria differs from that used in other types of malaria. Rapid diagnostic tests (RDTs) will help distinguish P vivax from other malaria species to help treatment and elimination. There are RDTs available that detect P vivax parasitaemia through the detection of P vivax-specific lactate dehydrogenase (LDH) antigens.
OBJECTIVES
To assess the diagnostic accuracy of RDTs for detecting P vivax malaria infection in people living in malaria-endemic areas who present to ambulatory healthcare facilities with symptoms suggestive of malaria; and to identify which types and brands of commercial tests best detect P vivax malaria.
SEARCH METHODS
We undertook a comprehensive search of the following databases up to 30 July 2019: Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (PubMed); Embase (OVID); Science Citation Index Expanded (SCI-EXPANDED) and Conference Proceedings Citation Index-Science (CPCI-S), both in the Web of Science.
SELECTION CRITERIA
Studies comparing RDTs with a reference standard (microscopy or polymerase chain reaction (PCR)) in blood samples from patients attending ambulatory health facilities with symptoms suggestive of malaria in P vivax-endemic areas.
DATA COLLECTION AND ANALYSIS
For each included study, two review authors independently extracted data using a pre-piloted data extraction form. The methodological quality of the studies were assessed using a tailored Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. We grouped studies according to commercial brand of the RDT and performed meta-analysis when appropriate. The results given by the index tests were based on the antibody affinity (referred to as the strength of the bond between an antibody and an antigen) and avidity (referred to as the strength of the overall bond between a multivalent antibody and multiple antigens). All analyses were stratified by the type of reference standard. The bivariate model was used to estimate the pooled sensitivity and specificity with 95% confidence intervals (CIs), this model was simplified when studies were few. We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
We included 10 studies that assessed the accuracy of six different RDT brands (CareStart Malaria Pf/Pv Combo test, Falcivax Device Rapid test, Immuno-Rapid Malaria Pf/Pv test, SD Bioline Malaria Ag Pf/Pv test, OnSite Pf/Pv test and Test Malaria Pf/Pv rapid test) for detecting P vivax malaria. One study directly compared the accuracy of two RDT brands. Of the 10 studies, six used microscopy, one used PCR, two used both microscopy and PCR separately and one used microscopy corrected by PCR as the reference standard. Four of the studies were conducted in Ethiopia, two in India, and one each in Bangladesh, Brazil, Colombia and Sudan. The studies often did not report how patients were selected. In the patient selection domain, we judged the risk of bias as unclear for nine studies. We judged all studies to be of unclear applicability concern. In the index test domain, we judged most studies to be at low risk of bias, but we judged nine studies to be of unclear applicability concern. There was poor reporting on lot testing, how the RDTs were stored, and background parasitaemia density (a key variable determining diagnostic accuracy of RDTs). Only half of the included studies were judged to be at low risk of bias in the reference standard domain, Studies often did not report whether the results of the reference standard could classify the target condition or whether investigators knew the results of the RDT when interpreting the results of the reference standard. All 10 studies were judged to be at low risk of bias in the flow and timing domain. Only two brands were evaluated by more than one study. Four studies evaluated the CareStart Malaria Pf/Pv Combo test against microscopy and two studies evaluated the Falcivax Device Rapid test against microscopy. The pooled sensitivity and specificity were 99% (95% CI 94% to 100%; 251 patients, moderate-certainty evidence) and 99% (95% CI 99% to 100%; 2147 patients, moderate-certainty evidence) for CareStart Malaria Pf/Pv Combo test. For a prevalence of 20%, about 206 people will have a positive CareStart Malaria Pf/Pv Combo test result and the remaining 794 people will have a negative result. Of the 206 people with positive results, eight will be incorrect (false positives), and of the 794 people with a negative result, two would be incorrect (false negative). For the Falcivax Device Rapid test, the pooled sensitivity was 77% (95% CI: 53% to 91%, 89 patients, low-certainty evidence) and the pooled specificity was 99% (95% CI: 98% to 100%, 621 patients, moderate-certainty evidence), respectively. For a prevalence of 20%, about 162 people will have a positive Falcivax Device Rapid test result and the remaining 838 people will have a negative result. Of the 162 people with positive results, eight will be incorrect (false positives), and of the 838 people with a negative result, 46 would be incorrect (false negative).
