Therapeutic Advances in Infectious Disease最新文献

Background: Hospitals within Nairobi County, Kenya, offer cervical cancer screening services. However, most female sex workers do not seek this service.

Objective: To determine uptake of cervical cancer screening among female sex workers living with HIV in Nairobi, Kenya.

Design: A descriptive cross-sectional study.

Methods: Computerized simple random sampling was used to select 75 study participants who met the inclusion criteria; data were collected using a structured questionnaire. The study was carried out among female sex workers living with HIV in Nairobi, Kenya, attending the Sex Workers Outreach Program.

Results: 40% (n = 30) of respondents were aged 18-25 years. Only 45.3% (34) had been screened for cervical cancer within the last 1 year. 65.3% (n = 49) of respondents knew that cervical cancer affects the cervix but were not aware of what caused the disease. 77.6% (n = 58) found the 8 am-5 pm health facility opening hours a hinderance to seeking services and 66.7% (n = 50) found the screening method uncomfortable. Cultural practices and beliefs fostered stigma in 39.2% (n = 29) of the sex workers; hence, they did not seek out services.

Conclusion: Lack of information, cultural barriers, and facility operating hours prevent female sex workers living with HIV from getting tested for cervical cancer. These barriers once addressed could improve cervical cancer screening uptake among this high-risk population.

Background: Isolated native tricuspid valve infective endocarditis remains a challenging disease to treat given the large number of patients with substance use disorder. There is limited data on the optimal treatment strategy and the impact of a multidisciplinary endocarditis program on outcomes for this population.

Objectives: To assess the clinical outcomes associated with management of native tricuspid valve infective endocarditis by a multidisciplinary team.

Design: Single-center, retrospective cohort study.

Methods: Patient cases were identified from the registry of the institutional multidisciplinary endocarditis team. Patients with left-sided endocarditis, multivalvular endocarditis, prosthetic tricuspid valves and cardiac implantable electronic devices were excluded.

Results: Between September 7th, 2021 and February 1st, 2024 72 consecutive patients with isolated native tricuspid valve infective endocarditis were identified. Sixty-six (91.7%) patients were managed medically. Five patients underwent percutaneous mechanical aspiration of tricuspid valve vegetations and one patient underwent tricuspid valve replacement during the index hospitalization. In-hospital mortality was 1.4% and 90-day mortality was 2.8%. Nineteen (26.4%) patients discharged before medically advised and 25% were re-admitted within 30 days. Ten (13.9%) patients underwent elective tricuspid valve replacements after outpatient follow-up.

Conclusion: Among 72 patients with isolated native tricuspid valve infective endocarditis managed by a multidisciplinary endocarditis program over a 2.5-year period, in-hospital, 90-day mortality and 1-year mortality were very low despite low rates of percutaneous mechanical aspiration and tricuspid valve surgery. Multidisciplinary follow-up can lead to elective tricuspid valve surgery in a delayed fashion.

Background: Invasive fungal infections (IFIs) represent a major cause of morbidity among allogeneic hematopoietic stem cell transplantation (allo-HSCT). Isavuconazole (ISA) is a broad-spectrum triazole with favorable safety profile.

Objectives and design: Herein, we evaluate the real life coadministration of ISA and sirolimus in allo-HSCT recipients in a single-center retrospective analysis, describing clinical efficacy, safety, and therapeutic drug monitoring (TDM) of both drugs.

Methods: All consecutive allo-HSCT recipients who received the coadministration of ISA and sirolimus for at least 2 weeks between July 2017 and December 2022 were included in this retrospective analysis. TDM was longitudinally performed during treatment. IFIs were classified according to the revised European Organization for Research and Treatment of Cancer/Mycoses Study Group consensus criteria.

Results: A total of 51 recipients were included in the analysis. A total of 17 patients received ISA as continuous antifungal treatment for IFI diagnosed before transplant: one patient experienced a probable invasive pulmonary aspergillosis, and one patient switched from ISA to liposomal amphotericin B for a possible IFI. A total of 34 patients started ISA as antifungal therapy for IFI diagnosed after transplant. Sixteen of 34 were treated for a proven/probable breakthrough IFI during mold-active prophylaxis: 6/16 patients died for IFI after a median of 51 days of ISA. Eighteen of 34 started ISA as empirical therapy for a possible IFI: 15/18 patients were alive with resolution of infection after 6 weeks, 1 died for disease progression, and 2 had empirically changed antifungal therapy due to pneumonia progression. Clinical and radiological response rate was 68% after 90 days from IFI diagnosis. No toxicities related to drug-drug interaction have been registered in patients reaching concomitant therapeutic levels of ISA and sirolimus.

