Individuals with trace-positive sputum during screening have a substantial 2-year risk of tuberculosis, even when extensive initial evaluations do not confirm disease. Treatment should be considered for most screening participants with trace-positive sputum and atypical chest imaging.

Intact proviral DNA (IPD) is a measure of the replication-competent HIV reservoir. Little is known about how IPD levels compare in people with HIV (PWH) who initiate antiretroviral therapy (ART) during acute HIV infection (AHI), chronic infection (CHI) or as HIV controllers (CON).MethodsParticipants with sustained plasma HIV RNA < 50 copies/mL on ART had longitudinal measurements of intact, defective and total proviral DNA in blood samples.ResultsTwenty-nine participants were evaluated: 14 CHI, 7 AHI and 8 CON. PWH-CON had lower IPD than PWH-AHI or PWH-CHI during ART. PWH-CON also had low intact and total provirus levels before initiating ART. During years 2–5 of ART, IPD decay half-life was 1.0 years in PWH-AHI, 1.6 years in PWH-CHI and 3.2 years in PWH-CON (P = .01 for PWH-CON vs PWH-AHI). Defective provirus levels did not decrease in PWH-AHI and PWH-CHI.ConclusionsDuring the initial years of ART, PWH treated during acute and chronic infection have decay in intact but not defective proviruses. PWH controllers have low intact and total provirus levels before and during ART, suggesting interactions between host and virus shape the proviral landscape. Variable proviral decay patterns in these populations provide insight into approaches to achieve ART-free HIV remission.

A next-generation, serum-free, highly purified Vero cell rabies vaccine, PVRV-NG2, is in development.MethodsThis multicenter, observer-blind, phase 3 study evaluated the immunogenicity and safety of PVRV-NG2, compared with 2 licensed rabies vaccines (purified Vero cell rabies vaccine [PVRV] and human diploid cell vaccine [HDCV]), as a preexposure prophylaxis (PrEP) regimen. Participants were randomized 3:1:1 to PVRV-NG2, PVRV, or HDCV, as a 3-dose (cohort 1; children and adults; day [D] 0, D7, and D28) or 2-dose (cohort 2; adults; D0 and D7) PrEP regimen. The primary objective was noninferiority of PVRV-NG2 to PVRV and HDCV as 3-dose PrEP, based on the proportion of participants with rabies virus–neutralizing antibody titer ≥0.5 IU/mL at D42. Noninferiority of immune responses for 2-dose PrEP at D28 and noninferiority of 2-dose (D28) versus 3-dose (D42) HDCV were also assessed as secondary immunogenicity objectives. Safety was assessed throughout.ResultsOverall, 1708 participants were enrolled (cohort 1: 505 children, 505 adults; cohort 2: 698 adults). All participants had rabies virus–neutralizing antibody titers ≥0.5 IU/mL after 3-dose PVRV-NG2 (D42), with noninferiority to PVRV and HDCV demonstrated. All secondary immunogenicity objectives were achieved, including noninferiority of 2-dose PVRV-NG2 versus 2-dose PVRV and HDCV (D28) and 3-dose HDCV (D42), and noninferiority of 2-dose HDCV versus 3-dose HDCV. The safety profile of PVRV-NG2 was comparable to those of PVRV and HDCV.ConclusionsThis study supports the use of PVRV-NG2 in 2- or 3-dose PrEP regimens, with no safety concerns identified.Clinical Trials RegistrationClinicalTrials.gov identifier: NCT04127786; EudraCT: 2019-000973-22; WHO: U1111-1217-3241.