AUTHORS' CONCLUSIONS
The CareStart Malaria Pf/Pv Combo test was found to be highly sensitive and specific in comparison to microscopy for detecting P vivax in ambulatory healthcare in endemic settings, with moderate-certainty evidence. The number of studies included in this review was limited to 10 studies and we were able to estimate the accuracy of 2 out of 6 RDT brands included, the CareStart Malaria Pf/Pv Combo test and the Falcivax Device Rapid test. Thus, the differences in sensitivity and specificity between all the RDT brands could not be assessed. More high-quality studies in endemic field settings are needed to assess and compare the accuracy of RDTs designed to detect P vivax.
Topics: Ambulatory Care; Antigens, Protozoan; Bias; Endemic Diseases; False Negative Reactions; False Positive Reactions; Humans; Malaria, Vivax; Microscopy; Plasmodium vivax; Point-of-Care Testing; Polymerase Chain Reaction; Reagent Kits, Diagnostic; Reference Standards; Sensitivity and Specificity; Species Specificity
PubMed: 33146932
DOI: 10.1002/14651858.CD013218.pub2 -
The Cochrane Database of Systematic... Sep 2020Plasmodium vivax malaria has a persistent liver stage that causes relapse of the disease and continued P vivax transmission. Primaquine (PQ) is used to clear the liver... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Plasmodium vivax malaria has a persistent liver stage that causes relapse of the disease and continued P vivax transmission. Primaquine (PQ) is used to clear the liver stage of the parasite, but treatment is required for 14 days. Primaquine also causes haemolysis in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Tafenoquine (TQ) is a new alternative to PQ with a longer half-life and can be used as a single-dose treatment.
OBJECTIVES
To assess the effects of tafenoquine 300 mg (single dose) on preventing P vivax relapse.
SEARCH METHODS
We searched the following up to 3 June 2020: the Cochrane Infectious Diseases Group Specialized Register; CENTRAL; MEDLINE; Embase; and three other databases. We also searched the WHO International Clinical Trial Registry Platform and the metaRegister of Controlled Trials for ongoing trials using "tafenoquine" and "malaria" as search terms up to 3 June 2020.
SELECTION CRITERIA
Randomized controlled trials (RCTs) that gave TQ to prevent relapse in people with P vivax malaria. We planned to include trials irrespective of whether participants had been screened for G6PD enzyme deficiency.
DATA COLLECTION AND ANALYSIS
All review authors independently extracted data and assessed risk of bias. As true relapse and reinfection are difficult to differentiate in people living in endemic areas, studies report "recurrences" of infection as a proxy for relapse. We carried out meta-analysis where appropriate, and gave estimates as risk ratios (RR) with 95% confidence intervals (CI). We assessed the certainty of the evidence using the GRADE approach.
