BACKGROUND: Fungal meningitis outbreaks are rare and entail high mortality rates. Beginning May 2023, we investigated fungal meningitis caused by Fusarium solani species complex occurring in U.S. patients who received epidural anesthesia in Matamoros, Mexico. METHODS: Early epidemiological information suggested U.S. patients with suspected fungal meningitis had undergone mostly cosmetic procedures under epidural anesthesia performed in two Matamoros clinics. U.S. patients known to have received surgery at these clinics during January 1-May 13, 2023, (clinic closures date) were identified and notified by public health officials. Epidemiological and clinical data were used to update diagnostic and clinical guidance for outbreak response, including use of the experimental antifungal fosmanogepix. Whole genome sequencing was conducted on outbreak isolates. RESULTS: U.S. public health officials attempted to contact 233 potentially exposed U.S. residents who underwent surgeries, mostly cosmetic, in Mexico, reaching 170 (73%). Of those, 104 (61%) reported receiving epidural anesthesia and were therefore considered potentially at risk for fungal meningitis. At least 30/104 (29%) at-risk patients received a diagnostic lumbar puncture; 24 (23 women, 17 Hispanic or Latino) were diagnosed with fungal meningitis, and six were not. Twelve (50%) with fungal meningitis died. All cases involved epidural anesthesia administered by the same anesthesiologist in Mexico. Whole genome sequencing showed that patient isolates of Fusarium from the two implicated clinics in Matamoros, Mexico, were genetically closely related. CONCLUSIONS: Clinicians should maintain suspicion for fungal meningitis in patients with negative bacterial culture, viral culture and molecular testing with a history of epidural anesthesia for any reason.

Echinocandins are the recommended antifungal therapy for Candida auris infections in many countries. While echinocandin resistance remains uncommon, recent reports demonstrate an increase in such cases, with the potential for echinocandin-resistant C. auris transmission between persons. The expansion of C. auris whole-genome sequencing capacity in public health laboratories provides a great opportunity to leverage genomic data to detect echinocandin resistance-conferring mutations. However, curated datasets for validating genomic tools for these purposes are lacking. Therefore, we developed a benchmark dataset comprising 100 whole-genome sequenced C. auris isolates categorized as echinocandin-susceptible (n = 53) and resistant (n = 47) by antifungal susceptibility testing. We implemented the fungal bioinformatics pipeline, MycoSNP-nf, to perform whole-genome sequencing analysis, including C. auris clade typing and the detection of FKS1 mutations in hotspot (HS) regions. Phylogenetic analysis classified isolates into four major clades (Clades I-IV). Of the 47 isolates considered resistant by AFST, 44 showed HS mutations identified by MycoSNP-nf-with 41 positioned in two well-described HS regions and 3 within a potential third hotspot that was recently reported. This benchmark dataset is designed to be a resource to build sequencing capacity to detect echinocandin resistance-conferring mutations in FKS1 and to help standardize comparisons across other bioinformatics tools. IMPORTANCE: Echinocandins are the recommended first-line treatment for invasive infections caused by Candida auris, a multi-drug-resistant yeast that has emerged in healthcare facilities globally. Increasing instances of echinocandin-resistant cases highlight the need for rapid detection and response. We developed a benchmark dataset comprising 100 C. auris echinocandin-resistant and -susceptible isolates to demonstrate the utility of the bioinformatics tool, MycoSNP-nf, for detecting echinocandin resistance-related FKS1 mutations and to assess their concordance with antifungal susceptibility testing results. This benchmark may help validate MycoSNP-nf and other bioinformatics tools aimed at detecting these mechanisms using whole-genome sequencing data.

We used metagenomic next-generation sequencing (mNGS) to investigate an outbreak of Fusarium solani meningitis in US patients who had surgical procedures under spinal anesthesia in Matamoros, Mexico, during 2023. Using a novel method called metaMELT (metagenomic multiple extended locus typing), we performed phylogenetic analysis of concatenated mNGS reads from 4 patients (P1-P4) in parallel with reads from 28 fungal reference genomes. Fungal strains from the 4 patients were most closely related to each other and to 2 cultured isolates from P1 and an additional case (P5), suggesting that all cases arose from a point source exposure. Our findings support epidemiologic data implicating a contaminated drug or device used for epidural anesthesia as the likely cause of the outbreak. In addition, our findings show that the benefits of mNGS extend beyond diagnosis of infections to public health outbreak investigation.

