-
The Cochrane Database of Systematic... 2003Four types of malaria vaccine, SPf66 and MSP/RESA vaccines (against the asexual stages of the Plasmodium parasite) and CS-NANP and RTS,S vaccines (against the sporozoite... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Four types of malaria vaccine, SPf66 and MSP/RESA vaccines (against the asexual stages of the Plasmodium parasite) and CS-NANP and RTS,S vaccines (against the sporozoite stages), have been tested in randomized controlled trials in endemic areas.
OBJECTIVES
To assess malaria vaccines against Plasmodium falciparum, P. vivax, P. malariae and P ovale in preventing infection, disease and death.
SEARCH STRATEGY
We searched the Cochrane Infectious Diseases Group trials register (July 2002), the Cochrane Controlled Trials Register (The Cochrane Library Issue 2, 2002), MEDLINE (1966 to July 2002), EMBASE (1980 to May 2002), Science Citation Index (1981 to July 2002), and reference lists of articles. We also contacted organizations and researchers in the field.
SELECTION CRITERIA
Randomized controlled trials comparing vaccines against Plasmodium falciparum, P. vivax, P. malariae or P. ovale with placebo or routine antimalarial control measures in people of any age receiving a challenge malaria infection.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed trial quality and extracted data.
MAIN RESULTS
Eighteen efficacy trials involving 10,971 participants were included. There were ten trials of SPf66 vaccine, four trials of CS-NANP vaccines, two trials of RTS,S vaccine, and two of MSP/RESA vaccine. Results with SPf66 in reducing new malaria infections (P. falciparum) were heterogeneous: it was not effective in four African trials (Peto odds ratio (OR) 0.96, 95% confidence interval (CI) 0.81 to 1.14), but in five trials outside Africa the number of first attacks was reduced (Peto OR 0.77, 95% CI 0.67 to 0.88). Trials to date have not indicated any serious adverse events with SPf66 vaccine. In three trials of CS-NANP vaccines, there was no evidence for protection by these vaccines against P. falciparum malaria (Peto OR 1.12, 95% CI 0.64 to 1.93). In a small trial in non-immune adults in the USA, RTS,S gave strong protection against experimental infection with P. falciparum. In a trial in an endemic area of the Gambia in semi-immune people, there was a reduction in clinical malaria episodes in the second year of follow up, corresponding to a vaccine efficacy of 66% (CI 14% to 85%). In a trial in Papua New Guinea, MSP/RESA had no protective effect against episodes of clinical malaria. There was evidence of an effect on parasite density, but this differed according to whether the participants had been pretreated with sulfadoxine/pyrimethamine or not. The prevalence of infections with the parasite subtype of MSP2 in the vaccine was reduced compared with the other subtype (Peto OR 0.35, CI 0.23 to 0.53).
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 or with new formulations of SPf66 may be justified. There was not enough evidence to evaluate the use of CS-NANP vaccines. The RTS,S vaccine showed promising result, as did the MSP/RESA vaccine, but it should include the other main allelic form of MSP2. The MSP/RESA trial demonstrated that chemotherapy during a vaccine trial may reduce vaccine efficacy, and trials should consider very carefully whether this practice is justified.
