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Metagenomic next-generation sequencing in the diagnosis of severe pneumonias caused by Chlamydia psittaci.

ABSTRACT: PURPOSE:Chlamydia psittaci infection in humans can lead to serious clinical manifestations, including severe pneumonia, adult respiratory distress syndrome, and, rarely, death. Implementation of metagenomic next-generation sequencing (mNGS) gives a promising new tool for diagnosis. The clinical spectrum of severe psittacosis pneumonia is described to provide physicians with a better understanding and to highlight the rarity and severity of severe psittacosis pneumonia. METHODS:Nine cases of severe psittacosis pneumonia were diagnosed using mNGS. Retrospective analysis of the data on disease progression, new diagnosis tool, treatments, and outcomes, and the findings were summarised. RESULTS:Frequent symptoms included chills and remittent fever (100%), cough and hypodynamia (100%), and headache and myalgia (77.8%). All patients were severe psittacosis pneumonia developed respiratory failure, accompanied by sepsis in 6/9 patients. mNGS takes 48-72 h to provide the results, and help to identify diagnosis of psittacosis. Laboratory data showed normal or slightly increased leucocytes, neutrophils, and procalcitonin but high C-reactive protein levels. Computed tomography revealed air-space consolidation and ground-glass opacity, which began in the upper lobe of one lung, and spread to both lungs, along with miliary, nodular, or consolidated shadows. One patient died because of secondary infection with Klebsiella pneumoniae, while the other eight patients experienced complete recoveries. CONCLUSIONS:The use of mNGS can improve accuracy and reduce the delay in diagnosis of psittacosis. Severe psittacosis pneumonia responds well to the timely use of appropriate antibiotics.

SUBMITTER: Chen X

PROVIDER: S-EPMC7223968 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Metagenomic next-generation sequencing in the diagnosis of severe pneumonias caused by Chlamydia psittaci.

Chen Xiancheng X Cao Ke K Wei Yu Y Qian Yajun Y Liang Jing J Dong Danjiang D Tang Jian J Zhu Zhanghua Z Gu Qin Q Yu Wenkui W

Infection 20200420 4

<h4>Purpose</h4>Chlamydia psittaci infection in humans can lead to serious clinical manifestations, including severe pneumonia, adult respiratory distress syndrome, and, rarely, death. Implementation of metagenomic next-generation sequencing (mNGS) gives a promising new tool for diagnosis. The clinical spectrum of severe psittacosis pneumonia is described to provide physicians with a better understanding and to highlight the rarity and severity of severe psittacosis pneumonia.<h4>Methods</h4>Nin ...[more]

PMID: 32314307

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Project description:Psittacosis is an uncommon disease which mainly presents as community-acquired pneumonia (CAP). We aim to apply metagenomic next-generation sequencing (mNGS) as a promising tool in the diagnosis of psittacosis pneumonia and to describe its clinical spectrum to provide physicians with a better understanding and recognition of this disease. Thirteen cases of psittacosis pneumonia were diagnosed by using mNGS. A retrospective analysis of the data on clinical manifestations, laboratory data, computed tomography (CT) images, new diagnosis tools, treatments, and outcomes was summarized. These patients had common symptoms of fever and weakness; some had poor appetite, cough, myalgia, and headache. Ten patients developed acute respiratory distress syndrome (ARDS), among which six patients were severe pneumonia cases and needed ventilator therapy. Most patients got psittacosis pneumonia during the cold season. Ten cases were sporadic, but three were family clustering. All of the 13 patients were traced to an exposure history to birds, cat, or poultry, among which 2 only touched the innards of killed poultry before cooking, which may be an atypical exposure history not been reported before, to our knowledge. Most patients had various degrees of liver dysfunction. Air-space consolidations, along with ground-glass opacities and reticular shadows, were detected on chest CT scan. mNGS takes 48 to 72 h to provide results and helps to diagnose psittacosis. After being diagnosed by mNGS, with effective medicines, all patients finally had complete recoveries. The use of mNGS can improve the diagnostic rate of psittacosis pneumonia and shorten the course of disease control. IMPORTANCE Psittacosis pneumonia is easily underdiagnosed and misdiagnosed. In this study, we use mNGS in the diagnosis of psittacosis pneumonia. We found this disease is prone in the cold season, and touching the innards of killed poultry during cooking may be an atypical exposure history which has not been reported before to our knowledge. There are sporadic cases and family outbreak cases as well. Except for typical symptoms of fever and weakness, headache may be the main and only symptom in some patients. The rate of severe pneumonia is high among inpatients with psittacosis pneumonia, and the incidence of hepatic involvements is also high. Psittacosis pneumonia can be cured if the diagnosis is accurate and in time, even if it is severe pneumonia on admission. Some problems worthy of our attention about psittacosis pneumonia were put forward, such as its sick season, special exposure history, the rate of severe disease, and the high cure rate. mNGS can quickly and objectively detect more rare pathogenic microorganisms in clinical specimens without the need for specific amplification and has an advantage in the diagnosis of rare pathogenic bacteria in difficult cases such as psittacosis pneumonia. The use of mNGS can improve the accuracy and reduce the delay in the diagnosis of psittacosis, which shortens the course of disease control.

