Molecular Characterization of G6PD Deficiency at a North Indian Centre: Implications for Diagnostic Testing Laboratories in Different Regions of India.
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ABSTRACT:
SUBMITTER: Singh N
PROVIDER: S-EPMC7573081 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background & objectivesAn outbreak of respiratory illness of unknown aetiology was reported from Hubei province of Wuhan, People's Republic of China, in December 2019. The outbreak was attributed to a novel coronavirus (CoV), named as severe acute respiratory syndrome (SARS)-CoV-2 and the disease as COVID-19. Within one month, cases were reported from 25 countries. In view of the novel viral strain with reported high morbidity, establishing early countrywide diagnosis to detect imported cases became critical. Here we describe the role of a countrywide network of VRDLs in early diagnosis of COVID-19.MethodsThe Indian Council of Medical Research (ICMR)-National Institute of Virology (NIV), Pune, established screening as well as confirmatory assays for SARS-CoV-2. A total of 13 VRDLs were provided with the E gene screening real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay. VRDLs were selected on the basis of their presence near an international airport/seaport and their past performance. The case definition for testing included all individuals with travel history to Wuhan and symptomatic individuals with travel history to other parts of China. This was later expanded to include symptomatic individuals returning from Singapore, Japan, Hong Kong, Thailand and South Korea.ResultsWithin a week of standardization of the test at NIV, all VRDLs could initiate testing for SARS-CoV-2. Till February 29, 2020, a total of 2,913 samples were tested. This included both 654 individuals quarantined in the two camps and others fitting within the case definition. The quarantined individuals were tested twice - at days 0 and 14. All tested negative on both occasions. Only three individuals belonging to different districts in Kerala were found to be positive.Interpretation & conclusionsSudden emergence of SARS-CoV-2 and its potential to cause a pandemic posed an unsurmountable challenge to the public health system of India. However, concerted efforts of various arms of the Government of India resulted in a well-coordinated action at each level. India has successfully demonstrated its ability to establish quick diagnosis of SARS-CoV-2 at NIV, Pune, and the testing VRDLs.
| S-EPMC7258754 | biostudies-literature
Project description:BackgroundPrimaquine is essential for malaria control and elimination since it is the only available drug preventing multiple clinical attacks by relapses of Plasmodium vivax. It is also the only therapy against the sexual stages of Plasmodium falciparum infectious to mosquitoes, and is thus useful in preventing malaria transmission. However, the difficulties of diagnosing glucose-6-phosphate dehydrogenase deficiency (G6PDd) greatly hinder primaquine's widespread use, as this common genetic disorder makes patients susceptible to potentially severe and fatal primaquine-induced haemolysis. The risk of such an outcome varies widely among G6PD gene variants.MethodsA literature review was conducted to identify surveys of G6PD variant frequencies among representative population groups. Informative surveys were assembled into two map series: (1) those showing the relative proportions of the different variants among G6PDd individuals; and (2) those showing allele frequencies of G6PD variants based on population surveys without prior G6PDd screening.ResultsVariants showed conspicuous geographic patterns. A limited repertoire of variants was tested for across sub-Saharan Africa, which nevertheless indicated low genetic heterogeneity predominated by the G6PD A(-202A) mutation, though other mutations were common in western Africa. The severe G6PD Mediterranean variant was widespread across western Asia. Further east, a sharp shift in variants was identified, with high variant heterogeneity in the populations of China and the Asia-Pacific where no single variant dominated.ConclusionsG6PD variants exhibited distinctive region-specific distributions with important primaquine policy implications. Relative homogeneity in the Americas, Africa, and western Asia contrasted sharply with the heterogeneity of variants in China, Southeast Asia and Oceania. These findings will inform rational risk assessments for primaquine in developing public health strategies for malaria control and elimination, and support the future development of regionally targeted policies. The major knowledge gaps highlighted here strongly advocate for further investigation of G6PD variant diversity and their primaquine-sensitivity phenotypes.
| S-EPMC3835423 | biostudies-literature
Project description:BackgroundRapid Diagnostic Tests (RDTs) for Ebola Virus Disease (EVD) at the point of care have the potential to increase access and acceptability of EVD testing and the speed of patient isolation and secure burials for suspect cases. A pilot program for EVD RDTs in high risk areas of Guinea was introduced in October 2015. This paper presents concordance data between EVD RDTs and PCR testing in the field as well as an assessment of the acceptability, feasibility, and quality assurance of the RDT program.Methods and findingsConcordance data were compiled from laboratory surveillance databases. The operational measures of the laboratory-based EVD RDT program were evaluated at all 34 sentinel sites in Guinea through: (1) a technical questionnaire filled by the lab technicians who performed the RDTs, (2) a checklist filled by the evaluator during the site visits, and (3) direct observation of the lab technicians performing the quality control test. Acceptability of the EVD RDT was good for technicians, patients, and families although many technicians (69.8%) expressed concern for their safety while performing the test. The feasibility of the program was good based on average technician knowledge scores (6.6 out of 8) but basic infrastructure, equipment, and supplies were lacking. There was much room for improvement in quality assurance of the program.ConclusionsThe implementation of new diagnostics in weak laboratory systems requires general training in quality assurance, biosafety and communication with patients in addition to specific training for the new test. Corresponding capacity building in terms of basic equipment and a long-term commitment to transfer supervision and quality improvement to national public health staff are necessary for successful implementation.
