Prevalence of Salmonella in Stool During the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015-2018.

BACKGROUND: Non-typhoidal Salmonella (NTS) is a common cause of gastroenteritis in young children, with limited data on NTS serovars and antimicrobial resistance in Africa. METHODS: We determined the prevalence of Salmonella spp. and frequency of antimicrobial resistance among serovars identified in stools of 0-59 month-old children with moderate-to-severe diarrhea (MSD) and controls enrolled in the Vaccine Impact on Diarrhea in Africa (VIDA) Study in The Gambia, Mali, and Kenya in 2015-2018, and compared with data from the Global Enteric Multicenter Study (GEMS; 2007-2010) and the GEMS-1A study (2011). Salmonella spp. was detected by quantitative real-time PCR (qPCR) and culture-based methods. Identification of serovars was determined by microbiological methods. RESULTS: By qPCR, the prevalence of Salmonella spp. among MSD cases was 4.0%, 1.6%, and 1.9% and among controls was 4.6%, 2.4%, and 1.6% in The Gambia, Mali, and Kenya, respectively, during VIDA. We observed year-to-year variation in serovar distribution and variation between sites. In Kenya, Salmonella enterica serovar Typhimurium decreased (78.1% to 23.1%; P < .001) among cases and controls from 2007 to 2018, whereas serogroup O:8 increased (8.7% to 38.5%; P = .04). In The Gambia, serogroup O:7 decreased from 2007 to 2018 (36.3% to 0%; P = .001) but S. enterica serovar Enteritidis increased during VIDA (2015 to 2018; 5.9% to 50%; P = .002). Only 4 Salmonella spp. were isolated in Mali during all 3 studies. Multidrug resistance was 33.9% in Kenya and 0.8% in The Gambia across all 3 studies. Ceftriaxone resistance was only observed in Kenya (2.3%); NTS isolates were susceptible to ciprofloxacin at all sites. CONCLUSIONS: Understanding variability in serovar distribution will be important for the future deployment of vaccines against salmonellosis in Africa.

Immunogenicity and Efficacy of Live-Attenuated Salmonella Typhimurium Vaccine Candidate CVD 1926 in a Rhesus Macaque Model of Gastroenteritis.

Salmonella Typhimurium is a common cause of foodborne gastroenteritis and a less frequent but important cause of invasive disease, especially in developing countries. In our previous work, we showed that a live-attenuated S. Typhimurium vaccine (CVD 1921) was safe and immunogenic in rhesus macaques, although shed for an unacceptably long period (10 days) postimmunization. Consequently, we engineered a new strain, CVD 1926, which was shown to be safe and immunogenic in mice, as well as less reactogenic in mice and human cell-derived organoids than CVD 1921. In this study, we assessed the reactogenicity and efficacy of CVD 1926 in rhesus macaques. Animals were given two doses of either CVD 1926 or saline perorally. The vaccine was well-tolerated, with shedding in stool limited to a mean of 5 days. All CVD 1926-immunized animals had both a serological and a T cell response to vaccination. At 4 weeks postimmunization, animals were challenged with wild-type S. Typhimurium I77. Unvaccinated (saline) animals had severe diarrhea, with two animals succumbing to infection. Animals receiving CVD 1926 were largely protected, with only one animal having moderate diarrhea. Vaccine efficacy in this gastroenteritis model was 80%. S. Typhimurium vaccine strain CVD 1926 was safe and effective in rhesus macaques and shed for a shorter period than other previously tested live-attenuated vaccine strains. This strain could be combined with other live-attenuated Salmonella vaccine strains to create a pan-Salmonella vaccine.

Evaluation of Molecular Serotyping Assays for Shigella flexneri Directly on Stool Samples.

