Diagnostic Accuracy and Reproducibility of WHO-Endorsed Phenotypic Drug Susceptibility Testing Methods for First-Line and Second-Line Antituberculosis Drugs

In an effort to update and clarify policies on tuberculosis drug susceptibility testing (DST), the World Health Organization (WHO) commissioned a systematic review evaluating WHO-endorsed diagnostic tests. We report the results of this systematic review and meta-analysis of the diagnostic accuracy and reproducibility of phenotypic DST for first-line and second-line antituberculosis drugs. This review provides support for recommended critical concentrations for isoniazid and rifampin in commercial broth-based systems. Further studies are needed to evaluate critical concentrations for ethambutol and streptomycin that accurately detect susceptibility to these drugs. Evidence is limited on the performance of DST for pyrazinamide and second-line drugs.     

Molecular Tools for Diagnosis of Visceral Leishmaniasis: Systematic Review and Meta-Analysis of Diagnostic Test Accuracy

Molecular methods have been proposed as highly sensitive tools for the detection of Leishmania parasites in visceral leishmaniasis (VL) patients. Here, we evaluate the diagnostic accuracy of these tools in a meta-analysis of the published literature. The selection criteria were original studies that evaluate the sensitivities and specificities of molecular tests for diagnosis of VL, adequate classification of study participants, and the absolute numbers of true positives and negatives derivable from the data presented. Forty studies met the selection criteria, including PCR, real-time PCR, nucleic acid sequence-based amplification (NASBA), and loop-mediated isothermal amplification (LAMP). The sensitivities of the individual studies ranged from 29 to 100%, and the specificities ranged from 25 to 100%. The pooled sensitivity of PCR in whole blood was 93.1% (95% confidence interval [CI], 90.0 to 95.2), and the specificity was 95.6% (95% CI, 87.0 to 98.6). The specificity was significantly lower in consecutive studies, at 63.3% (95% CI, 53.9 to 71.8), due either to true-positive patients not being identified by parasitological methods or to the number of asymptomatic carriers in areas of endemicity. PCR for patients with HIV-VL coinfection showed high diagnostic accuracy in buffy coat and bone marrow, ranging from 93.1 to 96.9%. Molecular tools are highly sensitive assays for Leishmania detection and may contribute as an additional test in the algorithm, together with a clear clinical case definition. We observed wide variety in reference standards and study designs and now recommend consecutively designed studies.     

Nitrate Reductase Assay for Rapid Detection of Isoniazid,Rifampin, Ethambutol,and Streptomycin Resistance in Mycobacterium tuberculosis: a Systematic Review and Meta-Analysis

Colorimetric phenotypic tests recently gained interest because traditional primary drug susceptibility testing of Mycobacterium tuberculosis isolates takes a long time. We used meta-analysis techniques to review the reliability and accuracy of the nitrate reductase assay (NRA), which is one of the most popular colorimetric methods to detect resistance to first-line drugs. Medline, PubMed, ISI Web, Web of Science, and Google Scholar were used to search for studies enrolled in the meta-analysis. The analysis included 35 studies for isoniazid (INH), 38 for rifampin (RIF), and 22 for ethambutol (EMB) and streptomycin (STR). Summary receiver operating characteristic (SROC) curves were applied to summarize diagnostic accuracy. The meta-analyses were performed by the use of Meta-DiSc software (version 1.4) and were focused on sensitivity and specificity values for measurements of accuracy. The pooled sensitivities were 96% for INH, 97% for RIF, 90% for EMB, and 82% for STR. The pooled specificities for INH, RIF, EMB, and STR were 99%, 100%, 98%, and 96%, respectively. The times required to obtain results were between 5 and 28 days by the direct NRA and between 5 and 14 days by the indirect test. In conclusion, the present meta-analysis showed that the NRA is a reliable low-cost rapid colorimetric susceptibility test that can be used for the detection of multidrug-resistant (MDR) tuberculosis, including detection of EMB resistance. However, the test appears to have a relatively low sensitivity for STR and needs further improvement.     

