In addition to oropharyngeal cancers, evidence suggests there may be an etiologic role for human papillomavirus (HPV) in some other head and neck cancers arising from the oral cavity and larynx. We estimated the burden of HPV16-attributable cancers of the oral cavity (ICD-O-3 site codes C02.0-C02.3, C02.9, C03.0, C03.1, C03.9, C04.0, C04.1, C04.8, C04.9, C05.0, C05.8, C05.9, C06.0-C06.2, C06.8, C06.9) and larynx (C32.0-C32.3, C32.8, C32.9) in the United States by pooling estimates from published case studies to calculate HPV16-attributable fractions (HPV16-AFs) and applying the HPV16-AFs to 2016-2020 US Cancer Statistics data. During 2016-2020, of an average annual number of 12,612 oral cavity cancers, 3.9% (n = 497) were estimated to be attributable to HPV16. Of an average annual number of 11,170 laryngeal cancers, 2.8% (n = 309) were estimated to be attributable to HPV16. This information can improve surveillance of HPV16-attributable cancers in the US population and inform our understanding of the potential impact of HPV vaccination on cancers at these two sites.

IMPORTANCE: Trichophyton indotineae is an emerging dermatophyte causing outbreaks of extensive tinea infections often unresponsive to terbinafine. This species has been detected worldwide and in multiple US states, yet detailed US data on infections with T indotineae are sparse and could improve treatment practices and medical understanding of transmission. OBJECTIVE: To correlate clinical features of T indotineae infections with in vitro antifungal susceptibility testing results, squalene epoxidase gene sequence variations, and isolate relatedness using whole-genome sequencing. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of patients with T indotineae infections in New York City spanned May 2022 to May 2023. Patients with confirmed T indotineae infections were recruited from 6 New York City medical centers. MAIN OUTCOME AND MEASURE: Improvement or resolution at the last follow-up assessment. RESULTS: Among 11 patients with T indotineae (6 male and 5 female patients; median [range] age, 39 [10-65] years), 2 were pregnant; 1 had lymphoma; and the remainder were immunocompetent. Nine patients reported previous travel to Bangladesh. All had widespread lesions with variable scale and inflammation, topical antifungal monotherapy failure, and diagnostic delays (range, 3-42 months). Terbinafine treatment failed in 7 patients at standard doses (250 mg daily) for prolonged duration; these patients also had isolates with amino acid substitutions at positions 393 (L393S) or 397 (F397L) in squalene epoxidase that correlated with elevated terbinafine minimum inhibitory concentrations of 0.5 μg/mL or higher. Patients who were treated with fluconazole and griseofulvin improved in 2 of 4 and 2 of 5 instances, respectively, without correlation between outcomes and antifungal minimum inhibitory concentrations. Furthermore, 5 of 7 patients treated with itraconazole cleared or had improvement at the last follow-up, and 2 of 7 were lost to follow-up or stopped treatment. Based on whole-genome sequencing analysis, US isolates formed a cluster distinct from Indian isolates. CONCLUSION AND RELEVANCE: The results of this case series suggest that disease severity, diagnostic delays, and lack of response to typically used doses and durations of antifungals for tinea were common in this primarily immunocompetent patient cohort with T indotineae, consistent with published data. Itraconazole was generally effective, and the acquisition of infection was likely in Bangladesh.

We estimated the population-level incidence of human papillomavirus (HPV) positive oropharyngeal, cervical, and anal cancers by smoking status. We combined HPV DNA genotyping data from the Centers for Disease Control and Prevention's Cancer Registry Sentinel Surveillance System with data from the Kentucky Cancer Registry and Behavioral Risk Factor Surveillance System across smoking status. During 2004-2005 and 2014-2015 in Kentucky, most cases of oropharyngeal (63.3%), anal (59.7%), and cervical (54.9%) cancer cases were among persons who ever smoked. Population-level incidence rate was higher among persons who ever smoked than never smoked for HPV-positive oropharyngeal (7.8 vs 2.1; adjusted incidence rate ratio [RRadj] = 2.6), cervical (13.7 vs 6.8; RRadj = 2.0), and anal (3.9 vs 1.6; RRadj = 2.5) cancers. These findings indicate that smoking is associated with increased risk of HPV-positive oropharyngeal, cervical, and anal cancers, and the population-level burden of these cancers is higher among persons who ever smoked.

In April 2023, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by one new family, 14 new genera, and 140 new species. Two genera and 538 species were renamed. One species was moved, and four were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.

