Open Forum Infectious Diseases最新文献

Background: India accounts for the highest Tuberculosis (TB) burden globally. The incidence and prevalence of TB are higher in tribal population than general population. In this study, we assessed the effectiveness of artificial intelligence (AI) based chest X-ray (CXR) interpretation software device (qXR version 3), in detecting TB from a predominantly tribal population setting.

Methods: In this multicenter prospective study, all the CXRs of patients aged > 15 years taken for any reason at 3 public health facilities in the Chhattisgarh state of India between 01 August 2023 and 31 March 2024 were included. Patients flagged by AI as TB presumptive were directed to undergo sputum testing, who are subsequently confirmed either microbiologically or clinically.

Results: Out of 2745 CXRs screened, 363 patients (median age, 44 years [IQR: 30-53]; 261 [71.9%] male) were identified as presumptive for TB. 162 cases were confirmed with TB positivity rate of 44.63% (95% CI: 39.44-49.91). Among the AI-flagged cases, 51 (14.04%) patients were asymptomatic, and 20 (39.22%) of them were confirmed with TB. Descriptively, when compared with baseline (August-2022 to March-2023), an 80.21% (P < .001) increase in the number of TB case notifications was observed during the AI implemented period.

Conclusions: This study highlights the potential of AI to enhance TB detection and feasibility in a resource-limited tribal setting. Above 40% of the patients flagged by AI were subsequently confirmed to have the TB disease. Additionally, the study demonstrated the potential of AI in identifying asymptomatic individuals who would otherwise have been missed or diagnosed late.

C-reactive protein (CRP) was evaluated as a biomarker for pulmonary tuberculosis (TB) diagnosis and treatment response monitoring in 292 Kenyan children. Although diagnostic sensitivity was suboptimal (35.5%-50.0%), the median CRP level decreased during TB treatment in children with confirmed (P = .02) or unconfirmed (P < .001) TB, primarily among those with baseline CRP elevation ≥5 mg/L (40% [39 of 97]).

Background: We aimed to estimate the burden of antibiotic-nonsusceptible nonbacteremic pneumonia and sinusitis due to Streptococcus pneumoniae (pneumococcus) in US adults (aged ≥18 years).

Methods: We estimated antibiotic-nonsusceptible pneumococcal sinusitis and nonbacteremic pneumonia incidence as products of pneumococcal pneumonia and sinusitis incidence rates, serotype distribution, and serotype-specific antimicrobial nonsusceptibility prevalences from 2016 through 2019. Nonsusceptibility was considered by antibiotic class and guideline-recommended agents. We estimated pneumonia and sinusitis incidence rates from national surveys and administrative datasets and derived pneumococcal-attributable percents and serotype distributions from published data. Serotype-specific nonsusceptibility estimates were from Active Bacterial Core surveillance data. We evaluated nonsusceptibility for all serotypes and those targeted by 15-, 20-, and 21-valent pneumococcal conjugate vaccines (PCV15/20/21).

Results: An estimated 16.4% (95% confidence interval, 12.8-21.4) of nonbacteremic pneumococcal pneumonia and 19.0% (14.8-24.9%) of sinusitis cases were nonsusceptible to ≥ 3 antibiotic classes, translating to 243 521 (179 673-333 675) and 1 844 726 (1 070 763-2 904 089) outpatient visits for pneumonia and sinusitis, respectively, and 10 155 (7542-13 803) pneumonia hospitalizations annually. An estimated 31.2% (26.6%-36.3%) of nonbacteremic pneumococcal pneumonia and 10.5% (9.4%-12.0%) of pneumococcal sinusitis cases were nonsusceptible to ≥ 1 outpatient first-line antibiotic agent. Cases attributable to serotypes targeted by PCV15, PCV20, and PCV21 that were nonsusceptible to ≥3 antibiotic classes accounted for 7.4% (4.7%-11.1%), 8.5% (5.8-12.1%), and 12.6% (9.2-17.5%) of nonbacteremic pneumococcal pneumonia, and 8.4% (5.3-12.5%), 9.4% (6.2-13.4), and 14.4% (10.4-20.0%) of pneumococcal sinusitis.

