Interim Influenza Vaccine Effectiveness Against Laboratory-Confirmed Influenza - California, October 2023-January 2024.

Surveillance data can provide rapid, within-season influenza vaccine effectiveness (VE) estimates to guide public health recommendations. Mandatory reporting of influenza vaccine administration to California's immunization information registry began January 1, 2023, and mandatory reporting of all influenza laboratory test results, including negative results, was instituted in California on June 15, 2023. These data, collected by the California Department of Public Health during October 1, 2023-January 31, 2024, were used to calculate interim influenza VE against laboratory-confirmed influenza by comparing the odds of vaccination among case-patients (persons who received a positive influenza laboratory test result) and control patients (those who received a negative influenza laboratory test result). VE was calculated as 1 - adjusted odds ratio using mixed-effects logistic regression, with age, race, and ethnicity as fixed effects and specimen collection week and county as random effects. Overall, during October 1, 2023-January 31, 2024, estimated VE was 45% among persons aged ≥6 months, 56% among children and adolescents aged 6 months-17 years, 48% among adults aged 18-49 years, 36% among those aged 50-64 years, and 30% among those aged ≥65 years. Consistent with some previous influenza seasons, influenza vaccination provided moderate protection against laboratory-confirmed influenza among infants, children, adolescents, and adults. All persons aged ≥6 months without a contraindication to vaccination should receive annual influenza vaccination to reduce influenza illness, severe influenza, and strain on health care resources. Influenza vaccination remains the best way to prevent influenza.

Pulse wave velocity as a tool for cardiometabolic risk stratification in individuals with hypertensive disorders of pregnancy and increased BMI.

OBJECTIVE: Obesity is one of the most prevalent risk factors for hypertensive disorders in pregnancy (HDP); however, the role of pre-pregnancy cardiometabolic health in the development of these conditions is not well understood. Carotid-femoral pulse wave velocity (PWV) is an established measure of arterial stiffness and cardiovascular health and is validated in pregnancy. Our objective was to examine the obesity-related changes in PWV in pregnant individuals with and without HDP. METHODS: Eighty-seven individuals with singleton pregnancies were recruited and classified into two groups: cases (HDP: including pre-existing/chronic hypertension, gestational hypertension, preeclampsia, or intrauterine growth restriction (IUGR); n = 39) and normotensive controls (no HDP or IUGR; n = 48). Patient data, including body mass index (BMI), were collected from patient charts. Measurements of PWV were performed weekly until discharge or delivery (gestational age 24-37 weeks) and placental growth factor (PlGF) was measured at routine blood draws. RESULTS: PWV did not significantly change over gestation for either group. Cases had significantly increased PWV and decreased PlGF compared to normotensive controls. An elevated BMI was associated with higher PWV in both cases and controls. Once grouped based on BMI, PWV was only significantly higher in cases with a BMI ≥ 25 kg/m2 compared to controls, whereas PlGF was less affected by BMI. As PWV increased, PlGF decreased; however, after controlling for BMI, there was no relationship between PWV and PlGF. CONCLUSION: PWV measurements in early pregnancy may be useful as an additional independent marker to PlGF for risk-stratifying for HDP, especially in individuals with increased BMI.

Influenza and SARS-CoV-2 Co-infections in California, USA, September 2020-April 2021.

During September 1, 2020-April 30, 2021, the California Department of Public Health, Richmond, California, USA, received 255 positive influenza molecular test results that matched with severe acute respiratory syndrome coronavirus 2 molecular test results; 58 (23%) persons were co-infected. Influenza activity was minimal in California, and co-infections were sporadic.

Identifying Dyslexia: Link between Maze Learning and Dyslexia Susceptibility Gene, DCDC2, in Young Children.