Public health agencies employ case definitions for influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections to optimize surveillance, monitor disease trends, and inform decision-making, particularly in limited resource settings.MethodsUsing a prospective healthcare personnel cohort in two hospitals in Lima, Peru (July 2022–June 2023), we compared and evaluated the performance of three symptom profiles of three common surveillance case definitions to identify influenza and SARS-CoV-2 infections: influenza-like illness, coronavirus disease 2019–like illness (CLI), and acute respiratory infection. Participants with an acute respiratory illness reported symptom progression twice weekly. Participants self-collected nasal swabs for SARS-CoV-2 and influenza reverse transcription real-time polymerase chain reaction testing. Sensitivity, specificity, and positive and negative predictive values of each case definition were evaluated.ResultsOf 1623 participants enrolled, 1450 illness episodes were reported; 92 (6%) were positive for influenza, 350 (24%) for SARS-CoV-2, and 3 (0.2%) were positive for both. For the four influenza-like illness case definitions evaluated, all yielded low sensitivity for detection of influenza (points estimate range, 23%–35%) and SARS-COV-2 (range, 21%–29%), but high specificity (83%–90% and 86%–92%, respectively). In contrast, the acute respiratory infection and coronavirus disease 2019–like illness definitions both yielded high sensitivity (83%–100%) and low specificity (2%–41%) for detection of both influenza and SARS-CoV-2.ConclusionsThe performance of case definitions was similar for influenza and SARS-CoV-2 supporting the use of the same definitions by surveillance networks. The substantial differences in sensitivity and specificity across the case definitions necessitate surveillance objectives and cost considerations in selecting a case definition fit for purpose.

To the  Editor—The comprehensive review by Nguyen et al. [1] on nontuberculosis mycobacteria (NTM) disease is highly informative; however, we believe it would have been further enriched by addressing an important complication—chronic pulmonary aspergillosis (CPA). CPA was the subject of a systematic review summarizing 507 articles comprising 1538 cases since 1977 [2]. Cavitary NTM disease was the main risk factor for a subsequent diagnosis of CPA, along with chronic corticosteroid use [3].

People with advanced HIV disease (CD4 ≤200 cells/µL) remain at high risk for opportunistic infections, hospitalization, and death, despite access to antiretroviral therapy (ART). We evaluated serum C-reactive protein (CRP) as a predictor of 30-day hospitalization or death among outpatients with advanced HIV disease.MethodsWe prospectively enrolled 1388 outpatient Ugandan adults with CD4 ≤200 cells/µL from May 2022 to February 2025, of whom 1378 had serum CRP measured at enrollment. Participants were ART-naïve or experienced, and people with known virologic suppression were excluded. Participants received tuberculosis and cryptococcosis screening and therapy per World Health Organization (WHO) recommendations. We examined CRP as a continuous and dichotomized predictor (≥10 mg/L) of 30-day hospitalization or death.ResultsAmong 1378 participants, 41.6% had CRP ≥10 mg/L. Participants with CRP ≥10 mg/L were more likely to be hospitalized (Relative Risk=4.2, 95%CI:2.3–7.8) or die (Relative Risk=9.8, 95%CI:2.9–32.8) within 30 days. In a multivariable Cox model adjusted for weight, CD4 count, ART status, and age, each two-fold increase in CRP was associated with a 36.9% higher hazard of 30-day hospitalization or death (Hazard Ratio=1.4, 95%CI:1.2–1.5). Including CRP in the multivariable model significantly improved prediction of 30-day hospitalization or death (AUC 0.80 with CRP vs. 0.72 without, DeLong’s p=.009).ConclusionCRP ≥10 mg/L is associated with increased risk of 30-day hospitalization or death among outpatients with advanced HIV disease receiving the WHO-recommended package of care. Prospective studies should evaluate whether point-of-care CRP testing can enable real-time risk stratification to reduce AIDS-related deaths.

AbstractLenacapavir, a first-in-class HIV capsid inhibitor, is under development by Gilead Sciences for human immunodeficiency virus (HIV) prevention as pre-exposure prophylaxis (PrEP). This article responds to inquiries into Gilead's access efforts for low- and lower-middle-income countries and reviews the science behind lenacapavir and its investigational use for HIV prevention, the current state of Gilead's planning for equitable access, and the necessity for partnership to end the HIV epidemic. Clinical trial results are a culmination of years of dedicated science, and they are just the beginning; we look forward to sharing updates as milestones are reached. Gilead is committed to working with scientists, clinicians, communities, advocates, governments, and other stakeholders to achieve broad, sustainable global access to lenacapavir for HIV prevention, if approved. Lenacapavir holds potential for helping to end new HIV infections around the world, a potential that reflects the vision we have at Gilead: to end the HIV epidemic for everyone, everywhere.

