Fatal Human Rabies Infection With Suspected Host-Mediated Failure of Post-Exposure Prophylaxis Following a Recognized Zoonotic Exposure-Minnesota, 2021.

BACKGROUND: No human rabies post-exposure prophylaxis (PEP) failure has been documented in the United States using modern cell culture-based vaccines. In January 2021, an 84-year-old male died from rabies 6 months after being bitten by a rabid bat despite receiving timely rabies PEP. We investigated the cause of breakthrough infection. METHODS: We reviewed medical records, laboratory results, and autopsy findings and performed whole-genome sequencing (WGS) to compare patient and bat virus sequences. Storage, administration, and integrity of PEP biologics administered to the patient were assessed; samples from leftover rabies immunoglobulin were evaluated for potency. We conducted risk assessments for persons potentially exposed to the bat and for close patient contacts. RESULTS: Rabies virus antibodies present in serum and cerebrospinal fluid were nonneutralizing. Antemortem blood testing revealed that the patient had unrecognized monoclonal gammopathy of unknown significance. Autopsy findings showed rabies meningoencephalitis and metastatic prostatic adenocarcinoma. Rabies virus sequences from the patient and the offending bat were identical by WGS. No deviations were identified in potency, quality control, administration, or storage of administered PEP. Of 332 persons assessed for potential rabies exposure to the case patient, 3 (0.9%) warranted PEP. CONCLUSIONS: This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture-based vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is any suspicion for immunocompromise.

Improving Foodborne Disease Surveillance and Outbreak Detection and Response Using Peer Networks-The Integrated Food Safety Centers of Excellence.

CONTEXT: Foodborne disease surveillance and outbreak investigations are foundational to the prevention and control of foodborne disease in the United States, where contaminated foods cause an estimated 48 million illnesses, 128 000 hospitalizations, and 3000 deaths each year. Surveillance activities and rapid detection and investigation of foodborne disease outbreaks require a trained and coordinated workforce across epidemiology, environmental health, and laboratory programs. PROGRAM: Under the 2011 Food Safety Modernization Act, the Centers for Disease Control and Prevention (CDC) was called on to establish Integrated Food Safety (IFS) Centers of Excellence (CoEs) at state health departments, which would collaborate with academic partners, to identify, implement, and evaluate model practices in foodborne disease surveillance and outbreak response and to serve as a resource for public health professionals. IMPLEMENTATION: CDC designated 5 IFS CoEs in August 2012 in Colorado, Florida, Minnesota, Oregon, and Tennessee; a sixth IFS CoE in New York was added in August 2014. For the August 2019-July 2024 funding period, 5 IFS CoEs were designated in Colorado, Minnesota, New York, Tennessee, and Washington. Each IFS CoE is based at the state health department that partners with at least one academic institution. EVALUATION: IFS CoEs have built capacity across public health agencies by increasing the number of workforce development opportunities (developing >70 trainings, tools, and resources), supporting outbreak response activities (responding to >50 requests for outbreak technical assistance annually), mentoring students, and responding to emerging issues, such as changing laboratory methods and the COVID-19 pandemic.

Transmission Dynamics of Severe Acute Respiratory Syndrome Coronavirus 2 in High-Density Settings, Minnesota, USA, March-June 2020.

Coronavirus disease has disproportionately affected persons in congregate settings and high-density workplaces. To determine more about the transmission patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in these settings, we performed whole-genome sequencing and phylogenetic analysis on 319 (14.4%) samples from 2,222 SARS-CoV-2-positive persons associated with 8 outbreaks in Minnesota, USA, during March-June 2020. Sequencing indicated that virus spread in 3 long-term care facilities and 2 correctional facilities was associated with a single genetic sequence and that in a fourth long-term care facility, outbreak cases were associated with 2 distinct sequences. In contrast, cases associated with outbreaks in 2 meat-processing plants were associated with multiple SARS-CoV-2 sequences. These results suggest that a single introduction of SARS-CoV-2 into a facility can result in a widespread outbreak. Early identification and cohorting (segregating) of virus-positive persons in these settings, along with continued vigilance with infection prevention and control measures, is imperative.

