Rapid diagnosis of Talaromyces marneffei infection assisted by metagenomic next-generation sequencing in a HIV-negative patient.
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ABSTRACT:
SUBMITTER: Zhang J
PROVIDER: S-EPMC7868811 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
Publications
Rapid diagnosis of <i>Talaromyces marneffei</i> infection assisted by metagenomic next-generation sequencing in a HIV-negative patient.
Zhang Jingjia J Zhang Dong D Du Juan J Zhou Yang Y Cai Yunting Y Sun Ruixue R Zhou Jiali J Tian Jingjing J Wu Honglong H Lu Minya M Xu Yingchun Y Yang Qiwen Q
IDCases 20210123
<i>Talaromyces marneffei (T. marneffei),</i> is an opportunistic pathogenic fungus commonly reported in southeast Asia. <i>T. marneffei</i> infection predominantly occurs in patients with immunodeficiency and can be fatal if diagnosis and treatment were delayed. Conventional diagnosis of <i>T. marneffei</i> infection relies heavily on tissue culture and histologic analysis, which is time consuming and has limited positive rate. Rapid and accurate diagnosis of <i>T. marneffei</i> remains urgent f ...[more]
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Project description:Talaromyces marneffei (T. marneffei) is an opportunistic pathogen. Patients with inborn errors of immunity (IEI) have been increasingly diagnosed with T. marneffei in recent years. The disseminated infection of T. marneffei can be life-threatening without timely and effective antifungal therapy. Rapid and accurate pathogenic microbiological diagnosis is particularly critical for these patients. A total of 505 patients with IEI were admitted to our hospital between January 2019 and June 2022, among whom T. marneffei was detected in 6 patients by metagenomic next-generation sequencing (mNGS), and their clinical and immunological characteristics were summarized. We performed a systematic literature review on T. marneffei infections with published immunodeficiency-related gene mutations. All patients in our cohort were confirmed to have genetic mutations in IL12RB1, IFNGR1, STAT1, STAT3, and CD40LG. T. marneffei was detected in both the blood and lymph nodes of P1 with IL12RB1 mutations, and the clinical manifestations were serious and included recurrent fever, weight loss, severe anemia, splenomegaly and lymphadenopathy, all requiring long-term antifungal therapy. These six patients received antifungal treatment, which relieved symptoms and improved imaging findings. Five patients survived, while one patient died of sepsis after hematopoietic stem cell transplantation. The application of mNGS methods for pathogen detection in IEI patients and comparison with traditional diagnosis methods were investigated. Traditional diagnostic methods and mNGS tests were performed simultaneously in 232 patients with IEI. Compared to the traditional methods, the sensitivity and specificity of mNGS in diagnosing T. marneffei infection were 100% and 98.7%, respectively. The reporting time for T. marneffei detection was approximately 26 hours by mNGS, 3-14 days by culture, and 6-11 days by histopathology. T. marneffei infection was first reported in IEI patients with IL12RB1 gene mutation, which expanded the IEI lineage susceptible to T. marneffei. For IEI patients with T. marneffei infection, we highlight the application of mNGS in pathogenic detection. mNGS is recommended as a front-line diagnostic test for rapidly identifying pathogens in complex and severe infections.
| S-EPMC9493038 | biostudies-literature
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.
