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International Journal of Infectious... Sep 2020Diagnosis is a challenging issue for eliminating malaria. Loop-mediated isothermal amplification (LAMP) could be an alternative to conventional methods. This study aimed... (Comparative Study)
Comparative Study Meta-Analysis
Systematic review and meta-analysis of diagnostic accuracy of loop-mediated isothermal amplification (LAMP) methods compared with microscopy, polymerase chain reaction and rapid diagnostic tests for malaria diagnosis.
BACKGROUND
Diagnosis is a challenging issue for eliminating malaria. Loop-mediated isothermal amplification (LAMP) could be an alternative to conventional methods. This study aimed to evaluate the diagnostic accuracy of LAMP for malaria compared with microscopy, polymerase chain reaction (PCR) and rapid diagnostic tests (RDTs).
METHODS AND DESIGN
MEDLINE, Web of Science and Scopus were searched from inception to 1 July 2019. Prospective and retrospective, randomised and non-randomised, mono-center and multi-center studies, including symptomatic or asymptomatic patients, that reported one LAMP method and one comparator (microscopy, RDT or PCR) were included. PROSPERO registration number: CRD42017075186.
RESULTS
Sixty-six studies published between 2006 and 2019 were included, leading to the analysis of 30,641 LAMP tests. The pooled sensitivity of LAMP remained between 96% and 98%, whichever the comparator. The pooled specificity of LAMP was around 95%, but was a little higher if the best PCR studies were considered. The AUC was found to be >0.98, whichever the subgroup of studies was considered. Diagnostic odds ratio (DOR) was found to be around 1000 for all subgroups, except for Plasmodium vivax.
CONCLUSION
This meta-analysis confirmed that the LAMP method is robust for diagnosing malaria, both in symptomatic and asymptomatic people. Thus, the impact of LAMP for controlling malaria is expected to be important.
Topics: Diagnostic Tests, Routine; Humans; Malaria; Microscopy; Nucleic Acid Amplification Techniques; Plasmodium; Polymerase Chain Reaction; Prospective Studies; Retrospective Studies; Sensitivity and Specificity
PubMed: 32659450
DOI: 10.1016/j.ijid.2020.07.009 -
International Emergency Nursing Jan 2022Malaria is a life-threatening disease. Prior to the pandemic, over a million people annually from non-endemic, high income countries such as Europe and North America... (Review)
Review
BACKGROUND
Malaria is a life-threatening disease. Prior to the pandemic, over a million people annually from non-endemic, high income countries such as Europe and North America visited countries with a risk of malaria transmission. Emergency care nurses in non-endemic countries frequently encounter returning travellers, presenting with symptoms suggestive of malaria. While rapid diagnostic tests are used in countries with endemic malaria, in countries such as the United Kingdom diagnosis is undertaken by microscopy and three negative tests are required to exclude.
QUESTION
Are rapid diagnostic tests effective for diagnosing imported malaria in non-endemic, high income countries?
METHOD
A systematic review of published research (January 2009 - November 2020) comparing rapid diagnostic tests with microscopy.
RESULTS
Fourteen studies were included, conducted in five countries with 14 different RDTs evaluated. Mean sensitivity and specificity for Plasmodium Falciparum was 91.8% and 97.7% and Plasmodium Vivax 81.6% and 99.2%. Higher sensitivities were related to higher parasite densities.
CONCLUSIONS
International travel will return post-pandemic and rapid, accurate and cost-efficient tests will be required. The rapid diagnostic tests in these studies showed significant variation and were not as accurate as microscopy. Consequently, it cannot be recommended that rapid diagnostic tests replace the gold standard of microscopy. Further research is required.
Topics: Developed Countries; Diagnostic Tests, Routine; Humans; Malaria; Plasmodium vivax; Sensitivity and Specificity
PubMed: 34953438
DOI: 10.1016/j.ienj.2021.101110 -
BMC Infectious Diseases May 2020Plasmodium vivax rarely develops severe complications when compared to severe falciparum malaria. However, severe vivax malaria also needs urgent, intensive care and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Plasmodium vivax rarely develops severe complications when compared to severe falciparum malaria. However, severe vivax malaria also needs urgent, intensive care and treatment as severe falciparum malaria. This systematic review aimed to explore pooled prevalence of severe vivax malaria and to identify factors related to poor outcome of patients who developed severe manifestation.
METHODS
The systematic review conducted by two reviewers independently through searching of research publications related to severe P. vivax malaria in three databases including MEDLINE, Web of Science (ISI), and Scopus until October, 22 2019. The pooled prevalence of severe vivax malaria was achieved using STATA and RevMan 5 Software. Factors related to poor outcome of patients with severe vivax malaria were analyzed using SPSS 11.5 Software.