Candida auris is a multidrug-resistant yeast which has emerged in healthcare facilities worldwide, however little is known about identification methods, patient colonization, spread, environmental survival, and drug resistance. Colonization on both biotic and abiotic surfaces, along with travel, appear to be the major factors for the spread of this pathogen across the globe. In this investigation, we present laboratory findings from an ongoing C. auris outbreak in NY from August 2016 through 2018. A total of 540 clinical isolates, 11,035 patient surveillance specimens, and 3,672 environmental surveillance samples were analyzed. Laboratory methods included matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for yeast isolate identification, real-time PCR for rapid surveillance sample screening, culture on selective/non-selective media for recovery of C. auris and other yeasts from surveillance samples, antifungal susceptibility testing to determine the C. auris resistance profile, and Sanger sequencing of ribosomal genes for C. auris genotyping. Results included: a) identification and confirmation of C. auris in 413 clinical isolates and 931 patient surveillance isolates, as well as identification of 277 clinical cases and 350 colonized cases from 151 healthcare facilities including 59 hospitals, 92 nursing homes, 1 long-term acute care hospital (LTACH), and 2 hospices, b) successful utilization of an in-house developed C. auris real-time PCR assay for the rapid screening of patient and environmental surveillance samples, c) demonstration of relatively heavier colonization of C. auris in nares compared to the axilla/groin, and d) predominance of the South Asia Clade I with intrinsic resistance to fluconazole and elevated minimum inhibitory concentration (MIC) to voriconazole (81%), amphotericin B (61%), 5-FC (3%) and echinocandins (1%). These findings reflect greater regional prevalence and incidence of C. auris and the deployment of better detection tools in an unprecedented outbreak.

Tinea is a common, highly contagious, superficial infection of the skin, hair, or nails caused by dermatophyte molds.* During the past decade, an epidemic of severe, antifungal-resistant tinea has emerged in South Asia because of the rapid spread of Trichophyton indotineae,† a novel dermatophyte species; the epidemic has likely been driven by misuse and overuse of topical antifungals and corticosteroids§ (1,2). T. indotineae infections are highly transmissible and characterized by widespread, inflamed, pruritic plaques on the body (tinea corporis), the crural fold, pubic region, and adjacent thigh (tinea cruris), or the face (tinea faciei) (1). T. indotineae isolates are frequently resistant to terbinafine, a mainstay of tinea treatment (1,3). T. indotineae infections have been reported throughout Asia and in Europe and Canada but have not previously been described in the United States (3). | | On February 28, 2023, a New York City dermatologist notified public health officials of two patients who had severe tinea that did not improve with oral terbinafine treatment, raising concern for potential T. indotineae infection; these patients shared no epidemiologic links. Skin culture isolates from each patient were previously identified by a clinical laboratory as Trichophyton mentagrophytes and were subsequently forwarded to the Wadsworth Center, New York State Department of Health, for further review and analysis. Sanger sequencing of the internal transcribed spacer region of the ribosomal gene, followed by phylogenetic analysis performed during March 2023, identified the isolates as T. indotineae (Supplementary Figure; https://stacks.cdc.gov/view/cdc/127678). Activity related to this investigation was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.¶

We agree with Chaturvedi and Ostrosky-Zeichner that Candida species are important health care–associated pathogens. The Emerging Infections Program of the Centers for Disease Control and Prevention has conducted population-based candidemia surveillance in metropolitan Atlanta and Baltimore since 2008. Although the incidence of candidemia decreased from 2008 through 2013, resistance to echinocandins and multidrug resistance increased.1 Data from our hospital surveys affirm that candida species are common causes of health care–associated infections,2 and there was no significant difference in the percentage of patients with infections caused by candida species in 2011 (32 of 504, 6.3%) and 2015 (26 of 427, 6.1%) (P=0.87 according to mid-P exact test). Among all patients surveyed, there was no significant difference in the percentage with a health care–associated infection due to candida species in 2011 (31 of 11,282, 0.27%) and 2015 (25 of 12,299, 0.20%) (P=0.26 according to mid-P exact test). Changes in the incidence of candida infections and the prevalence of antifungal resistance should be closely monitored, and more information is needed regarding the most effective approaches to the prevention of candida infections in health care facilities, particularly those infections caused by resistant and transmissible yeasts such as C. auris.