Shigella flexneri is prevalent worldwide and is the most common Shigella species in many countries. At least 19 S. flexneri serotypes exist, and serotype information is important for epidemiologic and vaccine development purposes. We evaluated the performance of real-time PCR assays for O-antigen modification genes to identify the major serotypes on isolates and direct stool samples. The assays were formulated into two multiplex panels: one panel included gtrII, gtrV, gtrX, oac, and wzx6 to identify S. flexneri serotypes 2a, 2b, 3a, 5a, 5b, 6, and X, and the other panel included ipaH, gtrI, gtrIc, and gtrIV to confirm Shigella detection and further identify S. flexneri serotypes 1a, 1b, 1d, 3b, 4a, 4b, 7a, and 7b. We first evaluated 283 Shigella isolates, and PCR serotyping demonstrated 97.0% (95% confidence interval, 93.0% to 99.0%) sensitivity and 99.9% (99.9% to 100%) specificity compared to conventional serotyping. The assays then were utilized on direct stool specimens. A quantitative detection algorithm was developed with a validation set of 174 Shigella culture-positive stool samples and further tested with a derivation set of 164 samples. The PCR serotyping on stool achieved 93% (89% to 96%) sensitivity and 99% (99% to 100%) specificity compared to serotyping. Most discrepancies were genotypic-phenotypic discordance, not genotypic failure. These real-time PCR assays provide an efficient and novel tool for S. flexneri serotype identification.

A Qualitative Study Among Mexican Americans to Understand Factors Influencing the Adoption and Enforcement of Home Smoking Bans.

INTRODUCTION: One-third of Mexican-American children, in addition to nonsmoker adults, are exposed to secondhand smoke at home, yet few interventions target Mexican-American households. An effective, brief English language program, tested with United Way 2-1-1 callers in Atlanta, increased home smoking bans (confirmed by air monitors). Two randomized controlled trials in North Carolina and Texas replicated those results. We explored factors determining adoption and enforcement of smoking bans in Mexican-American households to inform program linguistic and cultural adaptation to broaden program reach and relevance. METHODS: Bilingual interviewers recruited convenience samples of Mexican-American smokers and nonsmokers living with at least one smoker in Houston and San Diego households and asked open-ended questions regarding conditions for implementing home and vehicle smoking bans and conditions for varying acceptance of bans. Investigators independently reviewed English transcripts and completed a descriptive analysis using ATLAS.ti. RESULTS: Participants (n = 43) were predominantly female (n = 31), current smokers (n = 26), interviewed in Spanish (n = 26), had annual household incomes less than $30000 (n = 24), and allowed smoking inside the home (n = 24). Themes related to difficulty creating and enforcing bans included courtesy, respect for guests and heads of household who smoke, and gender imbalances in decision making. Participants viewed protecting children's health as a reason for the ban but not protecting adult nonsmokers' health. CONCLUSION: A dual-language, culturally adapted intervention targeting multigenerational Mexican-American households should address household differences regarding language and consider influences of cultural values on family dynamics and interactions with guests that may weaken bans. IMPLICATIONS: Qualitative interviews suggested cultural and family considerations to address in adapting a brief evidence-based smoke-free homes intervention for Mexican Americans, including traditional gender roles, unique contexts of multigenerational households, and language preferences. Our work confirms previous research among Latinos regarding importance of common cultural constructs, such as respeto (deference), simpatia (courtesy and agreeability), and familismo (family attachment), which inform behaviors that may impede or facilitate adopting and enforcing home smoking bans. Decision-making gender imbalances, high regard for head-of-household and guest smokers, and less sensitivity to the health of nonsmoker adults compared with children may lead to permission to smoke indoors.

Medical Assistant Health Coaching for Type 2 Diabetes in Primary Care: Results From a Pragmatic Cluster Randomized Controlled Trial.

