Suspected Legionella Transmission from a Single Donor to Two Lung Transplant Recipients - Pennsylvania, May 2022.

In July 2022, the Pennsylvania Department of Health received two reports of laboratory-confirmed Legionnaires disease in patients who had recently received lung transplants from the same donor at a single Pennsylvania hospital. The donor's cause of death was freshwater drowning in a river, raising suspicion of potential donor-derived transmission, because Legionella bacteria naturally live in fresh water. Further investigation of patients receiving other organs from the same donor did not identify additional legionellosis cases. Health care-associated infection caused by water exposure at the hospital was also evaluated as a potential source of infection and was found to be unlikely. Hospital water quality parameter measurements collected during May-June 2022 were within expected ranges and no water disruptions were noted, although no testing for Legionella was performed during this period. Notifiable disease data did not identify any other Legionnaires disease cases with exposure to this hospital within the 6 months before or after the two cases. Although laboratory testing did not confirm the source of recipient infections, available data suggest that the most likely source was the donor lungs. This cluster highlights the need for increased clinical awareness of possible infection with Legionella in recipients of lungs from donors who drowned in fresh water before organ recovery.

Suspected Legionella Transmission from a Single Donor to Two Lung Transplant Recipients - Pennsylvania, May 2022.

In July 2022, the Pennsylvania Department of Health received two reports of laboratory-confirmed Legionnaires disease in patients who had recently received lung transplants from the same donor at a single Pennsylvania hospital. The donor's cause of death was freshwater drowning in a river, raising suspicion of potential donor-derived transmission, because Legionella bacteria naturally live in fresh water. Further investigation of patients receiving other organs from the same donor did not identify additional legionellosis cases. Health care-associated infection caused by water exposure at the hospital was also evaluated as a potential source of infection and was found to be unlikely. Hospital water quality parameter measurements collected during May-June 2022 were within expected ranges and no water disruptions were noted, although no testing for Legionella was performed during this period. Notifiable disease data did not identify any other Legionnaires disease cases with exposure to this hospital within the 6 months before or after the two cases. Although laboratory testing did not confirm the source of recipient infections, available data suggest that the most likely source was the donor lungs. This cluster highlights the need for increased clinical awareness of possible infection with Legionella in recipients of lungs from donors who drowned in fresh water before organ recovery.

A Phylogeographic Description of Histoplasma capsulatum in the United States.

Histoplasmosis is one of the most under-diagnosed and under-reported endemic mycoses in the United States. Histoplasma capsulatum is the causative agent of this disease. To date, molecular epidemiologic studies detailing the phylogeographic structure of H. capsulatum in the United States have been limited. We conducted genomic sequencing using isolates from histoplasmosis cases reported in the United States. We identified North American Clade 2 (NAm2) as the most prevalent clade in the country. Despite high intra-clade diversity, isolates from Minnesota and Michigan cases were predominately clustered by state. Future work incorporating environmental sampling and veterinary surveillance may further elucidate the molecular epidemiology of H. capsulatum in the United States and how genomic sequencing can be applied to the surveillance and outbreak investigation of histoplasmosis.

Peer-Led Focus Groups Identify Barriers to Healthy Lifestyle in African American Adolescents from Baltimore City.

Objectives: Black youth are disproportionately affected by the US obesity epidemic. Early-age obesity often continues into adulthood and is associated with a higher risk of diabetes, cardiovascular disease, and premature death. Few studies have incorporated community-based participatory research (CBPR) facilitated by youth to provide frank discussions among teens living in inner cities about challenges and facilitators in maintaining a healthy weight and to design teen-identified interventions. Design: Black youth (n=10) were recruited from a Baltimore City high school during the 2019 to 2020 academic year and were trained by seasoned investigators and mentored by graduate and undergraduate students on qualitative methods using CBPR. These youth then implemented focus groups with their peers aged 15 to 18 years (10 focus groups of 10 teens each). Topics included healthy lifestyle knowledge, behaviors, attitudes, and suggested interventions. Content analyses were conducted using dual-rater techniques. Results: Focus group themes yielded strengths and challenges of weight maintenance for Black youth at various levels, including in their personal lives, families, school, and community. Themes also suggested several technology-based possibilities using social media to reach Black youth about healthy living practices. Conclusions: Engagement of Black youth in CBPR projects can yield valuable data to design more culturally responsive and developmentally appropriate interventions. Youth are competent collectors of information to identify needed changes in their schools/communities and about the use of technology/social media to facilitate improved health practices among their peers and should be involved early in the process of developing targeted obesity prevention interventions and/or programs.

