Recent Exposure Research Articles

Bacterial shedding and serologic responses following an outbreak of Salmonella Typhi in an endemic cohort

BackgroundSalmonella enterica serovar Typhi (Salmonella Typhi) is the cause of typhoid fever. Salmonella Typhi may be transmitted through shedding in the stool, which can continue after recovery from acute illness. Shedding is detected by culturing stool, which is challenging to co-ordinate at scale. We hypothesised that sero-surveillance would direct us to those shedding Salmonella Typhi in stool following a typhoid outbreak.MethodsIn 2016 a typhoid outbreak affected one in four residents of a Nursing School in Malosa, Malawi. The Department of Health asked for assistance to identify nursing students that might spread the outbreak to other health facilities. We measured IgG antibody titres against Vi capsular polysaccharide (anti-Vi IgG) and IgM / IgG antibodies against H:d flagellin (anti-H:d) three and six months after the outbreak. We selected participants in the highest and lowest deciles for anti-Vi IgG titre (measured at visit one) and obtained stool for Salmonella culture and PCR. All participants reported whether they had experienced fever persisting for three days or more during the outbreak (in keeping with the WHO definitions of ‘suspected typhoid’). We tested for salmonellae in the Nursing School environment. ResultsWe obtained 320 paired serum samples from 407 residents. We cultured stool from 25 residents with high anti-Vi IgG titres and 24 residents with low titres. We did not recover Salmonella Typhi from stool; four stool samples yielded non-typhoidal salmonellae; one sample produced a positive PCR amplification for a Salmonella Typhi target. Median anti-Vi and anti-H:d IgG titres fell among participants who reported persistent fever. There was a smaller fall in anti-H:d IgG titres among participants who did not report persistent fever. Non-typhoidal salmonellae were identified in water sampled at source and from a kitchen tap.ConclusionHigh titres of anti-Vi IgG did not identify culture-confirmed shedding of Salmonella Typhi. There was a clear serologic signal of recent typhoid exposure in the cohort, represented by waning IgG antibody titres over time. The presence of non-typhoidal salmonellae in drinking water indicates sub-optimal sanitation. Developing methods to detect and treat shedding remains an important priority to complement typhoid conjugate vaccination in efforts to achieve typhoid elimination.

A State-of-the-Science Review on Metal Biomarkers.

Biomarkers are commonly used in epidemiological studies to assess metals and metalloid exposure and estimate internal dose, as they integrate multiple sources and routes of exposure. Researchers are increasingly using multi-metal panels and innovative statistical methods to understand how exposure to real-world metal mixtures affects human health. Metals have both common and unique sources and routes of exposure, as well as biotransformation and elimination pathways. The development of multi-element analytical technology allows researchers to examine a broad spectrum of metals in their studies; however, their interpretation is complex as they can reflect different windows of exposure and several biomarkers have critical limitations. This review elaborates on more than 500 scientific publications to discuss major sources of exposure, biotransformation and elimination, and biomarkers of exposure and internal dose for 12 metals/metalloids, including 8 non-essential elements (arsenic, barium, cadmium, lead, mercury, nickel, tin, uranium) and 4 essential elements (manganese, molybdenum, selenium, and zinc) commonly used in multi-element analyses. We conclude that not all metal biomarkers are adequate measures of exposure and that understanding the metabolic biotransformation and elimination of metals is key to metal biomarker interpretation. For example, whole blood is a good biomarker of exposure to arsenic, cadmium, lead, mercury, and tin, but it is not a good indicator for barium, nickel, and uranium. For some essential metals, the interpretation of whole blood biomarkers is unclear. Urine is the most commonly used biomarker of exposure across metals but it should not be used to assess lead exposure. Essential metals such as zinc and manganese are tightly regulated by homeostatic processes; thus, elevated levels in urine may reflect body loss and metabolic processes rather than excess exposure. Total urinary arsenic may reflect exposure to both organic and inorganic arsenic, thus, arsenic speciation and adjustment for arsebonetaine are needed in populations with dietary seafood consumption. Hair and nails primarily reflect exposure to organic mercury, except in populations exposed to high levels of inorganic mercury such as in occupational and environmental settings. When selecting biomarkers, it is also critical to consider the exposure window of interest. Most populations are chronically exposed to metals in the low-to-moderate range, yet many biomarkers reflect recent exposures. Toenails are emerging biomarkers in this regard. They are reliable biomarkers of long-term exposure for arsenic, mercury, manganese, and selenium. However, more research is needed to understand the role of nails as a biomarker of exposure to other metals. Similarly, teeth are increasingly used to assess lifelong exposures to several essential and non-essential metals such as lead, including during the prenatal window. As metals epidemiology moves towards embracing a multi-metal/mixtures approach and expanding metal panels to include less commonly studied metals, it is important for researchers to have a strong knowledge base about the metal biomarkers included in their research. This review aims to aid metals researchers in their analysis planning, facilitate sound analytical decision-making, as well as appropriate understanding and interpretation of results.

