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Case Report: Metagenomic Next-Generation Sequencing in Diagnosis of Disseminated Tuberculosis of an Immunocompetent Patient.

ABSTRACT: Disseminated tuberculosis (TB) is a rare disease and mainly occurs in immunodeficient patients. It is marked by hematogenous or lymphatic dissemination of Mycobacterium tuberculosis, causing tuberculous infection involving any organ system. Here, we report a case of disseminated TB involving lung, liver, spine, mediastinum, and prostate in an immunocompetent man. The present patient found a hepatic mass without any symptom during health examination. In the next 2 years, further examinations revealed multiple lesions in the lung, mediastinum, spine, and prostate. Imaging examinations, such as contrast-enhanced abdominal CT, F-18 FDG-PET/CT, and radionuclide bone scan, suggested the diagnosis of malignancy or metastatic tumor. Furthermore, histopathological results of the biopsies of the hepatic mass, mediastinal mass, and prostatic mass demonstrated granulomatous inflammation. Therefore, metagenomic next-generation sequencing (mNGS) was utilized to confirm the diagnosis. Mycobacterium tuberculosis complex was simultaneously detected in the spinal surgical resection specimens and bronchoalveolar lavage fluid (BALF), indicating the diagnosis of disseminated TB. mNGS is an emerging molecular diagnostic technology, and its application in disseminated TB has been rarely reported. We highlight that disseminated TB should be considered even in an immunocompetent patient, and mNGS can be performed when the diagnosis is difficult.

SUBMITTER: Ye Y

PROVIDER: S-EPMC8310911 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMetagenomic next-generation sequencing (mNGS) technology has been widely used to diagnose various infections. Based on the most common pathogen profiles, targeted mNGS (tNGS) using multiplex PCR has been developed to detect pathogens with predesigned primers in the panel, significantly improving sensitivity and reducing economic burden on patients. However, there are few studies on summarizing pathogen profiles of pulmonary infections in immunocompetent and immunocompromised patients in Jilin Province of China on large scale.MethodsFrom January 2021 to December 2023, bronchoalveolar lavage fluid (BALF) or sputum samples from 546 immunocompetent and immunocompromised patients with suspected community-acquired pneumonia were collected. Pathogen profiles in those patients on whom mNGS was performed were summarized. Additionally, we also evaluated the performance of tNGS in diagnosing pulmonary infections.ResultsCombined with results of mNGS and culture, we found that the most common bacterial pathogens were Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii in both immunocompromised and immunocompetent patients with high detection rates of Staphylococcus aureus and Enterococcus faecium, respectively. For fungal pathogens, Pneumocystis jirovecii was commonly detected in patients, while fungal infections in immunocompetent patients were mainly caused by Candida albicans. Most of viral infections in patients were caused by Human betaherpesvirus 5 and Human gammaherpesvirus 4. It is worth noting that, compared with immunocompetent patients (34.9%, 76/218), more mixed infections were found in immunocompromised patients (37.8%, 14/37). Additionally, taking final comprehensive clinical diagnoses as reference standard, total coincidence rate of BALF tNGS (81.4%, 48/59) was much higher than that of BALF mNGS (40.0%, 112/280).ConclusionsOur findings supplemented and classified the pathogen profiles of pulmonary infections in immunocompetent and immunocompromised patients in Jilin Province of China. Most importantly, our findings can accelerate the development and design of tNGS specifically used for regional pulmonary infections.

Project description:Patients who were infected by the Human Immunodeficiency Virus (HIV) could have weakened immunity that is complicated by opportunistic infections, especially for Mycobacterium tuberculosis (MTB). Notably, the HIV-MTB co-infection will accelerate the course of disease progress and greatly increase the mortality of patients. Since the traditional diagnostic methods are time-consuming and have low sensitivity, we aim to investigate the performance of mNGS (metagenomic Next-Generation Sequencing) and mNPS (metagenomic NanoPore Sequencing) for the rapid diagnosis of tuberculosis in HIV-infected patients. The 122 HIV-infected patients were enrolled for the retrospective analysis. All of the patients underwent traditional microbiological tests, mNGS, and (or) mNPS tests. The clinical comprehensive diagnosis was used as the reference standard to compare the diagnostic performance of culture, mNGS, and mNPS on tuberculosis. We also investigate the diagnostic value of mNGS and mNPS on mixed-infection. Furthermore, the treatment adjustment directed by mNGS and mNPS was analyzed. Compared with the composite reference standard, the culture showed 42.6% clinical sensitivity and 100% specificity, and the OMT(other microbiological testing) had 38.9% sensitivity and 100% specificity. The mNGS had 58.6% clinical sensitivity and 96.8% specificity, and the mNPS had 68.0% clinical sensitivity and 100% specificity. The proportion of mixed-infection cases (88.9%) in the TB group was higher than those in the non-TB group (54.8%) and the mNGS and mNPS are more competitive on mixed-infection diagnosis compared with the traditional methods. Furthermore, there are 63 patients (69.2%) and 36 patients (63.2%) achieved effective treatment after receiving the detection of mNPS and mNGS, respectively. Our study indicated that mNPS and mNGS have high sensitivity and specificity for TB diagnosis compared with the traditional methods, and mNPS seems to have better diagnostic performance than mNGS. Moreover, mNGS and mNPS showed apparent advantages in detecting mixed infection. The mNPS and mNGS-directed medication adjustment have effective treatment outcomes for HIV-infected patients who have lower immunity.

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Case Report: Metagenomic Next-Generation Sequencing in Diagnosis of Disseminated Tuberculosis of an Immunocompetent Patient.

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