Yersinia enterocolitica Outbreak Associated with Pasteurized Milk.

In July 2019, we investigated a cluster of Yersinia enterocolitica cases affecting a youth summer camp and nearby community in northeastern Pennsylvania. After initial telephone interviews with camp owners and community members, we identified pasteurized milk from a small dairy conducting on-site pasteurization, Dairy A, as a shared exposure. We conducted site visits at the camp and Dairy A where we collected milk and other samples. Samples were cultured for Y. enterocolitica. Clinical and nonclinical isolates were compared using molecular subtyping. We performed case finding, conducted telephone interviews for community cases, and conducted a cohort study among adult camp staff by administering an online questionnaire. In total, we identified 109 Y. enterocolitica cases. Consumption of Dairy A milk was known for 37 (34%); of these, Dairy A milk was consumed by 31 (84%). Dairy A had shipped 214 gallons of pasteurized milk in 5 weekly shipments to the camp by mid-July. Dairy A milk was the only shared exposure identified between the camp and community. Y. enterocolitica was isolated from Dairy A unpasteurized milk samples. Five clinical isolates from camp members, two clinical isolates from community members, and nine isolates from unpasteurized milk were indistinguishable by whole-genome sequencing. The risk for yersinosis among camp staff who drank Dairy A milk was 5.3 times the risk for those who did not (95% confidence interval: 1.6-17.3). Because Dairy A only sold pasteurized milk, pasteurized milk was considered the outbreak source. We recommend governmental agencies and small dairies conducting on-site pasteurization collaborate to develop outbreak prevention strategies.

Enhanced Surveillance for Histoplasmosis-9 States, 2018-2019.

BACKGROUND: Histoplasmosis is often described as the most common endemic mycosis in the United States, but much remains unknown about its epidemiology among the general population. METHODS: We conducted enhanced surveillance in 9 states during 2018-2019 by identifying cases through routine surveillance and interviewing 301 patients about their clinical features and exposures. RESULTS: Before being tested for histoplasmosis, 60% saw a health care provider ≥3 times, and 53% received antibacterial medication. The median time from seeking health care to diagnosis (range) was 23 (0-269) days. Forty-nine percent were hospitalized, and 69% said that histoplasmosis interfered with their daily activities (median [range], 56 [2-3960] days). Possible exposures included handling plants (48%) and bird or bat droppings (24%); 22% reported no specific exposures. Only 15% had heard of histoplasmosis before their illness. CONCLUSIONS: Histoplasmosis can be severe and prolonged. Additional educational efforts to increase public and provider awareness and reduce delays in diagnosis are needed.

A cholecystokinin B receptor antagonist and cocaine interaction, phase I study.

AIMS: RPR 102681, a cholecystokinin-B antagonist, increased dopamine (DA) release and reduced cocaine self-administration in animals. This pilot study sought to assess the safety and pharmacokinetics (PK) of co-administration of RPR 102681 and cocaine, and to confirm the DA release mechanism of RPR 102681. METHODS: Sixteen cocaine-dependent participants were randomized to either placebo or RPR102681 at 3 ascending doses; cocaine was co-administered at steady state of RPR 102681. [11 C]raclopride positron emission tomography scans were conducted at baseline and at each RPR102681 dose. RESULTS: RPR 102681 was well tolerated, and safe to co-administer with cocaine. RPR 102681 did not alter the PK of either cocaine or its metabolite benzoylecgonine and showed no intrinsic abuse liability. There was a trend toward reduction of cocaine craving scores. In contrast to animal studies, RPR 102681 significantly increased the binding potential of [11 C]raclopride in the ventral striatum (t test, P < .001) and caudate nucleus (t test, P < .0001) in a small subset of patients, suggesting that it may reduce intrasynaptic striatal DA. CONCLUSION: Overall, this pilot study suggests that RPR 102681 would be unlikely candidate, as an agonist medication for the treatment for cocaine addiction but worth investigating further for possible role in reducing craving.