Unusual serological profile in hepatitis B virus (HBV) infection associated with a probable clinical case of acute exacerbation of pre-existing chronic HBV infection.

Acute or chronic HBV infection in an individual can be laboratory characterized according to the serological profile of the viral markers in the bloodstream, and the dynamics monitoring of these markers is necessary to assess the disorder course and the infection outcome. However, under certain circumstances unusual or atypical serological profiles may be observed in both acute and chronic HBV infection. They are considered as such because they do not properly characterize the form or infection clinical phase or because they seem inconsistent, considering the viral markers dynamics in both clinical contexts. This manuscript comprises the analysis of an unusual serological profile in HBV infection. This clinical-laboratory study, had as reference a patient who presented clinical profile suggestive of acute HBV infection after recent exposure, whose laboratory data were initially compatible with this clinical presentation. However, the serological profile analysis and its monitoring demonstrated unusual pattern of viral markers expression, which has been observed in several clinical contexts, and is often associated a number of agent- or host-related factors. The serological profile analyzed here, associated with the biochemical markers serum levels found, is indicative of active chronic infection, consequence of viral reactivation. This finding suggests that in the event of unusual serological profiles in HBV infection, if the influence of agent- or host-related factors is not properly considered and neither the viral markers dynamics properly analyzed, there may be mistake in the infection clinical diagnosis, especially when the patient's clinical and epidemiological history is unknown.

How do early and recent life stress shape cortisol reactivity and decision making in middle-to-older adulthood?

Greater lifetime stressor exposure and acute stress are both related to greater risky decision making; however, lifetime stressor exposure is also associated with blunted physiological response to acute stress, implying nuanced relations among life stress, acute stress, and decision making. In support of this, some work suggests that specific timings of stressor exposure (e.g., childhood vs. adulthood) may differentially relate to both physiology and decision making. To date, however, no work has concurrently examined lifetime and acute stressor exposure in relation to risky decision making. To address this issue, we examined how lifetime stressor exposure as assessed with the Stress and Adversity Inventory for Adults (STRAIN) is related to cortisol reactivity to the Trier Social Stress Test (TSST) and risky decision making in 63 middle-to-older aged adults (age range: 45-81 years). In the decision making task, participants made decisions about gambles framed as either gains or losses before and after the TSST. Regardless of age, participants with greater early and recent life stressor exposure exhibited lower cortisol reactivity than those with less of those exposures. Also regardless of age, participants made riskier decisions on loss trials than on gain trials. Finally, older adults reporting more early life and recent life stressor exposures showed the riskiest decision making after the TSST than younger adults who reported lower life stressor exposure. Early and recent life stressor exposure are associated with stress-related changes in physiology and decision making. These changes may lead to risky decision making in older age.

Changes in early postoperative outcomes and complications observed in a single center during the 2022 COVID-19 pandemic wave in China: A single-center ambispective cohort study.

Currently, the effect of the 2022 nationwide coronavirus disease 2019 (COVID-19) wave on the perioperative prognosis of surgical patients in China is unclear. Thus, we aimed to explore its influence on postoperative morbidity and mortality in surgical patients. An ambispective cohort study was conducted at Xijing Hospital, China. We collected 10-day time-series data from December 29 until January 7 for the 2018-2022 period. The primary outcome was major postoperative complications (Clavien-Dindo class III-V). The association between COVID-19 exposure and postoperative prognosis was explored by comparing consecutive 5-year data at the population level and by comparing patients with and without COVID-19 exposure at the patient level. The entire cohort consisted of 3350 patients (age: 48.5 ± 19.2 years), including 1759 females (52.5%). Overall, 961 (28.7%) underwent emergency surgery, and 553 (16.5%) had COVID-19 exposure (from the 2022 cohort). At the population level, major postoperative complications occurred in 5.9% (42/707), 5.7% (53/935), 5.1% (46/901), 9.4% (11/117), and 22.0% (152/690) patients in the 2018-2022 cohorts, respectively. After adjusting for potential confounding factors, the 2022 cohort (80% patients with COVID-19 history) had a significantly higher postoperative major complication risk than did the 2018 cohort (adjusted risk difference [aRD], 14.9% (95% confidence interval [CI], 11.5-18.4%); adjusted odds ratio [aOR], 8.19 (95% CI, 5.24-12.81)). At the patient level, the incidence of major postoperative complications was significantly greater in patients with (24.6%, 136/553) than that in patients without COVID-19 history (6.0% [168/2797]; aRD, 17.8% [95% CI, 13.6-22.1%]; aOR, 7.89 [95% CI, 5.76-10.83]). Secondary outcomes of postoperative pulmonary complications were consistent with primary findings. These findings were verified through sensitivity analyses using time-series data projections and propensity score matching. Based on a single-center observation, patients with recent COVID-19 exposure were likely to have a high incidence of major postoperative complications. NCT05677815 at https://clinicaltrials.gov/.