PCR-Single-Strand Conformational Polymorphism Method for Rapid Detection of Rifampin-Resistant Mycobacterium tuberculosis: Systematic Review and Meta-Analysis

The reference standard methods for drug susceptibility testing of Mycobacterium tuberculosis, such as culture on Lowenstein-Jensen or Middlebrook 7H10/11 medium, are very slow to give results; and due to the emergence of multidrug-resistant M. tuberculosis and extensively drug-resistant M. tuberculosis, there is an urgent demand for new, rapid, and accurate drug susceptibility testing methods. PCR-single-strand conformational polymorphism (PCR-SSCP) analysis has been proposed as a rapid method for the detection of resistance to rifampin, but its accuracy has not been systematically evaluated. We performed a systematic review and meta-analysis to evaluate the accuracy of PCR-SSCP analysis for the detection of rifampin-resistant tuberculosis. We searched the Medline, Embase, Web of Science, BIOSIS, and LILACS databases and contacted authors if additional information was required. Ten studies met our inclusion criteria for rifampin resistance detection. We applied the summary receiver operating characteristic (SROC) curve to perform the meta-analysis and to summarize diagnostic accuracy. The sensitivity of PCR-SSCP analysis for the rapid detection of rifampin-resistant tuberculosis was 0.79 (95% confidence interval [CI], 0.75 to 0.82), the specificity was 0.96 (95% CI, 0.94 to 0.98), the positive likelihood ratio was 16.10 (95% CI, 5.87 to 44.13), the negative likelihood ratio was 0.20 (95% CI, 0.10 to 0.40), and the diagnostic odds ratio was 100.93 (95% CI, 31.95 to 318.83). PCR-SSCP analysis is a sensitive and specific test for the rapid detection of rifampin-resistant M. tuberculosis. Additional studies in countries with a high prevalence of multidrug-resistant M. tuberculosis and also cost-effectiveness analysis are required in order to obtain a complete picture on the utility of this method for rapid drug resistance detection in M. tuberculosis.Tuberculosis (TB) is a major global health problem. Early detection of drug resistance in patients with tuberculosis allows the use of appropriate treatment regimens for the patient, which has an important impact for the better control of the disease. The development of rapid methods for drug susceptibility testing is very important due to the increasing rates of multidrug-resistant tuberculosis (MDR-TB) worldwide and the recently described extensively drug-resistant tuberculosis (XDR-TB). The World Health Organization (WHO) urgently called for expanded access to culture and drug susceptibility testing in response to the spread of MDR-TB and XDR-TB, declared serious emerging threats to public health (28). This poses significant challenges for TB laboratory capacity and the need for faster drug susceptibility testing methods.Conventional culture methods using egg- or agar-based media are still the most commonly used approaches in many countries. To test for drug resistance, the standard methods using Lowenstein-Jensen (LJ) medium include the proportion method, the absolute concentration method, and the resistant ratio method, which are well standardized with clinical isolates, at least for the major antituberculosis drugs. The proportion method was developed in the 1960s and is still the “gold standard” method used in many laboratories, especially in developing countries, because it is an inexpensive method easily accessible in these settings (1, 2). In recent years, due to the long turnaround times of conventional drug susceptibility testing methods, several new approaches have been proposed for the faster detection of MDR Mycobacterium tuberculosis, including both genotypic and phenotypic methods (23, 24). Among the genotypic methods proposed, PCR-single-strand conformational polymorphism (PCR-SSCP) analysis has been an important tool for detecting point mutations underlying genetic diseases since it was established in 1989 (9, 21). Under nondenaturing conditions, single-stranded DNA (ssDNA) has a folded structure that is determined by intramolecular interactions and, therefore, by its sequence. Even a single point mutation can alter the conformation of ssDNA, so that the altered conformation affects the migration of ssDNA, which can be detected as abnormal bands on a nondenaturing gel. Thus, SSCP analysis has a high resolving power to distinguish most conformational changes caused by subtle sequence differences even in a several-hundred-base fragment (9). The PCR-SSCP assay is relatively simple and was initially promising. Recently, the PCR-SSCP assay has been used in some studies for the rapid detection of rifampin-resistant M. tuberculosis (3, 11, 12, 17). However, individually, these trials found that the sensitivity and specificity were statistically inconsistent. The purpose of the present study was to perform a systematic review and meta-analysis to synthesize all available literature on the PCR-SSCP assay for the rapid detection of rifampin-resistant M. tuberculosis and to evaluate the overall accuracy of this method for the detection of rifampin resistance in isolates and in sputum samples.     