Hypothesis Generation During Foodborne-Illness Outbreak Investigations.

Hypothesis generation is a critical, but challenging, step in a foodborne outbreak investigation. The pathogens that contaminate food have many diverse reservoirs, resulting in seemingly limitless potential vehicles. Identifying a vehicle is particularly challenging for clusters detected through national pathogen-specific surveillance, because cases can be geographically dispersed and lack an obvious epidemiologic link. Moreover, state and local health departments could have limited resources to dedicate to cluster and outbreak investigations. These challenges underscore the importance of hypothesis generation during an outbreak investigation. In this review, we present a framework for hypothesis generation focusing on 3 primary sources of information, typically used in combination: 1) known sources of the pathogen causing illness; 2) person, place, and time characteristics of cases associated with the outbreak (descriptive data); and 3) case exposure assessment. Hypothesis generation can narrow the list of potential food vehicles and focus subsequent epidemiologic, laboratory, environmental, and traceback efforts, ensuring that time and resources are used more efficiently and increasing the likelihood of rapidly and conclusively implicating the contaminated food vehicle.

COVID-19 Outbreak Associated with a 10-Day Motorcycle Rally in a Neighboring State - Minnesota, August-September 2020.

During August 7-16, 2020, a motorcycle rally was held in western South Dakota that attracted approximately 460,000 persons from across the United States to numerous indoor and outdoor events over a 10-day period. During August-September 2020, the Minnesota Department of Health (MDH) investigated a coronavirus disease 2019 (COVID-19) outbreak associated with the rally in Minnesota residents. Fifty-one primary event-associated cases were identified, and 35 secondary or tertiary cases occurred among household, social, and workplace contacts, for a total of 86 cases; four patients were hospitalized, and one died. Approximately one third (34%) of 87 counties in Minnesota had at least one primary, secondary, or tertiary case associated with this rally. Genomic sequencing supported the associations with the motorcycle rally. These findings support current recommendations for mask use, physical distancing, reducing the number of attendees at gatherings, isolation for patients with COVID-19, and quarantine for close contacts to slow the spread of SARS-CoV-2 (1). Furthermore, although these findings did not capture the impact of the motorcycle rally on residents of other states, they demonstrate the rationale for consistent mitigation measures across states.

A Candidate Imaging Marker for Early Detection of Charcot Neuroarthropathy.

Inflammation-mediated foot osteopenia may play a pivotal role in the etiogenesis, pathogenesis, and therapeutic outcomes in individuals with diabetes mellitus (DM), peripheral neuropathy (PN), and Charcot neuroarthropathy (CN). Our objective was to establish a volumetric quantitative computed tomography-derived foot bone measurement as a candidate prognostic imaging marker to identify individuals with DMPN who were at risk of developing CN. We studied 3 groups: 16 young controls (27 ± 5 years), 20 with DMPN (57 ± 11 years), and 20 with DMPN and CN (55 ± 9 years). Computed tomography image analysis was used to measure metatarsal and tarsal bone mineral density in both feet. The mean of 12 right (7 tarsals and 5 metatarsals) and 12 left foot bone mineral densities, maximum percent difference in bone mineral density between paired bones of the right and the left feet, and the mean difference of the 12 right and the 12 left bone mineral density measurements were used as input variables in different classification analysis methods to determine the best classifier. Classification tree analysis produced no misclassification of the young controls and individuals with DMPN and CN. The tree classifier found 7 of 20 (35%) individuals with DMPN to be classified as CN (1 participant developed CN during follow-up) and 13 (65%) to be classified as healthy. These results indicate that a decision tree employing 3 measurements derived from volumetric quantitative computed tomography foot bone mineral density defines a candidate prognostic imaging marker to identify individuals with diabetes and PN who are at risk of developing CN.