Evidence of Rift Valley Fever Virus Circulation in Livestock and Herders in Southern Ghana.

Rift Valley fever (RVF) is a re-emerging zoonotic disease of domestic ruminants and humans. While neighbouring countries have reported outbreaks of RVF, Ghana has not yet identified any cases. The aim of this study was to determine whether RVF virus (RVFV) was circulating in livestock and herders in the southern part of Ghana, to estimate its seroprevalence, and to identify associated risk factors. The study surveyed 165 livestock farms randomly selected from two districts in southern Ghana. Serum samples of 253 goats, 246 sheep, 220 cattle, and 157 herdsmen were tested to detect IgG and IgM antibodies against RVFV. The overall seroprevalence of anti-RVF antibodies in livestock was 13.1% and 30.9% of farms had RVFV seropositive animals. The species-specific prevalence was 24.1% in cattle, 8.5% in sheep, and 7.9% in goats. A RVFV IgG seroprevalence of 17.8% was found among the ruminant herders, with 8.3% of all herders being IgM positive. RVFV was shown, for the first time, to have been circulating in southern Ghana, with evidence of a recent outbreak in Kwahu East; however, it was clinically undetected despite significant recent human exposure. A One Health approach is recommended to better understand RVF epidemiology and socio-economic impact in Ghana.

Clinical and genomic predictors of response and toxicity to sotorasib in a real-world cohort of patients with advanced KRAS G12C-mutant non-small cell lung cancer.

9083 Background: With the accelerated approval of the KRAS G12C inhibitor sotorasib for patients with advanced KRAS G12C-mutant non-small cell lung cancer (NSCLC), there is a new need to explore efficacy and identify clinical and genomic factors associated with activity and toxicity among patients treated in routine clinical practice. Methods: Patients(pts) treated with sotorasib outside of the clinical trial setting at three institutions (MSK, Columbia, NYU) were examined to identify factors associated with real-world PFS (rwPFS), overall survival (OS), real-world (rw) response, and clinically significant toxicity (CTCAE v5.0 grade 3 or higher treatment-related adverse events [G3+ TRAE]). TP53, STK11, and KEAP1 status were assessed by targeted NGS. Response and rwPFS were determined by investigator assessment of radiology reports. rwPFS and OS were estimated by Kaplan-Meier methods; log-rank tests were used for univariate group comparisons and Mantel-Haenszel method was used to determine hazard ratios (HRs). Fisher’s exact test was used to determine associations between categorical variables. Results: 105 pts with advanced KRAS G12C-mutant NSCLC treated with sotorasib were identified. The response rate for patients treated was 28%, with median rwPFS of 5.3 months, and median OS of 12.6 months. KEAP1 co-mutations were associated with shorter rwPFS and OS (rwPFS HR 3.19, P = 0.004; OS HR 4.10, P = 0.003); no significant differences in rwPFS or OS were observed among pts with or without TP53 co-mutations (rwPFS HR 1.10, P = 0.731; OS HR 1.19, P = 0.631) or STK11 co-mutations (rwPFS HR 1.66, P = 0.098; OS HR 1.73, P = 0.168). Dual STK11/ KEAP1 co-mutation status was associated with shorter OS compared to STK11 wild-type (WT)/ KEAP1 mutant (MUT) status (OS HR 4.04, P = 0.033) and STK11 MUT/ KEAP1 WT status (OS HR 5.41, P = 0.012). 16/105 (15%) pts experienced G3+ TRAEs. 15/16 (94%) patients with G3+ TRAE had previously been treated with immune checkpoint inhibitor (ICI). Among pts with prior ICI exposure (n = 86), last exposure within 12 weeks of sotorasib initiation was associated with G3+ sotorasib TRAEs ( P < 0.001) and TRAE-related sotorasib discontinuation ( P = 0.014); there was no association between prior irAE during ICI therapy and G3+ sotorasib TRAEs ( P = 0.757). In total, 15/53 (28%) pts with last ICI exposure within 12 weeks of sotorasib initiation experienced G3+ TRAEs, most commonly hepatotoxicity. No cases of G3+ TRAEs were observed in 33 pts with last ICI exposure > 12 weeks prior to sotorasib treatment. Conclusions: Among patients treated with sotorasib in routine clinical practice, KEAP1 co-mutations were associated with poor outcomes. Severe toxicity was almost exclusively associated with recent ICI exposure. These observations may help further guide sequencing of sotorasib and may help inform the next generation of KRAS G12C clinical trials.