Standardization of Operator-Dependent Variables Affecting Precision and Accuracy of the Disk Diffusion Method for Antibiotic Susceptibility Testing

Parameters like zone reading, inoculum density, and plate streaking influence the precision and accuracy of disk diffusion antibiotic susceptibility testing (AST). While improved reading precision has been demonstrated using automated imaging systems, standardization of the inoculum and of plate streaking have not been systematically investigated yet. This study analyzed whether photometrically controlled inoculum preparation and/or automated inoculation could further improve the standardization of disk diffusion. Suspensions of Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213 of 0.5 McFarland standard were prepared by 10 operators using both visual comparison to turbidity standards and a Densichek photometer (bioMérieux), and the resulting CFU counts were determined. Furthermore, eight experienced operators each inoculated 10 Mueller-Hinton agar plates using a single 0.5 McFarland standard bacterial suspension of E. coli ATCC 25922 using regular cotton swabs, dry flocked swabs (Copan, Brescia, Italy), or an automated streaking device (BD-Kiestra, Drachten, Netherlands). The mean CFU counts obtained from 0.5 McFarland standard E. coli ATCC 25922 suspensions were significantly different for suspensions prepared by eye and by Densichek (P < 0.001). Preparation by eye resulted in counts that were closer to the CLSI/EUCAST target of 10⁸ CFU/ml than those resulting from Densichek preparation. No significant differences in the standard deviations of the CFU counts were observed. The interoperator differences in standard deviations when dry flocked swabs were used decreased significantly compared to the differences when regular cotton swabs were used, whereas the mean of the standard deviations of all operators together was not significantly altered. In contrast, automated streaking significantly reduced both interoperator differences, i.e., the individual standard deviations, compared to the standard deviations for the manual method, and the mean of the standard deviations of all operators together, i.e., total methodological variation.     

Evaluation of Agar-Based Medium with Sheep Sera for Testing of Drug Susceptibility of Mycobacterium tuberculosis to Isoniazid,Rifampin, Ethambutol,and Streptomycin

The performance of sheep sera instead of sheep blood in agar-based media was investigated for susceptibility testing of Mycobacterium tuberculosis against primary drugs. The levels of agreement between agar-based medium supplemented with sheep sera and the proportion method on Middlebrook 7H11 agar as the reference method for determining susceptibility to isoniazid (INH), rifampin (RIF), ethambutol (EMB), and streptomycin (STR) were 98.4, 98.4, 95.3, and 100%, respectively.     

Interferon Gamma Release Assays for Diagnosis of Pleural Tuberculosis: a Systematic Review and Meta-Analysis