In patients with suspected infective endocarditis (IE), current guidelines recommend prompt initiation of empiric antimicrobial treatment after obtaining blood cultures. However, the clinical benefit of immediate treatment in hemodynamically stable patients remains uncertain. This study assessed the impact of deferring antimicrobial treatment in patients with suspected IE.MethodsWe conducted a multicenter cohort study of adult patients with bacteremia and clinical suspicion of IE from two university hospitals (2015-24). Patients presenting with sepsis, intensive care unit admission, neutropenia, or a clearly identifiably focus other than IE were excluded. All cases were adjudicated by a dedicated Endocarditis Team as either IE or not IE. The primary outcome for all episodes was 30-day mortality; for confirmed IE cases, the composite outcome included 30-day mortality, new embolic events, or new bone and joint infection.ResultsAmong 1,230 episodes, empirical antimicrobial treatment was initiated immediately (Group I) after blood culture collection in 675 episodes (55%) and deferred until preliminary blood culture results (Group D) in 555 episodes (45%). Thirty-day mortality was 5% (59 episodes), with no difference between Groups I and D (5% versus 5%; P=0.894). Of 597 confirmed IE episodes (49%) IE, 327 (55%) were in Group I and 270 (45%) in Group D. The composite primary endpoint occurred in 157 episodes (26%), with no difference between groups (28% versus 24%; P=0.304).ConclusionsIn clinically stable patients with suspected IE, deferring antimicrobial treatment until available blood culture results was not associated with worse clinical outcomes.

Recipients of allogeneic hematopoietic cell transplantation (alloHCT) are at risk of multiple viral infections. However, our knowledge about the clinical impact of viruses following alloHCT is predominantly focused on outcomes of a single viral infection such as cytomegalovirus (CMV). This retrospective cohort study aimed to evaluate the incidence, risk factors, and clinical outcomes of multiple viral infections in the first year following alloHCT.MethodsAll microbiologically confirmed viral infection of CMV, Epstein-Barr virus (EBV), BK polyomavirus (BKV), varicella zoster virus, human herpesvirus 6, herpes simplex virus, and various respiratory viruses were reviewed up to 12 months post-alloHCT.ResultsAmong 430 alloHCT recipients, 744 viral infections were observed within the first year posttransplantation, predominantly CMV (55%), followed by EBV (51%) and BKV (21%). Eighty-five percent of patients had at least 1 viral infection, of which 34% had 2 and 24% had ≥3 viruses. Independent risk factors of multiple viral infections included CMV serostatus (R+/D−: hazard ratio [HR], 2.59 [95% confidence interval {CI}, 2.03–3.30]; R−/D+: HR, 2.25 [95% CI, 1.66–3.05]), haploidentical donor (HR, 1.56 [95% CI, 1.18–2.06]), T-cell depletion use (HR, 1.44 [95% CI, 1.11–1.88]), and grade III–IV acute graft-versus-host disease (HR, 1.44 [95% CI, 1.15–1.80]). Patients experiencing multiple viral infections (≥3 vs 2 vs 1) had an earlier time to onset of first infection (median, 18 vs 25 vs 40 days), were hospitalized for an increased number of days (median, 53 vs 40 vs 37 days), and had lower survival probability at day 270 following infusion (P = .044).ConclusionsMultiple viral infections were frequently observed, with a significant impact on morbidity and mortality following alloHCT.

To the editor—We thank Denning and Kosmidis for reviewing our article on nontuberculous pulmonary disease (NTM-PD) [1] and bringing attention to chronic pulmonary aspergillosis (CPA) [2]. Indeed, it is not uncommon for patients with NTM-PD to have coinfections with other pathogens, such as Pseudomonas aeruginosa and/or Aspergillus species. We agree that CPA is an important disease that can co-occur with NTM-PD, increasing management complexity and portending poorer outcomes.

