Prenatal THC exposure induces long-term, sex-dependent cognitive dysfunction associated with lipidomic and neuronal pathology in the prefrontal cortex-hippocampal network.

With increasing maternal cannabis use, there is a need to investigate the lasting impact of prenatal exposure to Δ9-tetrahydrocannabinol (THC), the main psychotropic compound in cannabis, on cognitive/memory function. The endocannabinoid system (ECS), which relies on polyunsaturated fatty acids (PUFAs) to function, plays a crucial role in regulating prefrontal cortical (PFC) and hippocampal network-dependent behaviors essential for cognition and memory. Using a rodent model of prenatal cannabis exposure (PCE), we report that male and female offspring display long-term deficits in various cognitive domains. However, these phenotypes were associated with highly divergent, sex-dependent mechanisms. Electrophysiological recordings revealed hyperactive PFC pyramidal neuron activity in both males and females, but hypoactivity in the ventral hippocampus (vHIPP) in males, and hyperactivity in females. Further, cortical oscillatory activity states of theta, alpha, delta, beta, and gamma bandwidths were strongly sex divergent. Moreover, protein expression analyses at postnatal day (PD)21 and PD120 revealed primarily PD120 disturbances in dopamine D1R/D2 receptors, NMDA receptor 2B, synaptophysin, gephyrin, GAD67, and PPARα selectively in the PFC and vHIPP, in both regions in males, but only the vHIPP in females. Lastly, using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS), we identified region-, age-, and sex-specific deficiencies in specific neural PUFAs, namely docosahexaenoic acid (DHA) and arachidonic acid (ARA), and related metabolites, in the PFC and hippocampus (ventral/dorsal subiculum, and CA1 regions). This study highlights several novel, long-term and sex-specific consequences of PCE on PFC-hippocampal circuit dysfunction and the potential role of specific PUFA signaling abnormalities underlying these pathological outcomes.

Detecting Mpox Cases Through Wastewater Surveillance - United States, August 2022-May 2023.

In October 2022, CDC's National Wastewater Surveillance System began routine testing of U.S. wastewater for Monkeypox virus. Wastewater surveillance sensitivity, positive predictive value (PPV), and negative predictive value (NPV) for Monkeypox virus were evaluated by comparing wastewater detections (Monkeypox virus detected versus not detected) to numbers of persons with mpox in a county who were shedding virus. Case ascertainment was assumed to be complete, and persons with mpox were assumed to shed virus for 25 days after symptom onset. A total of 281 cases and 3,492 wastewater samples from 89 sites in 26 counties were included in the analysis. Wastewater surveillance in a single week, from samples representing thousands to millions of persons, had a sensitivity of 32% for detecting one or more persons shedding Monkeypox virus, 49% for detecting five or more persons shedding virus, and 77% for detecting 15 or more persons shedding virus. Weekly PPV and NPV for detecting persons shedding Monkeypox virus in a county were 62% and 80%, respectively. An absence of detections in counties with wastewater surveillance signified a high probability that a large number of cases were not present. Results can help to guide the public health response to Monkeypox virus wastewater detections. A single, isolated detection likely warrants a limited public health response. An absence of detections, in combination with no reported cases, can give public health officials greater confidence that no cases are present. Wastewater surveillance can serve as a useful complement to case surveillance for guiding the public health response to an mpox outbreak.

Longitudinal Analysis of Electronic Health Information to Identify Possible COVID-19 Sequelae.

Ongoing symptoms might follow acute COVID-19. Using electronic health information, we compared pre‒ and post‒COVID-19 diagnostic codes to identify symptoms that had higher encounter incidence in the post‒COVID-19 period as sequelae. This method can be used for hypothesis generation and ongoing monitoring of sequelae of COVID-19 and future emerging diseases.

Power Law for Estimating Underdetection of Foodborne Disease Outbreaks, United States.