| S-EPMC5708756 | biostudies-literature
Project description:The SARS-CoV-2 pandemic showed limitations in human outbreak testing. Veterinary diagnostic laboratories (VDLs) possess capabilities to bolster emergency test capacity. Surveys from 26 participating VDLs found human SARS-CoV-2 testing was mutually beneficial, including One Health benefits. VDLs indicated testing >3.8 million human samples during the pandemic, which included some challenges.
| S-EPMC10826766 | biostudies-literature
Project description:Accurate diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency is required to avoid the risk of acute hemolysis associated with 8-aminoquinoline treatment. The performance of the BinaxNOW G6PD test compared with the quantitative spectrophotometric analysis of G6PD activity was assessed in 356 Plasmodium vivax-infected subjects in Brazil, Peru, Thailand, and India. In the quantitative assay, the median G6PD activity was 8.81 U/g hemoglobin (range = 0.05-20.19), with 11 (3%) subjects identified as deficient. Sensitivity of the BinaxNOW G6PD to detect deficient subjects was 54.5% (6 of 11), and specificity was 100% (345 of 345). Room temperatures inadvertently falling outside the range required to perform the rapid test (18-25°C) together with subtlety of color change and insufficient training could partially explain the low sensitivity found. Ensuring safe use of 8-aminoquinolines depends on additional development of simple, highly sensitive G6PD deficiency diagnostic tests suitable for routine use in malaria-endemic areas.
| S-EPMC4347383 | biostudies-literature
Project description:BackgroundPlasmodium vivax occurs as a latent infection of liver and a patent infection of red blood cells. Radical cure requires both blood schizontocidal and hypnozoitocidal chemotherapies. The hypnozoitocidal therapies available are primaquine and tafenoquine, 8-aminoquinoline drugs that can provoke threatening acute hemolytic anemia in patients having an X-linked G6PD-deficiency. Heterozygous females may screen as G6PD-normal prior to radical cure and go on to experience hemolytic crisis.Methods & findingsThis study examined G6PD phenotypes in 1928 female subjects living in malarious Sumba Island in eastern Indonesia to ascertain the prevalence of females vulnerable to diagnostic misclassification as G6PD-normal. All 367 (19%) females having <80% G6PD normal activity were genotyped. Among those, 103 (28%) were G6PD wild type, 251 (68·4%) were heterozygous, three (0·8%) were compound heterozygotes, and ten (2·7%) were homozygous deficient. The variants Vanua Lava, Viangchan, Coimbra, Chatham, and Kaiping occurred among them. Below the 70% of normal G6PD activity threshold, just 18 (8%) were G6PD-normal and 214 (92%) were G6PD-deficient. Among the 31 females with <30% G6PD normal activity were all ten homozygotes, all three compound heterozygotes, and just 18 were heterozygotes (7% of those).ConclusionsIn this population, most G6PD heterozygosity in females occurred between 30% and 70% of normal (69·3%; 183/264). The prevalence of females at risk of G6PD misclassification as normal by qualitative screening was 9·5% (183/1928). Qualitative G6PD screening prior to 8-aminoquinoline therapies against P. vivax may leave one in ten females at risk of hemolytic crisis, which may be remedied by point-of-care quantitative tests.
| S-EPMC8318249 | biostudies-literature
Project description:BackgroundOver the past decade, the incidence of malaria has steadily declined in Myanmar, with Plasmodium vivax becoming predominant. The resilience of P. vivax to malaria control is attributed to the parasite's ability to form hypnozoites in the host's liver, which can cause relapse. Primaquine is used to eliminate hypnozoites but can cause haemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals. It is thus necessary to estimate the frequency and variant types of G6PD deficiency in areas where primaquine will be widely used for P. vivax elimination.MethodsIn this study, a descriptive cross-sectional survey was conducted to determine the prevalence of G6PD deficiency in a population residing in Nay Pyi Taw, Myanmar, using a standard spectrophotometric assay, a rapid diagnostic test (RDT), Biosensor, and by genotyping G6PD variants.ResultsG6PD enzyme activity was determined from 772 leukocyte-depleted samples, with an adjusted male median G6PD activity value of 6.3 U/g haemoglobin. Using a cut-off value of 30% enzyme activity, the overall prevalence of G6PD deficiency was 10.8%. Genotyping of G6PD variants was performed for 536 samples, of which 131 contained mutations. The Mahidol variant comprised the majority, and males with the Mahidol variant showed lower G6PD enzyme activity. The G6PD Andalus variant, which has not been reported in Myanmar before, was also identified in this study.ConclusionThis study provides a G6PD enzyme activity reference value for the Myanmar population and further information on the prevalence and variants of G6PD deficiency among the Myanmar population; it also evaluates the feasibility of G6PD deficiency tests.