Quantitative Computed Tomography Classification of Lung Nodules: Initial Comparison of 2- and 3-Dimensional Analysis.

OBJECTIVE: The aim of this study was to compare the performance of 2- (2D) and 3-dimensional (3D) quantitative computed tomography (CT) methods for classifying lung nodules as lung cancer, metastases, or benign. METHODS: Using semiautomated software and computerized analysis, we analyzed more than 50 quantitative CT features of 96 solid nodules in 94 patients, in 2D from a single slice and in 3D from the entire nodule volume. Multivariable logistic regression was used to classify nodule types. Model performance was assessed by the area under the receiver operating characteristic curve (AUC) using leave-one-out cross-validation. RESULTS: The AUC for distinguishing 53 primary lung cancers from 18 benign nodules and 25 metastases ranged from 0.79 to 0.83 and was not significantly different for 2D and 3D analyses (P = 0.29-0.78). Models distinguishing metastases from benign nodules were statistically significant only by 3D analysis (AUC = 0.84). CONCLUSIONS: Three-dimensional CT methods did not improve discrimination of lung cancer, but may help distinguish benign nodules from metastases.

Emerging Infections Program--State Health Department Perspective.

The Emerging Infections Program (EIP) is a collaboration between the Centers for Disease Control and Prevention and 10 state health departments working with academic partners to conduct active population-based surveillance and special studies for several emerging infectious disease issues determined to need special attention. The Centers for Disease Control and Prevention funds the 10 EIP sites through cooperative agreements. Our objective was to highlight 1) what being an EIP site has meant for participating health departments and associated academic centers, including accomplishments and challenges, and 2) the synergy between the state and federal levels that has resulted from the collaborative relationship. Sharing these experiences should provide constructive insight to other public health programs and other countries contemplating a collaborative federal-local approach to collective public health challenges.

Albendazole therapy and enteric parasites in United States-bound refugees.

BACKGROUND: Beginning on May 1, 1999, the Centers for Disease Control and Prevention (CDC) recommended presumptive treatment of refugees for intestinal parasites with a single dose of albendazole (600 mg), administered overseas before departure for the United States. METHODS: We conducted a retrospective cohort study involving 26,956 African and Southeast Asian refugees who were screened by means of microscopical examination of stool specimens for intestinal parasites on resettlement in Minnesota between 1993 and 2007. Adjusted prevalence ratios for intestinal nematodes, schistosoma species, giardia, and entamoeba were calculated among refugees who migrated before versus those who migrated after the CDC recommendation of presumptive predeparture albendazole treatment. RESULTS: Among 4370 untreated refugees, 20.8% had at least one stool nematode, most commonly hookworm (in 9.2%). Among 22,586 albendazole-treated refugees, only 4.7% had one or more nematodes, most commonly trichuris (in 3.9%). After adjustment for sex, age, and region, albendazole-treated refugees were less likely than untreated refugees to have any nematodes (prevalence ratio, 0.19), ascaris (prevalence ratio, 0.06), hookworm (prevalence ratio, 0.07), or trichuris (prevalence ratio, 0.27) but were not less likely to have giardia or entamoeba. Schistosoma ova were identified exclusively among African refugees and were less prevalent among those treated with albendazole (prevalence ratio, 0.60). After implementation of the albendazole protocol, the most common pathogens among 17,011 African refugees were giardia (in 5.7%), trichuris (in 5.0%), and schistosoma (in 1.8%); among 5575 Southeast Asian refugees, only giardia remained highly prevalent (present in 17.2%). No serious adverse events associated with albendazole use were reported. CONCLUSIONS: Presumptive albendazole therapy administered overseas before departure for the United States was associated with a decrease in the prevalence of intestinal nematodes among newly arrived African and Southeast Asian refugees.

De-identification of Medical Images with Retention of Scientific Research Value.