Real-time whole-genome sequencing surveillance for outbreak detection and intervention

Background: Detecting healthcare-associated transmission and outbreaks often relies on reactive whole-genome sequencing (WGS), which occurs after the suspected transmission has occurred. Additionally, reactive WGS frequently misidentifies transmission and misses transmission when it has occurred. We initiated weekly real-time WGS to detect bacterial transmission and direct infection prevention interventions. We describe our experience after 1 year of real-time WGS surveillance at the University of Pittsburgh Medical Center–Presbyterian Hospital, a large, tertiary-care facility. Methods: Weekly WGS surveillance was performed from November 1, 2021, to October 31, 2022. Cultured isolates of select bacterial pathogens from patients who were hospitalized for ≥3 days or had a recent healthcare exposure in the prior 30 days were collected and sequenced. Isolates that were ≤15 single-nucleotide polymorphisms (SNPs) were considered genetically related clusters except for Clostridioides difficile (≤2 SNPs). Genetically related clusters were investigated for epidemiological links and interventions to interrupt transmission were implemented at the discretion of the infection prevention team. We analyzed subsequent infections that occurred within an outbreak after an intervention was in place. Results: In total, 1,909 isolates were sequenced. Of 1,633 unique patient isolates clustered by sequence type, 74 clusters were identified comprising 210 (12.9%) patient isolates (Table 1). The median time from culture date to sequencing was 14 days (IQR, 5.25). The median cluster size was 2 (IQR, 1) (Table 2). Overall, 118 patient isolates (56.2%) had an epidemiological link to a prior isolate, indicating potential transmission. Of 74 clusters, 66 (89.2%) received infection prevention interventions after notification based upon epidemiological data. The infection prevention team performed 69 total interventions, which included unit education (n = 28), hand hygiene observations (n = 16), enhanced cleaning (n = 16), environmental cultures or removal of endoscope (n = 7), and enhanced microbiology surveillance (n = 2). The 59 subsequent infections after infection prevention notification included 17 (28.8%) with no clear epidemiological link, and 41 (69.5%) with an epidemiological link either to a new transmission route (n = 37) or the same route prior to infection prevention intervention (n = 4). Only 1 (1.7%) subsequent infection within a cluster occurred after an infection prevention intervention from the same potential route, which was a suspected unit-based transmission of vancomycin-resistant Enterococcus faecium. Conclusions: Real-time WGS was effective at detecting genetically related clusters, finding potential sources, and halting further transmission after interventions by the infection prevention team. Quick turnaround times from patient culture to sequencing and analysis were vital for successful WGS surveillance. Real-time WGS surveillance has the potential to substantially shift the infection prevention paradigm for outbreak detection.Disclosure: None

Colonization with extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) in hospitalized patients in Botswana

Background: The epidemiology of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) in hospitalized patients in low- and middle-income countries (LMICs) is poorly described. Although risk factors for ESCrE clinical infection have been studied, little is known of the epidemiology of ESCrE colonization. Identifying risk factors for ESCrE colonization, which can predispose to infection, is therefore critical to inform antibiotic resistance reduction strategies. Methods: This study was conducted in 3 hospitals located in 3 districts in Botswana. In each hospital, we conducted ongoing surveillance in sequential units hospitalwide. All participants had rectal swabs collected which were inoculated onto chromogenic media followed by confirmatory testing using MALDI-TOF MS and VITEK-2. Data were collected via interview and review of the inpatient medical record on demographics, comorbidities, antibiotic use, healthcare exposures, invasive procedures, travel, animal contact, and food consumption. Participants with ESCrE colonization (cases) were compared to noncolonized participants (controls) using bivariable and multivariable analyses to identify risk factors for ESCrE colonization. Results: Enrollment occurred from January 15, 2020, to September 4, 2020, and 469 participants were enrolled. The median age was 42 years (IQR, 31–58) and 320 (68.2%) were female. The median time from hospital admission to date of sampling was 5 days (IQR, 3–12). There were 179 cases and 290 controls (ie, 38.2% of participants were ESCrE colonized). Independent risk factors for ESCrE colonization were a greater number of days on antibiotic, recent healthcare exposure, and tending swine prior to hospitalization. (Table). Conclusions: ESCrE colonization among hospitalized patients was common and was associated with several exposures. Our results suggest prior healthcare exposure may be important in driving ESCrE. The strong link to recent antibiotic use highlights the potential role of antibiotic stewardship interventions for prevention. The association with tending swine suggests that animal husbandry practices may play a role in community exposures, resulting in colonization detected at the time of hospital admission. These findings will help to inform future studies assessing strategies to curb further emergence of hospital ESCrE in LMICs.Disclosures: None

Dermatomycosis Caused by Paranannizziopsis australasiensis in Nonnative Panther Chameleons (Furcifer pardalis) Captured in Central Florida, USA.

