U.S. Women with Invasive Cervical Cancer: Characteristics and Potential Barriers to Prevention.

Objectives: Although invasive cervical cancer (ICC) rates have declined since the advent of screening, the annual age-adjusted ICC rate in the United States remains 7.5 per 100,000 women. Failure of recommended screening and management often precedes ICC diagnoses. The study aimed to evaluate characteristics of women with incident ICC, including potential barriers to accessing preventive care. Materials and Methods: We abstracted medical records for patients with ICC identified during 2008-2020 in five U.S. population-based surveillance sites covering 1.5 million women. We identified evidence of adverse social and medical conditions, including uninsured/underinsured, language barrier, substance use disorder, incarceration, serious mental illness, severe obesity, or pregnancy at diagnosis. We calculated descriptive frequencies and compared potential barriers by race/ethnicity, and among women with and without symptoms at diagnosis using chi-square tests. Results: Among 1,606 women with ICC (median age: 49 years; non-White: 47.4%; stage I: 54.7%), the majority (68.8%) presented with symptoms. Forty-six percent of women had at least one identified potential barrier; 15% had multiple barriers. The most common potential barriers among all women were being underinsured/uninsured (17.3%), and language (17.1%). Presence of any potential barrier was more frequent among non-White women and women with than without symptoms (p < 0.05). Conclusions: In this population-based descriptive study of women with ICC, we identified adverse circumstances that might have prevented women from seeking screening and treatment to prevent cancer. Interventions to increase appropriate cervical cancer screening and management are critical for reducing cervical cancer rates.

Hookworm Anthelmintic Resistance: Novel Fecal Polymerase Chain Reaction Ancylostoma caninum Benzimidazole Resistance Marker Detection in a Dog.

A 4 yr old castrated male greyhound presented with a history of chronic (>3 wk) intermittent diarrhea. Initial fecal analysis identified infection with Ancylostoma caninum. Despite treatment with routine anthelmintics, the dog remained persistently A caninum positive for several months. A novel fecal gastrointestinal real-time polymerase chain reaction (qPCR) parasite panel detected A caninum and the genetic benzimidazole (BZ) F167Y resistance marker in multiple samplings over 48 hr. This finding, together with the dog's clinical signs (diarrhea) and lack of response to routine anthelmintics, prompted treatment with cyclooctadepsipeptide emodepside, a drug currently not registered for dogs in the United States. The dog's clinical signs resolved and post-treatment fecal qPCR testing was negative. However, 5 mo later, retesting with fecal qPCR detected A caninum and concurrent BZ resistance marker, as well as Giardia. A presumptive diagnosis of re-infection was made and the emodepside treatment was continued. The dog again reverted to undetected (A caninum and the 167 resistance marker) on reassessment fecal qPCR. This case report describes the use of a novel fecal qPCR panel for gastrointestinal parasites, persistent hookworm and BZ F167Y resistance marker detection in a dog, and highlights the importance of a stepwise approach to clinical management, treatment, and retesting.

Human Salmonellosis Outbreak Linked to Salmonella Typhimurium Epidemic in Wild Songbirds, United States, 2020-2021.

Salmonella infection causes epidemic death in wild songbirds, with potential to spread to humans. In February 2021, public health officials in Oregon and Washington, USA, isolated a strain of Salmonella enterica serovar Typhimurium from humans and a wild songbird. Investigation by public health partners ultimately identified 30 illnesses in 12 states linked to an epidemic of Salmonella Typhimurium in songbirds. We report a multistate outbreak of human salmonellosis associated with songbirds, resulting from direct handling of sick and dead birds or indirect contact with contaminated birdfeeders. Companion animals might have contributed to the spread of Salmonella between songbirds and patients; the outbreak strain was detected in 1 ill dog, and a cat became ill after contact with a wild bird. This outbreak highlights a One Health issue where actions like regular cleaning of birdfeeders might reduce the health risk to wildlife, companion animals, and humans.

HPV type-specific trends in cervical precancers in the United States, 2008 to 2016.

