Dataset Information

Association of glucose-6-phosphate dehydrogenase deficiency and malaria: a systematic review and meta-analysis.

ABSTRACT: Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency overlaps with malaria endemicity although it predisposes carriers to hemolysis. This fact supports the protection hypothesis against malaria. The aim of this systematic review is to assess the presence and the extent of protective association between G6PD deficiency and malaria. Thirteen databases were searched for papers reporting any G6PD alteration in malaria patients. Twenty-eight of the included 30 studies were eligible for the meta-analysis. Results showed absence of negative association between G6PD deficiency and uncomplicated falciparum malaria (odds ratio (OR), 0.77; 95% confidence interval (CI), 0.59-1.02; p?=?0.07). However, this negative association happened in Africa (OR, 0.59; 95% CI, 0.40-0.86; p?=?0.007) but not in Asia (OR, 1.24; 95% CI, 0.96-1.61; p?=?0.10), and in the heterozygotes (OR, 0.70; 95% CI, 0.57-0.87; p?=?0.001) but not the homo/hemizygous (OR, 0.70; 95% CI, 0.46-1.07; p?=?0.10). There was no association between G6PD deficiency and total severe malaria (OR, 0.82; 95% CI, 0.61-1.11; p?=?0.20). Similarly, there was no association with other malaria species. G6PD deficiency can potentially protect against uncomplicated malaria in African countries, but not severe malaria. Interestingly, this protection was mainly in heterozygous, being x-linked thus related to gender.

SUBMITTER: Mbanefo EC

PROVIDER: S-EPMC5382680 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Association of glucose-6-phosphate dehydrogenase deficiency and malaria: a systematic review and meta-analysis.

Mbanefo Evaristus Chibunna EC Ahmed Ali Mahmoud AM Titouna Afaf A Elmaraezy Ahmed A Trang Nguyen Thi Huyen NT Phuoc Long Nguyen N Hoang Anh Nguyen N Diem Nghi Tran T The Hung Bui B Van Hieu Mai M Ky Anh Nguyen N Huy Nguyen Tien NT Hirayama Kenji K

Scientific reports 20170406

Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency overlaps with malaria endemicity although it predisposes carriers to hemolysis. This fact supports the protection hypothesis against malaria. The aim of this systematic review is to assess the presence and the extent of protective association between G6PD deficiency and malaria. Thirteen databases were searched for papers reporting any G6PD alteration in malaria patients. Twenty-eight of the included 30 studies were eligible for the meta-analys ...[more]

PMID: 28382932

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Project description: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.

Project description:BackgroundHyperbilirubinaemia is a silent cause of newborn disease and death worldwide. However, studies of the disease in sub-Saharan Africa are highly variable with respect to its prevalence. Hence, this study aimed to estimate the overall magnitude of neonatal hyperbilirubinaemia and its association with glucose-6-phosphate dehydrogenase (G6PD) deficiency and blood-type incompatibility in sub-Saharan Africa.MethodsPubMed, Scopus, Google Scholar and the Cochrane Review were systematically searched online to retrieve hyperbilirubinaemia-related articles. All observational studies reported the prevalence of hyperbilirubinaemia in sub-Saharan Africa were included for analysis and excluded if the study failed to determine the desired outcome. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Heterogeneity across the included studies was evaluated using the inconsistency index (I2). Subgroup and meta- regression analysis were also done. Publication bias was examined by funnel plot and the Egger's regression test. The random-effect model was fitted to estimate the pooled prevalence of neonatal hyperbilirubinaemia. The meta-analysis was performed using the STATA V.14 software.ResultsA total of 30 486 studies were collected from the different databases and 10 articles were included for the final analysis. The overall magnitude of neonatal hyperbilirubinaemia was 28.08% (95% CI20.23 to 35.94, I2=83.2) in sub-Saharan Africa. Neonates with G6PD deficiency (OR 2.42, 95% CI 1.64 to 3.56, I2=37%) and neonates that had a blood type that was incompatible with their mother's (OR 3.3, (95% CI 1.96 to 5.72, I2=84%) were more likely to develop hyperbilirubinaemia.ConclusionThe failure to prevent and screen G6PD deficiency and blood-type incompatibility with their mother's results in high burden of neonatal hyperbilirubinaemia in sub-Saharan Africa. Therefore, early identification and care strategies should be developed to the affected neonates with G6PD deficiency and blood-type incompatibility with their mother's to address long-term medical and scholastic damages among those exposed to hyperbilirubinaemia.

Project description:BackgroundTo reduce the risk of drug-induced haemolysis, all patients should be tested for glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd) prior to prescribing primaquine (PQ)-based radical cure for the treatment of vivax malaria. This systematic review and individual patient meta-analysis assessed the utility of a qualitative lateral flow assay from Access Bio/CareStart (Somerset, NJ) (CareStart Screening test for G6PD deficiency) for the diagnosis of G6PDd compared to the gold standard spectrophotometry (International Prospective Register of Systematic Reviews [PROSPERO]: CRD42019110994).Methods and findingsArticles published on PubMed between 1 January 2011 and 27 September 2019 were screened. Articles reporting performance of the standard CSG from venous or capillary blood samples collected prospectively and considering spectrophotometry as gold standard (using kits from Trinity Biotech PLC, Wicklow, Ireland) were included. Authors of articles fulfilling the inclusion criteria were contacted to contribute anonymized individual data. Minimal data requested were sex of the participant, CSG result, spectrophotometry result in U/gHb, and haemoglobin (Hb) reading. The adjusted male median (AMM) was calculated per site and defined as 100% G6PD activity. G6PDd was defined as an enzyme activity of less than 30%. Pooled estimates for sensitivity and specificity, unconditional negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR-) were calculated comparing CSG results to spectrophotometry using a random-effects bivariate model. Of 11 eligible published articles, individual data were available from 8 studies, 6 from Southeast Asia, 1 from Africa, and 1 from the Americas. A total of 5,815 individual participant data (IPD) were available, of which 5,777 results (99.3%) were considered for analysis, including data from 3,095 (53.6%) females. Overall, the CSG had a pooled sensitivity of 0.96 (95% CI 0.90-0.99) and a specificity of 0.95 (95% CI 0.92-0.96). When the prevalence of G6PDd was varied from 5% to 30%, the unconditional NPV was 0.99 (95% CI 0.94-1.00), with an LR+ and an LR- of 18.23 (95% CI 13.04-25.48) and 0.05 (95% CI 0.02-0.12), respectively. Performance was significantly better in males compared to females (p = 0.027) but did not differ significantly between samples collected from capillary or venous blood (p = 0.547). Limitations of the study include the lack of wide geographical representation of the included data and that the CSG results were generated under research conditions, and therefore may not reflect performance in routine settings.ConclusionsThe CSG performed well at the 30% threshold. Its high NPV suggests that the test is suitable to guide PQ treatment, and the high LR+ and low LR- render the test suitable to confirm and exclude G6PDd. Further operational studies are needed to confirm the utility of the test in remote endemic settings.

Dataset Information

Association of glucose-6-phosphate dehydrogenase deficiency and malaria: a systematic review and meta-analysis.

Publications

Association of glucose-6-phosphate dehydrogenase deficiency and malaria: a systematic review and meta-analysis.

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