MAIN RESULTS
Three individually randomized RCTs met our inclusion criteria, all in endemic areas, and thus reporting recurrence. Trials compared TQ with PQ or placebo, and all participants received chloroquine (CQ) to treat the asexual infection). In all trials, pregnant and G6PD-deficient people were excluded. Tafenoquine 300 mg single dose versus no treatment for relapse prevention Two trials assessed this comparison. TQ 300 mg single dose reduces P vivax recurrences compared to no antihypnozoite treatment during a six-month follow-up, but there is moderate uncertainty around effect size (RR 0.32, 95% CI 0.12 to 0.88; 2 trials, 504 participants; moderate-certainty evidence). In people with normal G6PD status, there is probably little or no difference in any type of adverse events (2 trials, 504 participants; moderate-certainty evidence). However, we are uncertain if TQ causes more serious adverse events (2 trials, 504 participants; very low-certainty evidence). Both RCTs reported a total of 23 serious adverse events in TQ groups (One RCT reported 21 events) and a majority (15 events) were a drop in haemoglobin level by > 3g/dl (or >30% reduction from baseline). Tafenoquine 300 mg single dose versus primaquine 15 mg/day for 14 days for relapse prevention Three trials assessed this comparison. There is probably little or no difference between TQ and PQ in preventing recurrences (proxy measure for relapse) up to six months of follow-up (RR 1.04, 95% CI 0.8 to 1.34; 3 trials, 747 participants; moderate-certainty evidence). In people with normal G6PD status, there is probably little or no difference in any type of adverse events (3 trials, 747 participants; moderate-certainty evidence). We are uncertain if TQ can cause more serious adverse events compared to PQ (3 trials, 747 participants; very low-certainty evidence). Two trials had higher point estimates against TQ while the other showed the reverse. Most commonly reported serious adverse event in TQ group was a decline in haemoglobin level (19 out of 29 events). Some other serious adverse events, though observed in the TQ group, are unlikely to be caused by it (Hepatitis E infection, limb abscess, pneumonia, menorrhagia).
AUTHORS' CONCLUSIONS
TQ 300 mg single dose prevents relapses after clinically parasitologically confirmed P vivax malaria compared to no antihypnozoite treatment, and with no difference detected in studies comparing it to PQ to date. However, the inability to differentiate a true relapse from a recurrence in the available studies may affect these estimates. The drug is untested in children and in people with G6PD deficiency. Single-dose treatment is an important practical advantage compared to using PQ for the same purpose without an overall increase in adverse events in non-pregnant, non-G6PD-deficient adults.
Topics: Adult; Aminoquinolines; Antimalarials; Chloroquine; Drug Administration Schedule; Glucosephosphate Dehydrogenase Deficiency; Humans; Malaria, Vivax; Parasitemia; Placebos; Primaquine; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention
PubMed: 32892362
DOI: 10.1002/14651858.CD010458.pub3 -
The Cochrane Database of Systematic... Aug 2020Plasmodium vivax liver stages (hypnozoites) may cause relapses, prolonging morbidity, and impeding malaria control and elimination. The World Health Organization (WHO)...
BACKGROUND
Plasmodium vivax liver stages (hypnozoites) may cause relapses, prolonging morbidity, and impeding malaria control and elimination. The World Health Organization (WHO) recommends three schedules for primaquine: 0.25 mg/kg/day (standard), or 0.5 mg/kg/day (high standard) for 14 days, or 0.75 mg/kg once weekly for eight weeks, all of which can be difficult to complete. Since primaquine can cause haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, clinicians may be reluctant to prescribe primaquine without G6PD testing, and recommendations when G6PD status is unknown must be based on an assessment of the risks and benefits of prescribing primaquine. Alternative safe and efficacious regimens are needed.
OBJECTIVES
To assess the efficacy and safety of alternative primaquine regimens for radical cure of P vivax malaria compared to the standard or high-standard 14-day courses.
SEARCH METHODS
We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (Ovid); LILACS (BIREME); WHO International Clinical Trials Registry Platform and ClinicalTrials.gov up to 2 September 2019, and checked the reference lists of all identified studies.
SELECTION CRITERIA
Randomized controlled trials (RCTs) of adults and children with P vivax malaria using either chloroquine or artemisinin-based combination therapy plus primaquine at a total adult dose of at least 210 mg, compared with the WHO-recommended regimens of 0.25 or 0.5 mg/kg/day for 14 days.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial eligibility and quality, and extracted data. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous data. We grouped efficacy data according to length of follow-up, partner drug, and trial location. We analysed safety data where included.
