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Background Emergence of antibiotic resistant bacteria is a threat to public health. The aim of this study is to identify clinical and demographic features associated with beta-lactamase producing Enterobacterales, specifically extended spectrum beta-lactamase producing (ESBL) and carbapenem-resistant Enterobacterales (CRE), in patients at Loma Linda University Health, an academic medical center in Loma Linda, California. Methods This retrospective case control study compared patients with/without beta-lactamase producing Enterobacterales. Cases and controls were identified from microbiology records with Enterobacterales isolated between January 1, 2020, and December 31, 2021. Case subjects were individuals with ≥1 CRE isolate (confirmed by nuclear amplification testing, NAT) and control subjects were those with ≥1 isolate that were all non-CRE. We identified isolates of interest, defined as the first CRE isolate in cases and the first non-CRE isolate for controls. For each isolate of interest and corresponding specimen collection date, we extracted electronic medical record data including inpatient antibiotics received in the preceding 6 months, specimen type, patient sex and age. We performed similar analysis with ESBL-producing Enterobacterales confirmed by NAT. Results On multiple logistic regression, age (OR, 1.02; 95%CI, 1.01-1.04), isolation of klebsiella (10.75; 4.59-25.21), providentia (20.86; 2.47-176.17), and serratia (8.01; 1.59-40.40), receipt of non-carbapenem beta-lactams (1.06; 1.03-1.10), carbapenems (1.19; 1.12-1.27), doxycycline (1.26; 1.04-1.52), and tetracycline (1.89; 1.08-3.29), were independently associated with increased odds of CRE infection. Similarly, gender (2.59; 2.07-3.24), age (1.01; 1.01-1.02), isolation of proteus (1.47; 1.01-2.13), receipt of non-carbapenem beta-lactams (1.08; 1.06-1.11), carbapenems (1.33; 1.23-1.44), and vancomycin (1.07; 1.03-1.12) were associated with increased odds of infection with ESBL-producing Enterobacterales. Conclusion Age and receipt of beta-lactams (including carbapenems) were associated with odds of infection with both CRE and ESBL-producing Enterobacterales in an academic medical center in Southern California, highlighting the importance of antibiotic stewardship. Disclosures All Authors: No reported disclosures.

Dracunculiasis, slated for global eradication, typically is acquired by drinking stagnant water containing microscopic crustaceans (copepods) infected with Dracunculus medinensis larvae, causing clusters of case persons with worms emerging from the skin. Following a 10-year absence of reported cases, 9–26 sporadic human cases with few epidemiologic links have been reported annually in Chad since 2010; dog infections have also been reported since 2012. We conducted an investigation of human cases in Chad to identify risk factors. We conducted a case–control study using a standardized questionnaire to assess water and aquatic animal consumption, and links to dog infections. Case persons had laboratory-confirmed D. medinensis during 2013–2017. Each case person was matched to one to three controls without history of disease by age, gender, and residency in the village where the case person was likely infected. We estimated odds ratios (ORs) using simple conditional logistic regression. We enrolled 25 case persons with 63 matched controls. Dracunculiasis was associated with consumption of untreated water from hand-dug wells (OR: 13.4; 95% CI: 1.7–108.6), but neither with consumption of aquatic animals nor presence of infected dogs in villages. Unsafe water consumption remains associated with dracunculiasis. Education of populations about consuming safe water and using copepod filters to strain unsafe water should continue and expand, as should efforts to develop and maintain safe drinking water sources. Nevertheless, the peculiar epidemiology in Chad remains incompletely explained. Future studies of dogs might identify other risk factors.