| S-EPMC10150473 | biostudies-literature
Project description:G6PD deficiency is a monogenic, X-linked genetic defect with a worldwide prevalence of around 400 million people and an overall prevalence of 8.5% in India. Hemolytic anemia is encountered in only a small proportion of patients with G6PD variants and is usually triggered by some exogenous agent. Although G6PD deficiency was reported in India more than 50 years ago, there are very few studies on molecular characterization and phenotypic correlation in G6PD deficient patients. We aimed to study the epidemiology and correlate the phenotypic expression with molecular genotypes in symptomatic G6PD deficient patients. All symptomatic hemolytic anaemia patients with a possible etiology of G6PD deficiency based on the clinical, hematological and biochemical parameters and reduced G6PD enzyme levels were included in this study. Molecular analysis of the G6PD gene was done by direct Sanger sequencing. From a total of 38 patients with hemolytic anemia suspected for G6PD deficiency, 24 patients had reduced G6PD enzyme levels and were included for the molecular analysis and mutations in the G6PD gene were identified in 21 of them (83.3%). The different mutations identified in our study include 6 patients with c.131C > G (G6PD Orissa), 3 patients with c.563C > T (G6PD Mediterranean), two patients with c.825G > T (G6PD Bangkok), one patient each with c.208T > C (G6PD Namouru), c.487G > A (G6PD Mahidol), c.949G > A (G6PD Kerala-Kalyan), c.100 G > A (G6PD Chatham), c.1178C > G (G6PD Nashville), c.1361 G > A (G6PD Andalus) and 4 patients with novel mutations (2 patients with c.1186C > T and 1 patient each with c.1288-2A > T and c.1372C > T. No disease causing genetic variants were identified in the other three cases. Co-inheritance of other red cell and hemoglobin disorders can modify the clinical phenotype of G6PD patients and the diagnostic accuracy can be improved by molecular characterization of the variant.
| S-EPMC7229042 | biostudies-literature
Project description:Although the rates of disease gene discovery have steadily increased with the expanding use of genome and exome sequencing by clinical and research laboratories, only ~16% of genes in the genome have confirmed disease associations. Here we describe our clinical laboratory's experience utilizing GeneMatcher, an online portal designed to promote disease gene discovery and data sharing. Since 2016, we submitted 246 candidates from 243 unique genes to GeneMatcher, of which 111 (45%) are now clinically characterized. Submissions meeting our candidate gene-reporting criteria based on a scoring system using patient and molecular-weighted evidence were significantly more likely to be characterized as of October 2021 versus genes that did not meet our clinical-reporting criteria (p = 0.025). We reported relevant findings related to these newly characterized gene-disease associations in 477 probands. In 218 (46%) instances, we issued reclassifications after an initial negative or candidate gene (uncertain) report. We coauthored 104 publications delineating gene-disease relationships, including descriptions of new associations (60%), additional supportive evidence (13%), subsequent descriptive cohorts (23%), and phenotypic expansions (4%). Clinical laboratories are pivotal for disease gene discovery efforts and can screen phenotypes based on genotype matches, contact clinicians of relevant cases, and issue proactive reclassification reports.
| S-EPMC9313781 | biostudies-literature
Project description:Evidence from India, a country with unique and distinct food intake patterns often characterized by lifelong adherence, may offer important insight into the role of diet in breast cancer etiology. We evaluated the association between Indian dietary patterns and breast cancer risk in a multi-centre case-control study conducted in the North Indian states of Punjab and Haryana. Eligible cases were women 30⁻69 years of age, with newly diagnosed, biopsy-confirmed breast cancer recruited from hospitals or population-based cancer registries. Controls (hospital- or population-based) were frequency matched to the cases on age and region (Punjab or Haryana). Information about diet, lifestyle, reproductive and socio-demographic factors was collected using a structured interviewer-administered questionnaire. All participants were characterized as non-vegetarians, lacto-vegetarians (those who consumed no animal products except dairy) or lacto-ovo-vegetarians (persons whose diet also included eggs). The study population included 400 breast cancer cases and 354 controls. Most (62%) were lacto-ovo-vegetarians. Breast cancer risk was lower in lacto-ovo-vegetarians compared to both non-vegetarians and lacto-vegetarians with odds ratios (95% confidence intervals) of 0.6 (0.3⁻0.9) and 0.4 (0.3⁻0.7), respectively. The unexpected difference between lacto-ovo-vegetarian and lacto-vegetarian dietary patterns could be due to egg-consumption patterns which requires confirmation and further investigation.
| S-EPMC6164652 | biostudies-literature