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.

Effects of intranasal oxytocin on satiety signaling in people with schizophrenia.

Overweight and obesity in schizophrenia are prevalent, affecting half to three-quarters of people with schizophrenia. Hyperphagia and increased meal size have also been implicated as significant contributors to the weight gain problem. Oxytocin has shown to play a role in appetite control in humans and is considered an anorexigenic peptide. This two-day, within-subjects, challenge study involved the examination of satiety after administration of 24 IU oxytocin (intranasal) vs. placebo in participants with a DSM-IV diagnosis of schizophrenia (N = 16). Self reported satiety along with a preload-test meal paradigm were utilized as well as related laboratory measures (insulin, glucose, and leptin), and measures of taste and smell. There were no statistically significant differences between the groups on self-reported satiety or test meal consumption, insulin or glucose levels, or sensory measures. A significant treatment difference was found (F = 5.22, df = 1,97.6, p = 0.025), with a decrease in leptin in the oxytocin group post-administration, but no time effect (F = 1.67, df = 6,95.1, p = 0.180) or treatment by time interaction (F = 1.36. df = 3,4.16, p = 0.261). Despite the small sample and mostly negative findings, we encourage more work to use higher and repeated doses of oxytocin, and to further examine the effect of oxytocin on leptin in schizophrenia as this may be important for understanding both weight control and psychopathology.

Multistate Epidemiology of Histoplasmosis, United States, 2011-2014

Histoplasmosis is one of the most common mycoses endemic to the United States, but it was reportable in only 10 states during 2016, when a national case definition was approved. To better characterize the epidemiologic features of histoplasmosis, we analyzed deidentified surveillance data for 2011-2014 from the following 12 states: Alabama, Arkansas, Delaware, Illinois, Indiana, Kentucky, Michigan, Minnesota, Mississippi, Nebraska, Pennsylvania, and Wisconsin. We examined epidemiologic and laboratory features and calculated state-specific annual and county-specific mean annual incidence rates. A total of 3,409 cases were reported. Median patient age was 49 (interquartile range 33-61) years, 2,079 (61%) patients were male, 1,273 (57%) patients were hospitalized, and 76 (7%) patients died. Incidence rates varied markedly between and within states. The high hospitalization rate suggests that histoplasmosis surveillance underestimates the true number of cases. Improved surveillance standardization and surveillance by additional states would provide more comprehensive knowledge of histoplasmosis in the United States.

Role of chronic stress and depression in periodontal diseases.

An extensive body of experimental and clinical evidence documents the negative impact of chronic psychological stress and depression on the immune system and health. Chronic stress and depression can result in general dysregulation of the immune system, of both cellular and humoral pathways, which may contribute to pathogenic infection and concomitant periodontal tissue destruction. In general, the evidence is consistent with the hypothesis that stress can modify the host defense and progression of periodontal infections in patients susceptible to periodontitis. However, substantial evidence also indicates that these conditions can mediate risk for disease, including periodontitis, through changes in health-related behaviors, such as oral hygiene, smoking and diet. The unequivocal interpretation of studies has also been hampered, in part, by issues related to conceptualization of stress and depression, as well as commonly associated comorbidities, such as diabetes, that can modify the onset and progression of periodontal disease. In addition, stress and depression appear to fall into a spectrum, ranging from mild to severe, involving a complex interaction of genetic background, coping strategies and environment. Differences in the conceptualization of stress and depression are probably important in assessing associations with other biologic and clinical measures. Future studies are necessary to clarify the complex interactions of chronic stress and depression in periodontal diseases.

Alcohol and cannabis use and mortality in people with schizophrenia and related psychotic disorders.

