BMC Infectious Diseases最新文献

Introduction: Syphilis is a systemic bacterial infection caused by the spirochete Treponema pallidum. Head and neck mucosal manifestations of syphilis can be observed in each and all of primary, secondary and tertiary syphilis, especially in the secondary one. Therefore, oropharynx is an unusual localization of syphilitic lesions, mainly represented by ulcerous lesions, tissue hypertrophy, mucosal patches and cancer-like lesions. Serology is routinely considered the gold standard for the screening and diagnosis of syphilis. However, direct detection is routinely used during polymerase chain reaction (PCR) of oropharyngeal tissue and suspicious cervical lymphadenopathies.

Methods: PRISMA 2020 guidelines were applied to make a systematic literature review with the aim to make an overview of clinical manifestations and diagnostic tools of oropharyngeal syphilitic infection. A computerized MEDLINE search was performed using the PubMed, Web of Science and Cochrane databases.

Results: The intended analysis was based on 38 papers, including a total of 55 cases. The main localization of oropharyngeal infection was the tonsil (71%), followed by lateral and posterior wall of oropharynx (16%). Ulcerous lesions were the most frequently encountered lesions in the primary syphilis (56%) and secondary syphilis (36%), whereas gumma's lesions were encountered in the tertiary syphilis (57%). Diagnosis based on serological assays was used in combination with non-treponemal methods to determine disease activity (80% cases).

Conclusions: Oropharyngeal syphilis has historically been referred to as the "great imitator" due to its highly variable manifestations, which can resemble malignancies. Physicians have to recognize oropharyngeal luetic features early, in order to set up an effective diagnostic and therapeutic work-up.

Background: Antimicrobial stewardship programs (ASPs) refer to a set of coordinated actions that improve the quality of care and combat antimicrobial resistance. Currently, information regarding the status of ASPs in Mexico is scarce. We aimed to describe the status of ASPs in 12 hospitals from Christus Muguerza Healthcare System.

Methods: A cross-sectional study was conducted in 12 hospitals, with a previously developed self-assessment tool to calculate each hospital's ASP development score. The self-assessment tool includes 7 standards with 23 items. Score categories were defined as; high, medium, low, or none. The overall ASP development score was calculated using the proportional weight of each standard. Participating hospitals were divided into 2 groups according to their bed count. Statistical analysis was conducted in Excel program (Microsoft, Redmont, Washington).

Results: 12 hospitals completed the self-assessment survey. The median overall ASP development score was 32.3%. The highest overall development scores were observed for hospitals with > 40 beds. The core elements with the lowest development scores were Education and training, and Reporting and feedback. Unlike hospitals with over 40 beds, those with 40 beds or less had a low development score for Hospital leadership support. The core element with the highest development score was Infection prevention and control.

Conclusions: This is the first multicenter assessment of ASPs in Mexico, revealing a high proportion of low-score hospitals. National implementation of ASPs is required to combat antimicrobial resistance.

Background: Visceral leishmaniasis (VL) is a neglected tropical disease primarily affecting Brazil, East Africa, and India, with India accounting for 18% of the global burden. While VL typically presents with systemic symptoms like fever, weight loss, and splenomegaly, it can occasionally manifest atypically, posing significant diagnostic challenges. Neurological presentations of VL are extremely rare, making them difficult to suspect and diagnose. Cases where VL predominantly presents with neurological symptoms are particularly novel, underscoring the need for heightened awareness of such atypical manifestations in endemic regions.

Clinical case: A 38-year-old man with history of recurrent atypical VL presented with diffuse lower back pain, progressive tingling, numbness, weakness in the lower extremities, and double vision for one month. Clinical and radiological evaluations suggested cauda equina syndrome and cranial nerve palsy, accompanied by generalized lymphadenopathy, subcutaneous nodules, and skin papules. The differential diagnosis initially included disseminated tuberculosis, histoplasmosis, and lymphoma. Cerebrospinal fluid (CSF) analysis revealed an inflammatory syndrome. Histopathology of lymph node and bone marrow revealed Leishmania amastigotes and subcutaneous nodule and skin biopsy revealed inflammatory cells with granulomas. Furthermore, the qPCR test on DNA from a subcutaneous nodule, lymph node, and CSF was positive for Leishmania kinetoplast DNA. The species was further confirmed as Leishmania donovani through ITS-based PCR amplification and sequencing. Finally, a diagnosis of relapse of VL with lymph node, cutaneous, and neurological involvement, including abducens nerve palsy and cauda equina syndrome, was established. He was treated with combination of liposomal amphotericin B and miltefosine, along with intrathecal hyaluronidase, resulting in significant improvement.