We investigated a blastomycosis cluster among humans and canines in a neighborhood in Wisconsin, United States. We conducted interviews and collected serum specimens for Blastomyces antibody testing by enzyme immunoassay. Although no definitive exposure was identified, evidence supports potential exposures from the riverbank, riverside trails or yards, or construction dust.

BACKGROUND: Blastomycosis is an environmentally acquired fungal infection that can result in severe pulmonary illness and high hospitalization rates. In 2023, a blastomycosis outbreak was detected among workers at a paper mill in Delta County, Michigan. METHODS: We included patients with clinical and laboratory evidence of blastomycosis who had spent ≥40 hours in Delta County since September 1, 2022 and had illness onset December 1, 2022-July 1, 2023. We assessed epidemiological and clinical features of patients and evaluated factors associated with hospitalization. We performed whole-genome sequencing to characterize genetic relatedness of clinical isolates from eight patients. RESULTS: In total, 131 patients were identified; all had worked at or visited the mill. Sixteen patients (12%) were hospitalized; one died. Compared with non-hospitalized patients, more hospitalized patients had diabetes (p=0.03) and urine antigen titers above the lower limit of quantification (p<0.001). Hospitalized patients were also more likely to have had ≥1 healthcare visits before receiving a blastomycosis diagnostic test (p=0.02) and to have been treated with antibiotics prior to antifungal prescription (p=0.001). All sequenced isolates were identified as Blastomyces gilchristii and clustered into a distinct outbreak cluster. CONCLUSIONS: This was the largest documented blastomycosis outbreak in the United States. Epidemiologic evidence indicated exposures occurred at or near the mill, and genomic findings suggested a common exposure source. Patients with diabetes may have increased risk for hospitalization, and elevated urine antigen titers could indicate greater disease severity. Early suspicion of blastomycosis may prompt earlier diagnosis and treatment, potentially reducing unnecessary antibiotic prescriptions and improving patient outcomes.

Candida auris, initially identified in 2009, has rapidly become a critical concern due to its antifungal resistance and significant mortality rates in healthcare-associated outbreaks. To date, whole-genome sequencing (WGS) has identified five unique clades of C. auris, with some strains displaying resistance to all primary antifungal drug classes. In this study, we presented the first WGS analysis of C. auris from Bangladesh, describing its origins, transmission dynamics, and antifungal susceptibility testing (AFST) profile. Ten C. auris isolates collected from hospital settings in Bangladesh were initially identified by CHROMagar Candida Plus, followed by VITEK2 system, and later sequenced using Illumina NextSeq 550 system. Reference-based phylogenetic analysis and variant calling pipelines were used to classify the isolates in different clades. All isolates aligned ~90% with the Clade I C. auris B11205 reference genome. Of the 10 isolates, 8 were clustered with Clade I isolates, highlighting a South Asian lineage prevalent in Bangladesh. Remarkably, the remaining two isolates formed a distinct cluster, exhibiting >42,447 single-nucleotide polymorphism differences compared to their closest Clade IV counterparts. This significant variation corroborates the emergence of a sixth clade (Clade VI) of C. auris in Bangladesh, with potential for international transmission. AFST results showed that 80% of the C. auris isolates were resistant to fluconazole and voriconazole, whereas Clade VI isolates were susceptible to azoles, echinocandins, and pyrimidine analogue. Genomic sequencing revealed ERG11_Y132F mutation conferring azole resistance while FCY1_S70R mutation found inconsequential in describing 5-flucytosine resistance. Our study underscores the pressing need for comprehensive genomic surveillance in Bangladesh to better understand the emergence, transmission dynamics, and resistance profiles of C. auris infections. Unveiling the discovery of a sixth clade (Clade VI) accentuates the indispensable role of advanced sequencing methodologies.IMPORTANCECandida auris is a nosocomial fungal pathogen that is commonly misidentified as other Candida species. Since its emergence in 2009, this multidrug-resistant fungus has become one of the five urgent antimicrobial threats by 2019. Whole-genome sequencing (WGS) has proven to be the most accurate identification technique of C. auris which also played a crucial role in the initial discovery of this pathogen. WGS analysis of C. auris has revealed five distinct clades where isolates of each clade differ among themselves based on pathogenicity, colonization, infection mechanism, as well as other phenotypic characteristics. In Bangladesh, C. auris was first reported in 2019 from clinical samples of a large hospital in Dhaka city. To understand the origin, transmission dynamics, and antifungal-resistance profile of C. auris isolates circulating in Bangladesh, we conducted a WGS-based surveillance study on two of the largest hospital settings in Dhaka, Bangladesh.