We fit a power law distribution to US foodborne disease outbreaks to assess underdetection and underreporting. We predicted that 788 fewer than expected small outbreaks were identified annually during 1998-2017 and 365 fewer during 2018-2019, after whole-genome sequencing was implemented. Power law can help assess effectiveness of public health interventions.

Cholera Vaccine: Recommendations of the Advisory Committee on Immunization Practices, 2022.

THIS REPORT SUMMARIZES ALL RECOMMENDATIONS FROM CDC'S ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) FOR THE USE OF LYOPHILIZED CVD 103-HGR VACCINE (CVD 103-HGR) (VAXCHORA, EMERGENT BIOSOLUTIONS, GAITHERSBURG, MD) IN THE UNITED STATES. THE LIVE ATTENUATED ORAL CHOLERA VACCINE IS DERIVED FROM: Vibrio cholerae O1 and is administered in a single dose. Cholera is a toxin-mediated bacterial gastrointestinal illness caused by toxigenic V. cholerae serogroup O1 or, uncommonly, O139. Up to 10% of infections manifest as severe cholera (i.e., cholera gravis), profuse watery diarrhea that can cause severe dehydration and death within hours. Fluid replacement therapy can reduce the fatality rate to <1%. Risk factors for cholera gravis include high dose exposure, blood group O, increased gastric pH (e.g., from antacid therapy), and partial gastrectomy. Cholera is rare in the United States, but cases occur among travelers to countries where cholera is endemic or epidemic and associated with unsafe water and inadequate sanitation. Travelers might be at increased risk for poor outcomes from cholera if they cannot readily access medical services or if they have a medical condition that would be worsened by dehydration, such as cardiovascular or kidney disease. This report describes previously published ACIP recommendations about use of CVD 103-HgR for adults aged 18-64 years and introduces a new recommendation for use in children and adolescents aged 2-17 years. ACIP recommends CVD 103-HgR, the only cholera vaccine licensed for use in the United States, for prevention of cholera among travelers aged 2-64 years to an area with active cholera transmission. Health care providers can use these guidelines to develop the pretravel consultation for persons traveling to areas with active cholera transmission.

Identification and description of patients with multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection using the Premier Healthcare Database.

Multisystem inflammatory syndrome in adults (MIS-A) is a hyperinflammatory illness related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The characteristics of patients with this syndrome and the frequency with which it occurs among patients hospitalised after SARS-CoV-2 infection are unclear. Using the Centers for Disease Control and Prevention case definition for MIS-A, we created ICD-10-CM code and laboratory criteria to identify potential MIS-A patients in the Premier Healthcare Database Special COVID-19 Release, a database containing patient-level information on hospital discharges across the United States. Modified MIS-A criteria were applied to hospitalisations with discharge from March to December 2020. The proportion of hospitalisations meeting electronic health record criteria for MIS-A and descriptive statistics for patients in the potential MIS-A cohort were calculated. Of 34 515 SARS-CoV-2-related hospitalisations with complete clinical and laboratory data, 53 met modified criteria for MIS-A (0.15%). The median age was 62 years (IQR 52-74). Most patients met the severe cardiac illness criterion through either myocarditis (66.0%) or new-onset heart failure (35.8%). A total of 79.2% of patients required ICU admission, while 43.4% of patients in the cohort died. MIS-A appears to be a rare but severe outcome of SARS-CoV-2 infection. Additional studies are needed to investigate how this syndrome differs from severe coronavirus disease 2019 (COVID-19) in adults.

Inadequate Refrigeration of Some Commercial Foods Is a Continued Cause of Foodborne Botulism in the United States, 1994-2021.