Topics: Adult; Antigens, Protozoan; Humans; Malaria; Malaria Vaccines; Malaria, Falciparum; Protozoan Proteins; Randomized Controlled Trials as Topic; Recombinant Proteins; Vaccines, Synthetic
PubMed: 12535387
DOI: 10.1002/14651858.CD000129 -
The American Journal of Tropical... Sep 2020and form dormant liver hypnozoites that can reactivate weeks to months following initial infection. Malaria recurrences caused by relapses are an important cause of... (Meta-Analysis)
Meta-Analysis
and form dormant liver hypnozoites that can reactivate weeks to months following initial infection. Malaria recurrences caused by relapses are an important cause of morbidity and source of transmission. To estimate the proportions of malaria recurrences caused by relapses in different geographical locations, we systematically reviewed clinical efficacy studies of uncomplicated malaria, in which patients were randomized to treatment with or without radical cure primaquine regimens and were followed up for 1 year. The minimum proportion of recurrences caused by relapses was estimated for each study site by assuming primaquine prevented all relapses and did not augment blood-stage efficacy. Of the 261 studies identified, six were eligible enrolling 4,092 patients from 14 treatment arm comparisons across seven countries. Of the 2,735 patients treated with primaquine, 24.3% received low dose (2.5 to < 5.0 mg/kg total) and 75.7% received high-dose primaquine (≥ 5.0 mg/kg total). The overall pooled incidence rate ratio of relapses for patients treated with primaquine versus no primaquine was 0.15 (95% CI: 0.10-0.21; = 83.3%), equating to a minimum of 79% of recurrences attributable to relapse. Country-specific incidence rate ratios ranged from 0.05 (95% CI: 0.01-0.34; one estimate) in Pakistan to 0.34 in Nepal (95% CI: 0.12-0.83; one estimate) and Afghanistan (95% CI: 0.22-0.51; three estimates). Relapses account for a very high proportion of recurrent infections following schizontocidal treatment of acute malaria across diverse geographic locations. This emphasizes the importance of implementing hypnozoitocidal treatment.
Topics: Antimalarials; Geography; Humans; Malaria; Malaria, Vivax; Plasmodium vivax; Primaquine; Recurrence
PubMed: 32524950
DOI: 10.4269/ajtmh.20-0186 -
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 -
The Cochrane Database of Systematic... Jul 2007Four types of malaria vaccine, SPf66 and MSP/RESA vaccines (against the asexual stages of the Plasmodium parasite) and CS-NANP and RTS,S vaccines (against the sporozoite... (Review)
Review
BACKGROUND
Four types of malaria vaccine, SPf66 and MSP/RESA vaccines (against the asexual stages of the Plasmodium parasite) and CS-NANP and RTS,S vaccines (against the sporozoite stages), have been tested in randomized controlled trials in endemic areas.
OBJECTIVES
To assess malaria vaccines against Plasmodium falciparum, P. vivax, P. malariae and P ovale in preventing infection, disease and death.
SEARCH STRATEGY
We searched the Cochrane Infectious Diseases Group Specialized Register (April 2004), CENTRAL (The Cochrane Library Issue 2, 2004), MEDLINE (1966 to April 2004), EMBASE (1980 to April 2004), Science Citation Index (1981 to April 2004), and reference lists of articles. We also contacted organizations and researchers in the field.
SELECTION CRITERIA
Randomized controlled trials comparing vaccines against Plasmodium falciparum, P. vivax, P. malariae or P. ovale with placebo or routine antimalarial control measures in people of any age receiving a challenge malaria infection.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed trial quality and extracted data.
MAIN RESULTS
Eighteen efficacy trials involving 10,971 participants were included. There were ten trials of SPf66 vaccine, four trials of CS-NANP vaccines, two trials of RTS,S vaccine, and two of MSP/RESA vaccine. Results with SPf66 in reducing new malaria infections (P. falciparum) were heterogeneous: it was not effective in four African trials (Peto odds ratio (OR) 0.96, 95% confidence interval (CI) 0.81 to 1.14), but in five trials outside Africa the number of first attacks was reduced (Peto OR 0.77, 95% CI 0.67 to 0.88). Trials to date have not indicated any serious adverse events with SPf66 vaccine. In three trials of CS-NANP vaccines, there was no evidence for protection by these vaccines against P. falciparum malaria (Peto OR 1.12, 95% CI 0.64 to 1.93). In a small trial in non-immune adults in the USA, RTS,S gave strong protection against experimental infection with P. falciparum. In a trial in an endemic area of the Gambia in semi-immune people, there was a reduction in clinical malaria episodes in the second year of follow up, corresponding to a vaccine efficacy of 66% (CI 14% to 85%). In a trial in Papua New Guinea, MSP/RESA had no protective effect against episodes of clinical malaria. There was evidence of an effect on parasite density, but this differed according to whether the participants had been pretreated with sulfadoxine/pyrimethamine or not. The prevalence of infections with the parasite subtype of MSP2 in the vaccine was reduced compared with the other subtype (Peto OR 0.35, CI 0.23 to 0.53).
