Tuberculosis drug resistance profiling based on machine learning: A literature review

Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is one of the top 10 causes of death worldwide. Drug-resistant tuberculosis (DR-TB) poses a major threat to the World Health Organization's "End TB" strategy which has defined its target as the year 2035. In 2019, there were close to 0.5 million cases of DRTB, of which 78% were resistant to multiple TB drugs. The traditional culture-based drug susceptibility test (DST - the current gold standard) often takes multiple weeks and the necessary laboratory facilities are not readily available in low-income countries. Whole genome sequencing (WGS) technology is rapidly becoming an important tool in clinical and research applications including transmission detection or prediction of DR-TB. For the latter, many tools have recently been developed using curated database(s) of known resistance conferring mutations. However, documenting all the mutations and their effect is a time-taking and a continuous process and therefore Machine Learning (ML) techniques can be useful for predicting the presence of DR-TB based on WGS data. This can pave the way to an earlier detection of drug resistance and consequently more efficient treatment when compared to the traditional DST.

Molecular epidemiology of Mycobacterium tuberculosis in Brazil before the whole genome sequencing era: a literature review

Molecular-typing can help in unraveling epidemiological scenarios and improvement for disease control strategies. A literature review of Mycobacterium tuberculosis transmission in Brazil through genotyping on 56 studies published from 1996-2019 was performed. The clustering rate for mycobacterial interspersed repetitive units - variable tandem repeats (MIRU-VNTR) of 1,613 isolates were: 73%, 33% and 28% based on 12, 15 and 24-loci, respectively; while for RFLP-IS6110 were: 84% among prison population in Rio de Janeiro, 69% among multidrug-resistant isolates in Rio Grande do Sul, and 56.2% in general population in São Paulo. These findings could improve tuberculosis (TB) surveillance and set up a solid basis to build a database of Mycobacterium genomes.

Evaluation of drug susceptibility profile of Mycobacterium tuberculosis Lineage 1 from Brazil based on whole genome sequencing and phenotypic methods

BACKGROUND The evaluation of procedures for drug susceptibility prediction of Mycobacterium tuberculosis based on genomic data against the conventional reference method test based on culture is realistic considering the scenario of growing number of tools proposals based on whole-genome sequences (WGS). OBJECTIVES This study aimed to evaluate drug susceptibility testing (DST) outcome based on WGS tools and the phenotypic methods performed on isolates of M. tuberculosis Lineage 1 from the state of Pará, Brazil, generally associated with low levels of drug resistance. METHODOLOGY Culture based DST was performed using the Proportion Method in Löwenstein-Jensen medium on 71 isolates that had been submitted to WGS. We analysed the seven main genome sequence-based tools for resistance and lineage prediction applied to M. tuberculosis and for comparison evaluation we have used the Kappa concordance test. FINDINGS When comparing the WGS-based tools against the DST, we observed the highest level of agreement using TB-profiler. Among the tools, TB-profiler, KvarQ and Mykrobe were those which identified the largest number of TB-MDR cases. Comparing the four most sensitive tools regarding resistance prediction, agreement was observed for 43 genomes. MAIN CONCLUSIONS Drug resistance profiling using next-generation sequencing offers rapid assessment of resistance-associated mutations, therefore facilitating rapid access to effective treatment.

Genital tuberculosis in infertile women: role of hysterolaparoscopy and tuberculosis polymerase chain reaction

Background: Genital tuberculosis is an important cause of female infertility in developing countries like India. It is one of the major causes for severe tubal disease leading to infertility.Methods: A prospective study was conducted in which 100 women presented to hospital with infertility were subjected to hystero-laparoscopy over 1 year. Endometrium sent for tuberculosis polymerase chain reaction (TB-PCR) and HPE and results were formulated.Results: Out of 100 women, 28% were diagnosed with Genital tuberculosis (GTB) using accepted clinical criteria, TB-PCR and endometrial HPE. 25 of these 28 were diagnosed by hysterolaparoscopy (89.24%) alone, 16 by positive endometrial TB-PCR (57.14%) and another 2 by HPE (7.14%).Conclusions: In country like ours where TB is endemic, a multi-pronged approach to diagnosis increases the chances of successfully diagnosing this destructive disease.

Evaluation of effect of recasting of nickel‑chromium alloy on its castability using different investment materials: An in vitro study.

