Metagenomic next-generation sequencing promotes diagnosis and treatment of Pneumocystis jirovecii pneumonia in non-HIV infected children: a retrospective study.

Metagenomic next-generation sequencing (mNGS) excels in diagnosis of infection pathogens. We aimed to evaluate the performance of mNGS for the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-HIV infected children. Totally 36 PJP children and 61 non-PJP children admitted to the pediatric intensive care unit from March 2018 to December 2021 were retrospectively enrolled. Clinical features of PJP children were summarized. 1,3-β-D glucan (BDG) test and bronchoalveolar lavage fluid (BALF) mNGS were used for evaluation of PJP diagnostic performance. Antimicrobial management modifications for PJP children after the mNGS results were also reviewed. Pneumocystis jirovecii was detected in all PJP children by mNGS (36/36), and the sensitivity of mNGS was 100% (95% confidence interval [CI]: 90.26-100%). The sensitivity of BDG was 57.58% (95% CI: 39.22-74.52%). Of the 26 (72.2%) PJP patients with mixed infection, twenty-four (66.7%) were detected by BALF-mNGS. Thirteen patients (36.1%) had their antimicrobial management adjusted according to the mNGS results. Thirty-six PJP children included 17 (47.2%) primary immunodeficiency and 19 (52.8%) secondary immunodeficiency, of whom 19 (52.8%) survived and 17 (47.2%) died. Compared to survival subgroup, non-survival subgroup had a higher rate of primary immunodeficiency (64.7% vs. 31.6%, P = 0.047), younger age (7 months vs. 39 months, P = 0.011), lower body weight (8.0 kg vs. 12.0 kg, P = 0.022), and lower T lymphocyte counts. The mortality rate of PJP in immunosuppressed children without HIV infection is high and early diagnosis is challenging. BALF-mNGS could help identify PJP and guide clinical management.

Zhang Z ，Liu T ，Ming M ，Shen M ，Zhang Y ，Chen H ，Chen W ，Tao J ，Wang Y ，Liu J ，Zhou J ，Lu G ，Yan G ... -  《BMC Pulmonary Medicine》

Study on mNGS Technique in Diagnosing Pneumocystis jirovecii Pneumonia in Non-HIV-Infected Patients.

To investigate the value of metagenomic Next-Generation Sequencing (mNGS) in diagnosing Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus (HIV)-infected patients. In this retrospective study, non-HIV-infected patients with PJP and those diagnosed with non-PJP from August 2022 to December 2024 were selected as subjects. The presence of Pneumocystis jirovecii (PJ) and other co-pathogens in bronchoalveolar lavage fluid (BALF) was analyzed, and the diagnostic efficacy of NGS, polymerase chain reaction (PCR) and serum 1,3-β-D-glucan (BDG) in PJP was compared with the reference standard of clinical compound diagnosis. Eighty-nine non-HIV-infected patients were recruited, with dyspnea as the primary symptom (69.66%) and solid malignant tumor as the most common underlying disease (20.22%). Taking clinical compound diagnosis as the reference standard, the sensitivity, specificity, negative predictive value and positive predictive value of mNGS were higher than those detected by PCR and serum BDG. Among 42 non-HIV-infected patients with PJP who underwent mNGS and conventional pathogen detection of BALF, 6 had simple PJ infection and 36 had combined PJ infection. The detection rate of mNGS in mixed infections was significantly higher than that of conventional pathogen detection (85.71 vs 61.70%, P = 0.012). A total of 127 pathogens were detected in BALF using mNGS, among which fungi had the highest detection rate (46.46%). The fungi, viruses and bacteria detected were mainly Pneumocystis jirovecii, human gammaherpesvirus 4 and Acinetobacter baumannii. mNGS is highly effective in diagnosing non-HIV-infected patients with PJP and exhibits ideal performance in the detection of co-pathogens. In addition, it has certain value for clinical diagnosis and guidance of targeted anti-infective drug treatment.

Li S ，Han X ，Ma J ，Huang GH ，Yang ST ，Wang CM ... -  《Infection and Drug Resistance》

Pneumocystis jirovecii pneumonia increases the 3-months mortality of anti-MDA5-antibody-positive dermatomyositis patients.

Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (anti-MDA5+DM) patients are associated with considerable mortality, and opportunistic infections including Pneumocystis jirovecii pneumonia (PJP)is the main cause. This study was to identify clinical characteristics, risk factors, and prognostic factors of PJP diagnosed by bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) in anti-MDA5+ DM patients. In this retrospective observational study, all patients admitted with suspected pneumonia were detected for mNGS in BALF. The demographics, comorbidities, laboratory parameters, and treatments of the patients were compared and analyzed in both groups to identify the potential risk factors for PJP and death via Logistic regression and Cox proportional hazards regression, respectively. Overall, 92 patients were included in this study, 46(50.0%) were defined as PJP+ group, and the other 46 (50.0%) as PJP- group, and 31(67.4%) PJP occurred in the first 3 months. Increased neutrophil-lymphocyte ratio (NLR) and CRP were independent risk factors for PJP occurrence, while trimethoprim-sulfamethoxazole (TMP/SMZ) prophylaxis was an independent protective factor (all p<0.05). The three-months mortality rate was higher in the PJP+ group compared to PJP- group (43.5% vs 23.9%, p=0.047). Rapidly progressive interstitial lung disease (RPILD) was a main predictor of mortality in anti-MDA5+DM patients with PJP, whereas glucocorticoid use was a significant protective factor. PJP has high prevalence and mortality in anti-MDA5+DM, while TMP/SMZ prophylaxis significantly reduces PJP risk. Mortality in PJP+ patients is primarily concentrated within the first 3 months, associated with RPILD. Early intervention with corticosteroids and prophylactic measures are crucial in reducing mortality.

Gao C ，Wei G ，Zhang C ，Wang C ，Li C ，Li R ，Su Z ，Zheng Z ... -  《-》

Insights into Pneumocystis jirovecii pneumonia in South Africa (2018-2022).

Pneumocystis jirovecii causes P. jirovecii pneumonia (PJP)-a leading opportunistic infection among persons with advanced human immunodeficiency virus. Furthermore, individuals with underlying conditions such as cancer and transplant recipients are susceptible to PJP. Most data on PJP come from other countries, with limited knowledge about its prevalence in Africa. The aim was to describe changes in the proportion of positive PJP tests in South Africa from 2018 to 2022. A 5-year retrospective study was conducted on patients with suspected P. jirovecii, detected by polymerase chain reaction. Data were obtained from the National Health Laboratory Service, where laboratory diagnostics were done as part of routine patient care. Mann-Whitney test and Χ2 tests were used to compare the age, sex, and wards with both the negative and positive results of PJP. From 2018 to 2022, a total of 8110 patients' results were retrieved, and 8059 met the inclusion criteria. The positive test proportions of PJP in South Africa were 32.66%, 29.93%, 34.02%, 24.98%, and 25.78%, respectively. The median age was 35 years, with interquartile range of 24-43 years (P = .002). Female patients had a higher positive test proportion than males (59.39% vs. 38.74%, P < .001). The proportion of positive PJP tests was higher in general wards (48.54%) and intensive care units (18.99%) (P = .012). The epidemiology of PJP in South Africa is similar to that of other countries in some respects but is influenced by unique factors specific to the country. These findings are crucial for public health planning, emphasising the need for targeted PJP prevention strategies considering sex- and age-specific vulnerabilities in South Africa.

Nkosi MP ，Hoog KJ ，Lowe M 《-》

Clinical application value of simultaneous plasma and bronchoalveolar lavage fluid metagenomic next generation sequencing in patients with pneumonia-derived sepsis.

Despite the increasing use of metagenomic next-generation sequencing (mNGS) in sepsis, identifying clinically relevant pathogens remains challenging. This study was aimed to evaluate the clinical utility of simultaneous plasma and bronchoalveolar lavage fluid (BALF) detection using mNGS. This retrospective study enrolled 95 patients with pneumonia-derived sepsis (PDS) admitted to the intensive care unit (ICU) between October 2021 and January 2023. Patients were divided into two groups: mNGS group (n = 60) and the non-mNGS group (n = 35), based on whether simultaneous plasma and BALF mNGS were conducted. All patients underwent conventional microbiological tests (CMT), including bacterial/fungal culture of peripheral blood and BALF, as well as sputum culture, detection of 1, 3-beta-D- glucan in BALF and RT-PCR testing. The clinical data of the enrolled patients were collected, and the detection performance and prognosis of plasma mNGS, BALF mNGS and CMT were compared. The mNGS group exhibited a lower mortality rate than the non-mNGS group (35.0% vs. 57.1%, P = 0.034). Simultaneous detection in dual-sample resulted in a higher proportion of microorganisms identified as definite causes of sepsis alert compared to detection in either plasma or BALF alone (55.6% vs. 20.8% vs. 18.8%, P<0.001). Acinetobacter baumannii, Stenotrophomonas maltophilia, Candida albicans, and human mastadenovirus B were the primary strains responsible for infections in PDS patients. Patients with lower white blood cells and neutrophil indices had a greater consistency in dual-sample mNGS. Patients in the mNGS group had more antibiotic adjustments compared to the non-mNGS group (85.71% vs. 33.33%, P<0.001). The percentage of neutrophils was a risk factor for mortality in PDS patients (P = 0.002). Dual sample mNGS has the advantage of detecting and determining the pathogenicity of more pathogens and has the potential to improve the prognosis of patients with PDS.

Li J ，Pan D ，Guo Y ，Zhang B ，Lu X ，Deng C ，Xu F ，Lv Z ，Chen Q ，Zheng Y ，Nong S ，Su L ，Qin R ，Jiang F ，Gai W ，Qin G ... -  《-》