Dyslexia is a common learning disability that affects processing of written language despite adequate intelligence and educational background. If learning disabilities remain untreated, a child may experience long-term social and emotional problems, which influence future success in all aspects of their life. Dyslexia has a 60% heritability rate, and genetic studies have identified multiple dyslexia susceptibility genes (DSGs). DSGs, such as DCDC2, are consistently associated with the risk and severity of reading disability (RD). Altered neural connectivity within temporoparietal regions of the brain is associated with specific variants of DSGs in individuals with RD. Genetically altering DSG expression in mice results in visual and auditory processing deficits as well as neurophysiological and neuroanatomical disruptions. Previously, we demonstrated that learning deficits associated with RD can be translated across species using virtual environments. In this 2-year longitudinal study, we demonstrate that performance on a virtual Hebb-Williams maze in pre-readers is able to predict future reading impairment, and the genetic risk strengthens, but is not dependent on, this relationship. Due to the lack of oral reporting and use of letters, this easy-to-use tool may be particularly valuable in a remote working environment as well as working with vulnerable populations such as English language learners.

Public Health Responses to COVID-19 Outbreaks on Cruise Ships - Worldwide, February-March 2020.

An estimated 30 million passengers are transported on 272 cruise ships worldwide each year* (1). Cruise ships bring diverse populations into proximity for many days, facilitating transmission of respiratory illness (2). SARS-CoV-2, the virus that causes coronavirus disease (COVID-19) was first identified in Wuhan, China, in December 2019 and has since spread worldwide to at least 187 countries and territories. Widespread COVID-19 transmission on cruise ships has been reported as well (3). Passengers on certain cruise ship voyages might be aged ≥65 years, which places them at greater risk for severe consequences of SARS-CoV-2 infection (4). During February-March 2020, COVID-19 outbreaks associated with three cruise ship voyages have caused more than 800 laboratory-confirmed cases among passengers and crew, including 10 deaths. Transmission occurred across multiple voyages of several ships. This report describes public health responses to COVID-19 outbreaks on these ships. COVID-19 on cruise ships poses a risk for rapid spread of disease, causing outbreaks in a vulnerable population, and aggressive efforts are required to contain spread. All persons should defer all cruise travel worldwide during the COVID-19 pandemic.

Insulin glargine/lixisenatide fixed-ratio combination (iGlarLixi) compared with premix or addition of meal-time insulin to basal insulin in people with type 2 diabetes: A systematic review and Bayesian network meta-analysis.

AIM: To assess the efficacy and safety of iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide, relative to premix insulin and other insulin options through network meta-analysis. METHODS: A systematic literature search identified randomized controlled trials (RCTs) comparing iGlarLixi, premix insulin or basal insulin (BI) in combination with meal-time insulin, in people inadequately controlled with BI. Eligible RCTs were compared using Bayesian network meta-analysis. RESULTS: Eight RCTs, some open-label, involving 3538 participants, with a study duration of 24-30 weeks were included. The estimated difference in HbA1c reduction with iGlarLixi compared with premix insulin was -0.50%-units (95% credible interval: -0.93 to -0.06) with 98% probability of iGlarLixi being superior to premix. Estimates for iGlarLixi versus meal-time + BI (thrice-daily meal-time insulin + basal) and basal-plus (once-daily meal-time insulin + BI) were -0.35 (-0.89 to +0.13)%-units and -0.68 (-1.18 to -0.17)%-units with probabilities of real difference of 94% and 99%, respectively. Safety outcome analysis suggested that iGlarLixi had lower rates of both confirmed and documented symptomatic hypoglycaemia compared with premix insulin (probabilities of 85% and 93%, respectively) and lower weight gain (probability 98%). CONCLUSIONS: iGlarLixi showed similar or improved efficacy and safety versus other intensification choices from BI included in this study, providing a clinically relevant treatment option in people with type 2 diabetes not well controlled on BI.

Characteristics Associated With Delivery of an Infant With Congenital Syphilis and Missed Opportunities for Prevention-California, 2012 to 2014.