BACKGROUND: This pilot project implemented admission screening for Candida auris (C. auris) using real-time polymerase chain reaction (rt-PCR) in select high-risk units within health care facilities in New York City. METHODS: An admission screening encounter consisted of collecting 2 swabs, to be tested by rt-PCR, and a data collection form for individuals admitted to ventilator units at 2 nursing homes (NHA and NHB), and the ventilator/pulmonary unit, intensive care unit, and cardiac care unit at a hospital (Hospital C) located in New York City from November 2017 to November 2019. RESULTS: C. auris colonization was identified in 6.9% (n = 188/2,726) of admissions to participating units. Rates were higher among admissions to NHA and NHB (20.7% and 22.0%, respectively) than Hospital C (3.6%). Within Hospital C, the ventilator/pulmonary unit had a higher rate (5.7%) than the intensive care unit (3.8%) or cardiac care unit (2.5%). DISCUSSION: Consistent with prior research, we found that individuals admitted to ventilator units were at higher risk of C. auris colonization. CONCLUSIONS: This project demonstrates the utility of admission screening using rt-PCR testing to rapidly identify C. auris colonization among admissions to health care facilities so that appropriate transmission-based precautions and control measures can be implemented rapidly to help decrease transmission.

Combination antifungal therapy is widely used but not well understood. We analyzed the spectrophotometric readings from a multicenter study conducted by the New York State Department of Health to further characterize the in vitro interactions of the major classes of antifungal agents against Candida spp. Loewe additivity-based fractional inhibitory concentration index (FICi) analysis and Bliss independence-based response surface (BIRS) analysis were used to analyze two-drug inter- and intraclass combinations of triazoles (AZO) (voriconazole, posaconazole), echinocandins (ECH) (caspofungin, micafungin, anidulafungin), and a polyene (amphotericin B) against Candida albicans, C. parapsilosis, and C. glabrata. Although mean FIC indices did not differ statistically significantly from the additivity range of 0.5−4, indicating no significant pharmacodynamic interactions for all of the strain−combinations tested, BIRS analysis showed that significant pharmacodynamic interactions with the sum of percentages of interactions determined with this analysis were strongly associated with the FIC indices (Χ2 646, p < 0.0001). Using a narrower additivity range of 1−2 FIC index analysis, statistically significant pharmacodynamic interactions were also found with FICi and were in agreement with those found with BIRS analysis. All ECH+AB combinations were found to be synergistic against all Candida strains except C. glabrata. For the AZO+AB combinations, synergy was found mostly with the POS+AB combination. All AZO+ECH combinations except POS+CAS were synergistic against all Candida strains although with variable magnitude; significant antagonism was found for the POS+MIF combination against C. albicans. The AZO+AZO combination was additive for all strains except for a C. parapsilosis strain for which antagonism was also observed. The ECH+ECH combinations were synergistic for all Candida strains except C. glabrata for which they were additive; no antagonism was found.

About 55% of U.S. Candida auris clinical cases were reported from New York and New Jersey from 2016 through 2020. Nearly all New York-New Jersey clinical isolates (99.8%) were fluconazole resistant, and 50% were amphotericin B resistant. Echinocandin resistance increased from 0% to 4% and pan-resistance increased from 0 to <1% for New York C. auris clinical isolates but not for New Jersey, highlighting the regional differences.

Candida auris (C. auris) is a globally-emerging multi-drug resistant yeast. New York State (NYS) first detected C. auris in July 2016 and is the state most affected. This brief report describes characteristics of the first 114 individuals colonized with C. auris identified through active surveillance/screening by NYS Department of Health (NYSDOH). "Colonized/screened" individuals were old (median age,74 year), had extensive healthcare exposures and underlying conditions (multiple healthcare facility admissions in the 90 days prior with more than 80% requiring mechanical ventilation), and had 30 and 90 day mortality rates of 17.5% and 37.7%, respectively (with approximately 60% expired in the two-year follow-up period). This description is helpful to inform additional prevention measures and add to the collective understanding of C. auris in the U.S.

BACKGROUND: Candida auris, a multidrug-resistant yeast, can spread rapidly in ventilator-capable skilled-nursing facilities (vSNFs) and long-term acute care hospitals (LTACHs). In 2018, a laboratory serving LTACHs in southern California began identifying species of Candida that were detected in urine specimens to enhance surveillance of C auris, and C auris was identified in February 2019 in a patient in an Orange County (OC), California, LTACH. Further investigation identified C auris at 3 associated facilities. OBJECTIVE: To assess the prevalence of C auris and infection prevention and control (IPC) practices in LTACHs and vSNFs in OC. DESIGN: Point prevalence surveys (PPSs), postdischarge testing for C auris detection, and assessments of IPC were done from March to October 2019. SETTING: All LTACHs (n = 3) and vSNFs (n = 14) serving adult patients in OC. PARTICIPANTS: Current or recent patients in LTACHs and vSNFs in OC. INTERVENTION: In facilities where C auris was detected, PPSs were repeated every 2 weeks. Ongoing IPC support was provided. MEASUREMENTS: Antifungal susceptibility testing and whole-genome sequencing to assess isolate relatedness. RESULTS: Initial PPSs at 17 facilities identified 44 additional patients with C auris in 3 (100%) LTACHs and 6 (43%) vSNFs, with the first bloodstream infection reported in May 2019. By October 2019, a total of 182 patients with C auris were identified by serial PPSs and discharge testing. Of 81 isolates that were sequenced, all were clade III and highly related. Assessments of IPC identified gaps in hand hygiene, transmission-based precautions, and environmental cleaning. The outbreak was contained to 2 facilities by October 2019. LIMITATION: Acute care hospitals were not assessed, and IPC improvements over time could not be rigorously evaluated. CONCLUSION: Enhanced laboratory surveillance and prompt investigation with IPC support enabled swift identification and containment of C auris. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