Emergent fungal pathogens in herpetofauna are a concern in both wild and captive populations. We diagnosed dermatomycosis by Paranannizziopsis australasiensis in two panther chameleons (Furcifer pardalis) and suspected it in eight others captured from an established free-living nonnative population in Florida, USA. Chameleons developed skin lesions following recent exposure to cold weather conditions while housed in captivity, approximately 10 mo after capture and 12 wk after being placed in outdoor enclosures. Affected animals were treated with oral voriconazole and terbinafine until most cases resolved; however, medications were ultimately discontinued. Paranannizziopsis australasiensis has not previously been described in chameleons, nor in animals originating from a free-ranging population in the USA. Although the source of P. australasiensis infection is uncertain, we discuss several scenarios related to the pet trade and unique situation of chameleon "ranching" present in the USA.

Methicillin-resistant Staphylococcus aureus mupirocin resistance rates in a large healthcare system

Methicillin-resistant Staphylococcus aureus (MRSA) is a common etiology of hospital-acquired infections (HAIs). One strategy to reduce HAIs due to MRSA involves a multistep decolonization process. This often involves nasal application of mupirocin 2% ointment. In our institution, when individuals meet criteria for decolonization, we recommend 5 days of treatment given twice daily. High levels of mupirocin resistance have been reported in some hospital systems, with >80% of tested isolates being resistant. To better understand our resistance levels, we selected 238 MRSA isolates from blood cultures to be tested for mupirocin resistance to correlate the presence of resistance and use of mupirocin for decolonization. We choose to assess MRSA blood isolates rather than nasal swabs given that we aim to prevent invasive MRSA infections, including blood stream infections, with decolonization. The blood cultures were collected from 11 acute-care facilities within our system from March 2021 through June 2022. High-level resistance was defined as an MIC >1,024 μg/mL according to Clinical and Laboratory Standards Institute guidelines. Of those, 7.14% showed high level resistance, and 76.47% occurred in those who were exposed to mupirocin and 23.53% occurred in those without mupirocin exposure (P = .0094). On average, those with high-level resistance had had more recent exposure to mupirocin compared to those without resistance, which was statistically significant. Also, those with high resistance, on average, received more doses of mupirocin, although this was not statistically significant. Conclusions: More recent and higher number of doses of mupirocin were associated with the development of resistance, which is consistent with what we know from pharmacodynamics of antibiotic resistance with other agents. These findings may be particularly important for those patients who have frequent hospitalizations and often require decolonization. Understanding baseline mupirocin resistance levels in an institution can assist with determining decolonization strategies.Disclosures: None

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Bispecific antibodies (BsAbs) are a promising therapeutic approach for the treatment of B-cell lymphoproliferative disorders. Limited data is available regarding the impact of COVID-19 in patients treated with BsAbs. We assessed the impact of COVID-19 infection on BsAbs treatment and evaluated the severity of COVID-19 infection and the seroconversion rate. Methods: Patients treated with BsAbs at our institution were reviewed from March 2020 to January 2023. Severity of COVID-19 infection was defined according to World Health Organization (WHO) criteria. Seroconversion rate was assessed using chemiluminescence immunoassays for the determination of antibodies against SARS-CoV2 spike glycoprotein (cutoff, 40 BAU/mL). Patients who received convalescent plasma, sotrovimab or AZD7442 (cilgavimab and tixagevimab) were excluded from the seroconversion analysis. Results: One hundred and nine patients (median age, 62 years old) were included. Most frequent diagnoses were Diffuse Large B-Cell Lymphoma (73%) and Follicular Lymphoma (18%). Median number of previous lines was 2. Ninety-four patients (86%) received an anti-CD20/CD3, 13 (12%) an anti-CD22/CD3 and 2 (2%) an anti-CD19/4-1-bb. Anti-CD20 agents in the prior 6 months had been administered alone or in combination in 61 patients (56%). Twenty-two (20%) patients had received prior CAR-T cell therapy for a median of 5 months. Eighty-six patients (79%) were vaccinated (in general with Spikevax), with an average of 3 doses. COVID-19 infection was diagnosed in 61 patients (56%); 23 (38%) presented mild COVID-19 infection, 20 (33%) moderate, 11 (18%) severe and 7 (11%) critical. Ten patients were diagnosed with a second COVID-19 episode; of these, sequencing results confirmed a reinfection in 2 patients and a persistent infection in 8 patients. Median time to first negative PCR was 34 days and 62 days for those who presented a second infection. Twenty-five patients became infected during treatment causing 84% delays and 20% discontinuations. At the time of infection, 76% of the patients had negative serology. A higher seroconversion rate was observed in the post treatment setting with BsAbs after a median of 6 months. No differences were evidenced according to recent exposure to an anti-CD20 agent (figure 1D). Patients with positive serology (24%) presented milder infection (p = 0.009). After a median follow up of 34.3 months, 32 patients died (29%), 19 due to progressive disease, 6 from COVID-19 pneumoniae (10%, 5 of which were in complete response), 5 from other infections and 2 of unknown causes. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Immunotherapy, Indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract. A. Serna Consultant or advisory role: Pharmore Research M. Jiménez Honoraria: GSK, Sanofi A. Cabirta Honoraria: Jazz, AstraZeneca, Janssen A. Albasanz Consultant or advisory role: Gilead, GSK Honoraria: Gilead, GSK, Pfizer I. Ruiz-Camps Consultant or advisory role: GSK, AstraZeneca, BMS, MSD, Gilead, Pfizer, Janssen Honoraria: GSK, AstraZeneca, BMS, MSD, Gilead, Pfizer, Janssen T. García Consultant or advisory role: Janssen, Roche, Gilead, Celgene Research funding: Janssen, AbbVie C. Carpio Consultant or advisory role: Regeneron Pharmaceuticals, Takeda Honoraria: Gilead, Novartis, AstraZeneca, BMS S. Bobillo Consultant or advisory role: Janssen, Roche, Gilead Honoraria: Janssen, Roche, Gilead Educational grants: Gilead G. Iacoboni Consultant or advisory role: Novartis, Kite/Gilead, BMS/Celgene Honoraria: Novartis, Kite/Gilead, BMS/Celgene, AstraZeneca, Roche, AbbVie, Janssen, Miltenyi A. Marín-Niebla Consultant or advisory role: Lilly, Kite, Kiowa Kirin, Takeda, AstraZeneca, Roche, Janssen Honoraria: Lilly, Kite, Takeda, Janssen F. Bosch Consultant or advisory role: Novartis, Celgene/BMS, Roche, AstraZeneca, Takeda, Mundipharma, Gilead, AbbVie, Lilly, Beigene Honoraria: Novartis, Celgenes/BMS, Roche, AstraZeneca, Takeda, Karyospharm, Mundipharma, Gilead, AbbVie, Lilly, Beigene P. Abrisqueta Consultant or advisory role: Roche, AbbVie, BMS, AstraZeneca, Janssen, Incyte Honoraria: Roche, Abbvie, BMS, AstraZeneca, Janssen, Sandoz