The role of interferon gamma release assays (IGRAs), although established for identifying latent tuberculosis, is still evolving in the diagnosis of active extrapulmonary tuberculosis. We systematically evaluated the diagnostic performance of blood- and pleural fluid-based IGRAs in tuberculous pleural effusion (TPE). We searched the PubMed and Embase databases for studies evaluating the use of commercially available IGRAs on blood and/or pleural fluid samples for diagnosing TPE. The quality of the studies included was assessed through the QUADAS-2 tool. The pooled estimates of sensitivity and specificity with 95% confidence intervals (95% CI) were generated using a bivariate random-effects model and examined using forest plots and hierarchical summary receiver operating characteristic (HSROC) curves. Indeterminate IGRA results were included for sensitivity calculations. Heterogeneity was explored through subgroup analysis and meta-regression based on prespecified covariates. We identified 19 studies assessing the T.SPOT.TB and/or QuantiFERON assays. There were 20 and 14 evaluations, respectively, of whole-blood and pleural fluid assays, involving 1,085 and 727 subjects, respectively. There was only one good-quality study, and five studies used nonstandard assay thresholds. The pooled sensitivity and specificity for the blood assays were 0.77 (95% CI, 0.71 to 0.83) and 0.71 (95% CI, 0.65 to 0.76), respectively. The pooled sensitivity and specificity for the pleural fluid assays were 0.72 (95% CI, 0.55 to 0.84) and 0.78 (95% CI, 0.65 to 0.87), respectively. There was considerable heterogeneity; however, multivariate meta-regression did not identify any covariate with significant influence. There was no publication bias for blood assays. We conclude that commercial IGRAs, performed either on whole-blood or pleural fluid samples, have poor diagnostic accuracy in patients suspected to have TPE.     

Risk Factors of Acoustic Neuroma: Systematic Review and Meta-Analysis

PurposeMany epidemiological studies have investigated environmental risk factors for the development of acoustic neuroma. However, these results are controversial. We conducted a meta-analysis of case-control studies to identify any potential relationship between history of noise exposure, smoking, allergic diseases, and risk of acoustic neuroma.ResultsEleven case-control studies were included in our meta-analysis. Acoustic neuroma was found to be associated with leisure noise exposure [odds ratio (OR)=1.33, 95% confidence interval (CI): 1.05–1.68], but not with occupational noise exposure and ever noise exposure (OR=1.20, 95% CI: 0.84–1.72 and OR=1.15, 95% CI: 0.80–1.65). The OR of acoustic neuroma for ever (versus never) smoking was 0.53 (95% CI: 0.30–0.94), while the subgroup analysis indicated ORs of 0.95 (95% CI: 0.81–1.10) and 0.49 (95% CI: 0.41–0.59) for ex-smoker and current smoker respectively. The ORs for asthma, eczema, and seasonal rhinitis were 0.98 (95% CI: 0.80–1.18), 0.91 (95% CI: 0.76–1.09), and 1.52 (95% CI: 0.90–2.54), respectively.ConclusionOur meta-analysis is suggestive of an elevated risk of acoustic neuroma among individuals who were ever exposed to leisure noise, but not to occupational noise. Our study also indicated a lower acoustic neuroma risk among ever and current cigarette smokers than never smokers, while there was no significant relationship for ex-smokers. No significant associations were found between acoustic neuroma and history of any allergic diseases, such as asthma, eczema, and seasonal rhinitis.     

Telemedicine Technologies for Diabetes in Pregnancy: A Systematic Review and Meta-Analysis