Declines in cervical intraepithelial neoplasia grades 2 to 3 and adenocarcinoma in situ (CIN2+) observed among young women suggest impact from human papillomavirus (HPV) vaccination. To further evaluate vaccine impact including cross-protection and type replacement, we described high-risk (HR)-HPV type-specific cervical precancer incidence rates among women aged 20 to 39 years, 2008 to 2016. We analyzed cross-sectional population-based data on 18 344 cases of CIN2+ from a 5-site surveillance system. Diagnostic specimens were tested for individual HPV types, including 14 HR-HPV types (HPV16/18/31/33/35/39/45/51/52/56/58/59/66/68). We estimated age-specific annual HR-HPV type-specific CIN2+ incidence per 100 000 screened women for individual types, vaccine HR-HPV types (HPV16/18) and nonvaccine HR-HPV types (non-HPV16/18). We evaluated trends using average annual percent changes (AAPC) and 95% confidence intervals (CI), and estimated total declines by comparing 2015-2016 to 2008-2009 using incidence rate ratios. Among 20-24-year-olds, HPV16/18-CIN2+ declined from 2008 through 2016 (AAPC: -21.3%, 95% CI: -28.1%, -13.8%), whereas no trend was observed for non-HPV16/18-CIN2+ (AAPC: -1.8%, 95% CI: -8.1%, 4.9%). After 2010, CIN2+ among 20-24-year-olds was more often caused by nonvaccine vs vaccine HR-HPV types. No significant declining trends were observed in older age groups. In 2015-2016 compared with 2008-2009, HPV16-CIN2+ declined 78%, HPV18-CIN2+ 72% and HPV31-CIN2+ 51% among 20-24-year-olds; no increases were observed in type-specific CIN2+ incidence. Among 25-29-year-olds, HPV16-CIN2+ declined 18%; CIN2+ attributed to seven nonvaccine types increased significantly. No significant declines were observed in older groups. Significant declines in HPV16/18-CIN2+ in 20-24-year-olds and HPV16-CIN2+ in 25-29-year-olds corroborate impact of HPV vaccination. A declining trend in HPV31-CIN2+ is consistent with cross-protection from vaccination.

Case report: Persistent shedding of a live vaccine-derived rubella virus in a young man with severe combined immunodeficiency and cutaneous granuloma.

A young man with X-linked severe combined immunodeficiency developed a persistent vaccine-derived rubella virus (VDRV) infection, with the emergence of cutaneous granulomas more than fifteen years after receipt of two doses of measles-mumps-rubella (MMR) vaccine. Following nasopharyngeal swab (NP) collection, VDRV was detected by real-time polymerase chain reaction (RT-qPCR) and sequencing, and live, replication-competent VDRV was isolated in cell culture. To assess duration and intensity of viral shedding, sequential respiratory samples, one cerebrospinal fluid sample, and two urine samples were collected over 15 months, and VDRV RNA was detected in all samples by RT-qPCR. Live VDRV was cultured from nine of the eleven respiratory specimens and from one urine specimen. To our knowledge, this was the first reported instance of VDRV cultured from respiratory specimens or from urine. To assess potential transmission to close contacts, NP specimens and sera were collected from all household contacts, all of whom were immunocompetent and previously vaccinated with MMR. VDRV RNA was not detected in any NP swabs from the contacts, nor did serologic investigations suggest VDRV transmission to any contacts. This report highlights the need to understand the prevalence and duration of VDRV shedding in granuloma patients and to estimate the risk of VDRV transmission to immune and non-immune contacts.

Feline parasites and the emergence of feline lungworm in the Portland metropolitan area, Oregon, USA 2016-2017.

OBJECTIVES: The aim of this study was to determine the prevalence of internal parasites in feral and free-roaming owned cats in the region of Portland, Oregon, USA. METHODS: Fecal samples from asymptomatic cats were opportunistically collected from feral cats presented for surgical sterilization (n = 46), as well as free-roaming owned cats (n = 86) presented to primary care clinics. Fecal analysis was performed using the Baermann technique, centrifugal flotation, fluorescent auramine and fluorescent antibody for Giardia species. RESULTS: Lungworm infection was identified in 24.2% of owned cats and 17.2% of feral cats. At least 11 unique parasite species were identified in this study. Taenia species and Toxocara cati were identified in higher proportions in feral cats, whereas Giardia species were significantly higher in owned cats. CONCLUSIONS AND RELEVANCE: The prevalence of lungworm was higher than has been previously documented in other areas of the USA. In addition, feral cats were infected with a higher percentage of Toxocara species and Taenia but a significantly lower percentage of Giardia species.

MSG07: An International Cohort Study Comparing Epidemiology and Outcomes of Patients With Cryptococcus neoformans or Cryptococcus gattii Infections.