| S-EPMC6921575 | biostudies-literature
Project description:BackgroundMetagenomic next-generation sequencing (mNGS) is a promising technology that allows unbiased pathogen detection and is increasingly being used for clinical diagnoses. However, its application in urinary tract infection (UTI) is still scarce.MethodsThe medical records of 33 patients with suspected UTI who were admitted to the Second Hospital of Tianjin Medical University from March 2021 to July 2022 and received urine mNGS were retrospectively analyzed. The performance of mNGS and conventional urine culture in diagnosing infection and identifying causative organisms was compared, and the treatment effects were evaluated in terms of changes in urinalyses and urinary symptoms.ResultsIn the detection of bacteria and fungi, mNGS detected at least one pathogen in 29 (87.9%) cases, including 19 (57.6%) with positive mNGS but negative culture results and 10 (30.3%) with both mNGS and culture positive results. The remaining 4 (12.1%) patients were negative by both tests. Overall, mNGS performed better than culture (87.9% vs. 30.3%, P < 0.001). Within the 10 double-positive patients, mNGS matched culture results exactly in 5 cases, partially in 4 cases, and not at all in 1 case. In addition, mNGS detected a broader pathogen spectrum, detecting 26 species compared to only 5 species found in culture. The most abundant bacteria detected by mNGS was Escherichia coli, detected in 9 (27.2%) patients. All anaerobic bacteria, Mycobacterium Tuberculosis and all mixed pathogens were detected by mNGS. The final clinical diagnosis of UTI was made in 25 cases, and the sensitivity of mNGS was significantly higher than culture (100.0% vs 40.0%; P < 0.001) when using the diagnosis as a reference standard; the positive predictive value, negative predictive value and specificity were 86.2%, 100% and 50.0%, respectively. Importantly, targeted antibiotic therapy based on mNGS resulted in significant improvement in urinalyses and urinary symptoms in patients.ConclusionsmNGS is a technology that has shown clear advantages over culture, particularly in the context of mixed infections and UTIs that are difficult to diagnose and treat. It helps to improve the detection of pathogens, guide changes in treatment strategies, and is an effective complement to urine culture.
| S-EPMC10020507 | biostudies-literature
Project description:BACKGROUND:To examine the accuracy of Rapid Diagnosis of Talaromyces marneffei (RDTM) in order to improve diagnosis and treatment for clinical measures and reduce the mortality due to associated infections. METHODS:In this systematic review and meta-analysis, we screened PubMed, Ovid (Cochrane library) and Web of Science, Chinese database CNKI and Wanfang for articles published between 1956 and December, 2017. Data were taken from cross-sectional studies as well as from baseline measurements in longitudinal studies with clinical follow-up. Articles were excluded if they did not contain a cohort with T. marneffei and a control cohort or a cohort with standard fungus culture. Data were extracted by two authors and checked by three for accuracy. For quality assessment, modified QUADAS-2 criteria were used. RESULTS:The 26 included diagnostic studies enrolled 5,594 objectives in 632 patients with T. marneffei infections and 2,612 negative controls between 1996 and 2017 in Thailand, Vietnam and China. The total combined sensitivity and specificity of rapid diagnosis of T. marneffei was 0.82 (95% CI: 0.68-0.90) and 0.99 (95% CI: 0.98-1.00). According to the experimental method, the included studies can be divided into three subgroups, including PCR-based, ELISA-based and others. The results showed these three subgroups had a highly pooled specificity of 1.00 (95% CI: 0.99-1.00), 0.99 (0.98-1.00) and 0.97 (95% CI: 0.91-1.00), respectively, while combined sensitivity was 0.84 (95% CI: 0.37-0.98), 0.82 (95% CI: 0.64-0.92) and 0.77 (95% CI: 0.54-0.91), respectively. CONCLUSIONS:Although serological methods with a high specificity is essential for potential rapid diagnostic, false-negative results can be obtained in the serum samples, there is no suitable rapid serological test to refer to as is the case with TM infection.
| S-EPMC5886574 | biostudies-literature
Project description:Background: Streptococcus suis is a zoonotic pathogen that can cause severe infections such as meningitis and septicemia in both swine and humans. Rapid and accurate identification of the causative agent is very important for guiding clinical choices in administering countermeasures. Case Report: Here, we report a case of fatal S. suis infection in a patient who worked as a butcher in China. The 59-year-old man, who had previously undergone splenectomy, injured his finger while processing pork and developed severe sepsis. While blood cultures were negative following antibiotic treatment, S. suis was determined to be the causative agent by metagenomic next-generation sequencing (mNGS) and Sanger sequencing. Conclusion: Identification of etiological agents using techniques such as blood culture prior to antibiotic treatment is very important. mNGS may represent a useful method for diagnosis of infectious diseases, especially post-antibiotic treatment.