Foodborne botulism is a rapidly progressive potentially fatal paralyzing illness caused by the consumption of botulinum neurotoxin, which is most commonly produced by Clostridium botulinum. Refrigeration is the primary barrier to botulinum neurotoxin production in many processed foods. C. botulinum toxin production has occurred and caused botulism in the United States when foods that were not processed to destroy spores of C. botulinum were stored in an anaerobic environment and not properly refrigerated. We identified 37 cases, including 4 deaths, that occurred during 1994-2021 in the United States from 13 events associated with inadequate refrigeration of commercially produced products. In 11 events, the patient stored the product unrefrigerated at home; in 2 events, a product was kept unrefrigerated at the store before the consumer purchased it. In three events, refrigeration instructions were inadequate or not easily accessible (one label printed on outer but not inner packaging, one label not clearly visible, and one label was not in English). The number of people affected per event ranged from 1 to 16. Using enhanced cost estimates for foodborne botulism cases from a published economic model, these events were estimated to cost >$79M. Potential solutions to this recurring problem include the addition of a secondary barrier, such as an acidifier, to prevent botulinum toxin production, and better labeling to convey risks of refrigerated foods that have not been processed to destroy spores of C. botulinum and to decrease the occurrence of improper storage and handling.

Clinical and Laboratory Findings in Patients With Potential Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Reinfection, May-July 2020.

BACKGROUND: We investigated patients with potential severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection in the United States during May-July 2020. METHODS: We conducted case finding for patients with potential SARS-CoV-2 reinfection through the Emerging Infections Network. Cases reported were screened for laboratory and clinical findings of potential reinfection followed by requests for medical records and laboratory specimens. Available medical records were abstracted to characterize patient demographics, comorbidities, clinical course, and laboratory test results. Submitted specimens underwent further testing, including reverse transcription polymerase chain reaction (RT-PCR), viral culture, whole genome sequencing, subgenomic RNA PCR, and testing for anti-SARS-CoV-2 total antibody. RESULTS: Among 73 potential reinfection patients with available records, 30 patients had recurrent coronavirus disease 2019 (COVID-19) symptoms explained by alternative diagnoses with concurrent SARS-CoV-2 positive RT-PCR, 24 patients remained asymptomatic after recovery but had recurrent or persistent RT-PCR, and 19 patients had recurrent COVID-19 symptoms with concurrent SARS-CoV-2 positive RT-PCR but no alternative diagnoses. These 19 patients had symptom recurrence a median of 57 days after initial symptom onset (interquartile range: 47-76). Six of these patients had paired specimens available for further testing, but none had laboratory findings confirming reinfections. Testing of an additional 3 patients with recurrent symptoms and alternative diagnoses also did not confirm reinfection. CONCLUSIONS: We did not confirm SARS-CoV-2 reinfection within 90 days of the initial infection based on the clinical and laboratory characteristics of cases in this investigation. Our findings support current Centers for Disease Control and Prevention (CDC) guidance around quarantine and testing for patients who have recovered from COVID-19.

Predictors at Admission of Mechanical Ventilation and Death in an Observational Cohort of Adults Hospitalized With Coronavirus Disease 2019.

BACKGROUND: Coronavirus disease (COVID-19) can cause severe illness and death. Predictors of poor outcome collected on hospital admission may inform clinical and public health decisions. METHODS: We conducted a retrospective observational cohort investigation of 297 adults admitted to 8 academic and community hospitals in Georgia, United States, during March 2020. Using standardized medical record abstraction, we collected data on predictors including admission demographics, underlying medical conditions, outpatient antihypertensive medications, recorded symptoms, vital signs, radiographic findings, and laboratory values. We used random forest models to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for predictors of invasive mechanical ventilation (IMV) and death. RESULTS: Compared with age <45 years, ages 65-74 years and ≥75 years were predictors of IMV (aORs, 3.12 [95% CI, 1.47-6.60] and 2.79 [95% CI, 1.23-6.33], respectively) and the strongest predictors for death (aORs, 12.92 [95% CI, 3.26-51.25] and 18.06 [95% CI, 4.43-73.63], respectively). Comorbidities associated with death (aORs, 2.4-3.8; P < .05) included end-stage renal disease, coronary artery disease, and neurologic disorders, but not pulmonary disease, immunocompromise, or hypertension. Prehospital use vs nonuse of angiotensin receptor blockers (aOR, 2.02 [95% CI, 1.03-3.96]) and dihydropyridine calcium channel blockers (aOR, 1.91 [95% CI, 1.03-3.55]) were associated with death. CONCLUSIONS: After adjustment for patient and clinical characteristics, older age was the strongest predictor of death, exceeding comorbidities, abnormal vital signs, and laboratory test abnormalities. That coronary artery disease, but not chronic lung disease, was associated with death among hospitalized patients warrants further investigation, as do associations between certain antihypertensive medications and death.

