Clinical application of whole genome sequencing in management of extensively drug-resistant tuberculosis: A Case Report
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ABSTRACT:
PROVIDER: PRJEB74918 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR12945355_1.fastq.gz | Fastqsanger.gz | |||
| ERR12945355_2.fastq.gz | Fastqsanger.gz | |||
| ERR12945356_1.fastq.gz | Fastqsanger.gz | |||
| ERR12945356_2.fastq.gz | Fastqsanger.gz | |||
| ERR12945357_1.fastq.gz | Fastqsanger.gz |
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Project description:Typhoid fever is the result of a human host-restricted Salmonella enteric serotype typhi infection that causes enteric fever. Around 21 million people contract typhoid annually, with Pakistan's inhabitants at most risk amongst Asian countries where typhoid remains prevalent. Decades of indiscriminate antibiotic usage has driven the evolution of multidrug-resistant strains and more recently, extensively drug-resistant (XDR) strains of Salmonella enteric serotype typhi. Current reports of extensively drug-resistant typhoid fever outbreak in Pakistan are not only a major concern for Pakistan but also for health authorities worldwide: intercontinental transmission, spread, and replacement of native strains in neighboring countries and a major impediment to Pakistani health care management. The WHO records that there are 5274 cases of extensively drug-resistant (XDR) typhoid fever out of a total of 8188 total cases of typhoid fever reported in Pakistan. The last remaining feasible oral antibiotic that XDR typhoid remains susceptible to is azithromycin; this is a cause of major concern. Additionally, several cases of XDR typhoid fever have also been reported in patients travelling from Pakistan to the USA, UK, and Canada. This review article attempts to raise the issue of XDR typhoid with respect to its epidemiology, prevention, management, and future outlook and stresses a better understanding of antimicrobial stewardship and general surveillance of the disease. Although progress is being made to combat XDR typhoid locally, efficient, unified efforts on a national and international scale are required to contain the XDR outbreak before it is no longer manageable and leads us back to the preantibiotic era.
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Project description:Transcriptional profiling of mycobacterium tuberculosis clinical isolates in China comparing extensively drug-resistant tuberculosis with drug sensitive one. The same condition experiment. The samples were from the different drug-resistant strains. Only one replicate.
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Project description:Glioneuronal tumor (GN) is one type of biphasic central nervous system (CNS) tumor that exhibits both glial and neuronal immunohistological characteristics. We report a case of glioneuronal tumor (GN) with a discovery of novel gene fusion of CLIP2-MET resulting from aberrant chromosome 7 abnormalities. The tumor exhibited typical characteristics on histological examinations. We executed an elaborate genomic study on this case including whole-exome sequencing and RNA sequencing. Genomic analysis of the tumor revealed aberrations in chromosomes 1 and 7 and a CLIP2-MET fusion. Further analysis of the upregulated genes revealed substantial connections with MAPK pathway activation. We concluded that the chromosome 7 abnormalities prompted CLIP2-MET gene fusion which successively leads to MAPK pathway activation. We deliberated that MAPK pathway activation is responsible for the oncogenesis of GN based on our case and other previously reported ones.
