Infectious diseases (London, England)最新文献

Purpose: The northern part of India is hyperendemic for acute encephalitis syndrome (AES) among children. In a significant proportion of AES cases, the causative agent remained unknown. We prospectively investigated the etiologies in pediatric AES (pAES) cases.

Methods: The pAES cases hospitalized at the tertiary care center from January 2022 to December 2023 were recruited in this study. Serological and molecular investigation was done, using available cerebrospinal fluid/whole blood/serum samples. Sequencing was done for positive samples.

Results: A total of 557 confirmed AES cases were recruited for the study. A comprehensive investigation for infectious cause identified etiologies in 76.1% (424/557) of pAES cases. In non-JE associated AES, viral infections such as cytomegalovirus (CMV) and herpes simplex virus (HSV-1), along with bacterial infections caused by Orientia tsutsugamushi (OT), Rickettsia, and Leptospira, have emerged as the leading causes in the studied region. About 9.7% (45/463) of cases were fatal. Among fatalities, 62.2% were females; 28.9% were positive for OT, 6.8% for JE, and 2.3% for Leptospira. Either mixed viral or viral-bacterial infections were observed in 13.6% of fatalities. No identifiable causative agent was detected in 48.9% (22/45) of cases. The greatest number of deaths occurred in the post-monsoon season.

Conclusion: This research highlights a notable change in the profile of pathogens associated with pAES. Further, findings also suggest that the use of more comprehensive PCR panels can provide in-depth identification of etiologies associated with pAES. Finally, these findings could guide policymakers in updating diagnostic and treatment protocols for better management of pAES cases in India.

Background: HIV-positive organ transplant recipients are at high risk of anal cancer, but there are no data on the prevalence of high-risk human papillomavirus (hr-HPV) or anal dysplasia, in this population.

Objective: To assess the prevalence of anal hr-HPV, and anal cytological and histological abnormalities in this population.

Design and setting: Prospective single tertiary hospital.

Results: Twenty-five (53%) transplant recipients were recruited from 47 eligible individuals. Median (IQR) age was 56 years (52.5-60), 17 were male, 9 (36%) were men who have sex with men and 8 (32%) were active smokers. Twelve (48%) patients had abnormal anal cytology and 12 (48%) had detectable hr-HPV DNA. Six (50%) individuals with abnormal cytology had high-grade squamous intraepithelial lesions (HSIL) on biopsy. Abnormal anal cytology was significantly associated with current hr-HPV infection [crude prevalence rate ratio, cRR = 2.3, 95% CI (1.43-3.7); p = 0.001] and any previous history of HPV associated disease [cRR = 2.49, 95% CI (1.09-5.67); p = 0.030]. Anal HSIL on biopsy was associated with presence of condyloma [cRR = 3.00, 95% CI (1.31-6.88); p = 0.001] and any previous history of any HPV associated disease [cRR = 6.67, 95% CI (0.96-46.32); p = 0.055]. Anal hr-HPV infection was associated with any previous HPV disease (Crude risk ratios [cRR = 2.89, 95% CI (1.21-6.88); p = 0.017]) and presence of condyloma (Crude risk ratios [cRR = 2.00, 95% CI (1.28-3.13); p = 0.002]). No cases of invasive anal cancer were detected among study participants.

Conclusions: This highly medicalized population of HIV-positive organ transplant recipients have a high prevalence of HPV-associated anal dysplasia and screening to prevent anal cancer may need to be prioritised.

Background: Antibiotic-induced perturbations of the gut microbiome impair immunologic responses but whether they influence disease severity is unknown. The COVID-19 pandemic provided a unique opportunity to explore this question given widespread testing for SARS-CoV-2 infections.

Objective: To determine whether prior antibiotic exposure was associated with outcomes in patients with COVID-19.

Methods: Retrospective cohort study of all community-dwelling adults in Alberta, Canada with COVID-19 between March 2020 and June 2023. Subjects with antibiotic dispensations in the prior 3 months were compared (using multivariable logistic regression and propensity score (PS)-matching) to those without antibiotic exposure for differences in 30-day outcomes.

Results: Of 445,646 adults with COVID-19, 49,581 (11.1%) were exposed to at least one antibiotic course in the prior 3 months. Those exposed to antibiotics were more likely to present to an emergency department (13.4% vs. 7.4%, aOR 1.52, 95%CI 1.48-1.57, PS-matched OR 1.48, 1.42-1.54), be hospitalised (5.8% vs. 2.8%, aOR 1.40,1.33-1.46, PS-matched OR 1.37, 1.29-1.45), or die (1.7% vs. 0.6%, aOR 1.28, 1.18-1.40, PS-matched OR 1.27, 1.14-1.42) than patients without prior antibiotic exposure. The associations were similar whether the antibiotic prescriptions were appropriate or not or whether antibiotic exposure periods were 6 weeks, 6 months, or 12 months prior to the positive RT-PCR test. The associations were stronger in those individuals with the highest tertile of antibiotic exposure, or those exposed to broad-spectrum antibiotics, or younger patients.

