Open Forum Infectious Diseases最新文献

Background: Ocular candidiasis (OC) is a notorious complication of candidemia, but guidelines on fundoscopic screening are inconsistent. We aimed to determine the frequency of OC in patients with candidemia who underwent fundoscopy, regardless of visual symptoms, and to evaluate its impact on antifungal treatment selection and duration.

Methods: A retrospective cohort study was performed at 2 tertiary care hospitals in the Netherlands in adult patients with at least 1 positive blood culture with Candida species between January 2018 and December 2024. Primary outcomes were the incidence of OC (defined as proven or probable chorioretinitis or endophthalmitis), persistent vision loss, and changes in the choice and/or duration of antifungal therapy in patients with OC.

Results: Of 402 patients, 307 (76.4%) underwent fundoscopy. Ocular candidiasis was diagnosed in 15 of 307 patients (4.9%), including 12 with probable chorioretinitis (3.9%) and 3 with probable endophthalmitis (1.0%). Nine of the 15 patients (60%) were asymptomatic (n = 6) or unable to report symptoms (n = 3). In all 15 patients, the fundoscopic findings resulted in a change in therapy. This consisted of therapy prolongation (n = 15), addition of (n = 7) or switch to (n = 4) an azole, and intravitreal antifungal injections (n = 2). Persistent visual impairment of any degree occurred in 3 of 15 patients (20%), all of whom were initially symptomatic.

Conclusions: Ocular candidiasis is a relatively rare but clinically significant complication of candidemia. Fundoscopic findings are used to guide treatment decisions. Persistent vision loss was uncommon.

Background: Delayed HIV diagnosis and treatment may increase the risk of developing dementia later in life. We evaluated whether low CD4 count (<200 cells/µL) prior to first known use of antiretroviral therapy (ART)-a proxy for delayed HIV diagnosis or treatment-was associated with risk of age-associated dementia.

Methods: We conducted a retrospective cohort study (2000-2023) among U.S. adults with HIV aged ≥50 years, all on ART and dementia-free at baseline. The exposure of interest was low pre-ART CD4 count. Dementia diagnoses were identified via electronic health records. The association of low pre-ART CD4 with incident dementia was evaluated using Fine-Gray subdistribution hazard models, accounting for the competing risk of death and adjusting for sociodemographic and clinical confounders. Sub-analyses examined dementia risk among individuals who had low pre-ART CD4 but demonstrated CD4 recovery to ≥500 cells/µL after ART initiation.

Results: Among 21 354 people with HIV on ART (mean age 54; 87% men; 46% White, 23% Black, 21% Hispanic, 4% Asian), 30% had pre-ART CD4 < 200 cells/µL. Over a mean follow-up of 7 years, 618 were diagnosed with dementia. Low pre-ART CD4 was associated with greater risk of dementia (adjusted hazard ratio [aHR]: 1.33, 95% CI: 1.13-1.57). CD4 recovery with ART attenuated but did not eliminate dementia risk (aHR: 1.17, 95% CI: 0.85-1.60).

Conclusions: Low CD4 count prior to ART-reflecting delayed HIV diagnosis or treatment-was associated with higher dementia risk. Continuing assertive HIV screening and prompt ART initiation in the community will be important to support long-term cognitive health in people with HIV.

In this systematic literature review and meta-analysis, real-world data from high-income economies (excluding the US and Africa) on HIV-1 epidemiology (2019-2023), oral pre-exposure prophylaxis (PrEP) effectiveness (2017-2023), and prevalence of oral PrEP use (2017-2023) were assessed in key populations disproportionately affected by HIV-1. Overall, 204 unique data sources were identified from 38 high-income economies. In key populations, the pooled global HIV-1 prevalence estimate was 5.1% (95% confidence interval: 4.2%-6.1%), ranging from 0.2% in South Korea to 28.9% in Romania. Pooled global prevalence was lowest in transgender men (1.4%) and people in prison (2.2%); 7.0%-7.8% in men who have sex with men, people who inject drugs, sex workers, and transgender women; and highest in individuals who were in multiple key populations (19.4%). Global prevalence of oral PrEP use was 18.2% among key populations, with HIV-1 prevalence <0.4% in PrEP users, indicating high PrEP effectiveness. Targeted prevention strategies are needed to provide global equitable PrEP access and reduce HIV-1 acquisition.

Background: Current Mycosis Study Group Education and Research Consortium (MSGERC) and European Confederation of Medical Mycology (ECMM) response criteria for clinical trials often fail to comprehensively assess outcomes of the total patient experience, prompting the need for innovative methodologies.