RESULTS
Among 2615 research publications retrieved from three databases, 49 articles reporting on 42,325 severity cases were selected for calculating pooled prevalence. Seventy-six patients from case reports, case series, letter to editors, and research communications were collected to identify factors related to poor outcome of patients with severe vivax malaria. The results showed that severe anemia, jaundice, respiratory distress, impaired consciousness, and renal failure were the most common major manifestations of severe malaria guided by the World Health Organization (WHO) criterion. The meta-analysis indicated that severe malaria was less frequent in patient with P. vivax compared to those with P. falciparum (P -value < 0.00001, OR = 0.38, 95% CI = 0.25-0.56, I = 87%). In addition, thrombocytopenia, anemia, hepatitis, and severe thrombocytopenia were the most common minor complications. Analysis of cases indicated that convulsion, respiratory distress, renal failure, jaundice, anuria/oliguria, and complication during treatment impacted on longer hospital stays compared to other severe complications (P-value < 0.05). Respiratory distress was frequently found after first treatment with anti-malarial drugs (P-value = 0.002). Renal failure was frequently found before treatment with anti-malarial drugs (P-value = 0.016). Mean days of fever and higher pulse rates at presentation were predictors of poor outcome among patients with severe vivax malaria (P-value < 0.05).
CONCLUSIONS
Severe anemia was the most common major manifestation of P. vivax malaria guided by the WHO criterion. Severe anemia was found less frequently in patients with P. vivax than those with P. falciparum. Renal failure, jaundice, anuria/oliguria, and complication during treatment along with, mean days of fever and higher pulse rates at presentation might be predictors of poor outcome of patients with severe vivax malaria.
Topics: Adult; Anemia; Antimalarials; Anuria; Female; Fever; Heart Rate; Humans; Jaundice; Malaria, Falciparum; Malaria, Vivax; Male; Oliguria; Plasmodium falciparum; Plasmodium vivax; Prevalence; Renal Insufficiency; Risk Factors; Severity of Illness Index; Thrombocytopenia; Treatment Outcome; World Health Organization; Young Adult
PubMed: 32448216
DOI: 10.1186/s12879-020-05046-y -
Malaria Journal Sep 2021Rapid accurate diagnosis followed by effective treatment is very important for malaria control. Light microscopy remains the "golden standard" method for malaria... (Meta-Analysis)
Meta-Analysis
Performance of rapid diagnostic tests, microscopy, loop-mediated isothermal amplification (LAMP) and PCR for malaria diagnosis in Ethiopia: a systematic review and meta-analysis.
BACKGROUND
Rapid accurate diagnosis followed by effective treatment is very important for malaria control. Light microscopy remains the "golden standard" method for malaria diagnosis. Diagnostic test method must have sufficient level of accuracy for detecting malaria parasites. Therefore, this study aimed to investigate the diagnostic accuracy of rapid diagnostic tests (RDTs), microscopy, loop-mediated isothermal amplification (LAMP) and/or polymerase chain reaction (PCR) for the malaria diagnosis in Ethiopia.
METHODS
Data bases such as PubMed, PubMed central, Science direct databases, Google scholar, and Scopus were searched from September to October, 2020 for studies assessing the diagnostic accuracy of RDTs, microscopy, LAMP and PCR methods for malaria diagnosis.
RESULTS
A total of 29 studies published between 2001 and 2020 were analysed using review manager, Midas (Stata) and Meta-disc. The sensitivity and specificity of studies comparing RDT with microscopy varies from 79%-100% to 80%-100%, respectively. The sensitivity of LAMP (731 tests) was 100% and its specificity was varies from 85 to 99% when compared with microscopy and PCR. Considerable heterogeneity was observed between studies included in this meta-analysis. Meta-regression showed that blinding status and target antigens were the major sources of heterogeneity (P < 0.05). RDT had an excellent diagnostic accuracy (Area under the ROC Curve = 0.99) when compared with microscopy. Its specificity was quite good (93%-100%) except for one outlier (28%), but lower "sensitivity" was observed when PCR is a reference test. This indicates RDT had a good diagnostic accuracy (AUC = 0.83). Microscopy showed a very good diagnostic accuracy when compared with PCR.
CONCLUSIONS
The present study showed that microscopy and RDTs had high efficiency for diagnosing febrile malaria patients. The diagnostic accuracy of RDT was excellent when compared with microscopy. This indicates RDTs have acceptable sensitivities and specificities to be used in resource poor settings as an alternative for microscopy. In this study, LAMP showed an excellent sensitivities and specificities. Furthermore, the need of minimum equipment and relatively short time for obtaining results can made LAMP one of the best alternatives especially for accurate diagnosis of asymptomatic malaria.