Conclusion: The coadministration of ISA and sirolimus was safe and feasible in this cohort, confirming favorable clinical efficacy in patients with multiple-drug coadministration.

There have been several major advances in therapeutic options for the treatment of neurological infections over the past two decades. These advances encompass both the development of new antimicrobial therapies and the repurposing of existing agents for new indications. In addition, advances in our understanding of the host immune response have allowed for the development of new immunomodulatory strategies in the treatment of neurological infections. This review focuses on the key advances in the treatment of neurological infections, including viral, bacterial, fungal, and prion diseases, with a particular focus on immunomodulatory treatment options. This review also highlights the process by which clinicians can request access to therapeutic agents on a compassionate or emergency basis when they may not be commercially available. While many therapeutic advances have been achieved in the past several years, there remains a pressing need for the continued development of additional therapeutic agents in the treatment of neurological infections.

Neuroinfectious diseases represent a growing threat to public health globally. Infections of the central nervous system remain challenging to diagnose and treat, partially driven by the fact that a high proportion of emerging pathogens are capable of causing neurological disease. Many of the trends driving the emergence of novel pathogens, including climate change, ecological degradation, urbanization, and global travel, have accelerated in recent years. These circumstances raise concern for the potential emergence of additional pathogens of pandemic potential in the coming years, necessitating a stronger understanding of the forces that give rise to the emergence and spread of neuroinvasive pathogens and a commitment to public health infrastructure to identify and treat these diseases. In this review, we discuss the clinical and epidemiological features of three types of emerging neuroinvasive pathogens of significant public health consequences that are emblematic of key ongoing trends in global health. We first discuss dengue viruses in the context of climate change, considering the environmental factors that allow for the expansion of the geographic range and seasonal population of the viruses' vector. We then review the rising prevalence of fungal meningitis secondary to medical tourism, a trend representative of the highly globalized nature of modern healthcare. Lastly, we discuss the increasing prevalence of antibiotic-resistant neurological infections driven by the intersection of antibiotic overuse in medical and agricultural settings. Taken together, the rising prevalence of these conditions necessitates a recommitment to investment in public health infrastructure focused on local and global infectious disease surveillance coupled with ongoing development of novel therapeutics and vaccines for emerging pathogens. Such emerging threats also obviate the need to address the root causes driving the emergence of novel infectious diseases, including a sustained effort to address anthropogenic climate change and environmental degradation.

Background: Children with tuberculous meningitis (TBM) present with diagnostic challenges as they often have atypical clinical features.

Objective: To describe the baseline characteristic features of children diagnosed with central nervous system (CNS) TB (TBM and tuberculoma).

Design: Retrospective descriptive study.

Methods: Children less than 12 years presenting with neurological signs and symptoms were assessed for a therapeutic TBM trial eligibility. The results of their clinical, laboratory, neuroimaging, cerebrospinal fluid evaluations were analysed for TBM diagnosis.

Results: Of 600 children evaluated, 61(10%) had CNS tuberculosis; TBM 47, tuberculoma 14. 20(33%) had definite TBM. Mean age of children with TBM was 5 ± 3.4 years. Of 47, 13(28%), 21(45%) and 13(28%) had grade I, II, and III disease respectively. Abnormalities suggestive of TBM in MRI and computed tomography brain were observed in 76% (26/34) and 77% (24/31) respectively. Abnormal cerebrospinal fluid white blood cell count, protein and glucose were observed in 56% (24/43), 49% (22/45), 47% (21/45) respectively. Among 41 patients with TBM followed up until discharge, five died.

Conclusion: Younger children with TBM have severe forms. Confirmatory results may not be available in all. A holistic approach to care including addressing complications of hydrocephalus and strokes is needed.