Conclusion: Prior antibiotic exposure is associated with worsened disease severity in patients infected with SARS-CoV-2. These findings support efforts to reduce antibiotic use.

Background: Dengue infection is a major public health threat, especially to children.

Objectives: To comprehensively summarise the global epidemiological evidence on dengue in paediatric and adolescent populations by reporting incidence proportions, seroprevalence by region, country, and age group, and presenting pooled odds ratio (OR) estimates between age, sex, and infection risk.

Methods: MEDLINE and Embase were searched until April 2024. This meta-analysis included studies reporting or allowing calculation of incidence proportion, seroprevalence, and ORs; pooled estimates were derived using random-effects models.

Results: One-hundred fifty-eight articles were included. Incidence proportions were similar across the Americas, Africa, and Asia; country-specific incidence proportion was highest for Yemen (65%) and Brazil (53%). Seroprevalence was highest in Oceania and the Americas; country-specific seroprevalence was highest in Nicaragua (91%), and Honduras (88%). ORs of dengue infection did not differ between males and females [1.04 (95%CI: 0.95-1.14), p = 0.36]. However, dengue infection increased by age group with OR of 1.84 (95%CI: 1.51-2.24), p < 0.001 for children <10-years and 2.53 (95%CI: 2.03-3.16), p < 0.001 for those aged ≥10-years. The World Health Organisation's 2018 and 2024 position statements recommend CYD-TDV vaccination in countries where the seroprevalence reaches ≥80% and TAK-003 where it is ≥60% by nine years of age. However, our data indicate that no country meets the 80% threshold, and very few reach 60% seroprevalence by age 10.

Conclusion: Dengue infection affects youth globally across all endemic regions, with similar incidence distribution among continents. These findings illuminate the global and country-specific dengue epidemiology, emphasising the need for enhanced mitigation measures to reduce viral spread and impact.

Introduction: The development of predictive mortality scores for bacteraemia is fundamental for identifying patients in whom increasing our management efforts. However, it is necessary to assess the validity of the results obtained when they are applied to new cohorts.

Methods: We evaluated the ability of different scales (Charlson, also age-adjusted Charlson and updated Charlson, SOFA, Pitt, INCREMENT-ESBL and BSIMRS) to predict 30-day mortality in bacteraemia through the AUROC and calibration plots. The scales were applied to specific patient from PROBAC cohort (prospective, multicentre with bacteraemia of any aetiology) according to the population in which the scale was originally developed. We also applied the recently developed PROBAC score (this time applied to the entire PROBAC cohort, rather than only to patients who did not die within 48 h of blood culture collection as in the original development of the scale).

Results: After applying Charlson, age-adjusted Charlson, updated Charlson, SOFA, Pitt and PROBAC to the entire PROBAC cohort, we obtained AUROC values: 0.60 (95% CI: 0.58-0.62); 0.62 (95% CI: 0.60-0.64); 0.60 (95% CI: 0.58-0.62); 0.69 (95% CI: 0.66-0.71); 0.71 (95% CI: 0.69-0.82) and 0.80 (95% CI: 0.79-0.81), respectively. INCREMENT-ESBL was applied only to gram negative bacteraemia yielding 0.81 (95% CI: 0.79-0.82) and BSIMRS to gram negative bacteraemia who received adequate empirical antibiotic yielding 0.72 (95% CI: 0.70-0.75).

Conclusions: Scores that have been developed in bacteraemia cohorts and have been used for the prediction of short-term mortality were found to be better at predicting mortality in our analysis.

Background: Dengue fever (DF) a significant public health challenge globally, with clinical manifestations ranging from mild symptoms to severe dengue.

Objectives: To identify the clinico-epidemiological characteristics, management, and outcomes of severe dengue fever among inpatients of a tertiary care hospital.

Settings and design: Prospective observational study was conducted in a tertiary care hospital, Karnataka.

Materials and methods: Study included all laboratory-confirmed adult dengue patients admitted to Departments of General Medicine and Infectious Diseases during the study period. Socio-demographic, clinical, and laboratory data were collected and analysed.

Statistical analysis used: Descriptive and analytical tests, including multiple logistic regression analyses, were performed.

Results: Among 443 patients, 70% were males. Fever (91.9%) and aches/pains (81.7%) were most frequently reported symptoms with thrombocytopenia (81.9%), elevated AST (81.2%), and ALT (73.3%) were commonly observed. Severe dengue was observed in 12.1% of patients, frequently accompanied by acute kidney injury (32.9%), hepatitis (29.4%), and multiple organ dysfunction (22.4%). Severe cases were associated with age over 60 (COR = 4.6; 95% CI:2.1-9.9), low education status (COR = 3.6; 95% CI:1.3-10.4), unskilled occupations (COR = 4.2; 95% CI:1.1-15.8), presence of co-morbidities (COR = 2.5; 95% CI:1.4-4.4) and co-infections (COR = 5.2;95% CI:2.7-9.8), and supportive treatment (COR = 3.9; 95% CI:2.1-7). Independent predictor for severity was coinfection (AOR = 15.6; 95% CI:3.9-61.7). Supportive care was received by 36.3% patients, with 97.5% showing improvement, while 1.6% succumbed to death.