Topics: Diagnostic Tests, Routine; Ethiopia; Humans; Malaria; Microscopy; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Polymerase Chain Reaction
PubMed: 34579729
DOI: 10.1186/s12936-021-03923-8 -
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 -
Malaria Journal Jan 2021Globally, malaria is still a major public health challenge. Drug-based treatment is the primary intervention in malaria control and elimination. However, optimal use of...
BACKGROUND
Globally, malaria is still a major public health challenge. Drug-based treatment is the primary intervention in malaria control and elimination. However, optimal use of mass or targeted treatments remains unclear. A variety of radical, preventive and presumptive treatment regimens have been administrated in China and a systematic review was conducted to evaluate effectiveness, and discuss experiences, limitations, and lessons learnt in relation to the use of these regimens.
METHODS
The search for information includes both paper documents, such as books, malaria control annals and guidelines for malaria prevention and treatment, as well as three computer-based databases in Chinese (CNKI, WanFangdata and Xueshu.baidu) and two databases in English (PubMed and Google Scholar), to identify original articles and reports associated with drug administration for malaria in China.
RESULTS
Starting from hyperendemicity to elimination of malaria in China, a large number of radical, preventive and presumptive treatment regimens had been tried. Those effective regimens were scaled up for malaria control and elimination programmes in China. Between 1949 and 1959, presumptive treatment with available anti-malarial drugs was given to people with enlarged spleens and those who had symptoms suggestive of malaria within the last 6 months. Between 1960 and 1999, mass drug administration (MDA) was given for preventive and radical treatment. Between 2000 and 2009, the approach was more targeted, and drugs were administed only to prevent malaria infection in those at high risk of exposure and those who needed radical treatment for suspected malaria. Presumptive therapy was only given to febrile patients. From 2010, the malaria programme changed into elimination phase, radical treatment changed to target individuals with confirmed either Plasmodium vivax or Plasmodium ovale within the last year. Preventive treatment was given to those who will travel to other endemic countries. Presumptive treatment was normally not given during this elimination phase. All cases of suspected were confirmed by either microscopy or rapid diagnosis tests for malaria antigens before drugs were administered. The engagement of the broader community ensured high coverage of these drug-based interventions, and the directly-observed therapy improved patient safety during drug administration.
CONCLUSION
A large number of radical, preventive and presumptive treatment regimens for malaria had been tried in China with reported success, but the impact of drug-based interventions has been difficult to quantify because they are just a part of an integrated malaria control strategy. The historical experiences of China suggest that intervention trials should be done by the local health facilities with community involvement, and a local decision is made according to their own trial results.
Topics: Antimalarials; China; Humans; Malaria
PubMed: 33407512
DOI: 10.1186/s12936-020-03535-8 -
Parasite Epidemiology and Control Feb 2024Asymptomatic malaria during pregnancy is a significant public health concern in malaria-endemic regions, which worsens the various effects of malaria on the mother and... (Review)
Review
BACKGROUND
Asymptomatic malaria during pregnancy is a significant public health concern in malaria-endemic regions, which worsens the various effects of malaria on the mother and fetus and increases maternal and neonatal mortality. To date, no meta-analysis has been conducted on asymptomatic malaria in pregnant women in Ethiopia. Thus, we aimed to estimate the pooled prevalence of asymptomatic malaria and its associated factors in pregnant women in Ethiopia.
METHODS
PubMed/Medline, Google Scholar, Web of Science, Cochrane, AJOL, and Ethiopian University repositories were systematically searched to identify studies reporting the prevalence of asymptomatic malaria infection among pregnant women in Ethiopia. A random effects model was used to perform the analysis. The heterogeneity of the studies was assessed with the I-squared tests, and subgroup analyses were performed to identify the sources of heterogeneity.
RESULTS
Ten articles with 3277 study participants were included in this review. The pooled prevalence of asymptomatic malaria infection among pregnant women in Ethiopia was 7.03% (95% CI: 6.23-9.12); I = 81.2%). In the species-specific pooled prevalence estimate, Plasmodium falciparum prevalence was 5.34% (95%CI: 3.38-7.3; I2 = 87.8%), and Plasmodium vivax prevalence was 1.69% (95%CI: 1.2-5; I2 = 91.5%).Not using insecticide-treated bed nets [OR = 7.36, 95% CI (2.75, 19.73)], being primi-gravida [OR = 1.86, 95% CI (1.23, 2.82)]; lack of health education about malaria prevention [OR = 6.86, 95% CI (2.90, 11.44)] were predictors of asymptomatic malaria infection during pregnancy.