Conclusion: Unlike previously reported cases with both systemic and neurological symptoms, our patient predominantly presented with neurological manifestations, making this a unique and novel presentation of VL. This case highlights diagnostic challenges and management of atypical VL, emphasizing neurological involvement and successful therapeutic strategies.

Background: There are limited data from sub-Saharan Africa describing the demographic characteristics, clinical features and outcome of patients admitted to public hospitals with severe acute respiratory infections during the COVID-19 pandemic.

Methods: We conducted a prospective longitudinal hospital-based sentinel surveillance between May 2020 and December 2022 at 16 public hospitals in Kenya. All patients aged above 18 years admitted to adult medical wards in the participating hospitals were included. We collected data on demographic and clinical characteristics, SARS-CoV-2 infection and COVID-19 vaccination status and, admission episode outcomes. We determined COVID-19 vaccine effectiveness (VE) against admission with SARS-CoV-2 positive severe acute respiratory illness (SARI) (i.e., COVID-19) and progression to inpatient mortality among patients admitted with SARI, using a test-negative case control design.

Results: Of the 52,636 patients included in the study, 17,950 (34.1%) were admitted with SARI. The median age was 50 years. Patients were equally distributed across sexes. Pneumonia was the most common diagnosis at discharge. Hypertension, Human Immunodeficiency Virus (HIV) infection and Diabetes Mellitus were the most common chronic comorbidities. SARS-CoV-2 test results were positive in 2,364 (27.9%) of the 8,471 patients that underwent testing. After adjusting for age, sex and presence of a chronic comorbidity, SARI patients were more likely to progress to inpatient mortality compared to non-SARI patients regardless of their SARS-CoV-2 infection status (adjusted odds ratio (aOR) for SARI and SARS-CoV-2 negative patients 1.22, 95% CI 1.10-1.37; and aOR for SARI and SARS-CoV-2 positive patients 1.32, 95% CI 1.24-1.40). After adjusting for age, sex and presence of a chronic comorbidity, COVID-19 VE against progression to inpatient mortality following admission with SARI for those with a confirmed vaccination status was 0.59 (95% CI 0.27-0.77).

Conclusion: We have provided a comprehensive description of the demographic and clinical pattern of admissions with SARI in Kenyan hospitals during the COVID-19 pandemic period as well as the COVID-19 VE for these patients. These data were useful in providing situational awareness during the first three years of the pandemic in Kenya and informing national response measures.

Background: Bloodstream infection (BSI) is associated with poor outcomes especially when effective antimicrobial therapy and control of infection source are delayed. As the frequency of Enterobacterales producing metallo-β-lactamases (MBL) and/or OXA-48-like carbapenemases is increasing in some United States (US) medical centres, effective antimicrobials to treat the infections caused by these organisms are urgently needed. Aztreonam-avibactam is under clinical development for treatment of infections caused by Gram-negative bacteria, including MBL producers.

Objectives: To evaluate the antimicrobial susceptibility of Enterobacterales causing BSI in US medical centres and compare the activity of aztreonam-avibactam with ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol, and other antimicrobials used to treat BSI.

Methods: 4,802 Enterobacterales were consecutively collected (1/patient) from 72 US medical centres in 2020-2022 and susceptibility tested by broth microdilution. Aztreonam-avibactam was tested with avibactam at a fixed concentration of 4 mg/L. A pharmacokinetic/pharmacodynamic susceptible breakpoint of ≤ 8 mg/L was applied for aztreonam-avibactam for comparison. Carbapenem-resistant Enterobacterales (CRE) isolates were tested for β-lactamase-encoding genes using Next-generation sequencing.