Conclusions: We estimated high proportions of antibiotic-nonsusceptibility in nonbacteremic pneumococcal pneumonia and sinusitis in US adults. Use of PCVs and antibiotic stewardship may mitigate the burden of antibiotic-nonsusceptible pneumococcal disease.

In 57 periprosthetic joint infections with presumed acute presentations, the 2-year successful outcomes of debridement and implant retention were 64% (when sonication results revealed <1000 cfu/mL) and 21% (≥1000 cfu/mL). The odds for failure were 5.2 (P < .01) when the sonication result reported ≥1000 cfu/mL.

Background: People with HIV (PWH) have accelerated declines in physical function. Although exercise is highly effective for improving function, whether high-intensity interval training (HIIT) imparts greater physical function improvement than continuous moderate-intensity exercise (CME) among older PWH is unknown.

Methods: The HEALTH trial (NCT04550676) enrolled sedentary PWH ≥50 years old on stable antiretroviral therapy (ART). Participants were randomized to perform 16 weeks of HIIT or CME, both with resistance exercise. High-intensity interval training sessions included 5 high-intensity (90% of heart rate reserve [HRR] for 4 minutes) and 4 moderate-intensity (50% of HRR for 3 minutes) bouts; the CME arm walked continuously at 60% of HRR. The primary outcome was percent change in 400-meter walk time (400-MWT).

Results: Of the 118 randomized participants (n = 57 in HIIT, n = 54 in CME), 111 participants were included in the primary analysis; among these, the median age was 57 (interquartile range, 54-61) years, and 14% of participants were female. Participants in both HIIT (5.9% [95% CI], -7.7, -4.1) and CME (4.6% [95% CI, -6.4, -2.8]) had significant improvements in 400-MWT, with no significant difference between arms (P = .33). Among secondary outcomes of physical function and muscle strength, both arms demonstrated improvement (P < .05 for all), with no significant difference between arms at week 16.

Conclusions: Although HIIT demonstrated greater gains in physical function among PWH, the differences from CME were small and not statistically different. Given that both HIIT and CME improved physical function, PWH should be encouraged to select the aerobic exercise according to individual preference.

Older people with HIV (PWH) may benefit from long-acting cabotegravir/rilpivirine (LA-CAB/RPV), a population underrepresented in trials and observational cohorts. In the GEPPO cohort, 135 PWH >65 years of age received bimonthly LA-CAB/RPV. After 17.4 months, virological suppression (HIV-RNA <50 copies/mL) was maintained in all, while 15 participants discontinued them (11.1%, 10% in the first 12 months): 1 participant with isolated HbCAb at baseline showed a late HBV reactivation (19.4 months after starting). These findings support LA-CAB/RPV's efficacy and tolerability in older PWH.

An 8-year prospective cohort study of pelvic osteomyelitis in patients living with spinal cord injury shows that 4- to 6-week, post-debridement, quinolone-sparing oral antimicrobial regimens were effective within multidisciplinary care. Clinical cure (89% at 12 months) remained high with shorter durations. These real-world findings support stewardship and inform prescribing and future trials.

Background: Non-tuberculous mycobacterial (NTM) skin and soft tissue infections (SSTI) present a significant treatment challenge, requiring prolonged, multidrug antibiotic regimens often associated with substantial toxicity and suboptimal clinical outcomes. We aim to describe the clinical characteristics and treatment of patients with NTM-SSTI in the Netherlands, focusing on host immune status and drug toxicity.

Methods: We retrospectively collected data from adults with NTM-SSTI treated at 2 Dutch tertiary referral centers for mycobacterial disease between 2017 and 2024. Data included sociodemographics, medical history, antibiotic regimens, drug toxicity, and treatment outcomes.

Results: We included 73 patients, of whom 39 (49%) were immunocompromised. Disseminated disease was almost exclusively observed in immunocompromised patients (14/15). The most isolated species were Mycobacterium chelonae (23/73; 32%) and Mycobacterium marinum (17/73; 23%). Azithromycin, the most prescribed drug, was discontinued prematurely because of toxicity in 35% (18/52) of patients, ethambutol in 33% (9/27), and clofazimine in only 12% (3/26). These discontinuations occurred mostly within the first 4 months. Immunocompromised patients with disseminated infections had longer (median 10.1 vs 7.6 vs 6.4 months) treatment durations and lower remission rates (29% vs 59% vs 86%) compared to immunocompromised patients with localized disease and immunocompetent patients, respectively.