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Project description:The emergence of extensively drug-resistant tuberculosis (XDR-TB) is a challenging paradigm shift faced by the TB control programs worldwide today. The treatment is further compounded with unique management difficulties faced in pediatric patients. Treatment of XDR-TB requires prolonged chemotherapy with second-line drugs which offer lesser potency and increased risk of drug-related side effects. We present a case of spinal XDR-TB in a child, managed with extended second-line antitubercular chemotherapy (ATT).A 6-year-old, Caucasian male child complained of persistent back pain for 3 weeks, with lumbar tenderness without neurodeficit. Radiographs showed fourth lumbar (L4) vertebral body collapse. Magnetic resonance imaging showed features suggestive of TB spondylodiscitis. The erythrocyte sedimentation rate (ESR) was raised. In view of the high prevalence rate of TB, on clinical suspicion, empirical first-line ATT (isoniazid + rifampicin + ethambutol + pyrazinamide) was given for 6 months, under the Revised National Tuberculosis Control Program (RNTCP). In the course of ATT, child developed iliopsoas abscess which was drained surgically. Repeat radiological evaluation showed almost complete L4 body destruction and 10 cm × 8 cm pre-vertebral abscess. ESR was further raised. Vertebral biopsy culture showed growth of Mycobacterium tuberculosis complex susceptible only to capreomycin (Cm). Second-line ATT (moxifloxacin + clofazimine + linezolid + isoniazid + amoxicillin-clavulanate + para-aminosalicylic [PAS] acid) with daily intramuscular Cm was initiated, under the RNTCP Programmatic Management of Drug-Resistant TB initiative. At 3 months, tenderness was absent, ESR decreased, and radiology showed consolidation of L3 and L5 vertebral bodies and their interspace. At 6 months, injectable Cm was stopped, oral ATT continued for 18 months. No major drug-related side effects were noted. At final follow-up, imaging showed complete L4 body absence, intact posterior elements, surrounding bony consolidation, resolution of abscess without neurodeficit, or deformity.XDR-TB should be suspected if there is clinical and/or radiological progression of TB in spite of chemotherapy or a prior history of treatment for TB. Effective treatment of XDR-TB requires a high index of suspicion and prompt, aggressive drug sensitivity-based ATT.
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Project description:Carbapenem-resistant Acinetobacter pittii (CRAP) is a causative agent of nosocomial infections. This study aimed to characterize clinical isolates of CRAP from a tertiary hospital in Northeast Thailand. Six isolates were confirmed as extensively drug-resistant Acinetobacter pittii (XDRAP). The blaNDM-1 gene was detected in three isolates, whereas blaIMP-14 and blaIMP-1 were detected in the others. Multilocus sequence typing with the Pasteur scheme revealed ST220 in two isolates, ST744 in two isolates, and ST63 and ST396 for the remaining two isolates, respectively. Genomic characterization revealed that six XDRAP genes contained antimicrobial resistance genes: ST63 (A436) and ST396 (A1) contained 10 antimicrobial resistance genes, ST220 (A984 and A864) and ST744 (A56 and A273) contained 9 and 8 antimicrobial resistance genes, respectively. The single nucleotide polymorphism (SNP) phylogenetic tree revealed that the isolates A984 and A864 were closely related to A. pittii YB-45 (ST220) from China, while A436 was related to A. pittii WCHAP100020, also from China. A273 and A56 isolates (ST744) were clustered together; these isolates were closely related to strains 2014S07-126, AP43, and WCHAP005069, which were isolated from Taiwan and China. Strict implementation of infection control based upon the framework of epidemiological analyses is essential to prevent outbreaks and contain the spread of the pathogen. Continued surveillance and close monitoring with molecular epidemiological tools are needed.
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Project description:Extensively drug resistant tuberculosis (XDR-TB) showed many different characteristics including the extreme drug resistance versus the drug sensitive clinical isolates (DS-TB), to know better about the reasons we used the tuberculosis host cells named as THP-1 (one kind of the macrophage cells) to be infected by the XDR-TB and DS-TB.DS strain A36 and the XDR strain B42 and was typical and selected by our lab. Then the total RNA of infected or uninfected THP-1 cells was extract and purified for the analysis by the chip (22K Human Genome chip representing the 21522 ORF of human with the oligonucleotide probe of 70 mer from CapitalBio Corp., Beijing, China). The results reflected the different expressed genes involved in apoptosis, secreted cytokines and signal pathway and so on. Those results might indicate the how the XDR-TB cause the pathogenesis. In this study, the well grown THP-1 cells were separated and cultured in three ampoules. Cells in one ampoules were infected with XDR-TB strain of B42. Cells in another ampoules were infected with DS-TB strain of A36, with the cells in the third one were not infected and just treated with PBS as the control. Then the dual channel method was used for detecting the hybridization of B42 vs the control or A36 vs control. This work was repeated for three times.
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