OBJECTIVE: This cluster (clinic-level) randomized controlled trial (RCT) compared medical assistant (MA) health coaching (MAC) with usual care (UC) among at-risk adults with type 2 diabetes in two diverse real-world primary care environments: a federally qualified health center (FQHC; Neighborhood Healthcare) and a large nonprofit private insurance-based health system (Scripps Health). RESEARCH DESIGN AND METHODS: A total of 600 adults with type 2 diabetes who met one or more of the following criteria in the last 90 days were enrolled: HbA1c ≥8% and/or LDL cholesterol ≥100 mg/dL and/or systolic blood pressure (SBP) ≥140 mmHg. Participants at MAC clinics received in-person and telephone self-management support from a specially trained MA health coach for 12 months. Electronic medical records were used to examine clinical outcomes in the overall sample. Behavioral and psychosocial outcomes were evaluated in a subsample (n = 300). RESULTS: All clinical outcomes improved significantly over 1 year in the overall sample (P < 0.001). The reduction in HbA1c was significantly greater in the MAC versus UC group (unstandardized Binteraction = -0.06; P = 0.002). A significant time by group by site interaction also showed that MAC resulted in greater improvements in LDL cholesterol than UC at Neighborhood Healthcare relative to Scripps Health (Binteraction = -1.78 vs. 1.49; P < 0.05). No other statistically significant effects were observed. CONCLUSIONS: This was the first large-scale pragmatic RCT supporting the real-world effectiveness of MAC for type 2 diabetes in U.S. primary care settings. Findings suggest that this team-based approach may be particularly effective in improving diabetes outcomes in FQHC settings.

Dulce Digital-Me: protocol for a randomized controlled trial of an adaptive mHealth intervention for underserved Hispanics with diabetes.

BACKGROUND: By 2034, the number of US individuals with diabetes is predicted to increase from 23.7 to 44.1 million, and annual diabetes-related spending is expected to grow from $113 to $336 billion. Up to 55% of US Hispanics born in the year 2000 are expected to develop diabetes during their lifetime. Poor healthcare access and cultural barriers prevent optimal care, adherence, and clinical benefit, placing Hispanics at disproportionate risk for costly diabetes complications. Mobile technology is increasingly prevalent in all populations and can circumvent such barriers. Our group developed Dulce Digital, an educational text messaging program that improved glycemic control relative to usual care. Dulce Digital-Me (DD-Me) has been tailored to a participant's individual needs with a greater focus on health behavior change. METHODS: This is a three-arm, parallel group, randomized trial with equal allocation ratio enrolling Hispanic adults with low income and poorly managed type 2 diabetes (N = 414) from a San Diego County Federally Qualified Health Center. Participants are randomized to receive Dulce Digital, Dulce Digital-Me-Automated, or Dulce Digital-Me-Telephonic. The DD-Me groups include Dulce Digital components plus personalized goal-setting and feedback delivered via algorithm-driven automated text messaging (DD-Me-Automated) or by the care team health coach (DD-Me-Telephonic) over a 12-month follow-up period. The study will examine the comparative effectiveness of the three groups in improving diabetes clinical control [HbA1c, primary outcome; low-density lipoprotein cholesterol (LDL-C), and systolic blood pressure (SBP)] and patient-provider communication and patient adherence (i.e., medication, self-management tasks) over 12 months and will examine cost-effectiveness of the three interventions. DISCUSSION: Our comparative evaluation of three mHealth approaches will elucidate how technology can be integrated most effectively and efficiently within primary care-based chronic care model approaches to reduce diabetes disparities in Hispanics and will assess two modes of personalized messaging delivery (i.e., automated messaging vs. telephonic by health coach) to inform cost and acceptability. TRIAL REGISTRATION: NCT03130699-All items from the WHO Trial Registration data set are available in https://clinicaltrials.gov/ct2/show/study/NCT03130699 .

Hospital variability in emergency department length of stay for adult patients receiving psychiatric consultation: a prospective study.

