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The Cochrane Database of Systematic... 2000Despite continued efforts to control the disease, malaria remains a major health problem in many regions of the world, especially sub-Saharan Africa, and new ways to... (Review)
Review
BACKGROUND
Despite continued efforts to control the disease, malaria remains a major health problem in many regions of the world, especially sub-Saharan Africa, and new ways to control or eradicate the disease are urgently needed. Two types of vaccine, SPf66 vaccine against the asexual stages, and NANP vaccines against the sporozoite stages of the Plasmodium parasite, have been tested in randomised clinical trials in endemic areas.
OBJECTIVES
To assess the effects of malaria vaccines.
SEARCH STRATEGY
The Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles were searched. Organisations and researchers in the field were contacted.
SELECTION CRITERIA
Randomised trials comparing vaccines against Plasmodium falciparum, P. vivax, P. malariae or P. ovale, and placebo.
DATA COLLECTION AND ANALYSIS
Two independent reviewers assessed trial quality and conducted data extraction.
MAIN RESULTS
Thirteen efficacy trials involving about 7700 people were included. There were nine trials of the Spf66 vaccine and four trials of the NANP vaccines. There was large heterogeneity between trials when investigating the effect of SPf66 in reducing incidence of the first attack of P. falciparum malaria. When trials were subcategorised by location, there was no evidence for effect of SPf66 in reducing incidence of P. falciparum in four African trials conducted in children under 5 years of age (Peto odds ratio [OR] = 0.96, 95% confidence interval [CI] 0.81 to 1.14). In five trials outside Africa with participants aged 2 years to adult, there was a reduction in incidence by SPf66 vaccine (Peto OR = 0.77, 95% CI 0.67 to 0.88, fixed effects model). Significant heterogeneity remained between trials conducted outside Africa. Using a random effects model for these five trials, the OR was 0.74 (95% CI 0.54 to 1.01). In five trials, there was no evidence for effect of the SPf66 vaccine on the incidence of the first attack of P. vivax malaria (OR 1.01, 95% CI 0.87 to 1.17). Trials to date have not indicated any severe adverse effects of SPf66 vaccine. In three trials of NANP-based vaccines, there was no evidence for protection by these vaccines against P. falciparum malaria (OR 1.12, 95% CI 0.64 to 1.93).
REVIEWER'S CONCLUSIONS
There is no evidence for protection by SPf66 vaccines against P. falciparum in Africa. There is a modest reduction in attacks of P. falciparum malaria following vaccination with SPf66 in other regions. Further research with SPf66 vaccines in South America may be justified. Trials to date have not been of sufficient size to evaluate the effect of malaria vaccines on mortality or on severe malaria requiring admission to hospital. There was not enough evidence to evaluate the use of NANP vaccines.
Topics: Adult; Humans; Malaria; Malaria Vaccines; Malaria, Falciparum; Protozoan Proteins; Recombinant Proteins
PubMed: 10796492
DOI: 10.1002/14651858.CD000129 -
Malaria Journal Feb 2016Pregnancy has been reported to alter the pharmacokinetic properties of anti-malarial drugs, including the different components of artemisinin-based combination therapy... (Review)
Review
BACKGROUND
Pregnancy has been reported to alter the pharmacokinetic properties of anti-malarial drugs, including the different components of artemisinin-based combination therapy (ACT). However, small sample sizes make it difficult to draw strong conclusions based on individual pharmacokinetic studies. The aim of this review is to summarize the evidence of the influence of pregnancy on the pharmacokinetic properties of different artemisinin-based combinations.
METHODS
A PROSPERO-registered systematic review to identify clinical trials that investigated the influence of pregnancy on the pharmacokinetic properties of different forms of ACT 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 2015. The following components of ACT that are currently recommend by the World Health Organization as first-line treatment of malaria in pregnancy were reviewed: artemisinin, artesunate, dihydroartemisinin, lumefantrine, amodiaquine, mefloquine, sulfadoxine, pyrimethamine, piperaquine, atovaquone and proguanil.
RESULTS
The literature search identified 121 reports, 27 original studies were included. 829 pregnant women were included in the analysis. Comparison of the available studies showed lower maximum concentrations (Cmax) and exposure (AUC) of dihydroartemisinin, the active metabolite of all artemisinin derivatives, after oral administration of artemether, artesunate and dihydroartemisinin in pregnant women. Low day 7 concentrations were commonly seen in lumefantrine studies, indicating a low exposure and possibly reduced efficacy. The influence of pregnancy on amodiaquine and piperaquine seemed not to be clinically relevant. Sulfadoxine plasma concentration was significantly reduced and clearance rates were higher in pregnancy, while pyrimethamine and mefloquine need more research as no general conclusion can be drawn based on the available evidence. For atovaquone, the available data showed a lower maximum concentration and exposure. Finally, the maximum concentration of cycloguanil, the active metabolite of proguanil, was significantly lower, possibly compromising the efficacy.
CONCLUSION
These findings suggest that reassessment of the dose of the artemisinin derivate and some components of ACT are necessary to ensure the highest possible efficacy of malaria treatment in pregnant women. However, for most components of ACT, data were insufficient and extensive research with larger sample sizes will be necessary to identify the exact influences of pregnancy on the pharmacokinetic properties of different artemisinin-based combinations. In addition, different clinical studies used diverse study designs with various reported relevant outcomes. Future pharmacokinetic studies could benefit from more uniform designs, in order to increase quality, robustness and effectiveness.
STUDY REGISTRATION
CRD42015023756 (PROSPERO).
Topics: Antimalarials; Artemisinins; Drug Combinations; Female; Humans; Malaria; Plasmodium falciparum; Plasmodium ovale; Plasmodium vivax; Pregnancy
PubMed: 26891915
DOI: 10.1186/s12936-016-1160-6 -
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