Characteristics and Risk Factors of Hospitalized and Nonhospitalized COVID-19 Patients, Atlanta, Georgia, USA, March-April 2020.

We compared the characteristics of hospitalized and nonhospitalized patients who had coronavirus disease in Atlanta, Georgia, USA. We found that risk for hospitalization increased with a patient's age and number of concurrent conditions. We also found a potential association between hospitalization and high hemoglobin A1c levels in persons with diabetes.

Underlying Medical Conditions and Severe Illness Among 540,667 Adults Hospitalized With COVID-19, March 2020-March 2021.

INTRODUCTION: Severe COVID-19 illness in adults has been linked to underlying medical conditions. This study identified frequent underlying conditions and their attributable risk of severe COVID-19 illness. METHODS: We used data from more than 800 US hospitals in the Premier Healthcare Database Special COVID-19 Release (PHD-SR) to describe hospitalized patients aged 18 years or older with COVID-19 from March 2020 through March 2021. We used multivariable generalized linear models to estimate adjusted risk of intensive care unit admission, invasive mechanical ventilation, and death associated with frequent conditions and total number of conditions. RESULTS: Among 4,899,447 hospitalized adults in PHD-SR, 540,667 (11.0%) were patients with COVID-19, of whom 94.9% had at least 1 underlying medical condition. Essential hypertension (50.4%), disorders of lipid metabolism (49.4%), and obesity (33.0%) were the most common. The strongest risk factors for death were obesity (adjusted risk ratio [aRR] = 1.30; 95% CI, 1.27-1.33), anxiety and fear-related disorders (aRR = 1.28; 95% CI, 1.25-1.31), and diabetes with complication (aRR = 1.26; 95% CI, 1.24-1.28), as well as the total number of conditions, with aRRs of death ranging from 1.53 (95% CI, 1.41-1.67) for patients with 1 condition to 3.82 (95% CI, 3.45-4.23) for patients with more than 10 conditions (compared with patients with no conditions). CONCLUSION: Certain underlying conditions and the number of conditions were associated with severe COVID-19 illness. Hypertension and disorders of lipid metabolism were the most frequent, whereas obesity, diabetes with complication, and anxiety disorders were the strongest risk factors for severe COVID-19 illness. Careful evaluation and management of underlying conditions among patients with COVID-19 can help stratify risk for severe illness.

Characteristics and Clinical Outcomes of Adult Patients Hospitalized with COVID-19 - Georgia, March 2020.

SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in the United States during January 2020 (1). Since then, >980,000 cases have been reported in the United States, including >55,000 associated deaths as of April 28, 2020 (2). Detailed data on demographic characteristics, underlying medical conditions, and clinical outcomes for persons hospitalized with COVID-19 are needed to inform prevention strategies and community-specific intervention messages. For this report, CDC, the Georgia Department of Public Health, and eight Georgia hospitals (seven in metropolitan Atlanta and one in southern Georgia) summarized medical record-abstracted data for hospitalized adult patients with laboratory-confirmed* COVID-19 who were admitted during March 2020. Among 305 hospitalized patients with COVID-19, 61.6% were aged <65 years, 50.5% were female, and 83.2% with known race/ethnicity were non-Hispanic black (black). Over a quarter of patients (26.2%) did not have conditions thought to put them at higher risk for severe disease, including being aged ≥65 years. The proportion of hospitalized patients who were black was higher than expected based on overall hospital admissions. In an adjusted time-to-event analysis, black patients were not more likely than were nonblack patients to receive invasive mechanical ventilation† (IMV) or to die during hospitalization (hazard ratio [HR] = 0.63; 95% confidence interval [CI] = 0.35-1.13). Given the overrepresentation of black patients within this hospitalized cohort, it is important for public health officials to ensure that prevention activities prioritize communities and racial/ethnic groups most affected by COVID-19. Clinicians and public officials should be aware that all adults, regardless of underlying conditions or age, are at risk for serious illness from COVID-19.