BACKGROUND: Congenital syphilis (CS), the transmission of Treponema pallidum from mother to fetus during pregnancy, can cause adverse birth outcomes. In 2012 to 2014, the CS rate in California increased more than 200% from 6.6 to 20.3 cases per 100,000 live births. Our objectives were to identify characteristics associated with delivering an infant with CS and missed opportunities for prevention among syphilis-infected pregnant women in California. METHODS: We linked California Department of Public Health syphilis surveillance records from women aged 15 to 45 years-diagnosed from March 13, 2012, to December 31, 2014-to birth records. We compared characteristics among mothers who delivered an infant with CS (CS mothers) with mothers who delivered an infant without CS (non-CS mothers) by using χ or Fisher exact tests. To visualize gaps in prevention among syphilis-infected pregnant women, we constructed a CS prevention cascade, a figure that shows steps to prevent CS. RESULTS: During the selected period, 2498 women were diagnosed as having syphilis, and 427 (17%) linked to birth records; 164 (38%) were defined as CS mothers and 263 (62%) as non-CS mothers. Mothers with CS were more likely than non-CS mothers to have their first prenatal care visit in the third trimester. High proportions of mothers in both groups reported high-risk sexual behaviors, methamphetamine use, or incarceration (13%-29%). The CS prevention cascade showed decrements of 5% to 11% in prenatal care receipt, testing, and treatment steps; only 62% of potential CS births were prevented. CONCLUSIONS: Multifaceted efforts are needed to address gaps in the CS prevention cascade and reduce CS cases in California.

Risk Factors Associated With Infant Deaths From Pertussis: A Case-Control Study.

BACKGROUND: In the current era, most pertussis deaths occur in infants <3 months of age. Leukocytosis with lymphocytosis and pneumonia are commonly observed among cases of severe pertussis. METHODS: Risk factors associated with fatal pertussis were identified by comparing fatal pertussis cases among patients <120 days of age occurring from 1 January 1998 through 26 December 2014, matched by age (<120 days), county of residence, and closest symptom onset date with 1-4 nonfatal hospitalized cases. California Department of Public Health surveillance data were reviewed to identify cases; demographics, clinical presentation, and course were abstracted from corresponding birth and medical records. Logistic regression and classification tree analyses were used to examine the risk of fatal pertussis with respect to identified factors. RESULTS: Fifty-three fatal infant pertussis cases were identified and compared with 183 nonfatal hospitalized pertussis cases. Fatal cases had significantly lower birth weight, younger gestational age, younger age at time of cough onset, and higher peak white blood cell (WBC) and lymphocyte counts. Fatal cases were less likely to have received macrolide antibiotics and more likely to have received steroids or nitric oxide and to develop pulmonary hypertension, seizures, encephalitis, and pneumonia. Additionally, exchange transfusion, extracorporeal membrane oxygenation, and intubation occurred significantly more frequently among fatal cases. In multivariate analyses, peak WBC count, birth weight, intubation, and receipt of nitric oxide were predictors of death. CONCLUSIONS: Early recognition of pertussis in young infants and treatment with appropriate antibiotic therapy are important in preventing death. Several risk factors are strongly associated with fatal pertussis in infants.

Missed opportunities for tetanus postexposure prophylaxis--California, January 2008-March 2014.

Tetanus is an acute and sometimes fatal disease characterized by sudden muscle contractions. The number of tetanus cases reported annually in the United States has declined significantly since the 1930s and 1940s as a result of the introduction of tetanus vaccines. However, sporadic cases continue to occur in persons who are not up-to-date with tetanus toxoid-containing vaccinations (TT) and do not receive appropriate postexposure prophylaxis (PEP). To assess the extent of these cases, the California Department of Public Health reviewed all tetanus cases reported during January 2008-March 2014. A total of 21 tetanus patients were reported; five (24%) died. An average of three cases were reported each year during 2008-2013; the average annual incidence among patients aged ≥65 years (0.23 cases per 1 million population) was twice that among patients aged 21-64 years (0.10 cases per 1 million population). Of 16 patients with an acute injury before illness and diagnosis, nine (56%) sought medical care, and two (22%) of the nine received appropriate PEP. Although tetanus is rare, it is a life-threatening disease that is preventable. Health care providers should ensure that their patients are up-to-date with TT vaccination and provide appropriate postexposure prophylaxis for patients with wounds.