Context: Castability has been found to be affected by many aspects of the entire casting system. Very few references in dental literature are available regarding recasting of the base metal alloys. Aims: To evaluate and compare the castability of fresh and reused nickel‑chromium alloy and to evaluate the effect of two brands of investment materials on castability of nickel‑chromium alloy. Subjects and Methods: For the experimental purpose of evaluation of the effect of recasting of nickel‑chromium alloy on its castability, different percentages of new and casted alloy (Nickel‑chromium alloy‑(Wirolloy NB, Type 4 (Ni‑67%; Cr‑25%; Mo‑5%; Si‑1.5%; Mn, Nb, B, C each <1%) and two commercial brands of investment materials namely, Deguvest Impact (Degudent; Dentsply Germany) and Bellavest SH (Degudent; Dentsply Germany) was used to obtain 30 samples. Castability value was obtained using Whitlock’s formula. Student t-test and one way ANOVA using SPSS 20.0 software was done. Results: The results of this study confirm earlier works that demonstrate that there is no significant difference in castability values of new and recast alloys. In addition, it also demonstrated, there was no difference in castability using Deguvest Impact and Bellavest SH investment materials. Conclusions: Within the limitations of the study, it was concluded that there was no significant difference found in castability of different percentage combinations of new and once casted alloy using two investment materials. The addition of new alloy during recasting to maintain the castability of nickel‑chromium alloy may therefore not be required.

Time to recognize atypical celiac disease in Indian children.

BACKGROUND/OBJECTIVE: There is scant information about atypical (non-diarrheal) presentation of celiac disease (CD) from India. We conducted this study to compare non-diarrheal and diarrheal presentations of CD in children. METHODS: From November 2003 to December 2005, we prospectively screened two groups of children for CD, group I with diarrhea and group II without diarrhea but with atypical presentations (unexplained growth retardation, refractory anemia, refractory rickets, chronic constipation and abdominal distension). Screening was done with IgA antiendomysial antibody (EMA) followed by duodenal biopsy if EMA was positive. Celiac disease was diagnosed according to modified ESPGHAN criteria. RESULTS: A total of 200 children were screened (103 in group I and 97 in group II) and CD was diagnosed in 42 (classical 24, atypical 18). Presentation of atypical CD were; short stature 6, anemia 4, abdominal distension 3, rickets 2, and constipation, diabetes mellitus, delayed puberty in 1 case each. Patients with atypical CD were older (median age 10.4 years vs 5.5 years, p< 0.007) than classical cases. On mean (SD) follow-up of 12.6 (7.5) months all showed response to gluten-free-diet, and median gain in weight, height and final hemoglobin levels were similar in the two groups. CONCLUSION: Atypical CD is not uncommon in India. Children with atypical CD present at an older age. Likelihood of finding CD is high in children with anemia, short stature and rickets.

Superior sagittal sinus thrombosis and Budd-Chiari syndrome due to paroxysmal nocturnal hemoglobinuria managed with transjugular intrahepatic portosystemic shunt: a case report.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH), caused by somatic mutation of hematopoietic cells, is associated with complement-mediated hemolysis and a hypercoagulable state. Thrombotic complications in this disease are associated with reduced survival. We report a patient with PNH complicated by intracranial venous thrombosis and Budd-Chiari syndrome, who was managed with transjugular intrahepatic portosystemic shunt. CASE PRESENTATION: A 26-year-old man presented with thrombosis of the superior sagittal and right sigmoid sinuses. Initial investigations did not reveal any underlying cause. Nine months later, he developed hepatic venous thrombosis. At this time, Ham test was positive. Flow cytometry confirmed the diagnosis of PNH. The patient was treated with transjugular intrahepatic portosystemic shunt; one episode of stent blockage one month later was managed successfully with balloon dilatation and restenting. CONCLUSION: PNH should be considered in patients with unexplained venous thrombosis. Thrombosis in these patients needs to be managed with prolonged anticoagulation. For Budd-Chiari syndrome in patients with underlying PNH, transjugular intrahepatic portosystemic shunt may be a good option but caution is needed to prevent stent occlusion.

Cholangiocarcinoma presenting with severe gastroparesis and pseudoachalasia.

Tumor-associated gastroparesis, though reported in association with various malignancies, is rare in patients with cholangiocarcinoma. We report a 55-year-old woman who presented with dysphagia and recurrent vomiting. Esophagogastroduodenoscopy revealed dilated stomach and excess residue without organic obstruction. 99mTc sulfur colloid solid gastric emptying study, radio-opaque marker gut transit study, and esophageal manometry showed features suggestive of gastroparesis and achalasia cardia; electrogastrography revealed bradygastria. Cholangiocarcinoma was detected on CT scan performed after the patient developed jaundice two months later. The lesion was deemed surgically unresectable. She died four months later.