Online public repositories for sharing research data allow investigators to validate existing research or perform secondary research without the expense of collecting new data. Patient data made publicly available through such repositories may constitute a breach of personally identifiable information if not properly de-identified. Imaging data are especially at risk because some intricacies of the Digital Imaging and Communications in Medicine (DICOM) format are not widely understood by researchers. If imaging data still containing protected health information (PHI) were released through a public repository, a number of different parties could be held liable, including the original researcher who collected and submitted the data, the original researcher's institution, and the organization managing the repository. To minimize these risks through proper de-identification of image data, one must understand what PHI exists and where that PHI resides, and one must have the tools to remove PHI without compromising the scientific integrity of the data. DICOM public elements are defined by the DICOM Standard. Modality vendors use private elements to encode acquisition parameters that are not yet defined by the DICOM Standard, or the vendor may not have updated an existing software product after DICOM defined new public elements. Because private elements are not standardized, a common de-identification practice is to delete all private elements, removing scientifically useful data as well as PHI. Researchers and publishers of imaging data can use the tools and process described in this article to de-identify DICOM images according to current best practices.

Outbreak of Trichinella spiralis infections associated with a wild boar hunted at a game farm in Iowa.

BACKGROUND: Rates of trichinellosis have declined significantly in the United States due to improved pork production practices and public awareness of the danger of eating raw or undercooked pork. In April 2011, the Minnesota Department of Health received a report of presumptive trichinellosis in a 50-year-old man with a history of wild boar consumption. A public health investigation was initiated. METHODS: Medical record reviews and patient and family interviews were conducted. Trichinella species serology was performed on patient and family serum samples, and larval identification was attempted on clinical specimens and meat samples. RESULTS: The index patient harvested a wild boar from an Iowa game farm; he processed the meat after returning home and developed gastrointestinal symptoms 2 days later. Four days after his illness onset, all 5 family members consumed a roast from the boar. The index patient sought healthcare 4 times after illness onset before being definitively diagnosed with trichinellosis. Following initiation of albendazole therapy, the index patient developed atrial fibrillation. One additional family member who processed the raw meat was diagnosed with trichinellosis. Trichinella spiralis larvae were identified in wild boar meat samples. CONCLUSIONS: Trichinellosis has long been recognized as a potential hazard of consuming undercooked wild carnivore meat, and historically has been associated with consumption of pork from domestic swine, but may be unfamiliar to practicing clinicians in the United States. Education of hunters and the broader population on the potential for trichinellosis and the importance of proper handling and cooking meat from wild or free-range animals needs to be reinforced.

Raw milk consumption among patients with non-outbreak-related enteric infections, Minnesota, USA, 2001-2010.

Raw milk has frequently been identified as the source of foodborne illness outbreaks; however, the number of illnesses ascertained as part of documented outbreaks likely represents a small proportion of the actual number of illnesses associated with this food product. Analysis of routine surveillance data involving illnesses caused by enteric pathogens that were reportable in Minnesota during 2001-2010 revealed that 3.7% of patients with sporadic, domestically acquired enteric infections had reported raw milk consumption during their exposure period. Children were disproportionately affected, and 76% of those <5 years of age were served raw milk from their own or a relative's farm. Severe illness was noted, including hemolytic uremic syndrome among 21% of Escherichia coli O157-infected patients reporting raw milk consumption, and 1 death was reported. Raw milk consumers, potential consumers, and policy makers who might consider relaxing regulations regarding raw milk sales should be educated regarding illnesses associated with raw milk consumption.

Notes from the field: multistate outbreak of listeriosis linked to soft-ripened cheese--United States, 2013.