STUDY OBJECTIVE: We ascertain the components of emergency department (ED) length of stay for adult patients receiving psychiatric evaluation and to examine their variability across 5 hospitals within a health care system. METHODS: This was a prospective study of 1,092 adults treated between June 2008 and May 2009. Research staff abstracted length of stay and clinical information from the medical records. Clinicians completed a time log for each patient contact. Main outcomes were median times for the overall ED length of stay and its 4 components, or time from triage to request for psychiatric evaluation, request to start of psychiatric evaluation, start to completion of psychiatric evaluation with a disposition decision, and disposition decision to discharge from the ED. RESULTS: The overall median length of stay was more than 8 hours. Median times for the components were 1.8 hours from triage to request, 15 minutes from request to start of psychiatric evaluation, 75 minutes from start of psychiatric evaluation to disposition decision, and nearly 3 hours from disposition decision to ED discharge. The median disposition decision to discharge time was substantially shorter for patients who went home (40 minutes) than for patients who were admitted (2.5 hours) or transferred for psychiatric admission at other facilities (6.3 hours). When adjustments for patient and clinical factors were made, differences in ED length of stay persisted between hospitals. CONCLUSION: ED length of stay for psychiatric patients varied greatly between hospitals, highlighting differences in the organization of psychiatric services and inpatient bed availability. Findings may not generalize to other settings or populations.

Higher West Nile Virus Infection in Aedes albopictus (Diptera: Culicidae) and Culex (Diptera: Culicidae) Mosquitoes From Lower Income Neighborhoods in Urban Baltimore, MD.

The temperate United States has experienced increasing incidence of mosquito-borne diseases. Recent studies conducted in Baltimore, MD have demonstrated a negative relationship between abundances of Aedes albopictus (Skuse) and Culex mosquitoes and mean neighborhood income level, but have not looked at the presence of pathogens. Mosquitoes collected from five socioeconomically variable neighborhoods were tested for infection by West Nile, chikungunya, and Zika viruses in 2015 and 2016, and again from four of the neighborhoods in 2017. Minimum infection rates of pooled samples were compared among neighborhoods for each year, as well as among individual blocks in 2017. West Nile virus was detected in both Ae. albopictus and Culex pools from all neighborhoods sampled in 2015 and 2017. No infected pools were detected in any year for chikungunya or Zika viruses, and none of the target viruses were detected in 2016. Infection rates were consistently higher for Culex than for Ae. albopictus. Minimum infection rate was negatively associated with mean neighborhood income for both species in 2015. Although earlier work has shown a positive association between block-level abandonment and mosquito abundance, no association was detected in this study. Still, we demonstrate that viral infection in mosquito pools can differ substantially across adjacent urban neighborhoods that vary by income. Though trap security and accessibility often inform city sampling locations, detecting and managing arboviral risk requires surveillance across neighborhoods that vary in socioeconomics, including lower income areas that may be less accessible and secure but have higher infection rates.

Compassion Fatigue in Laboratory Animal Personnel during the COVID-19 Pandemic.

Compassion Fatigue (CF) is commonly observed in professions associated with human and animal care. The COVID-19 pandemic compelled laboratory animal research institutions to implement new work practices in order to maintain essential animal care operations. These modifications ranged from shift changes to last-resort measures, such as culling animal colonies, to accommodate reduced staffing. Such changes could cause personnel to experience increased stress, isolation, and helplessness-all of which can increase CF risk. In the current study, 200 persons involved with animal research completed an online survey to gauge whether CF among laboratory animal personnel had increased during the pandemic. The survey examined professional quality of life, self-assessed levels of CF, institutional changes, perceived changes in animal welfare, and institutional measures intended to alleviate CF. A total of 86% of participants had experienced CF at some point in their career, with 41% experiencing a CF event (new or worsening symptoms of CF) during the pandemic. In addition, 90% of participants who reported a CF event also reported subsequent effects on their personal or professional lives. Health, employment, and animal-related stress that arose due to the pandemic were all found to influence CF scores significantly. Although 96% of respondents were considered essential workers, 67% did not feel as valued for their work as other essential personnel. Furthermore, 88% of personnel responsible for the euthanasia of healthy animals who experienced a CF event reported that CF also affected their personal life, professional life, or both, and 78% responded that interventions from internal CF programs or leadership did not help to alleviate symptoms of CF. The COVID-19 pandemic and resultant institutional changes will likely have lasting effects on persons and organizations. By determining and subsequently mitigating sources of CF, we can better assist the laboratory animal community during future crises.

Refinement of a Live Attenuated Salmonella enterica Serovar Newport Vaccine with Improved Safety.