BACKGROUND: Patients colonized with multidrug-resistant Candida auris and discharged to a community setting can subsequently seek care in a different healthcare facility and might be a source of nosocomial transmission of C auris. METHODS: We designed a case management pilot program for a cohort of New York City residents who had a history of positive C auris culture identified during clinical or screening activities in healthcare settings and discharged to a community setting during 2017-2019. Approximately every 3 months, case managers coordinated C auris colonization assessments, which included swabs of groin, axilla, and body sites yielding C auris previously. Patients eligible to become serially negative were those with ≥2 C auris colonization assessments after initial C auris identification. Clinical characteristics of serially negative and positive patients were compared. RESULTS: The cohort included 75 patients. Overall, 45 patients were eligible to become serially negative and had 552 person-months of follow-up. Of these 45 patients, 28 patients were serially negative (62%; rate 5.1/100 person-months), 8 were serially positive, and 9 could not be classified as either. There were no clinical characteristics that were significantly different between serially negative and positive patients. The median time from initial C auris identification to being serially negative at assessments was 8.6 months (interquartile range, 5.7-10.8 months). CONCLUSIONS: A majority of patients, assessed at least twice after C auris identification, no longer had C auris detectable on serial colonization assessments.

BACKGROUND: Candida auris is an emerging, multidrug-resistant yeast that spreads in healthcare settings. People colonized with C. auris can transmit this pathogen and are at risk for invasive infections. New York State (NYS) has the largest U.S. burden (>500 colonized and infected people); many colonized individuals are mechanically ventilated or have tracheostomy and are residents of ventilator-capable skilled nursing facilities (vSNF). We evaluated factors associated with C. auris colonization among vSNF residents to inform prevention interventions. METHODS: During 2016-2018, the NYS Department of Health conducted point prevalence surveys (PPS) to detect C. auris colonization among residents of vSNFs. In a case-control investigation, we defined a case as C. auris colonization in a resident and identified up to four residents with negative swabs during the same PPS as controls. We abstracted data from medical records on facility transfers, antimicrobials, and medical history. RESULTS: We included 60 cases and 218 controls identified from 6 vSNFs. After controlling for potential confounders, the following characteristics were associated with C. auris colonization: being on a ventilator (aOR: 5.9; CI: 2.3-15.4), receiving carbapenem antibiotics in the prior 90 days (aOR: 3.5; CI: 1.6-7.6), having ≥1 acute care hospital visit in the prior six months (aOR: 4.2; CI: 1.9-9.6), and receiving systemic fluconazole in the prior 90 days (aOR: 6.0; CI: 1.6-22.6). CONCLUSIONS: Targeted screening of patients in vSNFs with the above risk factors for C. auris can help identify colonized patients and facilitate implementation of infection control measures. Antimicrobial stewardship may be an important factor in the prevention of C. auris colonization.

Candida auris is an emerging multidrug-resistant fungal pathogen reported worldwide. Infections due to C. auris are usually nosocomial and associated with high rates of fluconazole resistance and mortality. Echinocandins are utilized as the first-line treatment. However, echinocandins are only available intravenously and are associated with increasingly higher rates of resistance by C. auris. Thus, a need exists for novel treatments that demonstrate potent activity against C. auris. Ibrexafungerp is a first-in-class triterpenoid antifungal agent. Similar to echinocandins, ibrexafungerp inhibits (1→3)-β-D-glucan synthase, a key component of the fungal cell wall, resulting in fungicidal activity against Candida spp. Ibrexafungerp demonstrates broad in vitro activity against various Candida spp. including C. auris and C. auris isolates with fks mutations. Minimum inhibitory concentration (MIC(50) and MIC(90)) values in >400 C. auris isolates were 0.5 μg/mL and 1.0 μg/mL, respectively. Clinical results were reported for two patients with invasive candidiasis or candidemia due to C. auris treated during the CARES (Candidiasis Caused by Candida Auris) trial, an ongoing open-label study. These patients experienced a complete response after treatment with ibrexafungerp. Thus, ibrexafungerp represents a promising new antifungal agent for treating C. auris infections.