Evidence of the circulation of avian metapneumovirus in domestic backyard chickens in Eastern Saudi Arabia in 2019.

Avian metapneumovirus (aMPV) is a recently discovered respiratory virus in chickens. Avian metapneumovirus has been linked to respiratory syndromes, reproductive failure in affected chickens and turkeys, swollen head syndrome in chickens, and rhinotracheitis in turkeys. Wild birds are considered potential reservoirs of aMPV, particularly aMPV-C. However, little is known about the prevalence of aMPV in Saudi Arabia. Considering the relevance of backyard chickens in the transmission and sustainability of certain avian viral diseases, this study aimed to assess aMPV exposure in backyard chickens and wild birds circulating near selected locations. We collected 368 serum samples from unvaccinated backyard chickens in ten locations in Eastern Saudi Arabia. Furthermore, we collected 78 serum samples from species of free-ranging birds belonging to the Columbidae family, such as pigeons and doves, captured from the same areas. Using commercial enzyme-linked immunosorbent assay kits, we tested the sera of domestic backyard chickens and wild birds for antibodies against aMPV. Our results showed that 74/368 birds were positive for aMPV-related antibodies. Conversely, none of the tested wild birds seroconverted to aMPV. The antibody titers detected in the backyard chickens suggested recent exposure to aMPV. Considering these results, further large-scale serological and molecular studies are needed to evaluate the prevalence of aMPV in these birds and characterize the circulating strains of aMPV in this region.

Factors Affecting Parents' Knowledge Level In Providing Early Childhood Sexual Education

Introduction: In 2017, Indonesia were the most victims of sexual violence in children who were attending kindergarten or elementary school (1,443 children), while in Cirebon Regency there was an increase in the incidence of child sexual violence in 2018 and 2019. The aim : to find out what factors affect the level of knowledge parents in providing early childhood sexual education. Method :Using cross sectional technique, the population is all parents and students who are actively attending school as many as 43 respondents, using total sampling technique. Data analysis used frequency distribution and Chi Square test. Result : The last education of the majority of respondents was secondary as much as 22 (51.2%). The majority of respondents do not work as much as 23 (53.5%). The majority of respondents were exposed to information as much as 31 (72.1%). The knowledge of the majority of respondents is good as much as 35 (81.4%). For bivariate analysis of statistical test results with Chi Square test between the latest education, occupation, and information exposure with the level of knowledge of parents obtained p-values ​​of 0.026, 0.014. and 0.004 (<0.05). Conclusion: There is a close relationship between recent education, employment, and information exposure with parental knowledge in providing early childhood sexual education.