Klebsiella pneumoniae is a key opportunistic pathogen, and its emerging hyper-virulent strains pose a growing public health threat. An association exists between the phospholipid transporter MlaFEDCB and bacterial virulence; however, its regulatory role and underlying mechanisms remain elusive. Herein, we focused on K. pneumoniae virulence regulation via mlaFEDCB under in vitro and in vivo conditions.Methods and ResultsHomology analysis showed that mlaFEDCB gene cluster is highly conservative among gram-negative bacterial strains and is contiguously arranged and co-transcribed within the genome. Experiment involving murine intraperitoneal infection revealed that mice infected with KP-ΔmlaFEDCB strain showed substantially prolonged survival (P = 0.0005). Furthermore, transcriptomic analysis showed altered expression of virulence-associated genes, especially fimH and fimD, which are involved in fimbrial structure and host cell adherence. Scanning electron and transmission electron microscopy showed that the WT-KP strain demonstrated a complex fibrous fimbrial network, with several long, thin structures interwoven with those of neighboring bacteria, whereas the KP-ΔmlaFEDCB strain showed markedly fewer fimbriae and lacked the fimbrial network. Furthermore, bladder epithelial cells adhesion assay showed an apparent reduction in the KP-ΔmlaFEDCB strain compared to the WT-KP strain. The growth of the KP-ΔmlaFEDCB strain was significantly compromised in comparison to the wild-type strain under stress conditions.ConclusionThus, mlaFEDCB gene cluster increases the adhesion, invasion, and environmental adaptability of K. pneumoniae by modulating virulence-related gene expression, pilus synthesis, and growth under stress conditions.

AbstractMass incarceration is a national epidemic; all clinicians will encounter persons currently incarcerated or with a history of criminal-legal involvement. Infections are highly prevalent in these populations. This review will support clinicians to provide evidence-based infectious diseases treatment with explicit recognition of the interpersonal and structural intricacies in carceral care. Following a criminal-legal system primer, clinicians will have a finer understanding of the psychosocial complexities involved in building provider–patient relationships with those impacted by this system. By recognizing that care delivery can be subject to a potential conflict of interest in supporting both the health interests of persons incarcerated while respecting the unique carceral institution regulations in place to protect carceral staff, clinicians will navigate the concept of “dual loyalty.” With this, in conjunction with supporting patient autonomy in treatment decisions and providing infection-prevention counseling and treatment, clinicians can create a therapeutic patient alliance and reduce health disparities.

To the editor—We read with interest the recent article by Lewis et al [1]. In their study, starting treatment with oseltamivir early (on the day of hospital admission) compared with delayed (after the first day) or no treatment was associated with the primary outcome, lower peak pulmonary disease severity during hospital admission. Additionally, in a sensitivity analysis that excluded those patients who did not receive oseltamivir, the authors found that early treatment was associated with lower peak pulmonary severity compared with delayed treatment, which the authors interpreted as evidence that early oseltamivir administration was beneficial.

Transmitted drug resistance (TDR) may compromise the effect of antiretroviral therapy (ART), highlighting the necessity for continuous monitoring.MethodsThe study was conducted across 31 provincial-level administrative divisions of China. Demographic information and blood samples were collected from participants at diagnosis of human immunodeficiency virus (HIV) infection between April and June 2023. TDR and molecular transmission networks were analyzed based on partial pol sequences via the Stanford HIV drug resistance database and HIV-TRACE, respectively. Logistic regression was utilized to identify factors associated with TDR.ResultsHIV drug resistance genotyping was successfully performed on plasma samples from 6654 individuals. The overall TDR prevalence was 11.4% (95% confidence interval [CI], 10.6%–12.2%). Resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) was 7.9%, 0.8%, 2.4%, and 1.0%, respectively. TDR to efavirenz/nevirapine (EFV/NVP) was 6.5%. According to the surveillance drug resistance mutation list, the prevalence of TDR to total, NNRTIs, NRTIs, PIs, and INSTIs was 8.2%, 6.4%, 1.0%, 0.7%, and 0.4%. Multivariable analysis linked TDR to non-Han ethnicity (adjusted odds ratio [AOR], 1.45 [95% CI, 1.17–1.79]), unknown transmission routes (AOR, 2.56 [95% CI, 1.33–4.90]), and CD4 ≥500 cells/μL (AOR, 1.29 [95% CI, 1.05–1.58]). Higher education (high school or more) reduced TDR odds (AOR, 0.77 vs primary education).ConclusionsTDR among people with newly diagnosed HIV in China exceeds 10%, with EFV/NVP TDR >5%. Timely monitoring of TDR and adjustment of ART regimens are essential to mitigate the impact of drug resistance on treatment efficacy.