Background: Dolutegravir-based (DTG) regimens are rapidly becoming the preferred first-line antiretroviral therapy (ART) for people living with HIV (PLHIV) in low and middle-income countries. However, there are rising concerns over the development of hyperglycemia and, in some cases, diabetes mellitus in patients switched to DTG.

Objectives: To determine the prevalence and factors associated with hyperglycemia among PLHIV receiving DTG-based ART at Kiruddu National Referral Hospital (KNRH), Uganda.

Design: Cross-sectional study.

Methods: The study was conducted in the inpatient wards and the infectious disease outpatient clinic of KNRH from May to July 2022. Participants aged ⩾18 years on a DTG-based ART regimen for at least 3 months were consecutively enrolled and interviewed using a research assistant administered questionnaire for sociodemographic and clinical characteristics. HbA1c was measured using whole blood Architect Ci4100^® (Abbott, Illinois, USA), with hyperglycemia defined using a cut-off of ⩾5.7% as per the Uganda Diabetes Association guidelines. Factors associated with hyperglycemia were examined through logistic regression, adjusting for pertinent confounders, in STATA 17. A significance level was set at p < 0.05.

Results: A total of 398 PLHIV with a median age of 40.5 years (IQR: 32-49) were enrolled. More than half were females (58.3%, n = 232) and the majority (90%) had a CD4 count above 200 cells/µL. About 16% had a family history of diabetes, 11.73% (n = 46) showed elevated blood pressure levels, and 16.7% (n = 64) had obesity. Hyperglycemia was present in 12.8% (n = 51), with 10.3% having pre-diabetes (n = 41) and 2.5% with diabetes mellitus (n = 10). At bivariate analysis, hyperglycemia was significantly associated with age >40 years (p < 0.001), herbal medicine use (p = 0.03), being widowed (p < 0.001), obesity (p = 0.042), hypertension (p = 0.002) and >3 since diagnosis with HIV (p = 0.030). At multivariable regression, only age >40 (AOR 2.55, 95% CI: 1.05-6.23, p = 0.039) and hypertension (AOR 2.93, 95% CI: 1.07-8.02, p = 0.036) remained significantly associated with hyperglycemia.

Conclusion: More than 1 in 10 patients on DTG-based ART in our study had hyperglycemia. We recommend regular monitoring of plasma glucose, especially for patients >40 years old and those with other comorbidities, before starting/switching to DTG regimens. Longitudinal studies are recommended to determine the underlying mechanisms of hyperglycemia in this population.

Background: Cutaneous leishmaniasis (CL) ulcers exhibiting an inflammatory phenotype, characterized by purulent exudate, erythema, pain, and/or lymphatic involvement, are empirically treated with antibiotics.

Objective: The spectrum of bacteria present in localized versus inflammatory phenotypes of CL is elucidated herein.

Methods: Filter paper lesion impressions (FPLIs) from 39 patients with CL (19 inflammatory and 20 noninflammatory ulcers) were evaluated via real-time polymerase chain reaction (qPCR) and end-point PCR targeting: Staphylococcus aureus, Enterobacter cloacae, Streptococcus pyogenes, Enterococcus spp., Citrobacter freundii, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and 16S rDNA. Whole genome sequencing (WGS) was performed on six specimens.

Results: In total, 30/39 (77%) patients' ulcers had ⩾1 bacterium detected, which included the following species: S. aureus (n = 16, 41%), C. freundii (n = 13, 33%), P. aeruginosa (n = 12, 31%), E. cloacae (n = 12, 31%), K. pneumoniae (n = 11, 28%), Enterococcus spp. (n = 7, 18%), E. coli (n = 6, 15%), and S. pyogenes (n = 4, 10). Prevalence of bacterial species did not differ by CL phenotype (p = 0.63). However, patients with inflammatory phenotypes were, on average, over a decade older than patients with noninflammatory phenotypes (42 years vs 27 years) (p = 0.01). The inflammatory phenotype was more prevalent among ulcers of Leishmania Viannia braziliensis (58%) and L. V. panamensis (83%) compared to those of L. V. guyanensis (20%) (p = 0.0369).

Conclusion: The distribution of flora did not differ between inflammatory and noninflammatory CL phenotypes. Further prospective analysis, including additional WGS studies of all CL ulcers for nonbacterial organisms, is necessary to determine the role of empiric antibiotic therapy in inflammatory and purulent CL.