Notes from the field: measles - California, January 1-April 18, 2014.

Measles is a highly contagious, acute viral illness that can lead to severe complications and death. Even patients who experience uncomplicated acute measles have a small risk for developing a devastating neurologic illness, subacute sclerosing panencephalitis, years after their infection. Measles was documented as eliminated (defined as interruption of continuous transmission lasting ≥12 months) in the United States in 2000; however, importation of measles cases and limited local transmission continue to occur. During January 1-April 18, 2014, the California Department of Public Health received reports of 58 confirmed measles cases, the highest number reported for that period since 1995. Patients ranged in age from 5 months to 60 years. Three (5%) patients were aged <12 months, six (10%) were aged 1-4 years, 17 (29%) were aged 5-19 years, and 32 (55%) were aged ≥20 years. As of April 18, there had been 12 hospitalizations, and no deaths had been reported. During 2000-2013, the median annual number of measles cases reported in California was nine (range = four to 40).

Influenza-associated intensive-care unit admissions and deaths - California, September 29, 2013-January 18, 2014.

The California Department of Public Health (CDPH) conducts surveillance on severe influenza illness among California residents aged <65 years. Severe cases are defined as those resulting in admission to an intensive care unit (ICU) or death; reporting of ICU cases is voluntary, and reporting of fatal cases is mandatory. This report describes the epidemiologic, laboratory, and clinical characteristics of ICU and fatal influenza cases with symptom onset on or after September 29, 2013, and reported by January 18, 2014 of the 2013-14 influenza season. At the time of this report, local health jurisdictions (LHJs) in California had reported 94 deaths and 311 ICU admissions of patients with a positive influenza test result. The 405 reports of severe cases (i.e., fatal and ICU cases combined) were more than in any season since the 2009 pandemic caused by the influenza A (H1N1)pdm09 (pH1N1) virus. The pH1N1 virus is the predominant circulating influenza virus this season. Of 405 ICU and fatal influenza cases, 266 (66%) occurred among patients aged 41-64 years; 39 (10%) severe influenza illnesses occurred among children aged <18 years. Only six (21%) of 28 patients with fatal illness whose vaccination status was known had received 2013-14 seasonal influenza vaccine ≥2 weeks before symptom onset. Of 80 patients who died for whom sufficient information was available, 74 (93%) had underlying medical conditions known to increase the risk for severe influenza, as defined by the Advisory Committee on Immunization Practices (ACIP). Of 47 hospitalized patients with fatal illness and known symptom onset and antiviral therapy dates, only eight (17%) received neuraminidase inhibitors within 48 hours of symptom onset. This report supports previous recommendations that vaccination is important to prevent influenza virus infections that can result in ICU admission or death, particularly in high-risk populations, and that empiric antiviral treatment should be promptly initiated when influenza virus infection is suspected in hospitalized patients, despite negative results from rapid diagnostic tests.

Divergent gene expression patterns in alcohol and opioid use disorders lead to consistent alterations in functional networks within the dorsolateral prefrontal cortex.