BackgroundDiabetes in pregnancy is a global problem. Technological innovations present exciting opportunities for novel approaches to improve clinical care delivery for gestational and other forms of diabetes in pregnancy.ObjectiveTo perform an updated and comprehensive systematic review and meta-analysis of the literature to determine whether telemedicine solutions offer any advantages compared with the standard care for women with diabetes in pregnancy.MethodsThe review was developed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. Randomized controlled trials (RCT) in women with diabetes in pregnancy that compared telemedicine blood glucose monitoring with the standard care were identified. Searches were performed in SCOPUS and PubMed, limited to English language publications between January 2000 and January 2016. Trials that met the eligibility criteria were scored for risk of bias using the Cochrane Collaborations Risk of Bias Tool. A meta-analysis was performed using Review Manager software version 5.3 (Nordic Cochrane Centre, Cochrane Collaboration).ResultsA total of 7 trials were identified. Meta-analysis demonstrated a modest but statistically significant improvement in HbA1c associated with the use of a telemedicine technology. The mean HbA1c of women using telemedicine was 5.33% (SD 0.70) compared with 5.45% (SD 0.58) in the standard care group, representing a mean difference of −0.12% (95% CI −0.23% to −0.02%). When this comparison was limited to women with gestational diabetes mellitus (GDM) only, the mean HbA1c of women using telemedicine was 5.22% (SD 0.70) compared with 5.37% (SD 0.61) in the standard care group, mean difference −0.14% (95% CI −0.25% to −0.04%). There were no differences in other maternal and neonatal outcomes reported.ConclusionsThere is currently insufficient evidence that telemedicine technology is superior to standard care for women with diabetes in pregnancy; however, there was no evidence of harm. No trials were identified that assessed patient satisfaction or cost of care delivery, and it may be in these areas where these technologies may be found most valuable.     

Diagnostic Accuracy of PCR Alone Compared to Galactomannan in Bronchoalveolar Lavage Fluid for Diagnosis of Invasive Pulmonary Aspergillosis: a Systematic Review

PCR in bronchoalveolar lavage (BAL) fluid has not been accepted as a diagnostic criterion for invasive pulmonary aspergillosis (IPA). We conducted a systematic review assessing the diagnostic accuracy of PCR in BAL fluid with a direct comparison versus galactomannan (GM) in BAL fluid. We included prospective and retrospective cohort and case-control studies. Studies were included if they used the EORTC/MSG consensus definition criteria of IPA and assessed ≥80% of patients at risk for IPA. Two reviewers abstracted data independently. Risk of bias was assessed using QUADAS-2. Summary sensitivity and specificity values were estimated using a bivariate model and reported with a 95% confidence interval (CI). Nineteen studies published between 1993 and 2012 were included. The summary sensitivity and specificity values (CIs) for diagnosis of proven or probable IPA were 90.2% (77.2 to 96.1%) and 96.4% (93.3 to 98.1%), respectively. In nine cohort studies strictly adherent to the 2002 or 2008 EORTC/MSG criteria for reference standard definitions, the summary sensitivity and specificity values (CIs) were 77.2% (62 to 87.6%) and 93.5% (90.6 to 95.6%), respectively. Antifungal treatment before bronchoscopy significantly reduced sensitivity. The diagnostic performance of PCR was similar to that of GM in BAL fluid using an optical density index cutoff of 0.5. If either PCR or GM in BAL fluid defined a positive result, the pooled sensitivity was higher than that of GM alone, with similar specificity. We conclude that the diagnostic performance of PCR in BAL fluid is good and comparable to that of GM in BAL fluid. Performing both tests results in optimal sensitivity with no loss of specificity. Results are dependent on the reference standard definitions.     

Surgical Anatomy of the Marginal Mandibular Nerve: A Systematic Review and Meta-Analysis

The high number of marginal mandibular nerve (MMN) anatomical variants have a well-known clinical significance due to the risk of nerve injury in several surgical procedures. The aim of this study was to find and systematize the available anatomical data concerning this nerve. The PubMed and Scopus databases were investigated in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. All studies reporting extractable data on the origin, course, splitting, anastomosis and relationship of the MMN with the mandible or the facial vessels were included. We included 28 studies analyzing 1861 halves. The MMN had one (PP = 35% 95% CI:18–54%), two (PP =35% 95% CI:18–54%), three (PP = 18% 95% CI:0–35%), or four branches (PP = 2% 95% CI:0–8%). Anastomosis with the great auricular nerve, transverse cervical nerve, mental nerve, and other branches of the facial nerve were defined. The origin of the MMN in relation to the parotid and the mandible was variable. The MMN nearly always crossed the anterior facial vein laterally (PP = 38% 95% CI:9–72% if single, PP = 57% 95% CI:22–90% when multiple); its relation with other vessels was less constant. At least one branch of the MMN was found below the inferior border of the mandible (IBM), with a PP of 39% (95% CI:30–50%). The MMN has high anatomical variability and it is more often represented by one or two branches; its origin is frequently described at the parotid apex and above the IBM, although in its course at least one branch often runs below the IBM. Its most frequent anastomosis is with the buccal branch of the facial nerve. Clin. Anat., 33:739–750, 2020. © 2019 Wiley Periodicals, Inc.     