AUTHORS' 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 or with new formulations of SPf66 may be justified. There was not enough evidence to evaluate the use of CS-NANP vaccines. The RTS,S vaccine showed promising result, as did the MSP/RESA vaccine, but it should include the other main allelic form of MSP2. The MSP/RESA trial demonstrated that chemotherapy during a vaccine trial may reduce vaccine efficacy, and trials should consider very carefully whether this practice is justified.
Topics: Adult; Antigens, Protozoan; Humans; Malaria; Malaria Vaccines; Malaria, Falciparum; Protozoan Proteins; Randomized Controlled Trials as Topic; Recombinant Proteins; Vaccines, Synthetic
PubMed: 17636596
DOI: 10.1002/14651858.CD000129.pub2 -
The Cochrane Database of Systematic... Apr 2006A malaria vaccine is badly needed. SPf66 was one of the earliest vaccines developed. It is a synthetic peptide vaccine containing antigens from the blood stages of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A malaria vaccine is badly needed. SPf66 was one of the earliest vaccines developed. It is a synthetic peptide vaccine containing antigens from the blood stages of malaria linked together with an antigen from the sporozoite stage, and is targeted mainly against the blood (asexual) stages.
OBJECTIVES
To assess the effect of SPf66 malaria vaccines against Plasmodium falciparum, P. vivax, P. malariae, and P. ovale in preventing infection, disease, and death.
SEARCH STRATEGY
We searched the Cochrane Infectious Diseases Group Specialized Register (September 2005), CENTRAL (The Cochrane Library 2005, Issue 3), MEDLINE (1966 to September 2005), EMBASE (1980 to September 2005), LILACS (1982 to September 2005), Science Citation Index (1981 to September 2005), and reference lists of articles. We also contacted organizations and researchers in the field.
SELECTION CRITERIA
Randomized and quasi-randomized controlled trials comparing SPf66 vaccine with placebo or routine antimalarial control measures in people of any age receiving an artificial challenge or natural exposure to malaria infection (any species).
DATA COLLECTION AND ANALYSIS
Two people independently assessed trial quality and extracted data, including adverse events. Results were expressed as relative risks (RR) with 95% confidence intervals (CI).
MAIN RESULTS
Ten efficacy trials of SPf66 involving 9698 participants were included. Results with SPf66 in reducing new episodes of P. falciparum malaria were heterogeneous: it was not effective in four African trials (RR 0.98, 95% CI 0.90 to 1.07; 2371 participants) or in one Asian trial (RR 1.06, 95% CI 0.90 to 1.25; 1221 participants). In four trials in South America the number of first attacks with P. falciparum was reduced by 28% (RR 0.72, 95% CI 0.63 to 0.82; 3807 participants). It did not reduce episodes of P. vivax malaria or admission to hospital with severe malaria. Trials have not indicated any serious adverse events with SPf66 vaccine.
AUTHORS' 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 South America. There is no justification for further trials of SPf66 in its current formulation. Further research with SPf66 vaccines in South America or with new formulations of SPf66 may be justified.
Topics: Humans; Malaria; Malaria Vaccines; Protozoan Proteins; Randomized Controlled Trials as Topic; Recombinant Proteins; Vaccines, Synthetic
PubMed: 16625647
DOI: 10.1002/14651858.CD005966 -
Malaria Journal Jan 2018Transfusion-transmitted malaria (TTM) is an accidental Plasmodium infection caused by whole blood or a blood component transfusion from a malaria infected donor to a...
BACKGROUND
Transfusion-transmitted malaria (TTM) is an accidental Plasmodium infection caused by whole blood or a blood component transfusion from a malaria infected donor to a recipient. Infected blood transfusions directly release malaria parasites in the recipient's bloodstream triggering the development of high risk complications, and potentially leading to a fatal outcome especially in individuals with no previous exposure to malaria or in immuno-compromised patients. A systematic review was conducted on TTM case reports in non-endemic areas to describe the epidemiological characteristics of blood donors and recipients.