Conclusions: Immunocompromised status is associated with disseminated NTM-SSTI and worse treatment outcomes. Regardless of immune status, antimycobacterial drugs often cause toxicity, leading to treatment changes.

Background: Sixteen million children are HIV-exposed but uninfected (HEU) due to the prevention of vertical transmission. Despite avoiding HIV, children who are HEU face higher risks of infections and poorer growth and development than children HIV-unexposed (HU), though mechanisms remain unclear. We hypothesized that systemic and vascular inflammations contribute to disparities.

Methods: The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial recruited pregnant women at ∼12 gestational weeks between 2012 and 2015 in rural Zimbabwe (∼15% HIV prevalence, >80% antiretroviral therapy coverage). Plasma biomarkers were measured using enzyme-linked immunosorbent assay (ELISA) and multiplex assays in a subgroup of children at 1 month of age and compared using generalized estimating equations adjusted for trial arm, maternal age, birthweight, prematurity, sex, and age. Principal component analysis was used to reduce dimensionality of biomarkers.

Results: Seventy-one children who are HEU and 62 who are HU were included. Twenty-two of 27 biomarkers were raised in HEU versus HU. Systemic inflammatory markers (IL-1β/interferon-γ/TNF-α/sCD14) and vascular activation markers (L-selectin/VCAM-1) were significantly higher. HIV-exposed but uninfected infants gained 6.1 g/day less than HU infants in the first month after birth. Although one principal component, primarily driven by vascular endothelial growth factor, was associated with increased growth rate, the difference between HEU and HU growth trajectories was not affected by differences in any principal components, suggesting that inflammation does not explain lower growth amongst HEU children.

Conclusions: Children who are HEU have significantly elevated systemic and vascular inflammatory biomarkers compared with those who are HU. Understanding causes and consequences of this inflammatory imbalance may identify new intervention targets for improving outcomes in this vulnerable group.

Background: Lyme neuroborreliosis (LNB) is a common manifestation of Lyme disease in children. It is caused by the bacterium Borrelia burgdorferi and can affect both the peripheral nervous system (PNS) and the central nervous system (CNS). This study aimed to describe clinical and immunological features of LNB in children.

Methods: We performed a large retrospective cohort study of children diagnosed with LNB at the University Children's Hospital Zurich from 1 January 2006 to 31 December 2020.

Results: A total of 190 children diagnosed with LNB were included (median age, 7.6 years). Meningitis was the most frequent manifestation of LNB (n = 115, 60.5%), followed by isolated cranial neuropathy (iCN) (n = 55, 28.9%) and meningoradiculitis (n = 15, 7.9%). Five (2.7%) patients presented with rare, severe CNS manifestations, including acute myelitis and cerebral vasculitis. The most frequent specific clinical signs were facial palsy (n = 136, 71.6%) and a history of erythema migrans (n = 33, 17.4%). Borrelia burgdorferi-specific IgM and IgG antibody responses in cerebrospinal fluid (CSF) and blood were primarily directed against the following 3 antigens: VlsE, p41, and OspC, with broader responses in blood. Compared to patients with meningitis or meningoradiculitis, iCN patients had lower CSF inflammation, reduced positivity in B burgdorferi-specific tests (ELISA, immunoblot, and/or intrathecal antibody production), weaker antibody responses to VlsE, p41, and OspC, and shorter post-treatment symptom duration.

Conclusions: Lyme neuroborreliosis in children presents with a broad clinical spectrum, with meningitis and iCN being the most common manifestations. We observed distinct clinico-pathogenic subgroups of LNB: iCN reflects a more localized, PNS-restricted disease, whereas meningitis and meningoradiculitis represent a more systemic involvement of both PNS and CNS. These findings may improve diagnostic accuracy and guide the management of children with LNB.