Acupuncture for the Treatment of Adults with Posttraumatic Stress Disorder: A Systematic Review and Meta-Analysis

Acupuncture has been suggested as a treatment for posttraumatic stress disorder (PTSD), yet its clinical effects are unclear. This review aims to estimate effects of acupuncture on PTSD symptoms, depressive symptoms, anxiety symptoms, and sleep quality for adults with PTSD. We searched 10 databases in January 2016 to identify eligible randomized controlled trials (RCTs). We performed random effects meta-analyses and examined quality of the body of evidence (QoE) using the GRADE approach to rate confidence in meta-analytic effect estimates. Seven RCTs with 709 participants met inclusion criteria. We identified very low QoE indicating significant differences favoring acupuncture (versus any comparator) at post-intervention on PTSD symptoms (standardized mean difference [SMD] = ?0.80, 95% confidence interval [CI] [?1.59, ?0.01], 6 RCTs), and low QoE at longer follow-up on PTSD (SMD = ?0.46, 95% CI [?0.85, ?0.06], 4 RCTs) and depressive symptoms (SMD = ?0.56; 95% CI [?0.88, ?0.23], 4 RCTs). No significant differences were observed between acupuncture and comparators at post-intervention for depressive symptoms (SMD = ?0.58, 95% CI [?1.18, 0.01], 6 RCTs, very low QoE), anxiety symptoms (SMD = ?0.82, 95% CI [?2.16, 0.53], 4 RCTs, very low QoE), and sleep quality (SMD = ?0.46, 95% CI [?3.95, 3.03], 2 RCTs, low QoE). Safety data (7 RCTs) suggest little risk of serious adverse events, though some participants experienced minor/moderate pain, superficial bleeding, and hematoma at needle insertion sites. To increase confidence in findings, sufficiently powered replication trials are needed that measure all relevant clinical outcomes and dedicate study resources to minimizing participant attrition.     

Systematic Review and Meta-Analysis of Peer-Led Self-Management Programs for Increasing Physical Activity

Purpose

Approximately 85 % of Canadians are not physically active enough to achieve health benefits. Peer-led self-management programs are becoming an increasingly popular strategy for modifying health behaviors, including physical activity. The purpose of this study was to systematically review and meta-analyze the effect of peer-led self-management interventions on physical activity.

Methods

PubMed, MEDLINE, PsycINFO, EMBASE, CINAHL, and Cochrane Database of Systematic Reviews databases were systematically searched to identify all relevant randomized controlled trials that evaluated the effect of peer-led self-management on physical activity. The studies were described and effect size data were included in meta-analyses. Subgroup analyses were performed according to type of physical activity outcome (i.e., duration, frequency, other).

Results

Twenty-one studies were included in the review and 14 reported statistically significant improvements in physical activity. A meta-analysis of 17 studies showed a statistically significant moderate pooled effect (standardized mean difference (SMD)?=?0.4, p?<?0.001) of peer-led self-management programs on physical activity immediately post-intervention. The intervention had a large statistically significant effect based on the four studies that included follow-up measures (SMD?=?1.5, p?=?0.03). Meta-analysis of nine studies that used similar outcomes (i.e., minutes of physical activity) revealed a statistically significant small effect (SMD?=?0.2, p?<?0.001).