METHODS
Relevant articles were retrieved from Pubmed, EMBASE, Scopus, and LILACS. From each selected study the following data were extracted: study area, gender and age of blood donor and recipient, blood component associated with TTM, Plasmodium species, malaria diagnostic method employed, blood donor screening method, incubation period between the infected transfusion and the onset of clinical symptoms in the recipient, time elapsed between the clinical symptoms and the diagnosis of malaria, infection outcome, country of origin of the blood donor and time of the last potential malaria exposure.
RESULTS
Plasmodium species were detected in 100 TTM case reports with a different frequency: 45% Plasmodium falciparum, 30% Plasmodium malariae, 16% Plasmodium vivax, 4% Plasmodium ovale, 2% Plasmodium knowlesi, 1% mixed infection P. falciparum/P. malariae. The majority of fatal outcomes (11/45) was caused by P. falciparum whilst the other fatalities occurred in individuals infected by P. malariae (2/30) and P. ovale (1/4). However, non P. falciparum fatalities were not attributed directly to malaria. The incubation time for all Plasmodium species TTM case reports was longer than what expected in natural infections. This difference was statistically significant for P. malariae (p = 0.006). A longer incubation time in the recipient together with a chronic infection at low parasite density of the donor makes P. malariae a subtle but not negligible risk for blood safety aside from P. falciparum.
CONCLUSIONS
TTM risk needs to be taken into account in order to enhance the safety of the blood supply chain from donors to recipients by means of appropriate diagnostic tools.
Topics: Blood Transfusion; Humans; Malaria; Plasmodium; Transfusion Reaction
PubMed: 29338786
DOI: 10.1186/s12936-018-2181-0 -
PloS One 2021In Sub-Saharan Africa (SSA), where malaria transmission is stable, malaria infection in pregnancy adversely affects pregnant women, fetuses, and newborns and is often... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In Sub-Saharan Africa (SSA), where malaria transmission is stable, malaria infection in pregnancy adversely affects pregnant women, fetuses, and newborns and is often asymptomatic. So far, a plethora of primary studies have been carried out on asymptomatic malaria infection in pregnant women in SSA. Nevertheless, no meta-analysis estimated the burden of asymptomatic malaria infection in pregnant women in SSA, so this meta-analysis was carried out to bridge this gap.
METHODS
PubMed, Web of Science, Scopus, Embase, and ProQuest were systematically searched for relevant studies published until 4 August 2020, and also the expansion of the search was performed by October 24, 2020. We assessed heterogeneity among included studies using I-squared statistics (I2). Publication bias was assessed by visual inspection of the funnel plot and further quantitatively validated by Egger's and Begg's tests. The pooled prevalence and pooled odds ratio (OR) and their corresponding 95% Confidence Interval (CI) were estimated using the random-effects model in Stata 15 software.
RESULTS
For this meta-analysis, we included 35 eligible studies. The overall prevalence estimate of asymptomatic Plasmodium infection prevalence was 26.1%% (95%CI: 21-31.2%, I2 = 99.0%). According to species-specific pooled prevalence estimate, Plasmodium falciparum was dominant species (22.1%, 95%CI: 17.1-27.2%, I2 = 98.6%), followed by Plasmodium vivax, Plasmodium malariae and Plasmodium ovale, respectively, found to be 3% (95%CI: 0-5%, I2 = 88.3%), 0.8% (95%CI: 0.3-0.13%, I2 = 60.5%), and 0.2% (95%CI: -0.01-0.5%, I2 = 31.5%). Asymptomatic malaria-infected pregnant women were 2.28 times more likely anemic (OR = 2.28, 95%CI: 1.66-3.13, I2 = 56.3%) than in non-infected pregnant women. Asymptomatic malaria infection was 1.54 times higher (OR = 1.54, 95%CI: 1.28-1.85, I2 = 11.5%) in primigravida women compared to multigravida women.
CONCLUSION
In SSA, asymptomatic malaria infection in pregnant women is prevalent, and it is associated with an increased likelihood of anemia compared to non-infected pregnant women. Thus, screening of asymptomatic pregnant women for malaria and anemia should be included as part of antenatal care.