BACKGROUND: Cryptococcosis due to Cryptococcus neoformans and Cryptococcus gattii varies with geographic region, populations affected, disease manifestations, and severity of infection, which impact treatment. METHODS: We developed a retrospective cohort of patients diagnosed with culture-proven cryptococcosis during 1995-2013 from 5 centers in North America and Australia. We compared underlying diseases, clinical manifestations, treatment, and outcomes in patients with C. gattii or C. neoformans infection. RESULTS: A total of 709 patients (452 C. neoformans; 257 C. gattii) were identified. Mean age was 50.2 years; 61.4% were male; and 52.3% were white. Time to diagnosis was prolonged in C. gattii patients compared with C. neoformans (mean, 52.2 vs 36.0 days; P < .003), and there was a higher proportion of C. gattii patients without underlying disease (40.5% vs 10.2%; P < .0001). Overall, 59% had central nervous system (CNS) infection, with lung (42.5%) and blood (24.5%) being common sites. Pulmonary infection was more common in patients with C. gattii than in those with C. neoformans (60.7% vs 32.1%; P < .0001). CNS or blood infections were more common in C. neoformans-infected patients (P ≤ .0001 for both). Treatment of CNS disease with induction therapy of amphotericin B and flucytosine occurred in 76.4% of patients. Crude 12-month mortality was higher in patients with C. neoformans (28.4% vs 20.2%; odds ratio, 1.56 [95% confidence interval, 1.08-2.26]). CONCLUSIONS: This study emphasizes differences in species-specific epidemiology and outcomes of patients with cryptococcosis, including underlying diseases, site of infection, and mortality. Species identification in patients with cryptococcosis is necessary to discern epidemiologic patterns, guide treatment regimens, and predict clinical progression and outcomes.

Detection of parasites in canine feces at three off-leash dog parks in Portland, Oregon 2014.

Gastrointestinal parasitism is common in dogs attending parks, with variable prevalences of parasites based on geographical region and demographic factors. In this study, canine fecal samples were opportunistically collected from three off-leash dog parks in Portland, Oregon and analyzed for parasites. While some similarities with previous research was seen, much higher rates of Giardia (25.6%) and Toxocara canis (8.67%) were identified in this study. Additional findings of unexpected parasites and those with zoonotic potential make these results significant.

Humoral and Mucosal Immune Responses to Human Norovirus in the Elderly.

BACKGROUND: Most information on mucosal and systemic immune response to norovirus infection is derived from human challenge studies, birth cohort studies, or vaccine trials in healthy adults. However, few data are available on immune responses to norovirus in the elderly. METHODS: To study the mucosal and systemic immune response against norovirus, 43 long-term care facilities were enrolled prospectively in 2010-2014. Baseline saliva samples from 17 facilities, cases and controls up to day 84 from 10 outbreaks, as well as acute and convalescent sera were collected. RESULTS: Norovirus-specific immunoglobulin A (IgA) levels in baseline saliva samples were low and increased in both symptomatic patients and asymptomatic shedders at day 5 after onset during outbreaks. Receiver operating characteristics analysis correctly assigned prior norovirus infection in 23 (92%) of 25 participants. Cases and asymptomatic shedders showed seroconversion for IgG (80%), IgA (78%), and blockade antibodies (87%). Salivary IgA levels strongly correlated with increased convalescent serum IgA titers and blockade antibodies. CONCLUSIONS: Salivary IgA levels strongly correlated with serum IgA titers and blockade antibodies and remained elevated 3 months after a norovirus outbreak. A single salivary sample collected on day 14 could be used to identify recent infection in a suspected outbreak or to monitor population salivary IgA.

An investigation of Salmonella Fluntern illnesses linked to leopard geckos-United States, 2018.

Reptile contact can result in zoonotic non-typhoidal salmonellosis. In April 2018, Oregon Public Health Division contacted CDC about a cluster of four Salmonella serovar Fluntern (SF) illnesses in four states (OR, CA, IA, NY); patients reported contact with geckos, a popular reptile pet. PulseNet, the national molecular subtyping network of food-borne disease surveillance, subsequently identified additional SF clinical isolates. Twelve cases in 11 states were identified; median age was 5 years (range: <1-58 years). Three patients were hospitalized; no deaths were reported. Of those with exposure information (n = 10), all reported reptile exposure; 9 (90%) specified contact with leopard geckos. No common source of geckos was identified from reported purchase locations. Los Angeles County (LAC) health officials isolated SF from one patient's leopard gecko. Five reptile/gecko isolates were identified from the USDA National Veterinary Services Laboratories (NVSL) from 2015 to 2018. Five countries responded to an Epidemic Intelligence Information System post by PulseNet; reptile isolate sequence data were received from Czech Republic. A clinical case from England was identified through the National Center for Biotechnology Information pathogen detection pipeline; the patient did not report contact with leopard geckos. Whole genome sequencing analysis revealed substantial genetic diversity between clinical and animal isolates; however, gecko and clinical isolates from LAC were highly related (1 allele difference). This investigation linking SF illnesses to leopard geckos highlights an important public health risk from pets. A better understanding of how geckos are distributed by the pet industry in the United States could improve traceability to points of origin and mitigate Salmonella transmission at gecko breeders. Earlier NVSL reports of SF isolates from geckos suggest the risk of human SF infection from geckos is not new. This investigation demonstrates a need to educate gecko breeders, retailers and gecko owners about the continued Salmonella infection risk from pet geckos.