The incidence of spinal infections is increasing; However, pathogen identification remains challenging. Although Q fever spinal infection is reported infrequently, its accrual incidence is likely underestimated. The causative agent, Coxiella burnetii, cannot be routinely cultured. Consequently, physicians often misdiagnose Q fever spinal infection as spinal tuberculosis, leading to severe patient harm. Thus, improving clinicians’ awareness of the clinical characteristics of Q fever spinal infection is urgently needed.MethodsWe present a case of Q fever spinal infection and conducted literature searches in PubMed and the Chinese core journals of the Wanfang Database using keywords including “Q fever,” “Coxiella burnetii,” “spinal infection,” “osteomyelitis,” “spondylodiscitis,” and “psoas abscess.” Additional reports were identified through cross-referencing, with a cutoff date of 6 November 2024. Cases were included if patient age, sex, and baseline medical history were documented. Clinical data were retrospectively analyzed, and clinical features were compared between the aneurysm-associated group and the isolated spinal infection group. Fisher's exact probability test was used to evaluate the incidence difference.ResultsA total of 39 adult patients were enrolled (mean age: 67.82 ± 10.51 years, male: 34,87.2%), Eleven cases reported potential pathogen exposure. Thirty-three cases presented with early-onset of lower back pain, and 13 developed fever during the disease course. Thirty-four cases involved the lumbar spine, exhibiting continuous lesions of 1–3 vertebral bodies, with imaging features of vertebral osteomyelitis, discitis, paravertebral soft-tissue swelling, and/or adjacent aneurysmal changes. Among 21 cases with routine blood tests, 2 showed elevated leukocyte counts, 5 had mild anemia, and the remainder were normal. Serological testing was performed in 34 cases, with 29 testing positive on the first time; PCR testing was conducted in 25 cases, with 23 cases detecting positive specimens; and rapid diagnosis confirmed in all 3 cases via metagenomic next-generation sequencing (mNGS). Inflammatory reactions were identified in all 21 biopsied cases, with inflammatory granulomas reported in 7 and explicitly excluded in 4. There were 24 cases complicated with aneurysm and 15 cases with isolated spinal infection. A significant difference in CRP elevation rate was observed between the two groups (14/15, 93.33% vs 4/8, 50.00%, P = .033). Early local lesion debridement combined with doxycycline-based multidrug therapy showed favorable outcomes. Serological monitoring demonstrated low sensitivity for assessing therapeutic efficacy.ConclusionsThis study systematically summarizes the clinical characteristics of Q fever spinal infection and, for the first time, reports features associated with its distinct clinical subtypes. Q fever should be considered in case of chronic spinal infections—especially those complicated with vascular lesions. Based on clinical history evaluation, rapid diagnosis may be achieved through mNGS of specimens from local lesions. Combined with early initiation of doxycycline-based regimens, timely debridement of necrotic tissues and purulent material may improve treatment outcomes. Further investigations are needed to identify reliable biomarkers for monitoring therapeutic efficacy and to establish optimal treatment strategies for subtypes of Q fever spinal infection.