BACKGROUND: Zoonotic sporotrichosis is a neglected fungal disease, whereby outbreaks are primarily driven by Sporothrix brasiliensis and linked to cat-to-human transmission. To understand the emergence and spread of sporotrichosis in Brazil, the epicentre of the current epidemic in South America, we aimed to conduct whole-genome sequencing (WGS) to describe the genomic epidemiology. METHODS: In this genomic epidemiology study, we included Sporothrix spp isolates from sporotrichosis cases from Brazil, Colombia, and the USA. We conducted WGS using Illumina NovaSeq on isolates collected by three laboratories in Brazil from humans and cats with sporotrichosis between 2013 and 2022. All isolates that were confirmed to be Sporothrix genus by internal transcribed spacer or beta-tubulin PCR sequencing were included in this study. We downloaded eight Sporothrix genome sequences from the National Center for Biotechnology Information (six from Brazil, two from Colombia). Three Sporothrix spp genome sequences from the USA were generated by the US Centers for Disease Control and Prevention as part of this study. We did phylogenetic analyses and correlated geographical and temporal case distribution with genotypic features of Sporothrix spp isolates. FINDINGS: 72 Sporothrix spp isolates from 55 human and 17 animal sporotrichosis cases were included: 67 (93%) were from Brazil, two (3%) from Colombia, and three (4%) from the USA. Cases spanned from 1999 to 2022. Most (61 [85%]) isolates were S brasiliensis, and all were reported from Brazil. Ten (14%) were Sporothrix schenckii and were reported from Brazil, USA, and Colombia. For S schenckii isolates, two distinct clades were observed wherein isolates clustered by geography. For S brasiliensis isolates, five clades separated by more than 100 000 single-nucleotide polymorphisms were observed. Among the five S brasiliensis clades, clades A and C contained isolates from both human and cat cases, and clade A contained isolates from six different states in Brazil. Compared with S brasiliensis isolates, larger genetic diversity was observed among S schenckii isolates from animal and human cases within a clade. INTERPRETATION: Our results suggest that the ongoing epidemic driven by S brasiliensis in Brazil represents several, independent emergence events followed by animal-to-animal and animal-to human transmission within and between Brazilian states. These results describe how S brasiliensis can emerge and spread within a country. FUNDING: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil; the São Paulo Research Foundation; Productivity in Research fellowships by the National Council for Scientific and Technological Development, and Ministry of Science and Technology of Brazil.

Candida auris is an easily transmissible yeast with resistance to different antifungal compounds. Outbreaks of C. auris are mostly observed in intensive care units. To take adequate measures during an outbreak, it is essential to understand the transmission route, which requires isolate genotyping. In 2019, a short tandem repeat (STR) genotyping analysis was developed for C. auris. To determine the discriminatory power of this method, we performed STR analysis of 171 isolates with known whole-genome sequencing (WGS) data using Illumina reads, and we compared their resolutions. We found that STR analysis separated the 171 isolates into four clades (clades I to IV), as was also seen with WGS analysis. Then, to improve the separation of isolates in clade IV, the STR assay was optimized by the addition of 2 STR markers. With this improved STR assay, a total of 32 different genotypes were identified, while all isolates with differences of >50 single-nucleotide polymorphisms (SNPs) were separated by at least 1 STR marker. Altogether, we optimized and validated the C. auris STR panel for clades I to IV and established its discriminatory power, compared to WGS SNP analysis using Illumina reads. IMPORTANCE The emerging fungal pathogen Candida auris poses a threat to public health, mainly causing outbreaks in intensive care units. Genotyping is essential for investigating potential outbreaks and preventing further spread. Previously, we developed a STR genotyping scheme for rapid and high-resolution genotyping, and WGS SNP outcomes for some isolates were compared to STR data. Here, we compared WGS SNP and STR outcomes for a larger sample cohort. Also, we optimized the resolution of this typing scheme with the addition of 2 STR markers. Altogether, we validated and optimized this rapid, reliable, and high-resolution typing scheme for C. auris.