Enhanced Surveillance for Coccidioidomycosis, 14 US States, 2016.

Although coccidioidomycosis in Arizona and California has been well-characterized, much remains unknown about its epidemiology in states where it is not highly endemic. We conducted enhanced surveillance in 14 such states in 2016 by identifying cases according to the Council of State and Territorial Epidemiologists case definition and interviewing patients about their demographic characteristics, clinical features, and exposures. Among 186 patients, median time from seeking healthcare to diagnosis was 38 days (range 1-1,654 days); 70% had another condition diagnosed before coccidioidomycosis testing occurred (of whom 83% were prescribed antibacterial medications); 43% were hospitalized; and 29% had culture-positive coccidioidomycosis. Most (83%) patients from nonendemic states had traveled to a coccidioidomycosis-endemic area. Coccidioidomycosis can cause severe disease in residents of non-highly endemic states, a finding consistent with previous studies in Arizona, and less severe cases likely go undiagnosed or unreported. Improved coccidioidomycosis awareness in non-highly endemic areas is needed.

High Hand Contamination Rates During Norovirus Outbreaks in Long-Term Care Facilities.

We examined norovirus contamination on hands of ill patients during 12 norovirus outbreaks in 12 long-term care facilities (LTCFs). The higher frequency and norovirus titers on hands of residents compared to hands of heathcare workers highlights the importance of adhering to appropriate hand hygiene practices during norovirus outbreaks in LTCFs. Infect Control Hosp Epidemiol 2018;39:219-221.

Dating the Cryptococcus gattii Dispersal to the North American Pacific Northwest.

The emergence of Cryptococcus gattii, previously regarded as a predominantly tropical pathogen, in the temperate climate of the North American Pacific Northwest (PNW) in 1999 prompted several questions. The most prevalent among these was the timing of the introduction of this pathogen to this novel environment. Here, we infer tip-dated timing estimates for the three clonal C. gattii populations observed in the PNW, VGIIa, VGIIb, and VGIIc, based on whole-genome sequencing of 134 C. gattii isolates and using Bayesian evolutionary analysis by sampling trees (BEAST). We estimated the nucleotide substitution rate for each lineage (1.59 × 10-8, 1.59 × 10-8, and 2.70 × 10-8, respectively) to be an order of magnitude higher than common neutral fungal mutation rates (2.0 × 10-9), indicating a microevolutionary rate (e.g., successive clonal generations in a laboratory) in comparison to a species' slower, macroevolutionary rate (e.g., when using fossil records). The clonal nature of the PNW C. gattii emergence over a narrow number of years would therefore possibly explain our higher mutation rates. Our results suggest that the mean time to most recent common ancestor for all three sublineages occurred within the last 60 to 100 years. While the cause of C. gattii dispersal to the PNW is still unclear, our research estimates that the arrival is neither ancient nor very recent (i.e., <25 years ago), making a strong case for an anthropogenic introduction. IMPORTANCE The recent emergence of the pathogenic fungus Cryptococcus gattii in the Pacific Northwest (PNW) resulted in numerous investigations into the epidemiological and enzootic impacts, as well as multiple genomic explorations of the three primary molecular subtypes of the fungus that were discovered. These studies lead to the general conclusion that the subtypes identified likely emerged out of Brazil. Here, we conducted genomic dating analyses to determine the ages of the various lineages seen in the PNW and propose hypothetical causes for the dispersal events. Bayesian evolutionary analysis strongly suggests that these independent fungal populations in the PNW are all 60 to 100 years old, providing a timing that is subsequent to the opening of the Panama Canal, which allowed for more direct shipping between Brazil and the western North American coastline, a possible driving event for these fungal translocation events.

Characterization of leptospirosis among dogs in Oregon, 2007-2011.