Topics: Africa South of the Sahara; Asymptomatic Infections; Coinfection; Female; Humans; Malaria; Plasmodium falciparum; Pregnancy; Pregnancy Complications, Parasitic; Prenatal Care; Prevalence
PubMed: 33793584
DOI: 10.1371/journal.pone.0248245 -
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 -
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 -
PLoS Medicine May 2020The radical cure of Plasmodium vivax and P. ovale requires treatment with primaquine or tafenoquine to clear dormant liver stages. Either drug can induce haemolysis in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The radical cure of Plasmodium vivax and P. ovale requires treatment with primaquine or tafenoquine to clear dormant liver stages. Either drug can induce haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, necessitating screening. The reference diagnostic method for G6PD activity is ultraviolet (UV) spectrophotometry; however, a universal G6PD activity threshold above which these drugs can be safely administered is not yet defined. Our study aimed to quantify assay-based variation in G6PD spectrophotometry and to explore the diagnostic implications of applying a universal threshold.
METHODS AND FINDINGS
Individual-level data were pooled from studies that used G6PD spectrophotometry. Studies were identified via PubMed search (25 April 2018) and unpublished contributions from contacted authors (PROSPERO: CRD42019121414). Studies were excluded if they assessed only individuals with known haematological conditions, were family studies, or had insufficient details. Studies of malaria patients were included but analysed separately. Included studies were assessed for risk of bias using an adapted form of the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Repeatability and intra- and interlaboratory variability in G6PD activity measurements were compared between studies and pooled across the dataset. A universal threshold for G6PD deficiency was derived, and its diagnostic performance was compared to site-specific thresholds. Study participants (n = 15,811) were aged between 0 and 86 years, and 44.4% (7,083) were women. Median (range) activity of G6PD normal (G6PDn) control samples was 10.0 U/g Hb (6.3-14.0) for the Trinity assay and 8.3 U/g Hb (6.8-15.6) for the Randox assay. G6PD activity distributions varied significantly between studies. For the 13 studies that used the Trinity assay, the adjusted male median (AMM; a standardised metric of 100% G6PD activity) varied from 5.7 to 12.6 U/g Hb (p < 0.001). Assay precision varied between laboratories, as assessed by variance in control measurements (from 0.1 to 1.5 U/g Hb; p < 0.001) and study-wise mean coefficient of variation (CV) of replicate measures (from 1.6% to 14.9%; p < 0.001). A universal threshold of 100% G6PD activity was defined as 9.4 U/g Hb, yielding diagnostic thresholds of 6.6 U/g Hb (70% activity) and 2.8 U/g Hb (30% activity). These thresholds diagnosed individuals with less than 30% G6PD activity with study-wise sensitivity from 89% (95% CI: 81%-94%) to 100% (95% CI: 96%-100%) and specificity from 96% (95% CI: 89%-99%) to 100% (100%-100%). However, when considering intermediate deficiency (<70% G6PD activity), sensitivity fell to a minimum of 64% (95% CI: 52%-75%) and specificity to 35% (95% CI: 24%-46%). Our ability to identify underlying factors associated with study-level heterogeneity was limited by the lack of availability of covariate data and diverse study contexts and methodologies.
CONCLUSIONS
Our findings indicate that there is substantial variation in G6PD measurements by spectrophotometry between sites. This is likely due to variability in laboratory methods, with possible contribution of unmeasured population factors. While an assay-specific, universal quantitative threshold offers robust diagnosis at the 30% level, inter-study variability impedes performance of universal thresholds at the 70% level. Caution is advised in comparing findings based on absolute G6PD activity measurements across studies. Novel handheld quantitative G6PD diagnostics may allow greater standardisation in the future.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antimalarials; Child; Child, Preschool; Female; Glucosephosphate Dehydrogenase; Glucosephosphate Dehydrogenase Deficiency; Humans; Infant; Infant, Newborn; Malaria; Male; Middle Aged; Spectrophotometry; Young Adult
PubMed: 32407380
DOI: 10.1371/journal.pmed.1003084