Alaska Native (AN) people experience higher incidence of, and mortality from, gastric cancer compared to other U.S. populations(1, 2). Compared to the general U.S. population, gastric cancer in AN people occurs at a younger age, is diagnosed at later stages, is more evenly distributed between the sexes, and is more frequently signet-ring or diffuse histology(3). It is known that the prevalence of Helicobacter pylori (Hp) infection, a risk factor for gastric cancer, is high in AN people(4); however, high antimicrobial resistance combined with high reinfection rates in Alaska make treatment at the population level complex(5). In addition, health issues in AN people are uniquely challenging due to the extremely remote locations of many residents. A multiagency workgroup hosted a symposium in Anchorage that brought internationally-recognized experts and local leaders together to evaluate issues around gastric cancer in the AN population. The overall goal of this symposium was to identify the best strategies to combat gastric cancer in the AN population through prevention and early diagnosis.

OBJECTIVES: We evaluated the association between intentional delay of vaccine administration and timely vaccination coverage. METHODS: We used data from 2,921 parents of 19- to 35-month-old children that included parents' reports of intentional delay of vaccine administration. Timely vaccination was defined as administration with > or = 4 doses of diphtheria, tetanus, and pertussis; > or = 3 doses of polio vaccine; > or = 1 dose of measles, mumps, and rubella vaccine; > or = 3 doses of Haemophilus influenzae type b vaccine; > or = 3 doses of hepatitis B vaccine; and > or = 1 dose of varicella vaccine by 19 months of age, as reported by vaccination providers. RESULTS: In all, 21.8% of parents reported intentionally delaying vaccinations for their children. Among parents who intentionally delayed, 44.8% did so because of concerns about vaccine safety or efficacy and 36.1% delayed because of an ill child. Children whose parents intentionally delayed were significantly less likely to receive all vaccines by 19 months of age than children whose parents did not delay (35.4% vs. 60.1%, p < 0.05). Parents who intentionally delayed were significantly more likely to have heard or read unfavorable information about vaccines than parents who did not intentionally delay (87.6% vs. 71.9%, p < 0.05). Compared with parents who intentionally delayed only because their child was ill, parents who intentionally delayed only because of vaccine safety or efficacy concerns were significantly more likely to seek additional information about their decision from the Internet (11.4% vs. 1.1%, p < 0.05), and significantly less likely to seek information from a doctor (73.9% vs. 93.9%, p < 0.05). CONCLUSIONS: Intentionally delayed vaccine doses are not uncommon. Children whose parents delay vaccinations may be at increased risk of not receiving all recommended vaccine doses by 19 months of age and are more vulnerable to vaccine-preventable diseases. Providers should consider strategies such as educational materials that address parents' vaccine safety and efficacy concerns to encourage timely vaccination.

Increases in the number and cost of vaccines routinely recommended for children and adolescents have raised concerns about the ability of the current systems for vaccine financing and delivery to ensure that all children and adolescents have access to all routinely recommended vaccinations without financial barriers. The National Vaccine Advisory Committee (NVAC) was chartered in 1988 to advise and to make recommendations to the director of the National Vaccine Program and the Assistant Secretary for Health at the US Department of Health and Human Services on matters related to the prevention of infectious diseases through vaccination. In October 2006, NVAC established a Vaccine Financing Working Group to explore approaches for child and adolescent vaccine financing. The Vaccine Financing Working Group was charged with establishing a process for obtaining stakeholder input regarding challenges to creating optimal approaches to vaccine financing in both the public and private sectors. The goal of this process was to develop recommendations to ensure that all children and adolescents have access to all routinely recommended vaccinations without financial barriers. | The NVAC considered several overarching principles in formulating its recommendations. First, vaccine-preventable diseases are not constrained by geographic boundaries, and policies on vaccine financing should be national in scope. Second, vaccine financing solutions should address near-term problems with vaccine financing and should anticipate continued changes in recommended child and adolescent immunization schedules and the health care delivery system. Third, because vaccine financing problems are multifactorial, their solutions also should be multifactorial and all stakeholders will need to participate in implementing the solutions. Finally, because it is difficult to achieve uniform national implementation of policies that require state-based legislative or budgetary action, legislative or policy actions at the federal level, when appropriate, are recommended for achieving vaccine financing goals.