Perirhinal cortex automatically tracks multiple types of familiarity regardless of task-relevance

Perirhinal cortex (PrC) has long been implicated in familiarity assessment for objects and corresponding concepts. However, extant studies have focused mainly on changes in familiarity induced by recent exposure in laboratory settings. There is an increasing appreciation of other types of familiarity signals, in particular graded familiarity accumulated throughout one's lifetime. In prior work (Duke et al., 2017, Cortex, 89, 61–70), PrC has been shown to track lifetime familiarity ratings when participants make related judgements. A theoretically important characteristic of familiarity is its proposed automaticity. Support for automaticity comes from a documented impact of recent stimulus exposure on behavioral performance, and on PrC signals, under conditions in which this exposure is not task relevant. In the current fMRI study, we tested whether PrC also tracks lifetime familiarity of object concepts automatically, and whether this type of familiarity influences behavior even when it is not task relevant. During scanning, neurotypical participants (N = 30, age range 18–40, 7 males) provided animacy judgements about concrete object concepts presented at differing frequencies in an initial study phase. In a subsequent test phase, they made graded judgements of recent or lifetime familiarity. Behavioral performance showed sensitivity to lifetime familiarity even when it was not relevant for the task at hand. Across five sets of fMRI analyses, we found that PrC consistently tracked recent and lifetime familiarity of object concepts regardless of the task performed. Critically, while several other temporal-lobe regions also showed isolated familiarity effects, none of them tracked familiarity with the same consistency. These findings demonstrate that PrC automatically tracks multiple types of familiarity. They support models that assign a broad role in the representation of information about object concepts to this structure.

Persistent organic pollutants (POPs) and per- and polyfluoroalkyl substances (PFASs) in liver from wild and farmed tilapia (Oreochromis niloticus) from Lake Kariba, Zambia: Levels and geographic trends and considerations in relation to environmental quality standards (EQSs)

The current study was carried out to investigate a wide variety of persistent organic pollutants (POPs) in wild and farmed tilapia (Oreochromis niloticus) in Lake Kariba, Zambia, and assess levels of POPs in relation to Environmental Quality Standards (EQSs). Concentrations of organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyls (PBDEs), and perfluoroalkyl substances (PFASs) were determined in liver samples of tilapia. PFASs compounds PFOS, PFDA and PFNA were only detected in wild fish, with the highest median PFOS levels in site 1 (0.66 ng/g ww). Concentrations of POPs were in general highest in wild tilapia. The highest median ∑DDTs (93 and 81 ng/g lw) were found in wild tilapia from sites 1 and 2, respectively 165 km and 100 km west of the fish farms. Lower DDE/DDT ratios in sites 1 and 3 may indicate relatively recent exposure to DDT. The highest median of ∑17PCBs (3.2 ng/g lw) and ∑10PBDEs (8.1 ng/g lw) were found in wild tilapia from sites 1 and 2, respectively. The dominating PCB congeners were PCB-118, -138, −153 and −180 and for PBDEs, BDE-47, -154, and −209. In 78% of wild fish and 8% of farmed fish ∑6PBDE concentrations were above EQSbiota limits set by the EU. This warrants further studies.

Analytical approaches for antimalarial antibody responses to confirm historical and recent malaria transmission: an example from the Philippines

Assessing the status of malaria transmission in endemic areas becomes increasingly challenging as countries approach elimination. Serology can provide robust estimates of malaria transmission intensities, and multiplex serological assays allow for simultaneous assessment of markers of recent and historical malaria exposure. Here, we evaluated different statistical and machine learning methods for analyzing multiplex malaria-specific antibody response data to classify recent and historical exposure to Plasmodium falciparum and Plasmodium vivax. To assess these methods, we utilized samples from a health-facility based survey (n=9132) in the Philippines, where we quantified antibody responses against 8P.falciparum and 6P.vivax-specific antigens from 3 sites with varying transmission intensity. Measurements of antibody responses and seroprevalence were consistent with the 3 sites' known endemicity status. Among the models tested, a machine learning (ML) approach (Random Forest model) using 4 serological markers (PfGLURP R2, Etramp5.Ag1, GEXP18, and PfMSP119) gave better predictions for P.falciparum recent infection in Palawan (AUC: 0.9591, CI 0.9497-0.9684) than individual antigen seropositivity. Although the ML approach did not improve P.vivax infection predictions, ML classifications confirmed the absence of recent exposure to P.falciparum and P.vivax in both Occidental Mindoro and Bataan. For predicting historical P.falciparum and P.vivax transmission, seroprevalence and seroconversion rates based on cumulative exposure markers AMA1 and MSP119 showed reliable trends in the 3 sites. Our study emphasizes the utility of serological markers in predicting recent and historical exposure in a sub-national elimination setting, and also highlights the potential use of machine learning models using multiplex antibody responses to improve assessment of the malaria transmission status of countries aiming for elimination. This work also provides baseline antibody data for monitoring risk in malaria-endemic areas in the Philippines. Newton Fund, Philippine Council for Health Research and Development, UK Medical Research Council.