Project description:IntroductionRecently, the incidence of chlamydial pneumonia caused by rare pathogens such as C. psittaci or C. abortus has shown a significant upward trend. The non-specific clinical manifestations and the limitations of traditional pathogen identification methods determine that chlamydial pneumonia is likely to be poorly diagnosed or even misdiagnosed, and may further result in delayed treatment or unnecessary antibiotic use. mNGS's non-preference and high sensitivity give us the opportunity to obtain more sensitive detection results than traditional methods for rare pathogens such as C. psittaci or C. abortus.MethodsIn the present study, we investigated both the pathogenic profile characteristics and the lower respiratory tract microbiota of pneumonia patients with different chlamydial infection patterns using mNGS.ResultsMore co-infecting pathogens were found to be detectable in clinical samples from patients infected with C. psittaci compared to C. abortus, suggesting that patients infected with C. psittaci may have a higher risk of mixed infection, which in turn leads to more severe clinical symptoms and a longer disease course cycle. Further, we also used mNGS data to analyze for the first time the characteristic differences in the lower respiratory tract microbiota of patients with and without chlamydial pneumonia, the impact of the pattern of Chlamydia infection on the lower respiratory tract microbiota, and the clinical relevance of these characteristics. Significantly different profiles of lower respiratory tract microbiota and microecological diversity were found among different clinical subgroups, and in particular, mixed infections with C. psittaci and C. abortus resulted in lower lung microbiota diversity, suggesting that chlamydial infections shape the unique lung microbiota pathology, while mixed infections with different Chlamydia may have important effects on the composition and diversity of the lung microbiota.DiscussionThe present study provides possible evidences supporting the close correlation between chlamydial infection, altered microbial diversity in patients' lungs and clinical parameters associated with infection or inflammation in patients, which also provides a new research direction to better understand the pathogenic mechanisms of pulmonary infections caused by Chlamydia.

Project description:BackgroundPsittacosis, which is also known as parrot fever, is Chlamydia psittaci (C. psittaci) caused infectious disease. The clinical manifestations vary from asymptomatic infection to severe atypical pneumonia or even fatal meningitis. Early recognition of psittacosis is difficult because of its nonspecific clinical manifestations. Culture and gene probe techniques for C. psittaci are not available for routine clinical use, which makes the diagnosis difficult too. Although psittacosis has increasingly been recognized and reported in recent years, cure of severe pneumonia complicated with meningitis, with etiologic diagnosis aided by the use of metagenomic next-generation sequencing (mNGS), is still uncommon. So, it is necessary to report and review such potentially fatal case.Case presentationThis report describes a 54-year-old woman with C. psittaci caused severe atypical pneumonia and meningitis. She presented with symptoms of fever, dry cough and dyspnea, accompanied by prominent headache. Her condition deteriorated rapidly to respiratory failure and lethargy under the treatment of empirical antibacterial agents, and was treated with invasive mechanical ventilation soon. She denied contact with birds, poultry or horses, but unbiased mNGS of both the bronchoalveolar lavage fluid (BALF) and the cerebrospinal fluid (CSF) identified sequence reads corresponding to C. psittaci infection, and there was no sequence read corresponding to other probable pathogens. Combined use of targeted antimicrobial agents of tetracyclines, macrolides and fluoroquinolones was carried out, and the patient's condition improved and she was discharged home 28 days later. Her status returned close to premorbid condition on day 60 of follow-up.ConclusionsWhen clinicians come across a patient with atypical pneumonia accompanied by symptoms of meningitis, psittacosis should be taken into consideration. mNGS is a promising detection method in such condition and is recommended.

Project description:BackgroundMetagenomic next-generation sequencing (mNGS) is emerging as a promising technique for pathogens detection. However, reports on the application of mNGS in mixed pulmonary infection remain scarce.MethodsFrom July 2018 to March 2019, 55 cases were enrolled in this retrospective analysis. Cases were classified into mixed pulmonary infection (36 [65.5%]) and non-mixed pulmonary infection (19 [34.5%]) according to primary diagnoses. The performances of mNGS and conventional test on mixed pulmonary infection diagnosis and pathogen identification were compared.ResultsThe sensitivity of mNGS in mixed pulmonary infection diagnosis was much higher than that of conventional test (97.2% vs 13.9%; P < 0.01), but the specificity was the opposite (63.2% vs 94.7%; P = 0.07). The positive predictive value of mNGS was 83.3% (95% CI, 68.0-92.5%), and the negative predictive value was 92.3% (95% CI, 62.1-99.6%). A total of 5 (9.1%) cases were identified as mixed pulmonary infection by both conventional tests and mNGS, however, the pathogens identification results were consistent between these two methods in only 1 (1.8%) case. In summary, the pathogens detected by mNGS in 3 (5.5%) cases were consistent with those by conventional test, and only 1 (1.8%) case was mixed pulmonary infection. According to our data, mNGS had a broader spectrum for pathogen detection than conventional tests. In particular, application of mNGS improved the diagnosis of pulmonary fungal infections. Within the 55 cases, mNGS detected and identified fungi in 31 (56.4%) cases, of which only 10 (18.2%) cases were positive for the same fungi by conventional test. The most common pathogen detected by mNGS was Human cytomegalovirus in our study, which was identified in 19 (34.5%) cases of mixed pulmonary infection. Human cytomegalovirus and Pneumocystis jirovecii, which were detected in 7 (12.7%) cases, were the most common co-pathogens in the group of mixed pulmonary infection.ConclusionsmNGS is a promising technique to detect co-pathogens in mixed pulmonary infection, with potential benefits in speed and sensitivity.Trial registration(retrospectively registered): ChiCTR1900023727. Registrated 9 JUNE 2019.