On June 27, 2013, the Minnesota Department of Health notified CDC of two patients with invasive Listeria monocytogenes infections (listeriosis) whose clinical isolates had indistinguishable pulsed-field gel electrophoresis (PFGE) patterns. A query of PulseNet, the national molecular subtyping network for foodborne disease surveillance, identified clinical and environmental isolates from other states. On June 28, CDC learned from the Food and Drug Administration's Coordinated Outbreak Response and Evaluation Network that environmental isolates indistinguishable from those of the two patients had been collected from Crave Brothers Farmstead Cheese during 2010-2011. An outbreak-related case was defined as isolation of L. monocytogenes with the outbreak PFGE pattern from an anatomic site that is normally sterile (e.g., blood or cerebrospinal fluid), or from a product of conception, with an isolate upload date during May 20-June 28, 2013. As of June 28, five cases were identified in four states (Minnesota, two cases; Illinois, Indiana, and Ohio, one each). Median age of the five patients was 58 years (range: 31-67 years). Four patients were female, including one who was pregnant at the time of infection. All five were hospitalized. One death and one miscarriage were reported.

Foodborne outbreak of group a streptococcus pharyngitis associated with a high school dance team banquet--Minnesota, 2012.

BACKGROUND: On 20 March 2012, the Minnesota Department of Health (MDH) was notified of multiple Facebook postings suggestive of a foodborne outbreak of Group A Streptococcus (GAS) pharyngitis occurring among attendees of a high school dance team banquet. An investigation was initiated. METHODS: Associations between GAS pharyngitis and specific food items were assessed among banquet attendees. Pharyngeal swabs were performed on attendees, household contacts, and food workers. Patient GAS isolates from clinical laboratories were also obtained. Pharyngeal and food specimens were cultured for GAS by the MDH Public Health Laboratory. Isolates were further characterized by pulsed-field gel electrophoresis (PFGE) and emm typing. RESULTS: Among 63 persons who consumed banquet food, 18 primary illnesses occurred, yielding an attack rate of 29%. Although no food or beverage items were significantly associated with illness, pasta consumption yielded the highest relative risk (risk ratio, 3.56; 95% confidence interval, .25-50.6). GAS colonies with indistinguishable PFGE patterns corresponding to emm subtype 1.0 were isolated from 5 patients and from leftover pasta. The pasta was prepared at home by a dance team member parent; both parent and child reported GAS pharyngitis episodes 3 weeks before the banquet. CONCLUSIONS: In this foodborne outbreak of GAS pharyngitis, pasta was implicated as the vehicle. Recognition of foodborne GAS illness is challenging because transmission is typically assumed to occur by respiratory spread; foodborne transmission should be considered when clusters of GAS pharyngitis patients are encountered. DNA-based typing can reveal potentially epidemiologically related isolates during GAS disease outbreaks and facilitate understanding and control of GAS disease.

Norovirus surveillance among callers to foodborne illness complaint hotline, Minnesota, USA, 2011-2013.

Norovirus is the leading cause of foodborne disease in the United States. During October 2011-January 2013, we conducted surveillance for norovirus infection in Minnesota among callers to a complaint-based foodborne illness hotline who reported diarrhea or vomiting. Of 241 complainants tested, 127 (52.7%) were positive for norovirus.

An outbreak of foodborne illness among attendees of a wedding reception in Wisconsin likely caused by Arcobacter butzleri.

BACKGROUND: Arcobacter species, primarily Arcobacter butzleri, are widely distributed among animals, infrequently isolated from humans, and previously not associated with outbreaks of foodborne illness. We report results of an investigation of a foodborne outbreak that occurred among attendees of a wedding reception in Wisconsin, United States, and was likely caused by A. butzleri. METHODS: We conducted a case-control study among reception attendees and a laboratory investigation to determine the extent, source, and cause of the outbreak. A clinical case was defined as diarrhea in an attendee with illness onset ≤7 days following the wedding reception. RESULTS: The case-control study included 47 of 51 case patients and 43 non-ill attendees. Results demonstrated that consuming broasted chicken was the only factor significantly associated with illness (odds ratio 10.51; 95% confidence interval 1.28, 476.4). Five patients provided stool specimens. Comprehensive culture and polymerase chain reaction (PCR) testing did not detect common bacterial or viral pathogens. Subsequent testing with PCRs targeting 16S/23S rDNA of the three most clinically relevant Arcobacter spp. and the rpoB/C gene of A. butzleri provided products confirmed as A. butzleri (four patients) and A. cryaerophilus (one patient) by sequence analysis. CONCLUSIONS: The results of this investigation suggest that A. butzleri should be considered an agent that can cause outbreaks of foodborne illness. Rigorous investigation of outbreaks of undetermined etiology is valuable for incrementally increasing our understanding of emerging agents causing foodborne illnesses.