Streptococcus anginosus group (SAG) consists of oral facultative anaerobic bacteria that are increasingly identified as causative organisms of empyema, yet they are not often considered to be a cause of community-acquired pneumonia. The objective of this study was to determine the pathogenesis of empyema caused by SAG bacteria in pure culture (ie, no other organisms grown in culture or seen on Gram stain of the exudate) and in mixed cultures.MethodsThis retrospective cohort study was conducted in 3 hospitals in an urban region of Southern California. The sample included adult patients with empyema and pleural fluid cultures positive for 1 or more SAG microorganisms. We excluded patients with bronchopleural fistulas or lung abscess because SAG bacteria are known to be a cause of those infections and can breach the physical barrier of the visceral pleura.ResultsThirty-seven patients with SAG empyema were identified: 14 had had polymicrobial cultures including 1 or more species of SAG bacteria (pSAG) and 23 had pure cultures of SAG bacteria. The patients were mostly middle-aged men with comorbidities, some of which predispose to aspiration or the inability to clear aspirated secretions. The patients with pSAG empyema were more likely to have cancer and/or prior surgical disruption of the esophagus with resulting mediastinitis. Patients with SAG empyema were more likely to use substances such as alcohol, sedatives, and narcotics. All computed tomography (CT) scans were initially interpreted as atelectasis abutting the empyema, but 13 patients with SAG empyema had contrast-enhanced CT scans that were suitable for measuring Hounsfield units (HUs) in the areas of consolidation adjacent to the SAG empyema; these scans revealed that they all had pneumonia as the source of their empyema. The most common species isolated from the SAG cases was Streptococcus intermedius.ConclusionsCommunity-acquired SAG empyema is a complication of unrecognized SAG pneumonia. S intermedius was the most common species to cause SAG empyema and pneumonia in this small series. The pneumonias were subacute and misdiagnosed as “adjacent atelectasis.” Some cases of pSAG empyema were a complication of mediastinitis in patients with malignancies. Measurement of HUs in consolidations adjacent to empyema is useful for establishing the diagnosis of pneumonia in patients who present with what appears to be primary SAG empyema. In terms of limitations, this is a retrospective analysis, and not all patients with SAG empyema had contrast-enhanced CT scans. Furthermore, none of the pSAG cases were reanalyzed to measure HUs in the consolidated lungs. We also did not use molecular methods to speciate SAG isolates or detect fastidious anaerobes in the empyema fluids, although all the exudates were cultured anaerobically on multiple media for at least 5 days.

AbstractHerpes simplex virus (HSV) infection is one of the most prevalent viral infections worldwide. In general, host immunity is sufficient to clear viral shedding and recurrences, although it is insufficient to prevent subsequent virologic reactivations. In immunocompromised patients, prolonged and difficult-to-treat HSV infections may develop. The diagnosis of refractory HSV infection is based on the lack of clinical response to nucleoside analogs. Antiviral resistance is confirmed via genotypic and/or phenotypic testing. To provide consensus definitions of refractory and/or resistant (R/R) HSV mucocutaneous infections for clinical trial use, the HSV Resistance Working Group of the Transplant Associated Viral Infections Forum, which includes international clinicians, scientists, industry representatives, and regulatory officials, conducted a literature review of previously published data related to R/R HSV infections in immunocompromised patients. We propose definitions of R/R HSV mucocutaneous infections, which will be subject to re-evaluation and revision based on forthcoming data and future studies.

Coinfections of Mycobacterium tuberculosis (MTB) and human immunodeficiency virus (HIV) impose a substantial global health burden. Patients with MTB infection face a heightened risk of progression to incident active TB, which preventive therapy can mitigate. Current testing methods often fail to identify individuals who subsequently develop incident active TB.MethodsWe developed random forest models to predict incident active TB using patients' medical data at HIV-1 diagnosis. Training our model involved using clinical data routinely collected at enrollment from the Swiss HIV Cohort Study (SHCS). This dataset encompassed 55 people with HIV (PWH) who developed incident active TB 6 months after enrollment and 1432 matched PWH without TB enrolled between 2000 and 2023. External validation used data from the Austrian HIV Cohort Study, comprising 43 people with incident active TB and 1005 people without TB.ResultsWe predicted incident active TB with an area under the receiver operating characteristic curve of 0.83 (95% CI: .8–.86) in the SHCS. After adjusting for ethnicity and the region of origin and refitting the model with fewer parameters, we obtained comparable receiver operating characteristic curve values of 0.72 (SHCS) and 0.67 (Austrian HIV Cohort Study). Our model outperformed the standard of care (tuberculin skin test and interferon-gamma release assay) in identifying high-risk patients, demonstrated by a lower number needed to diagnose (1.96 vs 4).ConclusionsModels based on machine learning offer considerable promise for improving care for PWH, requiring no additional data collection and incurring minimal additional costs while enhancing the identification of PWH that could benefit from preventive TB treatment.

AbstractHuman immunodeficiency virus (HIV) viral suppression was evaluated after receipt of crushed or dissolved bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) administered via enteral tube during hospitalization. Eighty-nine percent of patients (17/19) were virally suppressed (<200 copies/mL) within 1 year of receiving B/F/TAF via tube, suggesting that administration via tube is a reasonable alternative to changing antiretroviral regimens.