Substance Use Disorders (SUDs) manifest as persistent drug-seeking behavior despite adverse consequences, with Alcohol Use Disorder (AUD) and Opioid Use Disorder (OUD) representing prevalent forms associated with significant mortality rates and economic burdens. The co-occurrence of AUD and OUD is common, necessitating a deeper comprehension of their intricate interactions. While the causal link between these disorders remains elusive, shared genetic factors are hypothesized. Leveraging public datasets, we employed genomic and transcriptomic analyses to explore conserved and distinct molecular pathways within the dorsolateral prefrontal cortex associated with AUD and OUD. Our findings unveil modest transcriptomic overlap at the gene level between the two disorders but substantial convergence on shared biological pathways. Notably, these pathways predominantly involve inflammatory processes, synaptic plasticity, and key intracellular signaling regulators. Integration of transcriptomic data with the latest genome-wide association studies (GWAS) for problematic alcohol use (PAU) and OUD not only corroborated our transcriptomic findings but also confirmed the limited shared heritability between the disorders. Overall, our study indicates that while alcohol and opioids induce diverse transcriptional alterations at the gene level, they converge on select biological pathways, offering promising avenues for novel therapeutic targets aimed at addressing both disorders simultaneously.

Divergent gene expression patterns in alcohol and opioid use disorders lead to consistent alterations in functional networks within the Dorsolateral Prefrontal Cortex.

Substance Use Disorders (SUDs) manifest as persistent drug-seeking behavior despite adverse consequences, with Alcohol Use Disorder (AUD) and Opioid Use Disorder (OUD) representing prevalent forms associated with significant mortality rates and economic burdens. The co-occurrence of AUD and OUD is common, necessitating a deeper comprehension of their intricate interactions. While the causal link between these disorders remains elusive, shared genetic factors are hypothesized. Leveraging public datasets, we employed genomic and transcriptomic analyses to explore conserved and distinct molecular pathways within the dorsolateral prefrontal cortex associated with AUD and OUD. Our findings unveil modest transcriptomic overlap at the gene level between the two disorders but substantial convergence on shared biological pathways. Notably, these pathways predominantly involve inflammatory processes, synaptic plasticity, and key intracellular signaling regulators. Integration of transcriptomic data with the latest genome-wide association studies (GWAS) for problematic alcohol use (PAU) and OUD not only corroborated our transcriptomic findings but also confirmed the limited shared heritability between the disorders. Overall, our study indicates that while alcohol and opioids induce diverse transcriptional alterations at the gene level, they converge on select biological pathways, offering promising avenues for novel therapeutic targets aimed at addressing both disorders simultaneously.

Leucine-rich repeat kinase 2 limits dopamine D1 receptor signaling in striatum and biases against heavy persistent alcohol drinking.

The transition from hedonic alcohol drinking to problematic drinking is a hallmark of alcohol use disorder that occurs only in a subset of drinkers. This transition requires long-lasting changes in the synaptic drive and the activity of striatal neurons expressing dopamine D1 receptor (D1R). The molecular mechanisms that generate vulnerability in some individuals to undergo the transition are less understood. Here, we report that the Parkinson's-related protein leucine-rich repeat kinase 2 (LRRK2) modulates striatal D1R function to affect the behavioral response to alcohol and the likelihood that mice transition to heavy, persistent alcohol drinking. Constitutive deletion of the Lrrk2 gene specifically from D1R-expressing neurons potentiated D1R signaling at the cellular and synaptic level and enhanced alcohol-related behaviors and drinking. Mice with cell-specific deletion of Lrrk2 were more prone to heavy alcohol drinking, and consumption was insensitive to punishment. These findings identify a potential novel role for LRRK2 function in the striatum in promoting resilience against heavy and persistent alcohol drinking.

Preexisting risk-avoidance and enhanced alcohol relief are driven by imbalance of the striatal dopamine receptors in mice.

Alcohol use disorder (AUD) is frequently comorbid with anxiety disorders, yet whether alcohol abuse precedes or follows the expression of anxiety remains unclear. Rodents offer control over the first drink, an advantage when testing the causal link between anxiety and AUD. Here, we utilized a risk-avoidance task to determine anxiety-like behaviors before and after alcohol exposure. We found that alcohol's anxiolytic efficacy varied among inbred mice and mice with high risk-avoidance showed heightened alcohol relief. While dopamine D1 receptors in the striatum are required for alcohol's relief, their levels alone were not correlated with relief. Rather, the ratio between striatal D1 and D2 receptors was a determinant factor for risk-avoidance and alcohol relief. We show that increasing striatal D1 to D2 receptor ratio was sufficient to promote risk-avoidance and enhance alcohol relief, even at initial exposure. Mice with high D1 to D2 receptor ratio were more prone to continue drinking despite adverse effects, a hallmark of AUD. These findings suggest that an anxiety phenotype may be a predisposing factor for AUD.