Competencies for Public Health Professionals and Epidemiologists Who Detect and Investigate Enteric Disease Outbreaks.

OBJECTIVE: Food safety progress depends on the ability of public health agencies to detect and investigate foodborne disease outbreaks. The Integrated Food Safety Centers of Excellence identify and implement best practices and serve as resources for public health professionals who investigate enteric disease outbreaks. To target the needs of this diverse workforce, the Integrated Food Safety Centers of Excellence developed and assessed a professional tier framework and competencies. METHODS: We described the characteristics of public health professionals who investigate enteric disease outbreaks in the epidemiology role in a conceptual tiered framework. We mapped core competencies to each tier and disseminated a survey to practitioners at local (June 2019) and state (August 2018) US public health agencies to evaluate the importance and frequency of each competency. RESULTS: We developed 15 competencies on surveillance, outbreak detection, interview skills, investigation team, specimen testing, data analysis, hypothesis generation, study design, communication, enteric disease biology, control measures, legal authority, quality improvement, environmental health, and reporting to surveillance. The 286 survey respondents selected interview skills, surveillance, control measures, and hypothesis generation as the competencies most important to their work and most frequently performed. CONCLUSION: The Integrated Food Safety Centers of Excellence created the first published workforce framework and competencies for public health professionals who detect and investigate enteric disease outbreaks in the epidemiology role, in collaboration with local, state, and federal public health agencies and national organizations. These tools have been integrated into existing programs and can be used to develop training curricula, assess workforce competency over time, and identify priorities for continuing education and training.

Fatal Naegleria fowleri infection acquired in Minnesota: possible expanded range of a deadly thermophilic organism.

BACKGROUND: Primary amebic meningoencephalitis (PAM), caused by the free-living ameba Naegleria fowleri, has historically been associated with warm freshwater exposures at lower latitudes of the United States. In August 2010, a Minnesota resident, aged 7 years, died of rapidly progressive meningoencephalitis after local freshwater exposures, with no history of travel outside the state. PAM was suspected on the basis of amebae observed in cerebrospinal fluid. METHODS: Water and sediment samples were collected at locations where the patient swam during the 2 weeks preceding illness onset. Patient and environmental samples were tested for N. fowleri with use of culture and real-time polymerase chain reaction (PCR); isolates were genotyped. Historic local ambient temperature data were obtained. RESULTS: N. fowleri isolated from a specimen of the patient's brain and from water and sediment samples was confirmed using PCR as N. fowleri genotype 3. Surface water temperatures at the times of collection of the positive environmental samples ranged from 22.1°C to 24.5°C. August 2010 average air temperature near the exposure site was 25°C, 3.6°C above normal and the third warmest for August in the Minneapolis area since 1891. CONCLUSIONS: This first reported case of PAM acquired in Minnesota occurred 550 miles north of the previously reported northernmost case in the Americas. Clinicians should be aware that N. fowleri-associated PAM can occur in areas at much higher latitude than previously described. Local weather patterns and long-term climate change could impact the frequency of PAM.

Non-O157 Shiga toxin-producing Escherichia coli associated with venison.

We investigated an outbreak of non-O157 Shiga toxin-producing Escherichia coli at a high school in Minnesota, USA, in November 2010. Consuming undercooked venison and not washing hands after handling raw venison were associated with illness. E. coli O103:H2 and non-Shiga toxin-producing E. coli O145:NM were isolated from ill students and venison.