Evaluation of cartridge-based nucleic acid amplification test for diagnosis of tuberculosis in children in various body fluids

Introduction: The paucibacillary nature presents a major challenge in the diagnosis of tuberculosis (TB) in children. The utilization of cartridge-based nucleic acid amplification test (CBNAAT) for the diagnosis of TB presents itself with added advantages such as detection to resistance to rifampicin and short turnaround time. Objectives: The aim of the study is to evaluate the diagnostic yield of CBNAAT in various body fluids and to compare with BACTEC-MGIT 960 and acid-fast bacilli (AFB) microscopy in children with suspected TB and to see the prevalence of rifampicin resistance in the study population using CBNAAT. Materials and Methods: This cross-sectional study included participants <14 years with suspected TB. Gastric aspirate samples obtained from pulmonary TB cases and body fluid specimens obtained from extrapulmonary TB cases were processed for the detection of Mycobacterium tuberculosis (MTB) using CBNAAT, BACTEC-MGIT 960, and AFB microscopy. The results obtained using CBNAAT were compared to other laboratory tests using an appropriate statistical method. Results: Fifty patients diagnosed with TB (34 pulmonary, 10 pleural effusion, and 6 abdominal) were included in the study, and clinical fluid specimens obtained from study participants were processed for the detection of MTB. Out of 34 gastric aspirate samples, 28 (82%) were positive by CBNAAT which was statistically higher than BACTEC-MGIT 960 (P < 0.05). Among extrapulmonary TB cases, only 2 pleural fluid specimens were positive by CBNAAT, whereas BACTEC-MGIT 960 and AFB microscopy could not detect MTB. Out of 34, 4 (11.76%) patients with newly diagnosed pulmonary TB were found to be rifampicin resistant using CBNAAT. Conclusions: CBNAAT showed promising results as a diagnostic tool in detecting MTB and rifampicin resistance in pulmonary TB using gastric aspirate. It, however, did not show good results in children with extrapulmonary TB in the clinical fluid specimen. The present study also showed the presence of high rifampicin resistance in treatment naïve pulmonary TB patients

Deciphering conversational complexity around a diabetic patient in a web based forum

Web based conversational forums have gained momentum as an aid to clinical decision making. This paper, written in an empirical explanatory manner, attempts to understand the flow of information and the process of sense-making in one such forum (Tabula-rasa) through considering a prototype discussion among participants

CD40 gene polymorphism and its expression in children with Kawasaki disease from North India: a preliminary case–control study and meta-analysis

IntroductionCD40 gene single-nucleotide polymorphisms (SNPs) have been associated with susceptibility and development of coronary artery abnormalities (CAAs) in children with Kawasaki disease (KD) in Japanese, Chinese, and Taiwanese populations. However, data on SNPs of the CD40 gene in patients with KD from the Indian subcontinent are not available. We studied the CD40 gene polymorphisms and its expression in children with KD from North India.MethodsSNPs of the CD40 gene (rs4810485, rs1535045) were studied using Sanger sequencing. CD40 expression was studied by flow cytometry. Meta-analysis was carried out to assess the role of both SNPs of the CD40 gene in KD. GRADEpro GDT software (v.3.2) was used to assess the “certainty of evidence.”ResultsForty-one patients with KD and 41 age-, sex-matched febrile controls were enrolled. However, none of the alleles and genotypes of the CD40 gene were found to be associated with KD. CD40 expression was higher in KD and in KD with CAAs compared to controls, but it failed to reach statistical significance. In a meta-analysis, the T allele of rs153045 was found to be significantly associated with KD (OR = 1.28; 95% confidence interval (: 1.09–1.50; p = 0.002). The GRADE of evidence for this outcome, however, is of “ very low certainty.”ConclusionThe present study found no association between SNPs (rs4810485 and rs153045) and susceptibility to KD. This could be a reflection of a modest sample size. CD40 expression was higher in KD and in KD with CAAs. In the meta-analysis, the T allele of rs153045 was significantly associated with KD. Our study confirms a significant genetic heterogeneity in KD among different ethnicities

Early prognosis prediction in acute myeloid and acute lymphoid leukemia patients using cell-free DNA concentration ratios

Background: Cell-free DNA (cfDNA) is a promising biomarker for disease prediction in many cancers, including acute leukemia (acute myeloid leukemia [AML] and acute lymphoblastic leukemia [ALL]). This study investigated the role of cfDNA in predicting relapse or unfavorable outcomes in acute leukemia patients upon initial diagnosis.Methods: Paired peripheral blood samples of 25 patients with ALL and AML were compared at baseline and induction/follow-up and clinically correlated with clinicopathological and outcome variables according to the risk category. cfDNA was isolated using commercial cfDNA extraction kits. The probability of poor outcomes in high-risk groups and a cut-off value for risk stratification minimal residual disease (MRD) positivity and outcome prediction were derived.Results: Twenty-five patients diagnosed with AML and ALL were risk-stratified based on NCI risk stratification, and of these 25 patients, 4 patients were of standard risk (SR) and 1 patient was of intermediate risk (IR), while a majority of patients (80%) were of high risk (HR). Of these, four HR patients passed away. The ratio of cfDNA reduction at baseline and the end of induction was a strong predictor of poor outcomes in high-risk patients, regardless of the MRD status. A cfDNA ratio score of 2.6 or higher at diagnosis/remission predicted poor outcomes, with higher accuracy than conventional MRD detection by flow cytometry.Conclusion: A higher cfDNA ratio at diagnosis/remission or at baseline predicts poor outcomes in acute leukemia patients. This pilot study suggests that cfDNA ratio scoring may be a useful tool for predicting prognosis in acute leukemia patients, regardless of the MRD status