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Project description:ObjectivesThe incidence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) has increased steadily globally, but the current culture-based diagnosis of NTM-PD is difficult and time-consuming, leading to a high possibility of misdiagnosis. Therefore, new methods should be introduced to improve the processes for clinical diagnosis of this disease.MethodsOur retrospective observational study enrolled 12 NTM-PD patients who were identified by way of metagenomic next-generation sequencing (mNGS), as well as the characteristic radiological presentation of slowly progressed, usually concomitant bronchiectasis, small cavitary opacity, and multiple nodules that respond poorly to empirical antibiotic therapy. These patients received the recommended drug regimen based on the identified non-tuberculous mycobacteria (NTM) species. Clinical data, including symptoms, laboratory tests, dynamic computed tomography imaging, treatment, and outcome, were recorded and analyzed.ResultsThe results of mNGS were all positive, with the standard specifically mapped read numbers (SDSMRN) of NTM ranging from 1 to 766; this was confirmed in six patients via quantitative polymerase chain reaction (qPCR) analysis. The duration fromsample collection tomNGS results was 1-4 days. Among our 12 patients (except for one lost to follow-up) the CT imaging for 11 patients showed significant absorption of lesions.ConclusionsOur results draw attention to NTM infection as a possible cause of community-acquired pneumonia, especially in patients with suggestive radiological presentation and poor responses to empirical antibiotic therapy. Our study also indicated that mNGS represented a potentially effective tool for the rapid identification of NTM in the respiratory sample. Improved clinician awareness combined with the utilization of mNGS could guide earlier diagnosis and targeted treatment, and finally improved the prognoses of patients with NTM-PD.
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Project description:Bartonella henselae, the pathogen that causes cat-scratch disease (CSD), is relatively rare in the clinic. CSD usually causes mild clinical manifestations, which self-heal in a matter of weeks. However, in immunocompromised patients, CSD may cause systemic disorders that can lead to critical illness. Due to the diversity of symptom signs and the lack of a golden standard for diagnosis, identifying atypical CSD in a timely manner presents a challenge. Metagenomic next-generation sequencing (mNGS), is a promising technology that has been widely used in the detection of pathogens in clinical infectious diseases in recent years. mNGS can detect multiple pathogens quickly and accurately from any given source. Here, we present a case of atypical CSD, which was diagnosed using mNGS. The patient manifested a fever of unknown infectious origin, and routine antibiotic treatment was ineffective. mNGS was employed to test the patient's peripheral blood, which led to the detection of B. henselae. This was rarely seen in previous CSD reports. We surmised that the patient presented with atypical CSD and thus a targeted therapy was recommended. Crucially, the patient recovered rapidly. Based on this case study findings, we recommend that CSD should be included in the differential diagnosis for fever of unknown origin and that mNGS may be helpful in the diagnosis of CSD.
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Project description:Microbial infections cause significant morbidity and mortality in neonates. Metagenomic next-generation sequencing is a hypothesis-free and culture-free test that enables broad identification of pathogens and antimicrobial resistance genes directly from clinical samples within 24 h. In this study, we used mNGS for etiological diagnosis and monitoring the efficacy of antibiotic treatment in a cohort of neonatal patients with severe infections. The median age was 19.5 (3-52) days, median gestational age was 37.96 (31-40+3) weeks, and the median birth weight was 3,261 (1,300-4,300) g. The types of infectious diseases included pneumonia, sepsis, and meningitis. mNGS reported microbial findings in all cases, which led to changes in antibiotic treatment. These included cases of Mycobacterium tuberculosis, Legionella pneumophila, and Bacillus cereus. Eight of ten infants recovered after antibiotic adjustment and showed normal development during follow-up. On the other hand, neurological retardation was seen in two infants with meningitis. mNGS enabled etiological diagnosis and guided antibiotic therapy when all conventional methods failed to discover the culprit. It has the potential to cut down the overall cost and burden of disease management in neonatal infections.
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