Structured Candida auris (C. auris) is an emerging fungal organism that has caused outbreaks in healthcare settings and become a major public health concern, particularly among medically vulnerable populations.MethodsUsing a retrospective case-control design, we investigated factors associated with C. auris clinical cases after prior colonization among patients identified in Florida healthcare facilities during January 1, 2019–December 31, 2023.ResultsWe identified 105 case-patients with documented clinical specimens after colonization and 578 control subjects with colonization only. Factors significantly associated with clinical cases included presence of ≥ 5 comorbid conditions (OR, 10.02; 95% CI, 4.07–24.7), ≥ 4 invasive devices (OR, 2.92; 95% CI, 1.70–5.03), or ≥ 3 recent medical procedures (OR, 2.32; 95% CI, 1.19–4.55). Also, fully dependent care required for eating (OR 2.80), mobility (OR 2.15), and transferring (OR 1.82) were associated with clinical case progression.DiscussionWe found a significant association with progression from screening colonization to clinical C. auris cases among patients with multiple comorbidities, invasive devices, recent invasive procedures, and poor functional status.ConclusionsIdentifying risk factors for clinical progression of C. auris after colonization could enable facilities to implement efficient testing protocols and infection prevention and control (IPC) measures to help prevent morbidity associated with invasive infections.

Rebound of COVID-19 is defined as return of symptoms and/or viral positivity after resolution of the initial infection. While rebound is typically mildly symptomatic and rarely associated with progression to severe disease, the benefit of repeated antiviral treatment has not been investigated.MethodsThis randomized, double-blind, placebo-controlled clinical trial evaluated the efficacy and safety of a second 5-day treatment course of nirmatrelvir/ritonavir versus placebo/ritonavir in participants with symptomatic mild to moderate COVID-19 with a positive SARS-CoV-2 rapid antigen test within 14 days of initial nirmatrelvir/ritonavir treatment. The primary efficacy endpoint was the change in viral SARS-CoV-2 RNA level from baseline to Day 5.ResultsThe full analysis set included 436 participants assigned to treatment (292, nirmatrelvir/ritonavir; 144, placebo/ritonavir). A second 5-day course of nirmatrelvir/ritonavir resulted in a significant reduction in viral RNA levels at Day 5 compared with placebo/ritonavir (P=0.0004; 95% CI, −1.09, −0.32). The median time to 2 consecutive negative RAT results was 4 versus 5 days, and the median time to sustained alleviation of all targeted signs/symptoms was 8 versus 9 days in the nirmatrelvir/ritonavir and placebo/ritonavir groups, respectively. Retreatment with nirmatrelvir/ritonavir was safe and well tolerated, and there were no occurrences of COVID-19−related hospitalizations or deaths.ConclusionA repeated 5-day course of nirmatrelvir/ritonavir was safe and well tolerated and was associated with a faster decline in viral RNA levels. In this study, there was no clear benefit of retreatment because rebound was transient, mild, and did not lead to severe COVID-19.Clinical Trial RegistrationNCT05567952; https://clinicaltrials.gov/study/NCT05567952

Malaria control in sub-Saharan Africa is typically focused on Plasmodium falciparum (Pf), but non-falciparum species like P. ovale curtisi (Poc) and P. ovale wallikeri (Pow) appear to be rising in prevalence, especially in parts of East Africa.MethodsWe conducted polymerase chain reaction (PCR)-based screening of 7,173 asymptomatic individuals over 5 years of age in coastal Tanzania from 2018-2022, employing real-time 18S rRNA PCR assays for P. falciparum and P. ovale, followed by Poc/Pow detection. Plasmodium positivity was compared across seasons and demographic groups, and interactions between species were analyzed via binomial regression.ResultsPf infection (prevalence 27.4%) was associated with younger age, male sex, and higher recent cumulative rainfall, whereas these associations were not apparent for P. ovale (Po, prevalence 11.5%). Po infections appeared to peak during months with lower Pf prevalence, especially during the long wet season, when Po mono-infections predominated and fewer Pf-Po co-infections were detected than expected by independent assortment. This apparent antagonism was reversed during the short wet season: Pf-Po co-infections were comparatively enriched despite low overall Po prevalence. In contrast, excess mixed Poc/Pow infections were detected across all seasons, composing 23% of the Po-positive isolates in which a specific Po species could be detected.ConclusionsThe epidemiology of P. ovale species in coastal Tanzania suggests they are frequently present when P. falciparum recedes, but also co-infect the same hosts during the short wet season. Meanwhile, the individual Poc and Pow species often co-exist within individuals, perhaps due to co-transmission or concurrent relapse.