Responses to hypothetical health scenarios overestimate healthcare utilization for common infectious syndromes: a cross-sectional survey, South Africa, 2012.

BACKGROUND: Asking people how they would seek healthcare in a hypothetical situation can be an efficient way to estimate healthcare utilization, but it is unclear how intended healthcare use corresponds to actual healthcare use. METHODS: We performed a cross-sectional survey between August and September 2012 among households in Soweto and Klerksdorp, South Africa, to compare healthcare seeking behaviors intended for hypothetical common infectious syndromes (pneumonia, influenza-like illness [ILI], chronic respiratory illness, meningitis in persons of any age, and diarrhea in a child < 5 years old) with the self-reported healthcare use among patients with those syndromes. RESULTS: For most syndromes, the proportion of respondents who intended to seek healthcare at any facility or provider (99-100%) in a hypothetical scenario exceeded the proportion that did seek care (78-100%). More people intended to seek care for a child < 5 years old with diarrhea (186/188 [99%]) than actually did seek care (32/41 [78%], P < 0.01). Although most people faced with hypothetical scenarios intended to seek care with licensed medical providers such as hospitals and clinics (97-100%), patients who were ill reported lower use of licensed medical providers (55-95%). CONCLUSIONS: People overestimated their intended healthcare utilization, especially with licensed medical providers, compared with reported healthcare utilization among patients with these illnesses. Studies that measure intended healthcare utilization should consider that actual use of healthcare facilities may be lower than intended use.

Association between health literacy and self-care behaviors among patients with chronic kidney disease.

BACKGROUND: We explored the association between health literacy and self-care behaviors among low-income patients with chronic kidney disease (CKD). METHODS: We used baseline data from the Kidney Awareness Registry and Education trial (n = 137 patients with CKD) and multivariable logistic regressions to cross-sectionally examine the association between health literacy, defined by a validated questionnaire, and healthy behaviors. RESULTS: Study participants had a mean age of 55 years, were racially diverse (6% White, 36% Hispanic, 43% Black, 15% Asian) and 26% had low health literacy. Over one-third (38%) had hypertension, 51% had diabetes, and 67% had CKD stage 3 or 4. Compared to individuals with adequate health literacy, those with low health literacy had non-statistically significant higher tobacco use (adjusted odds ratio [aOR] = 2.33; 95% CI 0.90-6.06) and lower consumption of sugary beverages (aOR = 0.50; 0.20-1.23) and statistically significant decreased fast food intake (aOR = 0.38; 0.16-0.93). Health literacy was not associated with differences in medication adherence (0.84; 0.38-1.89) or physical activity (aOR = 2.39; 0.54-10.53). CONCLUSIONS: Health literacy was not uniformly associated with all self-care behaviors important for CKD management. A more nuanced understanding of the association of health literacy and self-care may be necessary to promote participation in behaviors known to slow CKD progression.

Recommendations of the Advisory Committee on Immunization Practices for Use of Cholera Vaccine.