MAIN RESULTS
0.5 mg/kg/day for seven days versus standard 0.25 mg/kg/day for 14 days There may be little or no difference in P vivax recurrences at six to seven months when using the same total dose (210 mg adult dose) over seven days compared to 14 days (RR 0.96, 95% CI 0.66 to 1.39; 4 RCTs, 1211 participants; low-certainty evidence). No serious adverse events were reported. We do not know if there is any difference in the number of adverse events resulting in discontinuation of primaquine (RR 1.04, 95% CI 0.15 to 7.38; 5 RCTs, 1427 participants) or in the frequency of anaemia (RR 3.00, 95% CI 0.12 to 72.91, 1 RCT, 240 participants) between the shorter and longer regimens (very low-certainty evidence). Three trials excluded people with G6PD deficiency; two did not provide this information. Pregnant and lactating women were either excluded or no details were provided. High-standard 0.5 mg/kg/day for 14 days versus standard 0.25 mg/kg/day for 14 days There may be little or no difference in P vivax recurrences at six months with 0.5 mg/kg/day primaquine for 14 days compared to 0.25 mg/kg/day for 14 days (RR 0.84 (95% CI 0.49 to 1.43; 2 RCTs, 677 participants, low-certainty evidence). No serious adverse events were reported. We do not know whether there is a difference in adverse events resulting in discontinuation of treatment with the high-standard dosage (RR 4.19, 95% CI 0.90 to 19.60; 1 RCT, 778 participants, very low-certainty evidence). People with G6PD deficiency and pregnant or lactating women were excluded. 0.75 mg/kg/week for eight weeks versus high-standard 0.5 mg/kg/day for 14 days We do not know whether weekly primaquine increases or decreases recurrences of P vivax compared to high-standard 0.5 mg/kg/day for 14 days, at 11 months' follow-up (RR 3.18, 95% CI 0.37 to 27.60; 1 RCT, 122 participants; very low-certainty evidence). No serious adverse events and no episodes of anaemia were reported. G6PD-deficient patients were not randomized but included in the weekly primaquine group (only one patient detected). 1 mg/kg/day for seven days versus high standard 0.5 mg/kg/day for 14 days There is probably little or no difference in P vivax recurrences at 12 months between 1.0 mg/kg/day primaquine for seven days and the high-standard 0.5 mg/kg/day for 14 days (RR 1.03, 95% CI 0.82 to 1.30; 2 RCTs, 2526 participants; moderate-certainty evidence). There may be moderate to large increase in serious adverse events in the 1.0 mg/kg/day primaquine for seven days compared with the high-standard 0.5 mg/kg/day for 14 days, during 42 days follow-up (RR 12.03, 95% CI 1.57 to 92.30; 1 RCT, 1872 participants, low-certainty evidence). We do not know if there is a difference between 1.0 mg/kg/day primaquine for seven days and high-standard 0.5 mg/kg/day for 14 days in adverse events that resulted in discontinuation of treatment (RR 2.50, 95% CI 0.49 to 12.87; 1 RCT, 2526 participants, very low-certainty evidence), nor if there is difference in frequency of anaemia by 42 days (RR 0.93, 95% CI 0.62 to 1.41; 2 RCTs, 2440 participants, very low-certainty evidence). People with G6PD deficiency were excluded. Other regimens Two RCTs evaluated other rarely-used doses of primaquine, one of which had very high loss to follow-up. Adverse events were not reported. People with G6PD deficiency and pregnant or lactating women were excluded.
AUTHORS' CONCLUSIONS
Trials available to date do not detect a difference in recurrence between the following regimens: 1) 0.5 mg/kg/day for seven days versus standard 0.25 mg/kg/day for 14 days; 2) high-standard 0.5 mg/kg/day for 14 days versus standard 0.25 mg/kg/day for 14 days; 3) 0.75 mg/kg/week for eight weeks versus high-standard 0.5 mg/kg/day for 14 days; 4) 1 mg/kg/day for seven days versus high-standard 0.5 mg/kg/day for 14 days. There were no differences detected in adverse events for Comparisons 1, 2 or 3, but there may be more serious adverse events with the high seven-day course in Comparison 4. The shorter regimen of 0.5 mg/kg/day for seven days versus standard 0.25 mg/kg/day for 14 days may suit G6PD-normal patients. Further research will help increase the certainty of the findings and applicability in different settings.