Exploring state-of-the-art advances in targeted nanomedicines for managing acute and chronic inflammatory lung diseases

Diagnosis and treatment of lung diseases pose serious challenges. Currently, diagnostic as well as therapeutic methods show poor efficacy toward drug-resistant bacterial infections, while chemotherapy causes toxicity and nonspecific delivery of drugs. Advanced treatment methods that cure lung-related diseases, by enabling drug bioavailability via nasal passages during mucosal formation, which interferes with drug penetration to targeted sites, are in demand. Nanotechnology confers several advantages. Currently, different nanoparticles, or their combinations, are being used to enhance targeted drug delivery. Nanomedicine, a combination of nanoparticles and therapeutic agents, that delivers drugs to targeted sites increases the bioavailability of drugs at these sites. Thus, nanotechnology is superior to conventional chemotherapeutic strategies. Here, the authors review the latest advancements in nanomedicine-based drug-delivery methods for managing acute and chronic inflammatory lung diseases

Single-dose cholera vaccine in response to an outbreak in Zambia

Producción CientíficaKilled oral cholera vaccines (OCVs) are part of the standard response package to a cholera outbreak, although the two-dose regimen of vaccines that has been prequalified by the World Health Organization (WHO) poses challenges to timely and efficient reactive vaccination campaigns.1 Recent data suggest that the first dose alone provides short-term protection, similar to that of two doses, which may largely dictate the effect of OCVs during epidemic

Cholera epidemic in Yemen, 2016–18: an analysis of surveillance data

Summary: Background: In war-torn Yemen, reports of confirmed cholera started in late September, 2016. The disease continues to plague Yemen today in what has become the largest documented cholera epidemic of modern times. We aimed to describe the key epidemiological features of this epidemic, including the drivers of cholera transmission during the outbreak. Methods: The Yemen Health Authorities set up a national cholera surveillance system to collect information on suspected cholera cases presenting at health facilities. Individual variables included symptom onset date, age, severity of dehydration, and rapid diagnostic test result. Suspected cholera cases were confirmed by culture, and a subset of samples had additional phenotypic and genotypic analysis. We first conducted descriptive analyses at national and governorate levels. We divided the epidemic into three time periods: the first wave (Sept 28, 2016, to April 23, 2017), the increasing phase of the second wave (April 24, 2017, to July 2, 2017), and the decreasing phase of the second wave (July 3, 2017, to March 12, 2018). We reconstructed the changes in cholera transmission over time by estimating the instantaneous reproduction number, Rt. Finally, we estimated the association between rainfall and the daily cholera incidence during the increasing phase of the second epidemic wave by fitting a spatiotemporal regression model. Findings: From Sept 28, 2016, to March 12, 2018, 1 103 683 suspected cholera cases (attack rate 3·69%) and 2385 deaths (case fatality risk 0·22%) were reported countrywide. The epidemic consisted of two distinct waves with a surge in transmission in May, 2017, corresponding to a median Rt of more than 2 in 13 of 23 governorates. Microbiological analyses suggested that the same Vibrio cholerae O1 Ogawa strain circulated in both waves. We found a positive, non-linear, association between weekly rainfall and suspected cholera incidence in the following 10 days; the relative risk of cholera after a weekly rainfall of 25 mm was 1·42 (95% CI 1·31–1·55) compared with a week without rain. Interpretation: Our analysis suggests that the small first cholera epidemic wave seeded cholera across Yemen during the dry season. When the rains returned in April, 2017, they triggered widespread cholera transmission that led to the large second wave. These results suggest that cholera could resurge during the ongoing 2018 rainy season if transmission remains active. Therefore, health authorities and partners should immediately enhance current control efforts to mitigate the risk of a new cholera epidemic wave in Yemen. Funding: Health Authorities of Yemen, WHO, and Médecins Sans Frontières

Genomic insights into the 2016-2017 cholera epidemic in Yemen.

Yemen is currently experiencing, to our knowledge, the largest cholera epidemic in recent history. The first cases were declared in September 2016, and over 1.1 million cases and 2,300 deaths have since been reported1. Here we investigate the phylogenetic relationships, pathogenesis and determinants of antimicrobial resistance by sequencing the genomes of Vibrio cholerae isolates from the epidemic in Yemen and recent isolates from neighbouring regions. These 116 genomic sequences were placed within the phylogenetic context of a global collection of 1,087 isolates of the seventh pandemic V. cholerae serogroups O1 and O139 biotype El Tor2-4. We show that the isolates from Yemen that were collected during the two epidemiological waves of the epidemic1-the first between 28 September 2016 and 23 April 2017 (25,839 suspected cases) and the second beginning on 24 April 2017 (more than 1 million suspected cases)-are V. cholerae serotype Ogawa isolates from a single sublineage of the seventh pandemic V. cholerae O1 El Tor (7PET) lineage. Using genomic approaches, we link the epidemic in Yemen to global radiations of pandemic V. cholerae and show that this sublineage originated from South Asia and that it caused outbreaks in East Africa before appearing in Yemen. Furthermore, we show that the isolates from Yemen are susceptible to several antibiotics that are commonly used to treat cholera and to polymyxin B, resistance to which is used as a marker of the El Tor biotype