2024年 · 第04卷第01期

Background: Diagnosing latent tuberculosis (TB) infection (LTBI) and active TB (ATB) is crucial for preventing disease progression and transmission. However, current diagnostic tests have limitations in terms of accuracy and sensitivity, making it challenging to diagnose these different infection states. Therefore, this study intends to develop a promising biomarker for LTBI and ATB diagnosis to overcome the limitations of the current diagnostic tests. Methods: We developed a novel multiepitope-based diagnostic biomarker (MEBDB) from LTBI region of differentiation antigens using bioinformatics and immunoinformatics. Immune responses induced by MEBDM were detected using enzyme-linked immunosorbent spot and cytometric bead assays. This study was conducted from April 2022 to December 2022 in the Senior Department of Tuberculosis at the 8th Medical Center of PLA General Hospital, China. Blood samples were collected from participants with ATB, individuals with LTBI, and healthy controls (HCs). The diagnostic efficacy of MEBDB was evaluated using receiver operating characteristic curves. Results: A novel MEBDB, designated as CP19128P, was generated. CP19128P comprises 19 helper T lymphocyte epitopes, 12 cytotoxic T lymphocyte epitopes, and 8 B-cell epitopes. In silico simulations demonstrated that CP19128P possesses strong affinity for Toll-like receptors and elicits robust innate and adaptive immune responses. CP19128P generated significantly higher levels of tumor necrosis factor (TNF-α), interleukin 4 (IL-4), and IL-10 in ATB patients (n = 7) and LTBI (n = 8) individuals compared with HCs (n = 62) (P < 0.001). Moreover, CP19128P-induced specific cytokines could be used to discriminate LTBI and ATB from healthy subjects with high sensitivity and specificity. Combining IL-2 with IL-4 or TNF-α could differentiate LTBI from HCs (the area under the receiver operating characteristic curve [AUC], 0.976 [95% confidence interval [CI], 0.934-1.000] or 0.986 [0.956-1.000]), whereas combining IL-4 with IL-17A or TNF-α could differentiate ATB from HCs (AUC, 0.887 [0.782-0.993] or 0.984 [0.958-1.000]). Conclusions: Our study revealed that CP19128P is a potential MEBDB for the diagnosis of LTBI and ATB. Our findings suggest a promising strategy for developing novel, accurate, and sensitive diagnostic biomarkers and identifying new targets for TB diagnosis and management.

Background: "Chickenpox" is a highly infectious disease caused by the varicella-zoster virus, influenced by seasonal and spatial factors. Dealing with varicella-zoster epidemics can be a substantial drain on health-authority resources. Methods that improve the ability to locally predict case numbers from time-series data sets every week are therefore worth developing. Methods: Simple-to-extract trend attributes from published univariate weekly case-number univariate data sets were used to generate multivariate data for Hungary covering 10 years. That attribute-enhanced data set was assessed by machine learning (ML) and deep learning (DL) models to generate weekly case forecasts from next week (t0) to 12 weeks forward (t+12). The ML and DL predictions were compared with those generated by multilinear regression and univariate prediction methods. Results: Support vector regression generates the best predictions for weeks t0 and t+1, whereas extreme gradient boosting generates the best predictions for weeks t+3 to t+12. Long-short-term memory only provides comparable prediction accuracy to the ML models for week t+12. Multi-K-fold cross validation reveals that overall the lowest prediction uncertainty is associated with the tree-ensemble ML models. Conclusion: The novel trend-attribute method offers the potential to reduce prediction errors and improve transparency for chickenpox time series.

Background: Toxoplasmic encephalitis (TE) is the most frequent cause of expansive brain lesions among patients with acquired immunodeficiency syndrome (AIDS). However, the optimal timing of antiretroviral therapy (ART) initiation in these patients remains controversial. This study aims to investigate the differences in outcomes of ART initiation at different times, in order to help clarify the treatment timing of AIDS-associated TE. Methods: This multicenter prospective observational study included 87 patients recruited from 11 research centers in China (from March 2019 to December 2022). Of the patients, 38 were assigned to the early ART group (initiating ART within 2 weeks after anti-Toxoplasma treatment initiation), and the remaining 49 patients received deferred ART (initiating ART at least 2 weeks after anti-Toxoplasma treatment initiation). The main outcomes included mortality and emergence of immune reconstitution inflammatory syndrome (IRIS). Human immunodeficiency virus (HIV)-1 viral load and CD4+ T-cell counts at weeks 24 and 48 were observed. Results: The number of deaths (1 vs. 5, P = 0.225) and incidence of IRIS (2.6% vs. 0, P = 0.437) were not significantly different between the early and deferred ART groups at week 48. Early ART initiation did not contribute significantly to HIV-1 viral load control (<50 copies/mL, n = 8 vs. n = 3 at week 24, P = 0.142; n = 7 vs. n = 7 at week 48, P = 1.000). The median CD4+ T-cell counts between the two groups were not significantly different, either at week 24 (155 vs. 91 cells/mm3, P = 0.837) or at week 48 (181 vs. 146 cells/mm3, P = 0.219). Conclusion: In patients with AIDS-associated TE, early ART initiation was not significantly different from deferred ART initiation in terms of incidence of mortality, IRIS, and HIV virological and immunological outcomes. Trial registration: This study was registered (registration number: ChiCTR1900021195) as one of 12 clinical trials under the title of a general project at the Chinese Clinical Trial Registry (chictr.gov) on February 1, 2019. Enrollment for this study began in March 2019.

The outbreak of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has been influenced by the human response to the virus. These responses have undoubtedly impacted the evolutionary dynamics of the virus in ways distinct from a scenario lacking a widespread response. Two important pharmaceutical interventions, vaccination and the utilization of medications, particularly molnupiravir, known to have mutagenic properties, were the focus of this article. The impact of molnupiravir on human health was evaluated through 3 mechanisms: viral resistance, mutagenesis of SARS-CoV-2, and mutagenesis occurring in patients undergoing treatment with molnupiravir. These mechanisms, as well as the impact of vaccination, have inadvertently given rise to unforeseen challenges in the management of the COVID-19 crisis. Taking a systems view in future pandemic responses, and taking into account the evolution of the pandemic virus, may be critical to ending the pandemic at an earlier date.

Immunosuppression can lead to opportunistic infections in a host. The evidence of viral infections causing immunosuppression in a host for a transient period is gaining attention. In order to prolong their stay in the human body, viruses affect the human immune system in various ways. Common viral infections such as influenza can lead to transient lymphocytopenia, which lays the groundwork for more dangerous opportunistic infections. Cytomegalovirus (CMV) infection is a rare cause of inflammatory myelopathy. We present the case of a patient with an influenza infection who progressed to severe acute respiratory distress syndrome, methicillin-resistant Staphylococcus aureus necrotizing pneumonia, and idiopathic lymphocytopenia with a CD4 count of 61 per μL on arrival. After 2 weeks, the patient developed complete flaccid paralysis with sensory and autonomic dysfunction. Because his polymerase chain reaction results of cerebrospinal fluid and blood test were positive for CMV infection, he was treated with high doses of steroids and ganciclovir intravenously. Due to early diagnosis and intervention, the patient was able to recover in 2 months with only minimal residual weakness. Thus, this case stresses on the importance of looking out for opportunistic infections in patients affected by severe viral infections for their early recovery.