The impact of co-morbid substance use on mortality is not well studied in psychotic disorders. The objective of this study was to examine the impact of substance use on mortality in people with psychotic disorders and alcohol and/or drug use. We examined the rate of substance use and the risk of substance use on mortality risk over a 4-10 year period in 762 people with psychotic disorders. Deceased patients were identified from the Social Security Death Index and the Maryland Division of Vital Records. Substance use was defined as regular and heavy use or abuse or dependence. Seventy seven percent had co-morbid lifetime substance use, with co-morbid cannabis and alcohol use occurring most commonly. Out of 762 subjects, 62 died during follow up. In a Cox model, predicted mortality risk was higher in age group 35-55 compared to <35 years and in males, but reduced in cannabis users. Overall five- (3.1% vs 7.5%) and ten-year mortality risk (5.5% vs. 13.6%) was lower in cannabis users than in non-users with psychotic disorders (p = 0.005) in a survival model. Alcohol use was not predictive of mortality. We observed a lower mortality risk in cannabis-using psychotic disorder patients compared to cannabis non-users despite subjects having similar symptoms and treatments. Future research is warranted to replicate these findings and to shed light on the anti-inflammatory properties of the endocannabinoid system and its role in decreased mortality in people with psychotic disorders.

Placebo-controlled trial of atomoxetine for weight reduction in people with schizophrenia treated with clozapine or olanzapine.

BACKGROUND: In recent years, several pharmacological and psychosocial interventions have examined ways to prevent or treat weight gain in people receiving second-generation antipsychotics. While there has been some success, in general, results have not been compelling. Atomoxetine is a selective norepinepherine reuptake inhibitor found to be associated with appetite suppression. Therefore, we examined whether atomoxetine may be of benefit for those who have gained weight on either clozapine or olanzapine. METHODS: The study was a double-blind, placebo-controlled trial. All participants received the same psychosocial platform: a structured support and exercise group. People with schizophrenia or schizoaffective disorder, on olanzapine or clozapine, who had gained at least 7% of their pre-clozapine or pre-olanzapine weight were eligible for a 24-week, randomized, parallel group, double-blind comparison of adjunctive atomoxetine or placebo. RESULTS: Thirty-seven participants (20 atomoxetine, 17 placebo) were randomized and 26 participants (14 atomoxetine, 12 placebo; 70.2%) completed the study. There were no significant group differences in baseline BMI (atomoxetine: 34.5±4.9; placebo: 35.7±7.0) or weight (atomoxetine: 102.2±15.7 kg; placebo: 104.3±17.5 kg). Both treatment groups showed modest, not significant, trends in weight loss, averaging about 2 kg. Gender or baseline antipsychotic treatment did not modify treatment effects on weight. Secondary outcomes included neuropsychological assessments, symptom assessments (BPRS, SANS) and safety assessments. Of these, only the group difference in Gordon distractibility test scores was statistically significant and favored treatment with atomoxetine. CONCLUSIONS: Atomoxetine is not effective for weight loss in this population, but both olanzapine and clozapine participants can lose weight with structured group support and exercise.

Anticipatory vs. consummatory pleasure: what is the nature of hedonic deficits in schizophrenia?

Recent research has distinguished between anticipatory and consummatory pleasure. In the current study, we examined the psychometric properties of the Temporal Experience of Pleasure Scale (TEPS) to determine whether reliability and validity findings reported in previous research replicate in an additional sample of schizophrenia patients. Participants included 86 individuals with schizophrenia and 59 demographically matched healthy controls. Inconsistent with previous research, patients differed from controls in their reports of consummatory (TEPS-CON), but not anticipatory (TEPS-ANT) pleasure. We also failed to replicate some important correlational findings reported in previous research indicating relationships between the TEPS-ANT subscale and external validators. Analyses of the stability of the TEPS subscales were conducted in a sub-group of patients (n=19), and indicated excellent stability for the TEPS-CON (ICC (intraclass correlation coefficient)=0.93), but somewhat lower stability for the TEPS-ANT subscale (ICC=0.74). These findings suggest that additional studies are needed using the TEPS, as well as other measures, to determine the nature of anhedonia in individuals with schizophrenia.

Exercise program adherence using a 5-kilometer (5K) event as an achievable goal in people with schizophrenia.