Non-typhoidal Salmonella (NTS) is a major cause of gastroenteritis and is responsible for approximately 93 million cases annually. In healthy individuals, gastroenteritis caused by NTS is usually self-limiting, however, NTS can cause severe invasive disease in immunocompromised patients. Very little research has been directed towards development of vaccines against Salmonella serogroups O:6,7 or O:8. We have constructed a live attenuated serogroup O:8 vaccine, CVD 1979, by deleting guaBA, htrA, and aroA from the genome of S. Newport. We have shown that the candidate vaccine is well tolerated in mice and elicits serum immunoglobulin G (IgG) antibodies against core O-polysaccharide (COPS) when administered orally. Immunized mice were challenged intraperitoneally with wild-type S. Newport and bacterial burden in the liver and spleen was found to be significantly reduced in the livers of immunized mice compared to control mice. We also observed moderate vaccine efficacy (45%) against lethal challenge with the serogroup O:8 serovar, S. Muenchen, but low vaccine efficacy (28%) following lethal challenge with a serogroup O:6,7 serovar, S. Virchow. In vitro, we have shown that antibodies generated by CVD 1979 only recognize lipopolysaccharide (LPS) from serogroup O:8 but not serogroup O:6,7 serovars, and that they mediate opsonophagocytic antibody (OPA) activity against serogroup O:8 but not serogroup O:6,7 serovars. We also showed that OPA activity can be blocked by pre-incubating the antisera with serogroup O:8 lipopolysaccharide. Taken together, our data demonstrate that we have constructed a well-tolerated, effective live attenuated S. Newport vaccine which elicits functional antibodies against serogroup O:8 but not O:6,7 serovars.

Infection Prevention Considerations for a Multi-Mission Convention Center Field Hospital in Baltimore, Maryland, During the COVID-19 Pandemic.

The state of Maryland identified its first case of coronavirus disease 2019 (COVID-19) on March 5, 2020. The Baltimore Convention Center (BCCFH) quickly became a selected location to set up a 250-bed inpatient field hospital and alternate care site. In contrast to other field hospitals throughout the United States, the BCCFH remained open throughout the pandemic and took on additional COVID-19 missions, including community severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic testing, monoclonal antibody infusions for COVID-19 outpatients, and community COVID-19 vaccinations.To prevent the spread of pathogens during operations, infection prevention and control guidelines were essential to ensure the safety of staff and patients. Through multi-agency collaboration, use of infection prevention best practices, and answering what we describe as PPE-ESP, an operational framework was established to reduce infection risks for those providing or receiving care at the BCCFH during the COVID-19 pandemic.

Medical assistant health coaching ("MAC") for type 2 diabetes in diverse primary care settings: A pragmatic, cluster-randomized controlled trial protocol.

In the US, nearly 11% of adults were living with diagnosed diabetes in 2017, and significant type 2 diabetes (T2D) disparities are experienced by socioeconomically disadvantaged, racial/ethnic minority populations, including Hispanics. The standard 15-min primary care visit does not allow for the ongoing self-management support that is needed to meet the complex needs of individuals with diabetes. "Team-based" chronic care delivery is an alternative approach that supplements physician care with contact from allied health personnel in the primary care setting (e.g., medical assistants; MAs) who are specially trained to provide ongoing self-management support or "health coaching." While rigorous trials have shown MA health coaching to improve diabetes outcomes, less is known about if and how such a model can be integrated within real world, primary care clinic workflows. Medical Assistant Health Coaching for Type 2 Diabetes in Diverse Primary Care Settings - A Pragmatic, Cluster-Randomized Controlled Trial will address this gap. Specifically, this study compares MA health coaching versus usual care in improving diabetes clinical control among N = 600 at-risk adults with T2D, and is being conducted at four primary care clinics that are part of two health systems that serve large, ethnically/racially, and socioeconomically diverse populations in Southern California. Electronic medical records are used to identify eligible patients at both health systems, and to examine change in clinical control over one year in the overall sample. Changes in behavioral and psychosocial outcomes are being evaluated by telephone assessment in a subset (n = 300) of participants, and rigorous process and cost evaluations will assess potential for sustainability and scalability.