Results: Aztreonam-avibactam was highly active against Enterobacterales; only 2 isolates showed aztreonam-avibactam MICs > 8 mg/L: 1 meropenem-susceptible E. coli and 1 K. aerogenes (CRE). All carbapenemase producers and 98.0% of CRE were inhibited at an aztreonam-avibactam MIC of ≤ 8 mg/L. CRE susceptibility rates were 81.6% for ceftazidime-avibactam, 65.3% for meropenem-vaborbactam, 61.2% for imipenem-relebactam, and 87.8% for cefiderocol. Aztreonam-avibactam retained activity (MIC, ≤ 8 mg/L) against all (100.0%) meropenem-vaborbactam nonsusceptible (n = 17), 99.5% of imipenem-relebactam nonsusceptible (n = 206), and 90.0% of ceftazidime-avibactam nonsusceptible (n = 10) isolates. The most common carbapenemases were KPC-2/3 (57.1% of CREs), OXA-48-like (16.3%), and NDM (14.3%). A carbapenemase gene was not observed in 12.3% of CREs. Ceftazidime-avibactam and meropenem-vaborbactam were active against 100.0% of KPC producers, but ceftazidime-avibactam showed limited activity against MBL producers and meropenem-vaborbactam showed limited activity against OXA-48-like and MBL producers. The most active non-β-lactam comparators against CRE were gentamicin (49.0% susceptible) and amikacin (44.9% susceptible).

Conclusions: Aztreonam-avibactam demonstrated potent activity against a large collection of Enterobacterales isolated from patients with BSI in US hospitals, including CRE, MBL producers, and isolates resistant to recently approved β-lactamase inhibitor combinations.

Background: Coxsackievirus (CV) A6 has emerged as an important causative agent in global outbreaks of hand, foot, and mouth disease (HFMD), which typically presents as a mild illness with a large generalized rash, herpes. However, some patients can develop encephalitis, pneumonia, myocarditis and liver injury. Our previous study took the view that CVA6 could replicate in mouse liver, leading to acute liver injury; however, the precise underlying mechanism remains elusive.

Methods: 10-day-old wild-type (WT, C57BL/6J) and NLRP3 knock-out (KO) mice were intraperitoneal (i.p.) inoculated with a lethal dose of the CVA6 strain. The muscle homogenate supernatant from normal mice was used to inoculate mock-infected mice. At 5 days post infection (dpi), the mouse liver was taken out for histopathological analyses and molecular biology experiments.

Results: Our in vivo experiments demonstrated that CVA6 caused severe liver injury in mice, as evidenced by pathological changes in liver slices, elevated liver injury markers (e.g., AST, ALT, LDH) and pro-inflammatory cytokines (e.g., IL-6, MCP-1, TNF-α, IL-1β). Further results revealed the activation of NLRP3 inflammasome characterized by the increase in the expression of NLRP3, Cleaved-Casp-1 (p20), mature IL-1β and IL-18. Importantly, upon CVA6 infection, NLRP3 KO mice exhibited attenuated pathological damage and reduced levels of pro-inflammatory cytokines production (e.g., TNF-α and IL-1β) compared with WT mice. Finally, increased levels of blood ALT, AST, LDH were strongly correlated with the severity of CVA6 patients.

Conclusion: Collectively, our findings suggest that the activation of NLRP3 inflammasome is involved in CVA6 infection-induced acute liver injury, providing novel insights into CVA6 infection associated adverse clinical outcomes.

Background: Limited diagnostic testing for drug-resistant TB (DR-TB) may lead to high rates of misdiagnosis and undertreatment. Current diagnostic tests focus only on detection of rifampicin-resistant TB (RR-TB). This study aims to determine the impact of improved diagnostic testing for a wider range of drug resistance on DR-TB outcomes in high-burden TB settings, using the Philippines and Thailand as case studies.

Methods: A dynamic compartmental model was designed to simulate population level TB transmission, accounting for acquired drug resistance from treatment failure of drug susceptible TB. Three scenarios were analyzed: (1) Use of GeneXpert MTB/RIF on all presumptive TB cases (Status Quo); (2) GeneXpert MTB/RIF + GeneXpert XDR, (3) GeneXpert MTB/RIF + targeted Next Generation Sequencing (tNGS). Scenarios were modelled over a 10-year period, from 2025 to 2034.