Methods: Utilizing a modified Delphi process, members of MSGERC and ECMM were sent a series of surveys utilizing an online platform. Except for the first survey, participants' responses remained anonymous to the steering committee. The first survey was elaborated based on expert opinion, with each subsequent round building upon the responses from previous rounds. Agreement was predefined by consensus of the steering committee as majority support, set at >70% agreement, for each survey component.

Results: For invasive candidiasis, a composite of treatment failure and infectious complications were included to elaborate a DOOR scale, with endpoints measured at 2 weeks after initiation of therapy. For invasive aspergillosis, a composite of treatment failure, presence of disease-attributable complications, and treatment-related adverse events were included to elaborate a DOOR scale, with endpoints measured at 6 weeks after initiation of therapy. For cryptococcosis, a composite of treatment failure and adverse events were included to elaborate a DOOR scale, with endpoints measured at 4 weeks after initiation of therapy. For mucormycosis, treatment failure and adverse events were included to elaborate a DOOR scale, with endpoints measured at 6 and 12 weeks after initiation of therapy.

Conclusions: Consensus endpoints were developed for invasive candidiasis, invasive aspergillosis, cryptococcosis, and mucormycosis for use in clinical trials.

Background: We compared the effectiveness and safety profiles of doravirine, lamivudine, tenofovir disoproxil fumarate (DOR/3TC/TDF) with bictegravir, emtricitabine, tenofovir alafenamide fumarate (BIC/FTC/TAF) in people with HIV (PWH) who had achieved virological suppression on efavirenz (EFV)-based antiretroviral regimens.

Methods: This study was a single-center, real-world, prospective observational cohort study. The main inclusion criteria: PWH aged ≥18 years who had received an EFV-containing regimen for ≥6 months and achieved confirmed virological suppression. Participants were stratified according to clinical decisions to switch to DOR/3TC/TDF or BIC/FTC/TAF. The primary effectiveness end point was the proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48, with a preset 4% noninferiority margin.

Results: A total of 349 participants received at least 1 dose of study drugs (142 in DOR group, 207 in BIC group). At 48 weeks, 2 (1.4%) in the DOR group and 1 (0.5%) in the BIC group had HIV-1 RNA ≥50 copies/mL (estimated treatment difference [ETD], 1.0%; 95% CI, -1.6% to 3.7%), establishing noninferiority. In the BIC group, mean CD4 counts decreased significantly by ∼76.5 cells/µL at week 48 (95% CI, -111.801 to -41.218; P < .001) compared with baseline. Over 48 weeks, adverse event rates were comparable between the 2 groups (P = .758). At week 48, the BIC group exhibited a baseline-adjusted mean increase of 0.269 mmol/L in total cholesterol (TC) and 0.171 mmol/L in low-density lipoprotein cholesterol (LDL-C), while the DOR group demonstrated a mean reduction of 0.453 mmol/L in triglycerides (TG), 0.412 mmol/L in TC, and 0.241 mmol/L in LDL-C relative to baseline. All β values for the group-time interaction terms were negative (P < .001). The change in body weight from baseline to week 48 in the DOR group was 1.8 kg lower than that in the BIC group (95% CI, -2.474 to -1.114; P < .001).

Conclusions: In previously virologically suppressed PWH on an EFV-based regimen, the switch to DOR/3TC/TDF maintained virological suppression noninferior to that of BIC/FTC/TAF, with favorable metabolic profiles.

Parasitic infections are often perceived as diseases of low-resource countries, yet they impose a significant and overlooked burden in the United States-especially among immigrants, low-income individuals, and other marginalized populations. This perspectives article examines the case of Mr. X, a landscaper in Houston diagnosed with neurocysticercosis, who faced unaffordable drug costs despite the availability of effective, off-patent treatments. Through his story, we explore the broader issue of pricing for commonly and not-so-commonly prescribed antiparasitic medications, highlighting the role of systemic market failures, regulatory hurdles, and restrictive assistance programs in limiting access to care. The consequences of incomplete treatment include long-term disability, public health risks, and deepened health disparities. We propose policy solutions, including reforms to the Orphan Drug Act, expansion of Medicare negotiation powers, and investment in public-interest drug production, to improve affordability and ensure equitable access to essential antiparasitic drugs.

Background: People with HIV-associated cryptococcal antigenemia are at high risk for meningitis and death. In resource-limited settings, lumbar puncture to evaluate for meningitis is infrequently performed in asymptomatic individuals; therefore, symptomatic individuals are prioritized. We evaluated the predictive value of meningeal symptoms for cryptococcal meningitis in people with cryptococcal antigenemia.

Methods: We conducted a secondary analysis from 3 randomized clinical trials conducted in Uganda between 2017 and 2024. We included adults with meningeal symptoms who had cerebrospinal fluid cryptococcal antigen (CrAg) testing performed. Logistic regressions and classification trees were used to determine the associations between meningeal symptoms and meningitis. Area under the receiver operating characteristic curve (AUROC) and misclassification rate were used to evaluate model performance.