BACKGROUND: Direct measures of HIV incidence are needed to assess the population-level impact of prevention programs but are scarcely available in subnational epidemic hotspots of sub-Saharan Africa. We created a sentinel HIV incidence cohort within a community-based program that provided home-based HIV testing to all residents of Namibia's Zambezi region, where approximately 24% of the adult population was estimated to be living with HIV. OBJECTIVE: The aim of this study was to estimate HIV incidence, detect correlates of HIV acquisition, and assess the feasibility of the sentinel, community-based approach to HIV incidence surveillance in a subnational epidemic hotspot. METHODS: Following the program's initial home-based testing (December 2014-July 2015), we purposefully selected 10 clusters of 60 to 70 households each and invited residents who were HIV negative and aged >/=15 years to participate in the cohort. Consenting participants completed behavioral interviews and a second HIV test approximately 1 year later (March-September 2016). We used Poisson models to calculate HIV incidence rates between baseline and follow-up and multivariable Cox proportional hazard models to assess the correlates of seroconversion. RESULTS: Among 1742 HIV-negative participants, 1624 (93.23%) completed follow-up. We observed 26 seroconversions in 1954 person-years (PY) of follow-up, equating to an overall incidence rate of 1.33 per 100 PY (95% CI 0.91-1.95). Among women, the incidence was 1.55 per 100 PY (95% CI 1.12-2.17) and significantly higher among those aged 15 to 24 years and residing in rural areas (adjusted hazard ratio [aHR] 4.26, 95% CI 1.39-13.13; P=.01), residing in the Ngweze suburb of Katima Mulilo city (aHR 2.34, 95% CI 1.25-4.40; P=.01), who had no prior HIV testing in the year before cohort enrollment (aHR 3.38, 95% CI 1.04-10.95; P=.05), and who had engaged in transactional sex (aHR 17.64, 95% CI 2.88-108.14; P=.02). Among men, HIV incidence was 1.05 per 100 PY (95% CI 0.54-2.31) and significantly higher among those aged 40 to 44 years (aHR 13.04, 95% CI 5.98-28.41; P<.001) and had sought HIV testing outside the study between baseline and follow-up (aHR 8.28, 95% CI 1.39-49.38; P=.02). No seroconversions occurred among persons with HIV-positive partners on antiretroviral treatment. CONCLUSIONS: Nearly three decades into Namibia's generalized HIV epidemic, these are the first estimates of HIV incidence for its highest prevalence region. By creating a sentinel incidence cohort from the infrastructure of an existing community-based testing program, we were able to characterize current transmission patterns, corroborate known risk factors for HIV acquisition, and provide insight into the efficacy of prevention interventions in a subnational epidemic hotspot. This study demonstrates an efficient and scalable framework for longitudinal HIV incidence surveillance that can be implemented in diverse sentinel sites and populations.

Candida auris is a multidrug-resistant yeast which has emerged in healthcare facilities worldwide, however little is known about identification methods, patient colonization, environmental survival, spread, and drug resistance. Colonization on both biotic (patients) and abiotic (healthcare objects) surfaces, along with travel, appear to be the major factors for the spread of this pathogen across the globe. In this investigation, we present laboratory findings from an ongoing C. auris outbreak in New York (NY) from August 2016 through 2018. A total of 540 clinical isolates, 11,035 patient surveillance specimens, and 3,672 environmental surveillance samples were analyzed. Laboratory methods included matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for yeast isolate identification, real-time PCR for rapid surveillance sample screening, culture on selective/non-selective media for recovery of C. auris and other yeasts from surveillance samples, antifungal susceptibility testing to determine the C. auris resistance profile, and Sanger sequencing of the internal transcribed spacer (ITS) and D1/D2 regions of the ribosomal gene for C. auris genotyping. Results included: a) identification and confirmation of C. auris in 413 clinical isolates and 931 patient surveillance isolates, as well as identification of 277 clinical cases and 350 colonized cases from 151 healthcare facilities including 59 hospitals, 92 nursing homes, 1 long-term acute care hospital (LTACH), and 2 hospices, b) successful utilization of an in-house developed C. auris real-time PCR assay for the rapid screening of patient and environmental surveillance samples, c) demonstration of relatively heavier colonization of C. auris in nares compared to the axilla/groin, and d) predominance of the South Asia clade I with intrinsic resistance to fluconazole and elevated minimum inhibitory concentration (MIC) to voriconazole (81%), amphotericin B (61%), 5-FC (3%) and echinocandins (1%). These findings reflect greater regional prevalence and incidence of C. auris and the deployment of better detection tools in an unprecedented outbreak.