Project description:Background:Metagenome next-generation sequencing (mNGS) is a valuable diagnostic tool that can be used for the identification of early pathogens of acute respiratory distress syndrome (ARDS) in severe pneumonia. Little is known about the use of this technology in clinical application and the evaluation of the prognostic value of ARDS. Methods:We performed a retrospective cohort study of patients with ARDS caused by severe pneumonia. Samples were collected from patients in the intensive care unit (ICU) of Jiangmen Central Hospital from January 2018 to August 2019. The no-next generation sequencing (NGS) group was composed of patients given conventional microbiological tests to examine sputum, blood, or bronchoalveolar lavage fluid. The NGS group was composed of patients tested using mNGS and conventional microbiological tests. We evaluated the etiological diagnostic effect and clinical prognostic value of mNGS in patients with ARDS caused by severe pneumonia. Results:The overall positive rate (91.1%) detected by the mNGS method was significantly higher than that of the culture method (62.2%, P = 0.001), and antibody plus polymerase chain reaction (28.9%, P < 0.001). Following adjustment of the treatment plan based on microbial testing results, the Acute Physiology and Chronic Health Evaluation-II (APACHE II) score of the NGS group was lower than that of the no-NGS group 7 days after treatment (P < 0.05). The 28-day mortality rate of the NGS group was significantly lower than that of the no-NGS group (P < 0.05). Longer ICU stay, higher APACHE II score and sequential organ failure assessment score were risk factors for the death of ARDS, and adjusting the medication regimen based on mNGS results was a protective factor. The detection of mNGS can significantly shorten the ICU stay of immunosuppressed patients (P < 0.01), shorten the ventilation time (P < 0.01), and reduce the ICU hospitalization cost (P < 0.05). Conclusions:Metagenome next-generation sequencing is a valuable tool to determine the etiological value of ARDS caused by severe pneumonia to improve diagnostic accuracy and prognosis for this disease. For immunosuppressed patients, mNGS technology can be used in the early stage to provide more diagnostic evidence and guide medications.

Project description:Introduction: Scrub typhus is a mite-borne infection widespread in Southeast Asia, with clinical symptoms such as fever, chills, skin rash, eschar at the bite site, and other signs of acute febrile illness. The Rickettsia pathogen (Orientia tsutsugamushi) is always difficult to be diagnosed at an early stage by traditional clinical diagnostic methods, especially for patients without typical eschar. This greatly increases the mortality of patients with scrub typhus. A new approach should be introduced to improve its clinical diagnosis. Methods: During May 2018 to March 2021, 13 samples from 10 patients with suspected scrub typhus were collected. Metagenomic next-generation sequencing (mNGS) and other diagnostic methods (including serology using Weil-Felix reaction and indirect immunofluorescence test (IIFT) for scrub typhus and respiratory tract profile IgM as well as culture for routine bacteria) were used to identify the pathogens in this study. Results: The results of mNGS were all positive, with mapped reads of O. tsutsugamushi ranging from 1 to 460. Eight patients (80%) were diagnosed as scrub typhus. The other two were diagnosed as suspected scrub typhus due to the limited number of reads of the pathogen (one and two, respectively). According to clinical evidences, nine of the 10 patients were finally diagnosed as scrub typhus, except for patient 9 (suspected scrub typhus by mNGS with one specific reads of the pathogen) diagnosed as acute exacerbation of chronic obstructive pulmonary disease. For the five scrub typhus patients without typical eschar, mNGS gave all positive results (4-460 specific reads). For other methods, only Weil-Felix reaction of one patient detected the pathogen. In addition, the respiratory tract profile (IgM) detected various pathogens, but all were confirmed to be false positive. Conclusions: mNGS performed better than conventional clinical methods to early diagnose scrub typhus. This approach can be routinely carried out for early and precise diagnosis in clinical infections, especially for those hard to be identified by traditional diagnostic methods.

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Metagenomic next-generation sequencing in the diagnosis of severe pneumonias caused by Chlamydia psittaci.

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Metagenomic next-generation sequencing in the diagnosis of severe pneumonias caused by Chlamydia psittaci.

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