Topics: Adult; Antimalarials; Child; Drug Administration Schedule; Glucosephosphate Dehydrogenase; Humans; Malaria, Vivax; Primaquine; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention
PubMed: 32816320
DOI: 10.1002/14651858.CD012656.pub3 -
Scientific Reports Jul 2020Malaria rapid diagnostic tests (RDTs) are widely used to detect malaria parasites among patients who suspected malaria infections in malaria-endemic areas where... (Comparative Study)
Comparative Study Meta-Analysis
Summary of discordant results between rapid diagnosis tests, microscopy, and polymerase chain reaction for detecting Plasmodium mixed infection: a systematic review and meta-analysis.
Malaria rapid diagnostic tests (RDTs) are widely used to detect malaria parasites among patients who suspected malaria infections in malaria-endemic areas where microscopy is unavailable. Nevertheless, little is known about the performance of RDTs in detecting Plasmodium mixed infections. The present study aimed to evaluate the discordant results between RDTs and microscopy/polymerase chain reaction (PCR) in detecting Plasmodium mixed infections. The PubMed (MEDLINE), Web of Science, and Scopus databases were systematically reviewed to identify related studies that reported the performance of RDTs in detecting Plasmodium mixed infections. Studies were grouped according to the different RDT types including RDT type 2 (pf-HRP2/pan-aldolase), RDT type 3 (pf-HRP2/pan-pLDH), RDT type 4 (Pf-LDH/pan-pLDH), RDT type 5 (Pf/Pv-pLDH), and RDT type 6 (pf-HRP2/Pv-pLDH) for subgroup analysis. The estimates of the different proportions in each analysis group that were visually summarized in a forest plot showed the odds ratio (OR) and 95% confidence interval (CI). Plots were drawn using RevMan (version 5.3; Cochrane Community). Twenty-eight studies were included in the present study. Overall, the meta-analysis showed that RDTs could detect a significantly higher proportion of Plasmodium mixed infections than microscopy (p = 0.0007, OR = 3.33, 95% CI 1.66-6.68). Subgroup analysis demonstrated that only RDTs targeting Pf-specific histidine-rich protein 2 (HRP2)/pan-specific lactate dehydrogenase (LDH) could detect a significantly higher proportion of Plasmodium mixed infections than microscopy (p = 0.004, OR = 8.46, 95% CI 2.75-26.1). The subgroup analysis between RDTs and PCR methods demonstrated that RDTs targeting Pf-specific HRP2/Pv-specific LDH could detect a significantly lower proportion of Plasmodium mixed infections than PCR methods (p = 0.0005, OR = 0.42, 95% CI 0.26-0.68). This is the first study to summarize the discordant results between RDTs and microscopy/PCR in detecting Plasmodium mixed infections. Malaria RDTs targeting Pf-HRP2/pan-pLDH could detect a higher proportion of Plasmodium mixed infections than microscopy, while RDTs targeting Pf-HRP2/Pv-specific LDH could detect a lower proportion of Plasmodium mixed infections than PCR methods. The results of this study will support the selection and careful interpretations of RDTs for a better diagnosis of Plasmodium mixed-species infections and appropriate treatment of malaria patients in endemic and non-endemic settings.
Topics: Antigens, Protozoan; Cross-Sectional Studies; Diagnostic Tests, Routine; Humans; Malaria, Falciparum; Malaria, Vivax; Microscopy; Odds Ratio; Plasmodium falciparum; Plasmodium vivax; Polymerase Chain Reaction; Protozoan Proteins; Sensitivity and Specificity
PubMed: 32728145
DOI: 10.1038/s41598-020-69647-y