CONCLUSION
This study revealed that asymptomatic malaria was prevalent among pregnant women in Ethiopia. This suggests that relying merely on reported symptoms may result in missed malaria cases. Therefore, regular screening and treatment protocols for malaria are recommended in antenatal care. It is also crucial to ensure that pregnant women have access to insecticide-treated bed nets and other effective malaria prevention measures.
PubMed: 38323191
DOI: 10.1016/j.parepi.2024.e00339 -
PeerJ 2024COVID-19 and malaria cause significant morbidity and mortality globally. Co-infection of these diseases can worsen their impact on public health. This review aims to...
BACKGROUND
COVID-19 and malaria cause significant morbidity and mortality globally. Co-infection of these diseases can worsen their impact on public health. This review aims to synthesize literature on the clinical outcomes of COVID-19 and malaria co-infection to develop effective prevention and treatment strategies.
METHODS
A comprehensive literature search was conducted using MeSH terms and keywords from the start of the COVID-19 pandemic to January 2023. The review included original articles on COVID-19 and malaria co-infection, evaluating their methodological quality and certainty of evidence. It was registered in PROSPERO (CRD42023393562).
RESULTS
Out of 1,596 screened articles, 19 met the inclusion criteria. These studies involved 2,810 patients, 618 of whom had COVID-19 and malaria co-infection. Plasmodium falciparum and vivax were identified as causative organisms in six studies. Hospital admission ranged from three to 18 days. Nine studies associated co-infection with severe disease, ICU admission, assisted ventilation, and related complications. One study reported 6% ICU admission, and mortality rates of 3%, 9.4%, and 40.4% were observed in four studies. Estimated crude mortality rates were 10.71 and 5.87 per 1,000 person-days for patients with and without concurrent malaria, respectively. Common co-morbidities included Diabetes mellitus, hypertension, cardiovascular diseases, and respiratory disorders.
CONCLUSION
Most patients with COVID-19 and malaria co-infection experienced short-term hospitalization and mild to moderate disease severity. However, at presentation, co-morbidities and severe malaria were significantly associated with higher mortality or worse clinical outcomes. These findings emphasize the importance of early detection, prompt treatment, and close monitoring of patients with COVID-19 and malaria co-infection.
Topics: Humans; COVID-19; Coinfection; Malaria; SARS-CoV-2; Hospitalization; Comorbidity; Malaria, Falciparum
PubMed: 38646476
DOI: 10.7717/peerj.17160 -
Imported malaria in pregnancy in Europe: A systematic review of the literature of the last 25 years.Travel Medicine and Infectious Disease 2023Malaria during pregnancy is associated with a greater risk of complications for the mother and fetus. The aim of the study is to analyze the features of imported cases... (Review)
Review
BACKGROUND
Malaria during pregnancy is associated with a greater risk of complications for the mother and fetus. The aim of the study is to analyze the features of imported cases of malaria in pregnant women in Europe and evaluate which factors are associated with a non-favourable outcome.
METHODS
A computerized search of the literature was performed combining the terms plasmod*, malaria, pregnan*, maternal, gravid, parturient, expectant, and congenital, from January 1997 to July 2023.
RESULTS
28 articles reporting 57 cases of malaria in pregnant women immigrant in non-endemic areas were included. The patients mainly came from Sub-Saharan Africa. There were 10 asymptomatic cases, while the predominant clinical syndrome among the symptomatic women was fever associated with anaemia. The median latency period from permanence in endemic areas and diagnosis in European countries was 180 days (IQR 15-730). Pregnancy outcomes were favourable in 35 cases (61 %): all term pregnancies, no low-birth-weight newborns. There were 4 abortions; 1 child was delivered pre-term; 7 babies were reported to have a low birth weight; 10 cases of congenital malaria were documented. P. falciparum was found with a higher frequency in women with a favourable outcome, while P. vivax was, in all cases, associated with a worse prognosis.
CONCLUSIONS
Diagnosis of malaria in pregnant woman in non-endemic countries may be challenging and a delay in diagnosis may lead to an adverse outcome. Screening for malaria should be performed in pregnant women from endemic areas, especially if they present anaemia or fever.
Topics: Child; Female; Pregnancy; Infant, Newborn; Humans; Malaria; Malaria, Falciparum; Pregnancy Outcome; Malaria, Vivax; Anemia; Europe
PubMed: 38008239
DOI: 10.1016/j.tmaid.2023.102673 -
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