Substance use and survival after treatment for chronic myelogenous leukemia (CML) or myelodysplastic syndrome (MDS).

BACKGROUND: Patients' substance use problems are a particularly understudied aspect of psychosocial variables in cancer treatment. OBJECTIVES: The specific hypothesis tested was that lifetime substance use disorders increased the risk of adverse outcome, in the context of other psychosocial and clinical characteristics demonstrated in other studies to have an impact on treatment outcome. METHOD: Prospective cohort study of 106 adults with chronic myelogenous leukemia or primary myelodysplastic syndrome. None satisfied criteria for current substance abuse or dependence, but the lifetime rates of substance use disorders in this sample were 28% for alcohol, 12% for cannabis, and 9% for cocaine. RESULTS: Participants received treatment as directed by their physicians, and were followed until death or the end of the study (median 1.5 years). Twenty-eight died. Multivariate survival analysis identified three predictors of outcome: lifetime cocaine use, associated with a six-fold increased risk of death (p = .04), and two protective variables, baseline hemoglobin (p = .002) and estimated intelligence quotient (IQ) (p = .04). CONCLUSION: The results of this study highlight the potential significance of substance use disorders, and lifetime cocaine diagnoses in particular, on treatment outcome for people with chronic myelogenous leukemia or myelodysplastic syndrome. Whereas neither lifetime alcohol nor cannabis use were associated with survival on either the univariate or multivariate models of survival, lifetime cocaine diagnoses were associated with significant six-fold increased risk of death (p = .04).

Parent quit attempts after counseling to reduce children's secondhand smoke exposure and promote cessation: main and moderating relationships.

INTRODUCTION: This study explored predictors of smoking quit attempts in a sample of low-income smoking mothers who participated in a randomized trial of a 6-month, 14-session counseling intervention to decrease their children's secondhand smoke exposure (SHSe) and eliminate smoking. METHODS: Measures were taken at baseline and at 3, 6, 12, and 18 months on 150 mothers who exposed their children (aged <4 years) to > or = 10 cigarettes/week in the home. Reported 7-day quits were verified by saliva cotinine or urine anabasine and anatabine levels. RESULTS: There were few quits longer than 6 months. Mothers in the counseling group reported more 24-hr quits (p = .019) and more 7-day quits (p = .029) than controls. Multivariate modeling revealed that having quit for at least 24 hr in the year prior to baseline and the number of alternative cessation methods ever tried were predictive of the longest quit attempt during the 18-month study. Mothers in the counseling group who at baseline felt SHSe posed a health risk for their children or who at baseline had more permissive home smoking policies had longer quit attempts. DISCUSSION: Results confirm that attempts to quit smoking predict additional quit attempts. This suggests that practice may be necessary for many people to quit smoking permanently. Findings of interaction analyses suggest that participant factors may alter the effects of treatment procedures. Failure to account for or employ such factors in the analysis or design of community trials could confound the results of intervention trials.

Counseling to reduce children's secondhand smoke exposure and help parents quit smoking: a controlled trial.

INTRODUCTION: We tested a combined intervention to reduce children's secondhand smoke exposure (SHSe) and help parents quit smoking. METHODS: After baseline, mothers who exposed their children younger than 4 years to 10 or more cigarettes/week were randomized to the intervention (n = 76) or usual care control condition (n = 74). Outcomes were assessed at 3, 6, 12, and 18 months. Intervention families were offered 10 in-person at home and 4 telephone counseling sessions over 6 months, and additional pre- and postquit telephone sessions. Counseling procedures included behavioral contracting, self-monitoring, and problem solving. RESULTS: Parents' reports of their smoking and children's exposure showed moderate and significant correlations with children's urine cotinine levels and home air nicotine (r = .40-.78). Thirteen (17.1%) intervention group mothers and 4 (5.4%) controls reported that they quit smoking for 7 days prior to 1 or more study measurements, without biochemical contradiction (p = .024). Results of generalized estimating equations showed significantly greater decrease in reported SHSe and mothers' smoking in the counseled group compared with controls. Reported indoor smoking and children's urine cotinine decreased, yet group differences for changes were not significant. DISCUSSION: Nicotine contamination of the home and resulting thirdhand exposure may have contributed to the failure to obtain a differential decrease in cotinine concentration. Partial exposure to counseling due to dropouts and lack of full participation from all family members and measurement reactivity in both conditions may have constrained intervention effects. Secondhand smoke exposure counseling may have been less powerful when combined with smoking cessation.