Title evaluation of FluSight influenza forecasting in the 2021-22 and 2022-23 seasons with a new target laboratory-confirmed influenza hospitalizations.

Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. For the 2021-22 and 2022-23 influenza seasons, 26 forecasting teams provided national and jurisdiction-specific probabilistic predictions of weekly confirmed influenza hospital admissions for one-to-four weeks ahead. Forecast skill is evaluated using the Weighted Interval Score (WIS), relative WIS, and coverage. Six out of 23 models outperform the baseline model across forecast weeks and locations in 2021-22 and 12 out of 18 models in 2022-23. Averaging across all forecast targets, the FluSight ensemble is the 2nd most accurate model measured by WIS in 2021-22 and the 5th most accurate in the 2022-23 season. Forecast skill and 95% coverage for the FluSight ensemble and most component models degrade over longer forecast horizons. In this work we demonstrate that while the FluSight ensemble was a robust predictor, even ensembles face challenges during periods of rapid change.

Neisseria gonorrhoeae outbreak: unintended consequences of electronic medical records and using an out-of-state laboratory-California, July 2009-February 2010.

Twenty of 37 gonorrhea cases identified during an outbreak were diagnosed at one health care organization that used an out-of-state laboratory. The results were transmitted into electronic medical records without provider notification. Delays in treatment and reporting were identified. Systems should be implemented to ensure provider notification of electronic laboratory results.

Receipt of COVID-19 and seasonal influenza vaccines in California (USA) during the 2021-2022 influenza season.

BACKGROUND: Despite lower circulation of influenza virus throughout 2020-2022 during the COVID-19 pandemic, seasonal influenza vaccination has remained a primary tool to reduce influenza-associated illness and death. The relationship between the decision to receive a COVID-19 vaccine and/or an influenza vaccine is not well understood. METHODS: We assessed predictors of receipt of 2021-2022 influenza vaccine in a secondary analysis of data from a case-control study enrolling individuals who received SARS-CoV-2 testing. We used mixed effects logistic regression to estimate factors associated with receipt of seasonal influenza vaccine. We also constructed multinomial adjusted marginal probability models of being vaccinated for COVID-19 only, seasonal influenza only, or both as compared with receipt of neither vaccination. RESULTS: Among 1261 eligible participants recruited between 22 October 2021-22 June 2022, 43% (545) were vaccinated with both seasonal influenza vaccine and >1 dose of a COVID-19 vaccine, 34% (426) received >1 dose of a COVID-19 vaccine only, 4% (49) received seasonal influenza vaccine only, and 19% (241) received neither vaccine. Receipt of >1 COVID-19 vaccine dose was associated with seasonal influenza vaccination (adjusted odds ratio [aOR]: 3.72; 95% confidence interval [CI]: 2.15-6.43); this association was stronger among participants receiving >1 COVID-19 booster dose (aOR = 16.50 [10.10-26.97]). Compared with participants testing negative for SARS- CoV-2 infection, participants testing positive had lower odds of receipt of 2021-2022 seasonal influenza vaccine (aOR = 0.64 [0.50-0.82]). CONCLUSIONS: Recipients of a COVID-19 vaccine were more likely to receive seasonal influenza vaccine during the 2021-2022 season. Factors associated with individuals' likelihood of receiving COVID-19 and seasonal influenza vaccines will be important to account for in future studies of vaccine effectiveness against both conditions. Participants who tested positive for SARS-CoV-2 in our sample were less likely to have received seasonal influenza vaccine, suggesting an opportunity to offer influenza vaccination before or after a COVID-19 diagnosis.