OBJECTIVE: To characterize the demographics, exposure risks, and outcomes for dogs with leptospirosis in Oregon between 2007 and 2011 and to identify geographic and temporal distributions of known cases of canine leptospirosis within the state during this period. DESIGN: Retrospective descriptive epidemiological study. ANIMALS: 72 dogs. PROCEDURES: Reports of laboratory tests for leptospirosis and zoonosis reporting forms voluntarily submitted by veterinarians to the Oregon Health Authority were evaluated to identify dogs with leptospirosis during the study period; data were also collected by examination of medical records or by telephone surveys with veterinarians from reporting facilities. RESULTS: 72 confirmed cases of leptospirosis were identified; surveys were completed for 65 cases. Seasonal and spatial distributions coincided with rainfall patterns for the state, with most cases diagnosed in the spring and in the western part of the state. Common exposure risks included contact with water in the environment (14/65) and contact with wildlife (14); 33 dogs had no history of known exposure risks. Among dogs with other conditions at the time of diagnosis (26/64), dermatitis, otitis, or both were the most commonly reported findings (9/26). Of 65 dogs, 44 recovered, 12 died or were euthanized because of leptospirosis, and 9 were lost to follow-up. CONCLUSIONS AND CLINICAL RELEVANCE: Distribution of canine leptospirosis cases in Oregon fit the rainfall theory pattern. Dermatologic conditions were present in 9 of 64 (14%) dogs that had a diagnosis of leptospirosis; however, further investigation is needed to determine whether such conditions predispose dogs to the disease.

Incidence of Norovirus and Other Viral Pathogens That Cause Acute Gastroenteritis (AGE) among Kaiser Permanente Member Populations in the United States, 2012-2013.

Noroviruses and other viral pathogens are increasingly recognized as frequent causes of acute gastroenteritis (AGE). However, few laboratory-based data are available on the incidence of AGE caused by viral pathogens in the U.S. This study examined stool specimens submitted for routine clinical diagnostics from patients enrolled in Kaiser Permanente (KP) health plans in metro Portland, OR, and the Maryland, District of Columbia, and northern Virginia geographic areas to estimate the incidence of viral enteropathogens in these populations. Over a one-year study period, participating laboratories randomly selected stools submitted for routine clinical diagnostics for inclusion in the study along with accompanying demographic and clinical data. Selected stools were tested for norovirus, rotavirus, sapovirus, and astrovirus using standardized real-time RT-PCR protocols. Each KP site provided administrative data which were used in conjunction with previously published data on healthcare utilization to extrapolate pathogen detection rates into population-based incidence rates. A total of 1,099 specimens collected during August 2012 to September 2013 were included. Mean age of patients providing stool specimens was 46 years (range: 0-98 years). Noroviruses were the most common viral pathogen identified among patients with AGE (n = 63 specimens, 6% of specimens tested). In addition, 22 (2%) of specimens were positive for rotavirus; 19 (2%) were positive for sapovirus; and 7 (1%) were positive for astrovirus. Incidence of norovirus-associated outpatient visits was 5.6 per 1,000 person-years; incidence of norovirus disease in the community was estimated to be 69.5 per 1,000 person-years. Norovirus incidence was highest among children <5 years of age (outpatient incidence = 25.6 per 1,000 person-years; community incidence = 152.2 per 1,000 person-years), followed by older adults aged >65 years (outpatient incidence = 7.8 per 1,000 person-years; community incidence = 75.8 per 1,000 person-years). Outpatient incidence rates of rotavirus, sapovirus, and astrovirus were 2.0, 1.6, 0.6 per 1,000 person-years, respectively; community incidence rates for these viruses were 23.4, 22.5, and 8.5 per 1,000 person-years, respectively. This study provides the first age-group specific laboratory-based community and outpatient incidence rates for norovirus AGE in the U.S. Norovirus was the most frequently detected viral enteropathogen across the age spectrum with the highest rates of norovirus disease observed among young children and, to a lesser extent, the elderly. These data provide a better understanding of the norovirus disease burden in the United States, including variations within different age groups, which can help inform the development, targeting, and future impacts of interventions, including vaccines.

Diagnosis of Tuberculosis in Three Zoo Elephants and a Human Contact - Oregon, 2013.

In 2013, public health officials in Multnomah County, Oregon, started an investigation of a tuberculosis (TB) outbreak among elephants and humans at a local zoo. The investigation ultimately identified three bull elephants with active TB and 118 human contacts of the elephants. Ninety-six (81%) contacts were evaluated, and seven close contacts were found to have latent TB infection. The three bulls were isolated and treated (elephants with TB typically are not euthanized) to prevent infection of other animals and humans, and persons with latent infection were offered treatment. Improved TB screening methods for elephants are needed to prevent exposure of human contacts.

Identification of Source of Brucella suis Infection in Human by Using Whole-Genome Sequencing, United States and Tonga.

Brucella suis infection was diagnosed in a man from Tonga, Polynesia, who had butchered swine in Oregon, USA. Although the US commercial swine herd is designated brucellosis-free, exposure history suggested infection from commercial pigs. We used whole-genome sequencing to determine that the man was infected in Tonga, averting a field investigation.