Cholera, caused by infection with toxigenic Vibrio cholerae bacteria of serogroup O1 (>99% of global cases) or O139, is characterized by watery diarrhea that can be severe and rapidly fatal without prompt rehydration. Cholera is endemic in approximately 60 countries and causes epidemics as well. Globally, cholera results in an estimated 2.9 million cases of disease and 95,000 deaths annually (1). Cholera is rare in the United States, and most U.S. cases occur among travelers to countries where cholera is endemic or epidemic. Forty-two U.S. cases were reported in 2011 after a cholera epidemic began in Haiti (2); however, <25 cases per year have been reported in the United States since 2012.

Systematic Selection of Reference Genes for the Normalization of Circulating RNA Transcripts in Pregnant Women Based on RNA-Seq Data.

RNA transcripts circulating in peripheral blood represent an important source of non-invasive biomarkers. To accurately quantify the levels of circulating transcripts, one needs to normalize the data with internal control reference genes, which are detected at relatively constant levels across blood samples. A few reference gene candidates have to be selected from transcriptome data before the validation of their stable expression by reverse-transcription quantitative polymerase chain reaction. However, there is a lack of transcriptome, let alone whole-transcriptome, data from maternal blood. To overcome this shortfall, we performed RNA-sequencing on blood samples from women presenting with preterm labor. The coefficient of variation (CV) of expression levels was calculated. Of 11,215 exons detected in the maternal blood whole-transcriptome, a panel of 395 genes, including PPP1R15B, EXOC8, ACTB, and TPT1, were identified to comprise exons with considerably less variable expression level (CV, 7.75-17.7%) than any GAPDH exon (minimum CV, 27.3%). Upon validation, the selected genes from this panel remained more stably expressed than GAPDH in maternal blood. This panel is over-represented with genes involved with the actin cytoskeleton, macromolecular complex, and integrin signaling. This groundwork provides a starting point for systematically selecting reference gene candidates for normalizing the levels of circulating RNA transcripts in maternal blood.

Assessment of the Incubation Period for Invasive Listeriosis.

We characterized incubation periods among outbreak-associated listeriosis cases, using a simulation model to account for patients with multiple exposure dates. The median was 11 days; 90% of cases occurred within 28 days, and incubation periods varied by clinical manifestation.

Use of Postexposure Prophylaxis After Occupational Exposure to Zaire ebolavirus.

From September 2014 to April 2015, 6 persons who had occupational exposures to Zaire ebolavirus in West Africa received investigational agent rVSV-ZEBOV or TKM-100802 for postexposure prophylaxis and were monitored in the United States. All patients experienced self-limited symptoms after postexposure prophylaxis; none developed Ebola virus disease.

Estimating the United States demand for influenza antivirals and the effect on severe influenza disease during a potential pandemic.

Following the detection of a novel influenza strain A(H7N9), we modeled the use of antiviral treatment in the United States to mitigate severe disease across a range of hypothetical pandemic scenarios. Our outcomes were total demand for antiviral (neuraminidase inhibitor) treatment and the number of hospitalizations and deaths averted. The model included estimates of attack rate, healthcare-seeking behavior, prescription rates, adherence, disease severity, and the potential effect of antivirals on the risks of hospitalization and death. Based on these inputs, the total antiviral regimens estimated to be available in the United States (as of April 2013) were sufficient to meet treatment needs for the scenarios considered. However, distribution logistics were not examined and should be addressed in future work. Treatment was estimated to avert many severe outcomes (5200-248,000 deaths; 4800-504,000 hospitalizations); however, large numbers remained (25,000-425,000 deaths; 580,000-3,700,000 hospitalizations), suggesting that the impact of combinations of interventions should be examined.

Supportive Care of the First 2 Ebola Virus Disease Patients at the Monrovia Medical Unit.

We describe the first 2 patients admitted to the Monrovia Medical Unit, a facility established to treat Liberian and international response workers with suspected or known Ebola virus disease (EVD). Their recoveries illustrate the value of local point-of-care diagnostics, parenteral therapies, and electrolyte replacement in EVD supportive care.