Conclusion: The study highlights the significant burden of severe dengue, stressing the importance of early detection, supportive care, and treatment of co-infections.

Background: Residual immune activation is common in people living with HIV (PWH) despite antiretroviral therapy (ART) and may be associated with HIV-specific, as well as lifestyle-related factors.

Objective: We aimed to investigate markers of immune activation and neuronal injury in PWH on ART compared with controls with similar lifestyle.

Methods: Cerebrospinal fluid (CSF) and blood were collected from 50 men who have sex with men (MSM) with HIV on ART, 50 HIV-negative MSM on preexposure prophylaxis (PrEP), and 25 HIV-negative controls without PrEP. β2-microglobulin, neopterin, and neurofilament light protein (NfL) were analyzed. Cytomegalovirus and herpes simplex virus-2 serostatus, as well as sexually transmitted bacterial infections were registered.

Results: Serum and CSF β2-microglobulin and neopterin did not differ significantly between MSM with HIV and MSM on PrEP. However, both groups had significantly higher serum levels of β2-microglobulin and neopterin compared with HIV-negative controls without PrEP. Age-adjusted CSF NfL levels were also similar in MSM with HIV and MSM on PrEP, but higher than in controls without PrEP. A recent syphilis infection was associated with increased immune activation in CSF and blood.

Conclusion: Increased levels of immune activation and neuronal injury markers were found in virologically suppressed MSM with HIV and MSM on PrEP compared with controls. These findings imply that other factors than HIV contribute to the residual immune activation and impact on neurons observed in MSM with HIV on ART, and emphasize the importance of appropriate controls with similar lifestyle in studies of biomarkers in PWH.

Background: Soluble thrombomodulin, a marker of endothelial cell injury, is released into the circulation during endothelial damage and has been observed at elevated concentrations in bacterial infections. This study aimed to investigate the correlation of thrombomodulin concentrations in plasma and sputum with disease severity and etiology in bacterial community-acquired pneumonia (CAP).

Methods: A prospective study was conducted on adults hospitalized with radiologically confirmed bacterial CAP. Plasma and sputum samples were collected upon admission, and thrombomodulin concentrations were quantified using an enzyme-linked immunosorbent assay. The study included a multivariate analysis to assess whether thrombomodulin concentrations were associated with disease severity and/or bacterial etiology.

Results: Of 111 patients with bacterial CAP, including 15 with severe CAP (as defined by the American Thoracic Society/Infectious Diseases Society of America criteria) and 63 with pneumococcal etiology, thrombomodulin was measured in plasma in all patients and in sputum in 42 patients. Elevated plasma thrombomodulin concentrations were independently associated with severe CAP. Stratification by bacterial etiology showed that higher plasma thrombomodulin concentrations were linked to severe pneumonia only in patients with pneumococcal infection. The area under the receiver operating characteristic curve for detecting severe pneumococcal CAP was 0.87. Conversely, sputum thrombomodulin concentrations showed no association with disease severity or bacterial etiology.

Conclusions: Plasma thrombomodulin is a promising biomarker for identifying severe pneumococcal CAP. Sputum thrombomodulin did not correlate with disease severity or bacterial etiology. These findings support further investigation into the diagnostic and prognostic role of plasma thrombomodulin in bacterial infections.

Background: Acute respiratory infections (ARIs) are a major global health concern, particularly for children and the elderly. Although rhinoviruses are the primary pathogens causing ARIs, their epidemiology during reduced population mobility and behavioral changes is not well understood. This study aimed to assess whether the Swedish COVID-19 measures changed the epidemiology of Rhinovirus and ARI-causing viruses other than SARS-CoV-2 in the western part of Sweden in 2020.

Methods: A total of 13,791 nasopharyngeal samples from ARI-patients were analyzed for 19 different viruses and bacteria by qPCR. Of the 3,607 samples positive for any virus, 2,018 were positive for rhinovirus (RV) and enterovirus (EV), and 106 contained adenoviruses. Among the EV/RV reactive samples, 249 strains were typed using partial sequencing of 5'UTR and 204 by VP1 or VP4-VP2.

Results: After week 12 when the interventions were implemented, most of the ARI-causing viruses were EV/RV and adenoviruses, besides SARS-CoV-2. In September-October 2020, an outbreak caused by RV-A strains predominantly infected children younger than 13 years and individuals within the age range of their parents. RV-A strains were identified in 118 of 242 (49%) RV-positive samples, followed by RV-C (36%) and RV-B (10%). Before the first wave of SARS-CoV-2, a RV-C outbreak affected all age groups.

Conclusions: This study shows that the moderate Swedish interventions against SARS-CoV-2 were more effective against the spread of ARI-causing virus among adults over 56 years than among young children. These results suggest the need for new strategies for preventing the spread of ARI pathogens like RV and EV, which cause disease in all age groups and can lead to large outbreaks.