People with schizophrenia have a higher prevalence of obesity than the general population. Many people with this illness struggle with weight gain, due, in part, to medications and other factors that act as obstacles to exercise and healthy eating. Several studies have shown the benefits of behavioral weight loss programs targeting eating and/or exercise in people with schizophrenia. Fewer studies have used competitive events as a goal for an exercise program. The current study tested the feasibility of preparing, using an exercise program, for a 5-kilometer (5K) event in people with schizophrenia. The exercise program was a 10-week training program consisting of three supervised walking/jogging sessions per week and a weekly educational meeting on healthy behaviors. Almost 65% (11/17) of the subjects participated in all of the training sessions, and 82% (14/17) participated in the 5K event. Participants did not gain a significant amount of weight during the exercise program (median weight change = 0.7 kg; 25th percentile 0.5, 75th percentile 3.9, p = .10). This study suggests that using an achievable goal, such as a 5K event, promotes adherence to an exercise program and is feasible in a population of people with chronic schizophrenia.

Cigarette smoking and mortality risk in people with schizophrenia.

This study examined effects of cigarette smoking on mortality risk in 1213 persons aged 19-69 years with schizophrenia-related psychotic disorders admitted to State of Maryland Hospitals between 1994 and 2000. Inpatient medical records from 7 hospitals were reviewed to obtain demographic information, diagnosis, medication use, as well as smoking and other substance use. Social Security Death Index data were used to identify deaths in the study group between 1994 and 2004. Death records were reviewed to obtain manner of death and underlying disorders. Of the 1213, 55% were smokers and 71% abused substances. There was an age × smoking interaction (χ(2) = 14.6, df = 1, P = .0001) for mortality, with estimated hazard ratios (HRs) for smokers vs nonsmokers of 2.1 among 35- to 54-year olds and HR of 0.7 among those aged 55-69 years. Five- and 10-year mortality rates for smokers aged 35-54 years were 7.0% and 14.2%, compared with 3.3% and 10.0% for nonsmokers, respectively (χ(2) = 5.53, df = 1, P = .019). Cardiac causes were identified in 43% of deaths in smokers but only 19% of deaths in nonsmokers (P < .006). For those aged 35-54 years, the odds of cardiac related death was increased by 12 fold in smokers relative to nonsmokers (HR = 12.4, χ(2) = 12.0, df = 1, P = .0005). Among people aged 35-54 years, those smoking greater than one pack daily have a significantly increased total mortality risk (HR = 2.7) vs nonsmokers. Cigarette smoking, particularly in people aged 35-54 years, contributes to an increased risk of death. Greater smoking severity significantly increases this risk. Smoking cessation in people with schizophrenia deserves significant attention.

Effects of the cannabinoid-1 receptor antagonist rimonabant on psychiatric symptoms in overweight people with schizophrenia: a randomized, double-blind, pilot study.

Weight gain is a major adverse effect of several second-generation antipsychotic medications. Rimonabant is a cannabinoid-1 receptor antagonist that promotes weight loss in the general population. We conducted a 16-week, double-blind, placebo-controlled study of rimonabant (20 mg/d) in people with schizophrenia or schizoaffective disorder, based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, who were clinically stable on second-generation antipsychotics. Participants had a body mass index of 27 kg/m or higher with hyperlipidemia or body mass index of 30 kg/m or higher, and no current substance abuse/dependence (except nicotine), more than weekly cannabis use, or recent depressive symptoms/suicidality. An exercise and dietary counseling group was offered weekly. Target enrollment was 60; the trial was terminated early because of withdrawal of rimonabant from the European market. Fifteen participants were randomized (7 rimonabant, 8 placebo); 5 completed in each group. Rimonabant was associated with a greater reduction in Brief Psychiatric Rating Scale total score versus placebo (mean ± SE difference, -1.9 ± 0.8, P = 0.02), driven by differences in the Brief Psychiatric Rating Scale anxiety/depression (-1.4 ± 0.35, P = 0.0004) and hostility (-0.7 ± 0.3, P = 0.02) factors. Group differences were not significant for the Calgary Depression Scale total score (P = 0.24), Scale for the Assessment of Negative Symptoms total score (P = 0.13), weight, blood pressure, or fasting lipids or glucose. Rimonabant was well tolerated with no significant adverse events. No significant weight loss, metabolic effects, or adverse psychiatric effects were associated with the cannabinoid-1 receptor antagonist rimonabant in this small sample of people with schizophrenia. The endocannabinoid system remains a promising target for pharmacotherapy of schizophrenia and obesity.