Candida auris is an emerging yeast that causes healthcare-associated infections. It can be misidentified by laboratories and often is resistant to antifungal medications. We describe an outbreak of C. auris infections in healthcare facilities in New York City, New York, USA. The investigation included laboratory surveillance, record reviews, site visits, contact tracing with cultures, and environmental sampling. We identified 51 clinical case-patients and 61 screening case-patients. Epidemiologic links indicated a large, interconnected web of affected healthcare facilities throughout New York City. Of the 51 clinical case-patients, 23 (45%) died within 90 days and isolates were resistant to fluconazole for 50 (98%). Of screening cultures performed for 572 persons (1,136 total cultures), results were C. auris positive for 61 (11%) persons. Environmental cultures were positive for samples from 15 of 20 facilities. Colonization was frequently identified during contact investigations; environmental contamination was also common.

In January 2017, CDC identified a cluster of Salmonella enterica serotype Newport infections with isolates sharing an indistinguishable pulsed-field gel electrophoresis (PFGE) pattern, JJPX01.0010 (pattern 10), through PulseNet, the national molecular subtyping network for foodborne disease surveillance. This report summarizes the investigation by CDC, state and local health and agriculture departments, and the U.S. Department of Agriculture's Food Safety and Inspection Service (USDA-FSIS) and discusses the possible role of dairy cows as a reservoir for strains of Salmonella that persistently cause human illness. This investigation combined epidemiologic and whole genome sequencing (WGS) data to link the outbreak to contaminated ground beef; dairy cows were hypothesized to be the ultimate source of Salmonella contamination.

Acute vaso-occlusive pain episodes are a hallmark of sickle cell anemia (SCA), one of the most common Mendelian disorders worldwide with an estimated >300 000 births annually.1-3 Although SCA is a monogenic disorder, manifestations and disease severity are highly variable, suggesting additional phenotypic modifiers. The few genetic factors known to act as phenotypic modifiers do not completely explain the clinical heterogeneity in SCA. Previous genetic association studies identified that variants at 3 distinct loci (BCL11A, HBS1L-MYB, and HBB) are strong determinants of fetal hemoglobin level, and the single-nucleotide polymorphism (SNP) variant rs6141803 located upstream of COMMD7 is associated with acute chest syndrome.4 Also, heme oxygenase-1 gene promoter polymorphisms influence heme oxygenase (HO-1) activity and the incidence of acute chest syndrome in children with sickle cell disease (SCD).5,6 We conducted this genome-wide association study (GWAS) to identify the variants associated with acute, severe vaso-occlusive pain in children with SCA enrolled in the Cooperative Study for Sickle Cell Disease (CSSCD) and Silent Infarct Transfusion (SIT) trial. | The CSSCD, a multi-institutional prospective cohort, natural history study of SCD, enrolled 3538 individuals with SCD between 1979 and 1981.7 The SIT trial, a multicenter international trial, screened 1210 children with SCA to test the hypothesis that regular blood transfusions attenuate progression of cerebral infarcts in children with preexisting silent strokes.8 Both studies were approved by the Institutional Review Boards at Boston University School of Medicine and Vanderbilt University Medical Center.

In June 2016, CDC released a clinical alert about the emerging, and often multidrug-resistant, fungus Candida auris and later reported the first seven U.S. cases of infection through August 2016 (1). Six of these cases occurred before the clinical alert and were retrospectively identified. As of May 12, 2017, a total of 77 U.S. clinical cases of C. auris had been reported to CDC from seven states: New York (53 cases), New Jersey (16), Illinois (four), Indiana (one), Maryland (one), Massachusetts (one), and Oklahoma (one) (Figure). All of these cases were identified through cultures taken as part of routine patient care (clinical cases). Screening of close contacts of these patients, primarily of patients on the same ward in health care facilities, identified an additional 45 patients with C. auris isolated from one or more body sites (screening cases), resulting in a total of 122 patients from whom C. auris has been isolated.