Deletions in guaBA and htrA but not clpX or rfaL constitute a live-attenuated vaccine strain of Salmonella Newport to protect against serogroup C2-C3Salmonella in mice.

Non-typhoidal Salmonella (NTS) are a leading cause of foodborne infections worldwide, and serogroups B, C1, C2-C3 and D are the most common serogroups associated with human disease. While live vaccine candidates that protect against S. Typhimurium (serogroup B) and S. Enteritidis (serogroup D) have been described by us and others, far less effort has been directed towards vaccines that target either serogroup C1 or C2-C3Salmonella. Here we describe a Salmonella Newport-based live-attenuated vaccine (serogroup C2-C3). Deletion of the genes clpX or rfaL, previously used in live vaccines to attenuate S. Typhimurium and/or S. Enteritidis, failed to attenuate S. Newport. However, we found that deletion of either guaBA or htrA raised the 50% lethal dose of S. Newport in an intraperitoneal infection model in BALB/c mice. Our live-attenuated vaccine candidate CVD 1966 (S. Newport ΔguaBA ΔhtrA) elicited strong antibody responses against COPS, flagellin and outer membrane proteins when administered intraperitoneally or orally. Following lethal challenge with the parental virulent strain of S. Newport, we observed vaccine efficacies of 53% for immunization via the intraperitoneal route and 47% for immunization via the oral route. Following intraperiteonal immunization, the vaccine also significantly reduced the bacterial burden of challenge organisms in the liver and spleen. Interestingly, reducing the LPS chain length by deleting rfaL did not induce a stronger immune response towards surface antigens, and failed to elicit any protection against lethal homologous challenge. In conclusion, we have developed a live-attenuated Salmonella serogroup C2-C3 vaccine that we are further evaluating.

Characterization of Invasive Salmonella Serogroup C1 Infections in Mali.

Nontyphoidal Salmonella (NTS) are the leading cause of foodborne infections worldwide and a major cause of bloodstream infections in infants and HIV-infected adults in sub-Saharan Africa (SSA). Salmonella Typhimurium (serogroup B) and Salmonella Enteritidis (serogroup D) are the most common serovars in this region. However, data describing rarer invasive NTS serovars, particularly those belonging to serogroups C1 and C2, circulating in SSA are lacking. We previously conducted systematic blood culture surveillance on pediatric patients in Bamako, Mali, from 2002 to 2014, and the results showed that serovars Typhimurium and Enteritidis accounted for 32% and 36% of isolates, respectively. Here, we present data on 27 Salmonella serogroup C1 strains that were isolated during this previous study. The strains were typed by serum agglutination and multilocus sequence typing (MLST). Sixteen strains were Salmonella Paratyphi C, four were Salmonella Colindale, and two were Salmonella Virchow. Interestingly, five strains were identified as the very rare Salmonella Brazzaville using a combination of serum agglutination and flagellin gene typing. Phenotypic characterization showed that Salmonella Brazzaville produced biofilm and exhibited catalase activity, which were not statistically different from the gastroenteritis-associated Salmonella Typhimurium sequence type (ST) 19. All tested Salmonella Paratyphi C strains were poor biofilm producers and showed significantly less catalase activity than Salmonella Typhimurium ST19. Overall, our study provides insight into the Salmonella serogroup C1 serovars that cause invasive disease in infants in Mali. In addition, we show that MLST and flagellin gene sequencing, in association with traditional serum agglutination, are invaluable tools to help identify rare Salmonella serovars.

