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      Pneumonia Caused by Coinfection with Cytomegalovirus and Pneumocystis jirovecii in an HIV-Negative Infant Diagnosed by Metagenomic Next-Generation Sequencing

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          Abstract

          Background

          Pneumonia produced by coinfection with Pneumocystis jirovecii (PJ) and cytomegalovirus (CMV) in infants and young children without timely diagnosis and treatment is often fatal due to the limitations of traditional tests. More accurate and rapid diagnostic methods for multiple infections are urgently needed.

          Case Presentation

          Here, we report a case of a 2-month-old boy with pneumonia caused by Pneumocystis jirovecii (PJ) and cytomegalovirus (CMV) without HIV infection. Chest computed tomography (CT) showed massive exudative consolidation in both lungs. Microscopic examination of stained sputum and smear specimens and bacterial and fungal culture tests were all negative, and CMV nucleic acid and antibody tests were positive. After a period of antiviral and anti-infective therapy, pulmonary inflammation was not relieved. Subsequently, sputum and venous blood samples were analysed by metagenomic next-generation sequencing (mNGS), and the sequences of PJ and CMV were acquired. The patient was finally diagnosed with pneumonia caused by PJ and CMV coinfection. Anti-fungal combined with anti-viral therapy was given immediately. mNGS re-examination of bronchoalveolar lavage fluid (BALF) also revealed the same primary pathogen. Therapy was stopped due to the request of the patient’s guardian. Hence, the child was discharged from the hospital and eventually died.

          Conclusion

          This case emphasizes the combined use of mNGS and traditional tests in the clinical diagnosis of mixed lung infections in infants without HIV infection. mNGS is a new adjunctive diagnostic method that can rapidly discriminate multiple causes of pneumonia.

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          Most cited references29

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          Clinical metagenomics

          Clinical metagenomic next-generation sequencing (mNGS), the comprehensive analysis of microbial and host genetic material (DNA and RNA) in samples from patients, is rapidly moving from research to clinical laboratories. This emerging approach is changing how physicians diagnose and treat infectious disease, with applications spanning a wide range of areas, including antimicrobial resistance, the microbiome, human host gene expression (transcriptomics) and oncology. Here, we focus on the challenges of implementing mNGS in the clinical laboratory and address potential solutions for maximizing its impact on patient care and public health.
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            Next-generation sequencing diagnostics of bacteremia in septic patients

            Background Bloodstream infections remain one of the major challenges in intensive care units, leading to sepsis or even septic shock in many cases. Due to the lack of timely diagnostic approaches with sufficient sensitivity, mortality rates of sepsis are still unacceptably high. However a prompt diagnosis of the causative microorganism is critical to significantly improve outcome of bloodstream infections. Although various targeted molecular tests for blood samples are available, time-consuming blood culture-based approaches still represent the standard of care for the identification of bacteria. Methods Here we describe the establishment of a complete diagnostic workflow for the identification of infectious microorganisms from seven septic patients based on unbiased sequence analyses of free circulating DNA from plasma by next-generation sequencing. Results We found significant levels of DNA fragments derived from pathogenic bacteria in samples from septic patients. Quantitative evaluation of normalized read counts and introduction of a sepsis indicating quantifier (SIQ) score allowed for an unambiguous identification of Gram-positive as well as Gram-negative bacteria that exactly matched with blood cultures from corresponding patient samples. In addition, we also identified species from samples where blood cultures were negative. Reads of non-human origin also comprised fragments derived from antimicrobial resistance genes, showing that, in principle, prediction of specific types of resistance might be possible. Conclusions The complete workflow from sample preparation to species identification report could be accomplished in roughly 30 h, thus making this approach a promising diagnostic platform for critically ill patients suffering from bloodstream infections. Electronic supplementary material The online version of this article (doi:10.1186/s13073-016-0326-8) contains supplementary material, which is available to authorized users.
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              Opportunistic infections in patients with and patients without Acquired Immunodeficiency Syndrome.

              In the next decade, longer survival of patients with cancer and more-aggressive therapies applied to common conditions, such as asthma and rheumatoid arthritis, will result in a larger population with significant immune system defects. Many in this population will be at risk for opportunistic infections, which are familiar to doctors who have treated people infected with human immunodeficiency virus (HIV). However, the epidemiology, presentation, and outcome of these infections in patients with an immune system defect, other than that caused by HIV infection, may be different than those encountered in patients with acquired immunodeficiency syndrome. Reviewed are 4 common opportunistic infections: Pneumocystis carinii pneumonia, cryptococcosis, atypical mycobacterial infection, and cytomegalovirus infection. Emphasized are the important differences among these groups at risk.
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                Author and article information

                Journal
                Infect Drug Resist
                Infect Drug Resist
                idr
                Infection and Drug Resistance
                Dove
                1178-6973
                30 June 2022
                2022
                : 15
                : 3417-3425
                Affiliations
                [1 ]Xuzhou Key Laboratory of Laboratory Diagnostics, School of Medical Technology, Xuzhou Medical University , Xuzhou, 221004, People’s Republic of China
                [2 ]Laboratory Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences , Guangzhou, 510000, People’s Republic of China
                [3 ]Jiangsu Province Key Laboratory of Immunity and Metabolism, Xuzhou Medical University , Xuzhou, 221004, People’s Republic of China
                Author notes
                Correspondence: Maohua Zhou; Bing Gu, Laboratory Medicine, Guangdong Provincial People’s Hospital , 106 Zhongshan 2nd Road, Yuexiu District, Guangzhou, Guangdong, 510000, People’s Republic of China, Tel +86-20-83827812-62462, Email zhoumaohua@gdph.org.cn; gb20031129@163.com
                [*]

                These authors contributed equally to this work

                Article
                364241
                10.2147/IDR.S364241
                9253620
                efd8f52f-171b-4160-af06-5c184ea095f1
                © 2022 Lyu et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 28 March 2022
                : 09 June 2022
                Page count
                Figures: 3, Tables: 2, References: 29, Pages: 9
                Funding
                Funded by: the National Natural Science Foundation of China;
                Funded by: Key R & D Program of Jiangsu Province;
                Funded by: Research Foundation for advanced talents of Guangdong Provincial People’s Hospital;
                This research was supported by the National Natural Science Foundation of China (81871734, 82072380), Key R & D Program of Jiangsu Province (BE2020646), Research Foundation for advanced talents of Guangdong Provincial People’s Hospital (KJ012021097).
                Categories
                Case Report

                Infectious disease & Microbiology
                metagenomic next-generation sequencing,pneumocystis jirovecii,cytomegalovirus,pneumonitis,hiv-negative

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