OBJECTIVES: The survival outcomes of antiretroviral treatment (ART) programs have not been systematically evaluated at the state level in India. This retrospective study assessed the survival rates and factors associated with survival among adult human immunodeficiency virus (HIV)-infected patients in Andhra Pradesh, India. METHODS: The present study used data from 139 679 HIV patients aged ≥15 years on ART who were registered from 2007 to 2011 and were followed up through December 2013. The primary end point was death of the patient. Mortality densities (per 1000 person-years) were calculated. Kaplan-Meier and Cox-regression models were used to estimate survival and explore the factors associated with survival. RESULTS: The overall median follow-up time was 16.0 months (2.0 months for the deceased and 14.0 months for those lost to follow-up). Approximately 13.2% of those newly initiated on ART died during follow-up. Of those deaths, 56% occurred in the first three months. The crude mortality rate was 80.9 per 1000 person-years at risk. The CD4 count (adjusted hazard ratio [aHR],4.88; 95% confidence interval [CI], 4.36 to 5.46 for <100 cells/mm3 vs. >350 cells/mm3), functional status (aHR, 3.05; 95% CI, 2.82 to 3.30 for bedridden vs. normal), and body weight (aHR, 3.69; 95% CI, 3.42 to 3.97 for <45 kg vs. >60 kg) were strongly associated with the survival of HIV patients. CONCLUSIONS: The study findings revealed that high mortality was observed within the first three months of ART initiation. Patients with poor baseline clinical characteristics had a higher risk of mortality. Expanded testing and counseling should be encouraged, with the goal of ensuring early enrollment into the program followed by the initiation of ART in HIV-infected patients.

INTRODUCTION: Recently, Salmonella enterica serovar Poona caused a multistate outbreak, with 245 out of 907 cases occurring in California. We report a comparison of pulsed-field gel electrophoresis (PFGE) results with whole genome sequencing (WGS) for genotyping of Salmonella Poona isolates. METHODS: CA Salmonella Poona isolates, collected from July to August 2015, were genotyped by PFGE using XbaI restriction enzyme. WGS was done using Nextera XT library kit with 2x300 bp or 2x250 bp sequencing chemistry on the Illumina MiSeq Sequencer. Reads were mapped to the de novo assembled serovar Poona draft genome (48 contigs, N50= 223,917) from the outbreak using CLCbio GW 8.0.2. The phylogenetic tree was generated based on hqSNPs calling. Genomes were annotated with CGE and PHAST online tools. In silico MLST was performed using the CGE online tool. RESULTS: Human (14) and cucumber (2) Salmonella Poona isolates exhibited 3 possibly related PFGE patterns (JL6X01.0018 [predominant], JL6X01.0375, JL6X01.0778). All isolates that were related by PFGE also clustered together according to the WGS. One isolate with a divergent PFGE pattern (JL6X01.0776) served as an outlier in the phylogenetic analysis and substantially differed from the outbreak clade by WGS. All outbreak isolates were assigned to MLST sequence type 447. The majority of the outbreak-related isolates possessed the same set of Salmonella Pathogenicity Islands with few variations. One outbreak isolate was sequenced and analyzed independently by CDC and CDPH laboratories; there was 0 SNP difference in results. Additional two isolates were sequenced by CDC and the raw data was processed through CDPH and CDC analysis pipelines. Both data analysis pipelines also generated concordant results. Discussion: PFGE and WGS results for the recent CA Salmonella enterica serovar Poona outbreak provided concordant assignment of the isolates to the outbreak cluster. WGS allowed more robust determination of genetic relatedness, provided information regarding MLST-type, pathogenicity genes, and bacteriophage content. WGS data obtained independently at two laboratories showed complete agreement.

Candida auris, an emerging fungus that can cause invasive infections, is associated with high mortality and is often resistant to multiple antifungal drugs. C. auris was first described in 2009 after being isolated from external ear canal discharge of a patient in Japan. Since then, reports of C. auris infections, including bloodstream infections, have been published from several countries, including Colombia, India, Israel, Kenya, Kuwait, Pakistan, South Africa, South Korea, Venezuela, and the United Kingdom. To determine whether C. auris is present in the United States and to prepare for the possibility of transmission, CDC issued a clinical alert in June 2016 informing clinicians, laboratorians, infection control practitioners, and public health authorities about C. auris and requesting that C. auris cases be reported to state and local health departments and CDC. This report describes the first seven U.S. cases of C. auris infection reported to CDC as of August 31, 2016. Data from these cases suggest that transmission of C. auris might have occurred in U.S. health care facilities and demonstrate the need for attention to infection control measures to control the spread of this pathogen.

Four laboratories tested three isolates of Candida species and two isolates of Aspergillus fumigatus using 96-well plates containing combinations of amphotericin B, anidulafungin, caspofungin, micafungin, fluconazole, itraconazole, posaconazole, and voriconazole. The majority of summation fractional inhibitory concentration indices (SigmaFICI) based on the Lowe additivity formula, suggested indifferent drug interactions (SigmaFICI > 0.5 and ≤ 4.0) and no instance of drug antagonism (SigmaFICI > 4.0). The intra- and inter- laboratory agreement rates were superior when MIC100 readings were used as end-points (CI=99%).

