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   Table of Contents - Current issue
February 2023
Volume 16 | Issue 2
Page Nos. 49-96

Online since Monday, February 27, 2023

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Acknowledgment to Reviewers, 2022 p. 49

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Application of next-generation sequencing in thalassemia screening: A systematic review and meta-analysis p. 51
Xingyi Fang, Yi Gong, Yanlin Ma, Yuanhua Huang
Objective: To evaluate the value of next-generation sequencing (NGS) in the prevention and management of thalassemia. Methods: A systematic search was performed in eight databases including China Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese Scientific Journals Database, Wanfang database, PubMed, EMBASE, Web of Science, and Cochrane Library from the inception to 1 June 2022. Stata 17.0 and Review Manager 5.4 were used for the meta-analysis. Results: Nine studies containing 14794 participants were included in the meta-analysis. Compared with the routine genetic testing (including Gap-PCR and reverse dot blot), NGS had higher detection rates in screening thalassemia (RR 1.22, 95% CI 1.13-1.31, P<0.01), particularly for the α-thalassaemia mutation carriers (RR 1.24, 95% CI 1.07-1.44, P<0.01). However, no significant difference was found in the screening of β-thalassemia (RR 1.10, 95% CI 0.99-1.23, P>0.05). Conclusions: Compared with routine genetic testing, NGS had a higher detection rate in general, particularly in the detection of α-thalassemia.
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Treatment outcomes and adverse drug reactions among patients with drug–resistant tuberculosis receiving all-oral, long–term regimens: First record viewing report from Pakistan p. 58
Hira Aslam, Asad Omar, Razia Fatima, Usman Rasool, Aashifa Yaqoob, Waseem Ullah, Aamir Khan, Yusra Habib Khan, Tauqeer Hussain Mallhi
Objective: To assess the effectiveness and adverse drug reactions of all-oral regimens for patients with multidrug-resistant tuberculosis. Methods: This retrospective study was conducted at 10 Programmatic Management of Drug Resistant Tuberculosis sites in Punjab province of Pakistan. Patients receiving treatment for drug resistant tuberculosis from July 2019 to December 2020 with at least interim result i.e. 6th month culture conversion or final outcomes (cured, complete, lost to follow-up, failure, death) available, were included in the study. Data was extracted from electronic data management system. For the reporting and management of adverse drug events, active tuberculosis drug safety monitoring and management was implemented across all sites. All the data was analyzed using SPSS version 22. Results: Out of 947 drug resistant tuberculosis patients included in this study, 579 (68%) of the patients had final outcomes available. Of these, 384 (67.9%) successfully completed their treatment. Out of 368 (32%) patients who had their interim results available, all had their 6th month culture negative. Combining new medications was thought to result in serious adverse outcomes such as QT prolongation. However, this study did not record any severe adverse events among patients. Conclusions: All-oral regimens formulation guided by overall treatment effectiveness resulted in treatment outcomes comparable to those obtained with traditional injectable treatment.
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Coagulation abnormalities and their relationship with bleeding manifestations in patients with dengue-A single center observational study p. 65
Govind R Patel, Indu Thanvi, Mohammad Nadeem, Rahul Kanwaria
Objective: To evaluate coagulation abnormalities and their relationship with bleeding manifestations among patients with dengue. Methods: This observational study was conducted on 292 adult dengue patients who were admitted to a tertiary care hospital of Western India from July 2021 to June 2022. Coagulation tests including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, and D-dimer were performed. Patients were monitored for bleeding manifestations. Results: Coagulation abnormalities were reported in 42.8% of the patients. Overall, prolonged aPTT was the most common coagulation abnormality (40.8%), followed by low fibrinogen (38.7%), raised D-dimer (31.2%), raised INR (26.0%) and prolonged PT (19.2%). Bleeding manifestations were present in 19.9% patients. PT, INR, aPTT and D-dimer levels were significantly higher (P<0.01) and fibrinogen level was significantly lower (P<0.001) in patients with bleeding compared to patients without bleeding. Patients with bleeding had a significantly higher rate of all coagulation abnormalities than patients without bleeding (P<0.01). Conclusions: Patients with bleeding showed a significantly higher frequency of coagulation abnormalities compared to patients without bleeding. Patients with dengue should be assessed for coagulation abnormalities.
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Mutations in Plasmodium knowlesi Kelch protein 13 and the dihydropteroate synthase gene in clinical samples p. 72
Ahmed Saif