Conclusion

Peer-led self-management programs appear to be effective at increasing weekly duration of physical activity in various populations, but the effect size is small. Training peers to encourage increased physical activity may provide an effective method for reaching various clinical and non-clinical populations. More research is needed using validated and consistent physical activity outcomes.

     

Risk Factors for Severe COVID-19 in Children: A Systematic Review and Meta-Analysis

BackgroundCoronavirus disease 2019 (COVID-19) has been the most important global issue since December 2019. Although the clinical course of COVID-19 is known to be milder in children than in adults, associated hospitalizations among children have increased since the emergence of contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the achievement of a high vaccination rate in adults. Considering these global and domestic situations, we believe that risk stratification in children with COVID-19 is urgently needed for decision making regarding hospitalization priority in children infected with SARS-CoV-2 and vaccination priority against COVID-19.MethodsThis systematic review and meta-analysis was performed by comprehensively searching the PubMed, EMBASE, Scopus and KoreaMed databases through August 25, 2021. The criteria for enrollment were “severe COVID-19” as poor outcomes (intensive care unit admission, invasive mechanical ventilation, and/or death) and underlying comorbidities before SARS-CoV-2 infection.ResultsAmong 872 screened studies, 17 articles were included in the systematic review, and 10 articles were included in the meta-analysis. Neonate (risk ratio [RR], 2.69; 95% confidence interval [CI], 1.83–3.97), prematurity in young infants (RR, 2.00; 95% CI, 1.63–2.46), obesity (RR, 1.43; 95% CI, 1.24–1.64), diabetes (RR, 2.26; 95% CI, 1.95–2.62), chronic lung disease (RR, 2.62; 95% CI, 1.71–4.00), heart disease (RR, 1.82; 95% CI, 1.58–2.09), neurologic disease (RR, 1.18; 95% CI, 1.05–1.33), and immunocompromised status (RR, 1.44; 95% CI, 1.01–2.04) were significant risk factors for severe COVID-19 in children. In the subgroup analysis, age younger than 3 months (RR, 0.26; 95% CI, 0.11–0.66), asthma (RR, 1.08; 95% CI, 0.98–1.20), and neurodevelopmental disorders (RR, 0.88; 95% CI, 0.75–1.04) were not risk factors for severe COVID-19.ConclusionChildren with comorbidities such as obesity, diabetes, heart disease, chronic lung diseases other than asthma, seizure disorders, and an immunocompromised status had a high prevalence of severe COVID-19. Neonate and premature infants had a high risk of severe COVID-19. Defining the high-risk group for severe COVID-19 could help to guide hospital admission and priority for vaccination against SARS-CoV-2.     

Laboratory Diagnosis of Tuberculosis: Advances in Technology and Drug Susceptibility Testing

There have been rapid technological advances in the detection of Mycobacterium tuberculosis and its drug susceptibility in clinical samples. These include advances in microscopic examination, in vitro culture and application of molecular techniques. The World Health Organization (WHO) has played a large role in evaluating these technologies for their efficacy and feasibility, especially in the developing countries. Amongst these, the Revised National Tuberculosis Control Programme (RNTCP), through its national network of designated microscopy centres and intermediate reference laboratories, has adopted certain technologies that are currently implemented in India. Advances in microscopy technology include fluorescent microscopy using light-emitting diode source, sodium hypochlorite microscopy and vital fluorescent staining of sputum smears. Automation of in vitro culture has markedly reduced the turnaround time (TAT), even in smear-negative samples, and permits simultaneous detection of resistant mutants. Molecular detection of drug resistance has further reduced the TAT, and the cartridge-based nucleic acid amplification test with its performance convenience and rapid results, appears poised to become the future of tuberculosis (TB) diagnosis in all settings, provided the cost of testing is reduced especially for use in private diagnostic settings. This article reviews technologies currently available for the diagnosis of TB, keeping in mind the WHO recommendations and the RNTCP practices. This is a thematic synthesis of data available on diagnosis in literature, preserving the conclusions of the primary studies.