In this article, we describe a chronic case of rhinofacial mucormycosis caused by Mucor irregularis, formerly known as Rhizomucor variabilis var. variabilis, a rare mycotic agent in humans. The infection caused progressive destruction of the nasal septum and soft and hard palate, leading to collapse of the nose bridge and an ulcerative gaping hole. The mucoralean mold cultured from a nasal biopsy specimen was determined by multilocus DNA sequence data to be conspecific with M. irregularis.

BACKGROUND: Effective antiretroviral therapy has reduced the risk of AIDS and dramatically prolonged the survival of HIV-infected people in the United States. Consequently, an increasing number of HIV-infected people are at risk of non-AIDS-defining cancers that typically occur at older ages. We estimated the annual number of cancers in the HIV-infected population, both with and without AIDS, in the United States. METHODS: Incidence rates for individual cancer types were obtained from the HIV/AIDS Cancer Match Study by linking 15 HIV and cancer registries in the United States. Estimated counts of the US HIV-infected and AIDS populations were obtained from Centers for Disease Control and Prevention surveillance data. We obtained estimated counts of AIDS-defining (ie, Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer) and non-AIDS-defining cancers in the US AIDS population during 1991-2005 by multiplying cancer incidence rates and AIDS population counts, stratified by year, age, sex, race and ethnicity, transmission category, and AIDS-relative time. We tested trends in counts and standardized incidence rates using linear regression models. We multiplied overall cancer rates and HIV-only (HIV infected, without AIDS) population counts, available from 34 US states during 2004-2007, to estimate cancers in the HIV-only population. All statistical tests were two-sided. RESULTS: The US AIDS population expanded fourfold from 1991 to 2005 (96,179 to 413,080) largely because of an increase in the number of people aged 40 years or older. During 1991-2005, an estimated 79,656 cancers occurred in the AIDS population. From 1991-1995 to 2001-2005, the estimated number of AIDS-defining cancers decreased by greater than threefold (34,587 to 10,325 cancers; P(trend) < .001), whereas non-AIDS-defining cancers increased by approximately threefold (3193 to 10,059 cancers; P(trend) < .001). From 1991-1995 to 2001-2005, estimated counts increased for anal (206 to 1564 cancers), liver (116 to 583 cancers), prostate (87 to 759 cancers), and lung cancers (875 to 1882 cancers), and Hodgkin lymphoma (426 to 897 cancers). In the HIV-only population in 34 US states, an estimated 2191 non-AIDS-defining cancers occurred during 2004-2007, including 454 lung, 166 breast, and 154 anal cancers. CONCLUSIONS: Over a 15-year period (1991-2005), increases in non-AIDS-defining cancers were mainly driven by growth and aging of the AIDS population. This growing burden requires targeted cancer prevention and treatment strategies.

There are few multilaboratory studies on antifungal combinations testing to suggest a format for use in clinical laboratories. In the present study, eight laboratories tested quality control (QC) strain Candida parapsilosis ATCC 22019 and clinical isolates Candida albicans 20533.043, C. albicans 20464.007, Candida glabrata 20205.075, and C. parapsilosis 20580.070. The clinical isolates had relatively high azole and echinocandin MICs. A modified CLSI M-27A3 protocol was used, with 96-well custom-made plates containing checkerboard pair-wise combinations of amphotericin B (AMB), anidulafungin (AND), caspofungin (CSP), micafungin (MFC), posaconazole (PSC), and voriconazole (VRC). The end points were scored visually and on a spectrophotometer or ELISA reader for 50% growth reduction (IC50). Combination IC50 were used to calculate summation FICIs (SigmaFIC, fractional inhibitory concentration indices) based on the Lowe additivity formula. Results revealed that IC50 values of all drug combinations were lower or equal to the IC50 of individual drugs in the combination. A majority of the SigmaFIC values were indifferent (SigmaFIC = 0.51 -2.0), but no antagonism was observed (SigmaFIC ≥ 4). Synergistic combinations (SigmaFIC ≤ 0.5) were found from both visual and spectrophotometric readings for AMB-PSC against C. glabrata and for AMB-AND and AMB-CSP against C. parapsilosis. Additional synergistic interactions were revealed by either of the two end points for AMB-AND, AMB-CSP, AMB-MCF, AMB-PSC, AMB-VRC, AND-PSC, CSP-MCF, and CSP-PSC. The percent agreements among participating laboratories ranged from 37.5 % (lowest) for AND-CAS and POS-VOR and 87.5% (highest) for AB-MF and AND-CAS. Median SigmaFIC values showed wide dispersion, and inter-laboratory agreements were less than 85% in most instances. Additional studies are needed to improve inter-laboratory reproducibility of antifungal combination testing.