Children and adolescents face a significantly higher risk of various PASC outcomes after reinfection with SARS-CoV-2. These findings add to previous evidence linking paediatric long COVID to multisystem effects and highlight the need to promote vaccination in younger populations and support ongoing research to better understand PASC, identify high-risk subgroups, and improve prevention and care strategies.

Respiratory virus infections (RVI) are common after hematopoietic cell transplantation (HCT), but their effect on pulmonary outcomes, including bronchiolitis obliterans syndrome (BOS), and mortality is poorly defined.MethodsProspective cohort study of 471 allogeneic HCT recipients transplanted in the pre-COVID-19 pandemic era in an academic cancer center. Participants were prospectively followed for one year with serial handheld spirometry, symptom questionnaires, and multiplex 11-virus PCR. Pulmonary function testing occurred at recommended intervals. Cox proportional hazard and generalized estimating equation models were used to estimate associations between RVI and weekly spirometry with late airflow obstruction (AFO), BOS, and overall mortality.ResultsThe one-year cumulative incidence of at least one RVI was 62%; lower respiratory tract disease (LRTD) occurred in 7.6% of patients. Late AFO developed in 15.6% of patients and BOS in 3.9% of patients. Any symptomatic viral upper respiratory tract infections (URTI) were associated with AFO (adjusted HR [aHR] 1.87, 95% CI 1.11-3.16) and BOS (aHR 2.65, 95% CI 1.02-6.91). Individually, PIV-3 URTI were associated with AFO (aHR 2.83, 95% CI 1.01-7.97) and RSV URTI were associated with BOS (aHR 6.32, 95% CI 2.04-19.6). Short-term airflow decline was associated with AFO. Any LRTD (aHR 3.49, 95% CI 2.18-5.57), as well as symptomatic influenza URTI (aHR 2.68, 95% CI 1.52-4.72), were associated with mortality.ConclusionsRVI after HCT, particularly those caused by RSV, PIV-3 and influenza, increase the risk of pulmonary impairment and mortality. These infections should be targeted for specific anti-viral approaches and intensified monitoring for late onset pulmonary disease.

It is unknown whether within-patient Candida albicans diversity is common during bloodstream infections (BSIs).MethodsWe determined whole genome sequences of 10 C. albicans strains from blood cultures (BCs) in each of 4 patients. We performed detailed phenotypic studies on strains from 1 patient.ResultsBCs in 3 patients contained mixed populations of strains that differed by large-scale genetic variants, including chromosome (Chr) 5 or 7 aneuploidy and Chr1 loss of heterozygosity (n=1 each). In patient M, Chr7 trisomy (Tri7) strains were attenuated for hyphal and biofilm formation in vitro, due at least in part to NRG1 over-expression. Nevertheless, representative Tri7 strain M1 underwent filamentation during disseminated candidiasis (DC) in mice. M1 was more fit than euploid strain M2 during DC and mouse gastrointestinal colonization, and in blood ex vivo. M1 and M2 exhibited identical echinocandin minimum inhibitory concentrations, but M2 was more tolerant to micafungin in vitro. Furthermore, M2 was more competitive with M1 in mouse kidneys following micafungin treatment than it was in absence of micafungin. Tri7 strains represented 74% of patient M’s baseline BC population, but euploid strains were 98% of the population after 3d of echinocandin treatment. Findings suggest that echinocandin tolerant, euploid strains were a subpopulation to more fit Tri7 strains at baseline and then were selected upon echinocandin exposure.ConclusionsBCs in some patients are comprised of diverse C. albicans populations not recognized by the clinical lab, rather than single strains. Clinical relevance of C. albicans diversity and echinocandin tolerance merits further investigation.