Objective: To determine the genetic diversity, natural selection and mutations in Plasmodium (P.) knowlesi drug resistant molecular markers Kelch 13 and dhps gene in clinical samples of Malaysia. Methods: P. knowlesi full-length gene sequences Kelch 13 gene (PkK13) from 40 samples and dhps gene from 30 samples originating from Malaysian Borneo were retrieved from public databases. Genetic diversity, natural selection, and phylogenetic analysis of gene sequences were analysed using DNAsp v5.10 and MEGA v5.2. Results: Seventy-two single nucleotide polymorphic sites (SNPs) across the full-length PkK13 gene (63 synonymous substitutions and 9 non-synonymous substitutions) with nucleotide diversity of π~0.005 was observed. Analysis of the full-length Pkdhps gene revealed 73 SNPs and π~0.006 (44 synonymous substitutions and 29 non-synonymous substitutions). A high number of haplotypes (PkK13; H=37 and Pkdhps; H=29) with haplotype diversity of Hd ~0.99 were found in both genes, indicating population expansion. Nine mutant alleles were identified in PkK13 amino acid alignment of which, 7 (Asp3Glu, Lys50Gln, Lys53Glu, Ser123Thr, Ser127Pro, Ser149Thr and Ala169Thr) were within the Plasmodium specific domain, 2 (VaI372Ile and Lys424Asn) were in the BTB/POZ domain and no mutation was observed within the kelch propeller domain. The 29 non-synonymous mutations in the Pkdhps gene were novel and only presented in exon 1 and 2. Conclusions: Monitoring the mutations from clinical samples collected from all states of Malaysia along with clinical efficacy studies will be necessary to determine the drug resistance in P. knowlesi.
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Molecular epidemiology of piliated pneumococcal isolates at a major tertiary hospital in the Klang Valley, Malaysia p. 80
Nurul Diana Dzaraly, Mohd Nasir Mohd Desa, AbdulRahman Muthanna, Siti Norbaya Masri, Niazlin Mohd Taib, Nurul Hana Zainal Baharin, Nurshahira Sulaiman, Nurul Asyikin Abdul Rahman, Navindra Kumari Palanisamy, Zarizal Suhaili, Semiat Opeyemi Yusuff, Nor Iza A. Rahman, Tuan Suhaila Tuan Soh, Fatimah Haslina Abdullah8
Objective: To characterise a collection of pili-carrying and none pili-carrying pneumococcal isolates of clinical origin for serotypes, antibiotic resistance and genotype. Methods: In total, 42 clinical isolates were collected between October 2017 and December 2019. Those isolates were analysed for antimicrobial susceptibility, serotype distribution, detection of pneumococcal virulence and pilus genes. Multilocus sequence typing was performed only for piliated isolates, followed by phylogenetic analysis. Results: The common isolation sites among the pneumococcal isolates were tracheal aspirate (28.6%), blood (26.2%), and sputum (23.8%). Fifty percent isolates were resistant to erythromycin, tetracycline (50.0%) and trimethoprim-sulfamethoxazole (43.0%). The most frequent were serotypes 19F (28.6%), 6A/B (23.8%) and 19A (14.3%). Piliated isolates were detected in a small proportion (33.3%); 64.3% were multidrug-resistant. ST320 was the prevalent sequence type among the piliated isolates and genetically related to the Pneumococcal Molecular Epidemiology Network clones Taiwan19F-14 (CC271). In the phylogenetic analysis, some piliated isolates showed a close association having similar ST320, carrying serotype 19A and both pilus genes indicating their clonal spread. Conclusions: Pneumococcal lineages of piliated isolates have been globally disseminated and pili could have played a role in the spread of antibiotic resistant clones.
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Long-term albendazole therapy for diffuse parenchymal neurocysticercosis in an immunocompetent patient: A case report p. 89
Paulus Sugianto, Abdulloh Machin, Wardah Rahmatul Islamiyah, Cindy Cecilia
Rationale: Neurocysticercosis is a neglected tropical disease caused by the larvae of Taenia solium and may occur in immunocompetent people. We report a case of diffuse parenchymal neurocysticercosis mimicking tuberculous meningitis in an immunocompetent patient. Patient concerns: A 24-year-old immunocompetent woman presented with serial focal to generalized seizure, left body weakness, left abducens palsy, chronic cough, and body weight loss. She came from an area where she was unlikely to have contact with Taenia solium. Diagnosis: Diffuse parenchymal neurocysticercosis. Intervention: Valproic acid, dexamethasone and 15 months of albendazole therapy. Outcome: Complete recovery without any neurological sequelae. Lessons: Prolonged anthelminthic treatment may benefit neurocysticercosis patients with multiple cerebral parenchymal lesions.
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Neutralizing possibilities of whole virion and mRNA vaccine triggered antibodies of Wuhan strain of SARS-CoV-2 with receptor binding domains of spike proteins of Delta and Omicron strains p. 92
Shilpa Barthwal, Bennet Angel, Annette Angel, Vinod Joshi, BM Shareef, Nuzhat M Peer, Poorna Khaneja, Ambreen S Khan, Bhawna Sharma, Neha Singh, Ramesh Joshi, Komal Tomar, Kiran Yadav, Satendra P Singh
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Seroprevalence of dengue virus among adults presenting with acute febrile illness at a tertiary care hospital in South India p. 95
Lavanya Mohanam, Priyadarshini Shanmugam
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