Results: Among 344 participants, median CrAg titer was 1:1280 (interquartile ratio, 1:100-1:2560). Overall, 285 (83%) presented with headache and 205 (60%) participants had meningitis. Presence of headache was associated with meningitis (adjusted odds ratio 11.7; 95% confidence interval [CI], 5.23-28.50). The AUROC of headache alone to predict meningitis was 0.65 (95% CI, 0.61-0.69), with 95% sensitivity and 35% specificity. The AUROC improved to 0.86 (95% CI, 0.82-0.90) when stiff neck, photophobia, confusion, sex, and CrAg titer ≥1:160 were added to the logistic regression model. In the final classification tree, headache combined with CrAg titer ≥1:160 demonstrated the highest probability (79%) of meningitis.

Conclusions: Headache and high CrAg titer is the most reliable predictor for meningitis. In the absence of plasma CrAg titration, symptoms of headache, stiff neck, photophobia, and confusion predict meningitis for individuals with cryptococcal antigenemia.

Background: Neurocysticercosis (NCC) is the most prevalent helminth infection affecting the human central nervous system. Although neuroimaging is required for definitive diagnosis, serology supports case confirmation and clarifies diagnostic doubts. Serology gold standard is antibody detection using the enzyme-linked immunoelectrotransfer blot assay, which uses 7 antigenic lentil-lectin purified parasite glycoproteins (LLGP-EITB). LLGP-EITB is poorly accessible to low-resource settings due to its technical complexity and costs, and it is inaccessible in many settings in which parasitic material to produce antigens is not readily available. We recently developed a 3-antigen multiantigen print immunoassay (MAPIA) based on recombinant/synthetic antigens (rGP50, rT24H, and sTs14), corresponding to the 3 principal diagnostics antigenic families from LLGP-EITB, that is simpler and does not require parasite-derived materials.

Methods: MAPIA performance was evaluated using a well-defined set of serum samples from NCC patients confirmed by imaging, including 73 samples from subarachnoid NCC, 72 with >5 parenchymal cysts, 59 with 3-5 parenchymal cysts, 95 with 1-2 parenchymal cysts, and 77 healthy negative controls and compared it with the LLGP-EITB performance.

Results: Overall, our MAPIA presented a sensitivity of 97.7% and a specificity of 97.4%. Subgroup analyses by NCC type demonstrated a sensitivity of 100% for subarachnoid and parenchymal NCC with >5 cysts and a slight decrease for the groups with 3-5 cysts (96.6%) and 1-2 cysts (94.7%). Observed agreement with the LLGP-EITB assay was 98.33%.

Conclusions: Our 3-antigen MAPIA obtained comparable results to LLGP-EITB and emerges as a simpler, reproducible, and easy-access alternative tool for antibody diagnosis in NCC.

Background: Klebsiella pneumoniae (KPn) is a leading cause of invasive bacterial disease in African children, albeit with a scarcity of genotypic characterization.

Methods: We sequenced invasive KPn isolates from infants ≤90 days, collected through observational hospital surveillance (n = 226) between March 4, 2019 and February 27, 2021, and between May 13, 2022 and October 31, 2023, and postmortem sampling (n = 111) between February 15, 2018 and April 18, 2023. Postmortem Kpn isolates were attributed in the causal pathway to death by the determination of the cause of death panel, which consists of local experts.

Results: Three hundred and thirty-seven isolates (226 identified during hospital surveillance and 111 from postmortem sampling) were included in the final analysis. Genomic analysis identified 85 distinct clonotypes. Sequence type (ST) 17 (22.0%) predominated, followed by ST39 (12.7%). The dominant K-locus (KL) were KL25 (24.0%), KL2 (14.5%), and KL149 (13/4%), while the dominant O-antigens included O1αβ,2α(48.4%), and O5 (19.9%). Eighty-five percent (287/337) of the KPn isolates harbored multidrug resistant genes, including 32.9% to carbapenems. Notably, bla_OXA-181, bla_NDM-5, and bla_NDM-1 were detected in 26.4%, 2.1% (7/337), and 0.3% (1/337) of isolates, respectively.

Conclusions: Although a wide diversity of strains were associated with Kpn invasive disease, over 80% of the cases were attributed to 11 K loci. These data provide critical insights into KPn epidemiology and highlight potential antigen targets for vaccine development in young African children.

The limited but rising threat of ceftaroline-resistant MRSA poses a therapeutic challenge. We show that ceftaroline plus carbapenems restores activity against a resistant strain both in vitro and in a murine bacteremia model. These findings support combination therapy as a potential strategy for difficult MRSA infections, warranting further clinical investigation.