Predictors of neuropsychological change in patients with chronic myelogenous leukemia and myelodysplastic syndrome.

This study examined the course of neuropsychological functioning in patients with chronic myelogeous leukemia (n = 91) or myelodysplastic syndrome (n = 15) who underwent standard treatment for their disease or allogeneic hematopoietic stem cell transplantation (HSCT) at baseline, 12 months, and 18 months post-treatment. At baseline, 23% of the participants (n = 75) in the longitudinal sample had Z-scores on at least one of the neuropsychological tests that were <1.4. Participants in the study showed improvement over baseline at the 12 and 18 months assessments. The average Z-scores for the six cognitive domains in the longitudinal data set over the course of the study ranged from -0.89 to 0.59. Significant predictors of change in neuropsychological test scores included age, with older participants showing less improvement over time. Other predictors included baseline cognitive domains (language, memory, and attention), previous cocaine use, disease status, intelligence quotient, and quality of life measures. Findings support previous studies in patients with hematological malignancies who showed cognitive impairments at baseline prior to HSCT. However, there was little evidence for further cognitive decline over the course of 18 months.

Self-reported alcohol and drug use in pregnant young women: a pilot study of associated factors and identification.

OBJECTIVES: This study describes the factors associated with self-reported substance use in pregnant young women attending a hospital clinic and evaluates 3 ways in its identification. METHODS: A cross-sectional study of 30 pregnant young adults who responded to a mail survey containing the CRAFFT screening tool. All completed a diagnostic interview that included self-report information on their use of alcohol and drugs before and during pregnancy, the T-ACE screening tool, and the contexts in which they would be likely to use. Medical records were reviewed. RESULTS: One-third of participants consumed alcohol, marijuana, or both while pregnant. Many had lifetime diagnoses of alcohol (23%) or cannabis (30%) use disorders, but only 1 met criteria for current diagnosis. Age, race, education, and children at home were not associated with either prenatal alcohol or cannabis use. Before pregnancy, alcohol drinking was associated with prenatal alcohol use (P = .02) and prenatal cannabis use (P = .06). Another trend of the before-pregnancy cannabis use being associated with prenatal cannabis use (P = .08) was observed. Most participants indicated little likelihood of substance use in convivial, intimate, or negative coping contexts while pregnant. However, participants with prenatal substance use had significantly higher convivial (P = .02) and intimate (P = .01) subscale scores of the Drinking Context Scale before pregnancy. Compared to the medical record and the T-ACE, the CRAFFT was best in identifying prenatal substance use (c-statistic = 0.9). CONCLUSIONS: The CRAFFT screening instrument and asking about the contexts during which alcohol might have been consumed before pregnancy are promising approaches in the identification of prenatal substance use.

A second reporter matters: agreement between parents' and children's reports of smoking bans in families.

BACKGROUND: Home and car smoking bans implemented by caregivers are important approaches to reducing children's secondhand smoke (SHS) exposure and attendant health risks. Such private smoking bans are usually informal and are subject to individuals' interpretation, observation, and recall. Relying on a single reporter may lead to misclassification of bans in families. PURPOSE: To determine (1) proportion of families with discordant reports of bans; (2) association between parent-child report agreement and SHS exposure; and (3) whether including a second reporter of bans improves prediction of child SHS exposure. METHODS: In each of 386 participating families a preteen and a parent reported separately on their home and car smoking bans, and agreement was determined. ANOVA, chi-square, and multiple linear regression were used to determine relationships between SHS exposure (measured by urine cotinine and reported exposure) and home/car smoking bans reported by preteens and parents. RESULTS: In 19% of families, reports disagreed for home smoking bans; 30%, for car smoking bans. Families who agreed on the presence of a ban had the lowest exposure, families who agreed on the absence of a ban had the highest exposure, and intermediate exposure for those who disagreed. Parent and child reports of bans each explained significant, unique variance in child SHS exposure. CONCLUSIONS: Due to relatively high prevalence of discordant reporting, a more accurate classification of home/car smoking bans may result from including multiple reporters.