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Metagenomic Next-Generation Sequencing in Diagnosis of a Case of Pneumocystis jirovecii Pneumonia in a Kidney Transplant Recipient and Literature Review.

ABSTRACT: Background:Despite the increasing incidences of Pneumocystis jirovecii pneumonia (PCP) in renal transplant recipients, diagnosis of PCP remains challenging due to its nonspecific clinical presentation and the inadequate performance of conventional diagnostic methods. There is a need for novel diagnostic methods. Case Presentation:A 27-year-old woman developed acute pneumonia 4 months after renal transplantation. Blood tests revealed a low CD4 count, a normal 1,3-beta-D-glucan level and other changes typical of inflammatory responses. Chest imaging showed bilateral diffuse infiltrates. Microscopic examination of stained sputum and bronchoalveolar lavage fluid (BALF) smear specimens did not find Pneumocystis organisms. There was also no evidence for other pathogens known to cause pneumonia in various antibody and culture tests. Direct metagenomic next-generation sequencing (mNGS) analysis of a BALF specimen identified a large number of P. jirovecii reads, allowing to confirm the diagnosis of PCP. Following treatment with trimethoprim-sulfamethoxazole for two weeks, the patient was cured and discharged. Conclusion:This case report supports the value of mNGS in diagnosing PCP, highlights the inadequate sensitivity of conventional diagnostic methods for PCP, and calls for the need to add PCP prophylaxis to the current Diagnosis and Treatment Guideline of Invasive Fungal Infections in Solid Organ Transplant Recipients in China.

SUBMITTER: Chen J

PROVIDER: S-EPMC7431457 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Metagenomic Next-Generation Sequencing in Diagnosis of a Case of <i>Pneumocystis jirovecii</i> Pneumonia in a Kidney Transplant Recipient and Literature Review.

Chen Jie J He Ting T Li Xiujun X Wang Xue X Peng Li L Ma Liang L

Infection and drug resistance 20200813

<h4>Background</h4>Despite the increasing incidences of <i>Pneumocystis jirovecii</i> pneumonia (PCP) in renal transplant recipients, diagnosis of PCP remains challenging due to its nonspecific clinical presentation and the inadequate performance of conventional diagnostic methods. There is a need for novel diagnostic methods.<h4>Case presentation</h4>A 27-year-old woman developed acute pneumonia 4 months after renal transplantation. Blood tests revealed a low CD4 count, a normal 1,3-beta-D-gluc ...[more]

PMID: 32884306

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Project description:BackgroundPneumocystis jirovecii (PJ) is an opportunistic pathogenic fungus, and PJ pneumonia (PJP) is a commonly problem in HIV-positive patients. While PJP is not caused by HIV, it generally advances rapidly and can quickly lead to severe respiratory failure. To improve pediatricians' understanding of the condition and aid early accurate diagnoses and therapy, we examined the clinical characteristics of five instances of non-HIV related PJP (NH-PJP) in children and the efficacy of metagenomic next-generation sequencing (mNGS) in its diagnosis.MethodsFrom January 2020 to June 2022, five children with NH-PJP were admitted to the PICU of the First Affiliated Hospital of Zhengzhou University. We retrospectively summarize the clinical presentation, previous histories, routine laboratory findings, treatment, outcome of regression, and results of mNGS in these five children.ResultsFive male children between the ages of 11 months and 14 years had an acute onset on NH-PJP, three of the children had chest tightness after activity, shortness of breath and paroxysmal dry cough, - and two had high fever and dry cough. All five of the children had several flocculent high-density pictures in both lungs at the beginning of the disease, and lung auscultation revealed coarse breath sounds in both lungs, one of which was accompanied by a modest quantity of dry rales. PJ nuclear sequences were found in one patient and four patients' blood and alveolar lavage fluid. All five children were treated with Trimethoprim-sulfamethoxazole (TMP-SMX) in combination with Caspofungin and corresponding symptomatic treatment. Four patients were cured and one patient died.ConclusionChildren commonly encounter an initial exposure to NH-PJP, which manifests as a high fever, dry cough, chest discomfort, dyspnea that worsens over time, fast disease progression, and a high death rate. The clinical presentation of children with PJ infection should be taken into consideration along with the results for diagnose. mNGS has higher sensitivity and a shorter detection period compared to identification of PJP.

Project description:BackgroundPneumocystis jirovecii pneumonia (PJP) remains an important cause of morbidity and mortality in non-HIV immunocompromised patients especially in transplant recipients. But its diagnosis remains challenging due to the insuffificient performance of conventional methods for diagnosing Pneumocystis jirovecii(P. jirovecii) infection. Therefore, the auxiliary diagnostic function of metagenomics next-generation sequencing (mNGS) in clinical practice is worth of exploring.Method34 non-HIV immunocompromised patients who were diagnosed as PJP by clinical manifestations, imaging findings, immune status of the host, and Methenamine silver staining were tested by mNGS from October 2018 to December 2020 in Sichuan Provincial People's Hospital. The clinical performances of mNGS for P. jirovecii infection diagnosis were also evaluated with genome reads abundance and comparing with other traditional diagnostic methods.ResultsWe diagnosed a total of 34 non-HIV PJP patients by the clinical composite diagnosis. Our data shows that, compared with the clinical microbiological test, the detection rate of mNGS for P. jirovecii in non-HIV infected PJP patients is significantly higher than that of Methenamine silver staining and serum 1-3-β-D-glucan. mNGS can be used as an auxiliary diagnostic tool to help diagnosis. The number of reads mapped to the genome of P. jirovecii and the duration of patients from onset to sampling collection were statistically significant between the two groups (Reads>100 and Reads ≤ 100) (8days vs. 23days, p=0.020). In addition, univariate analysis showed that C-reactive protein (15.8mg/L vs.79.56mg/L, p=0.016), lactate dehydrogenase (696U/l vs. 494U/l, p=0.030) and procalcitonin (0.09ng/ml vs. 0.59ng/ml, p=0.028) was also statistically significant between the two groups.ConclusionsAn effective detection rate was achieved in PJP patients using mNGS testing of bronchoalveolar lavage fluid (BALF) or blood. The study also confirmed that the abundance of reads of P. jirovecii is related to the interval between the onset and sample collection. And the inflammation status during simultaneous mNGS detection might determine the abundance of pathogens. Hence, we conclude that the mNGS strategy could benefit disease diagnosis as well as treatment when complicated clinical infections appeared.

Dataset Information

Metagenomic Next-Generation Sequencing in Diagnosis of a Case of Pneumocystis jirovecii Pneumonia in a Kidney Transplant Recipient and Literature Review.

Publications

Metagenomic Next-Generation Sequencing in Diagnosis of a Case of <i>Pneumocystis jirovecii</i> Pneumonia in a Kidney Transplant Recipient and Literature Review.

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