Infective Endocarditis due to Non-HACEK Gram-Negative Bacilli: Clinical Characteristics and Risk Factors from a Prospective Multicenter Brazilian Cohort.

Background: Non-HACEK Gram-negative bacilli (NGNB) infective endocarditis (IE) has a growing frequency. We aimed to describe cases of NGNB IE and find associated risk factors. Methods: We conducted a prospective observational study of consecutive patients with definitive IE according to the modified Duke criteria in four institutions in Brazil. Results: Of 1154 adult patients enrolled, 38 (3.29%) had IE due to NGNB. Median age was 57 years, males predominated, accounting for 25/38 (65.8%). Most common etiologies were Pseudomonas aeruginosa and Klebsiella spp. (8 episodes, 21% each). Worsening heart failure occurred in 18/38 (47.4%). Higher prevalence of embolic events was found (55,3%), mostly to the central nervous system 7/38 (18.4%). Vegetations were most commonly on aortic valves 17/38 (44.7%). Recent healthcare exposure was found in 52.6% and a central venous catheter (CVC) in 13/38 (34.2%). Overall mortality was 19/38 (50%). Indwelling CVC (OR 5.93; 95% CI, 1.29 to 27.3; p = 0.017), hemodialysis (OR 16.2; 95% CI, 1.78 to 147; p = 0.008) and chronic kidney disease (OR 4.8; 95% IC, 1.2 to 19.1, p = 0.049) were identified as risk factors for mortality. Conclusions: The rate of IE due to NGNB was similar to that in previous studies. Enterobacterales and P. aeruginosa were the most common etiologies. NGNB IE was associated with central venous catheters, prosthetic valves, intracardiac devices and hemodialysis and had a high mortality rate.

Neighbourhood social deprivation and risk of prostate cancer.

Striking geographic variations in prostate cancer incidence suggest an aetiological role for spatially-distributed factors. We assessed whether neighbourhood social deprivation, which can reflect limited social contacts, unfavourable lifestyle and environmental exposures, is associated with prostate cancer risk. In 2005-2012, we recruited 1931 incident prostate cancer cases and 1994 controls in a case-control study in Montreal, Canada. Lifetime residential addresses were linked to an area-based social deprivation index around recruitment (2006) and about 10 years earlier (1996). Logistic regression estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Men residing in areas characterised by greater social deprivation had elevated prostate cancer risks (ORs of 1.54 and 1.60 for recent and past exposures, respectively; highest vs lowest quintiles), independently from area- and individual-level confounders and screening patterns. The increase in risk with recent high social deprivation was particularly elevated for high-grade prostate cancer at diagnosis (OR 1.87, 95% CI 1.32-2.64). Associations were more pronounced for neighbourhoods with higher proportions of separated/divorced or widowed individuals in the past, and with higher percentages of residents living alone recently. These novel findings, suggesting that neighbourhood-level social deprivation increases the risk of prostate cancer, point out to potential targeted public health interventions.

138 Interpretation of Occupational Biomonitoring Data of 1,3-Butadiene Exposure in the Form of Urinary Markers and Estimation of Urinary Half-Lives

Abstract 1,3-Butadiene (BD) is classified as a human carcinogen and occupational exposure should be minimized in industrial installations. During the clean-up and repair of a storage tank that contained BD-contaminated sludge, the effectiveness of personal protection was checked with urinary biomonitoring of 1,2-dihydroxy-4-(N-acetylcysteinyl)-butane (DHBMA) and isomers of hydroxy-1-(N-acetylcysteinyl)-3-butene (MHBMA), biomarkers of recent BD exposure. Correlations exist between airborne BD shift exposure and end-of-shift urinary concentrations. 65 workers involved in the tank operation provided repeat urine samples before and after the shift across consecutive days for a total of 1286 samples. Inhalation exposure monitoring was not conducted as the workers used respiratory protective equipment. Different conclusions emerged from the samples regarding limit value exceedance for the two biomarkers. This large, unique dataset was investigated for patterns and apparent urinary half-lives of DHBMA and MHBMA not published yet in the scientific literature. The pattern across consecutive days for DHBMA was consistent with a low-level exposure, well below the exposure limit of 1 ppm (8-hour average), with a small increase of the body burden, whereas the pattern for MHBMA remained uninterpretable. Using a sub-set of the data, the urinary half-lives were estimated at 18.9 ± 2.6 hr (MHBMA) and 11.1 ± 3.4 hr (DHBMA). DHBMA would be the preferred biomarker to apply in situations when it is known that exposure to BD might occur to check whether protective measures are sufficient.