Results: Compared to the status quo, Scenario 2 results in a fourfold increase in annual DR-TB cases diagnosed in the Philippines and a fivefold increase in Thailand. DR-TB treatment failure decreases by 20% in the Philippines and 23% in Thailand. Scenario 3 further increases DR-TB case detection, reducing DR-TB treatment failure by 26% in the Philippines and 29% in Thailand. Reductions in DR-TB incidence and mortality ranged from 3 to 6%.

Conclusion: The use of GeneXpert XDR or tNGS as an additional diagnostic test for DR-TB significantly improves DR-TB case detection and reduces treatment failure, supporting their consideration for use in high burden settings. These findings highlight the importance of detecting a wider range of TB resistance in addition to RR-TB, the potential impact these improved diagnostic tests can have on DR-TB outcomes, and the need for additional research on cost-effectiveness of these interventions.

Background: The fast spread of the coronavirus disease 2019 (COVID-19) epidemic and its high mortality were quickly considered by the health community. Dietary patterns play an important role in strengthening or weakening the immune system and thus incidence of diseases.

Aim: The present study can provide a comprehensive picture of the association between adherence to unhealthy plant-based diet (uPDI) and COVID-19 incidence.

Methods: This study was undertaken on 8157 adults' participants of the Yazd Health Study (YaHS) and Taghzieh Mardom-e-Yazd (TAMIZ) study aged 20 to 70 years. Data on dietary intakes were obtained using a validated food frequency questionnaire (FFQ). Multivariable logistic regression analysis was used to assess the association between uPDI and COVID-19.

Results: We found a significant association between uPDI and the risk of COVID-19 (OR: 1.36; 95% CI: 1.05-1.75) in the crude model. After adjusting potential confounders, a significant increasing trend in the odds of COVID-19 across increasing quintiles of uPDI (OR: 1.58;95% CI: 1.05-2.37; P-value: 0.027) was observed. Stratified analysis based on sex indicated that uPDI significantly increased the risk of COVID-19 only in males (OR: 1.73;95% CI: 1.12-2.67; P-value: 0.012) and had no effect on females.

Conclusions: Participants in the highest quintiles of the uPDI had 58% higher odds of COVID-19 compared to subjects in the lowest quintile of uPDI. Although our study has promising results, stronger clinical studies are needed.

Background: The emergence of Multidrug-Resistant Tuberculosis (MDR-TB) poses a significant threat to global tuberculosis control efforts. This study aimed to examine the influence of mutations in Toxin-Antitoxin system genes on the global transmission of MDR-TB caused by Mycobacterium tuberculosis (M. tuberculosis).

Methods: Whole-genome sequencing was conducted on 13,518 M. tuberculosis isolates. Genes of the Toxin-Antitoxin system were obtained from the National Center for Biotechnology Information (NCBI) Gene database. Techniques such as Random Forest, Gradient Boosting Decision Tree, and Generalized Linear Mixed Models were employed to identify mutation sites in Toxin-Antitoxin system-related genes that facilitated the transmission of MDR-TB.

Results: 4,066 (30.08%) were identified as MDR-TB strains of all analyzed isolates. We found significant associations between specific gene mutations and MDR-TB transmission clusters including mutations in Rv0298 (G213A), Rv1959c (parE1, C88T), Rv1960c (parD1, C134T), Rv1991A (maze, G156A), Rv2547 (vapB, C54G), Rv2862A (vapB23, T2C), and Rv3385c (vapB46, G70A). Additionally, several gene mutations associated with MDR-TB transmission clades such as Rv1956 (higA, G445T), Rv1960c (parD1, C134T), and Rv1962A (vapB35, G99A) were noted. Certain gene mutations including vapB35 (G99A), higA (G445T), and parD1 (C134T) correlated with cross-regional transmission clades.

Conclusion: This study highlights the significant association between specific gene mutations in the Toxin-Antitoxin system and the global transmission of MDR-TB, providing valuable insights for developing targeted interventions to control MDR-TB.