Purpose Trichomoniasis is the most prevalent non-viral sexually transmitted infection in the United States. It can present with vaginitis in women and urethritis in men, but is most often asymptomatic or occurs with minimal symptoms. It is associated with other sexually transmitted infections (STIs), adverse pregnancy outcomes and pelvic inflammatory disease. For these reasons, healthcare provider awareness of trichomoniasis is of public health importance. Methods To assess practitioner knowledge, attitudes, and practices concerning trichomoniasis management, the American College of Obstetricians and Gynecologists (ACOG) conducted an online survey in 2016 of its members, and we analyzed results from 230 respondents. Results We note discrepancies between practice and recommendations amongst surveyed providers: a minority of respondents routinely screen HIV positive patients for trichomoniasis (10.7% “most of the time” 95% confidence interval [CI]: 6.7-15.8, 33.0% “always” 95% CI: 26.5%-40.0%), treat trichomoniasis in HIV positive patients with the recommended dose of metronidazole 500 mg twice a day for 7 days (25.8% 95% CI: 20.0%-32.3%), or retest patients diagnosed with trichomoniasis 3 months after treatment (9.6% 95% CI: 6.1%-14.3R). Only 29.0% (95% CI: 23.0%-35.5%) retreat with metronidazole 500 mg twice a day for 7 days in patients who have failed prior treatment. Conclusions Screening for and treatment of trichomoniasis in HIV positive patients, as well as retesting and retreatment for trichomoniasis in the general population appear to be suboptimal. Continuing education for providers is needed for this common but “neglected” STI.

We investigated an autochthonous case of cutaneous leishmaniasis caused by a genetically different Leishmania sp. in a patient in Arizona, USA. This parasite was classified into the subgenus Leishmania on the basis of multilocus DNA sequence and phylogenetic analyses of the rRNA locus and 11 reference genes.

Angiostrongyliasis is caused by infection and migration to the brain of larvae of the parasitic nematode Angiostrongylus cantonensis, or rat lungworm. Adult A. cantonensis reside in the lungs of the definitive wild rodent host, where they produce larvae passed in feces, which are then ingested by snails and slugs (gastropods). Human infection typically occurs when gastropods containing mature larvae are inadvertently ingested by humans. Although human infection often is asymptomatic or involves transient mild symptoms, larval migration to the brain can lead to eosinophilic meningitis, focal neurologic deficits, coma, and death. The majority of cases of human angiostrongyliasis occur in Asia and the Pacific Islands, including Hawaii, but autochthonous and imported cases have been reported in the continental United States (1,2), underscoring the importance of provider recognition to ensure prompt identification and treatment. The epidemiologic and clinical features of 12 angiostrongyliasis cases in the continental United States were analyzed. These cases were identified through A. cantonensis polymerase chain reaction (PCR) testing (3) of cerebrospinal fluid (CSF) submitted to CDC from within the continental United States. Six cases were likely a result of autochthonous transmission in the southern United States. All 12 patients had CSF pleocytosis and eosinophilia, consistent with eosinophilic meningitis. Health care providers need to be aware of the possibility of angiostrongyliasis in patients with eosinophilic meningitis, especially in residents in the southern United States or persons who have traveled outside the continental United States and have a history of ingestion of gastropods or contaminated raw vegetables.

The magnitude of antibody responses varies across the individual proteins that constitute any given microorganism, both in the context of natural infection and vaccination with attenuated or inactivated pathogens. The protein-specific factors underlying this variability are poorly understood. In 267 individuals exposed to intense seasonal malaria, we examined the relationship between immunoglobulin G (IgG) responses to 861 Plasmodium falciparum proteins and specific features of these proteins, including their subcellular location, relative abundance, degree of polymorphism, and whether they are predicted to have human orthologs. We found that IgG reactivity was significantly higher to extracellular and plasma membrane proteins and also correlated positively with both protein abundance and degree of protein polymorphism. Conversely, IgG reactivity was significantly lower to proteins predicted to have human orthologs. These findings provide insight into protein-specific factors that are associated with variability in the magnitude of antibody responses to natural P. falciparum infection—data that could inform vaccine strategies to optimize antibody-mediated immunity as well as the selection of antigens for sero-diagnostic purposes.

Accurately measuring antibody repertoire sequence composition in a small amount of blood is challenging yet important for understanding repertoire responses to infection and vaccination. We develop molecular identifier clustering-based immune repertoire sequencing (MIDCIRS) and use it to study age-related antibody repertoire development and diversification before and during acute malaria in infants (, Somatic hypermutation of antibodies can occur in infants but are difficult to track. Here the authors present a new method called MIDCIRS for deep quantitative repertoire sequencing with few cells, and show infants as young as 3 months can expand antibody lineage complexity in response to malaria infection.

Background Toxocariasis results from infection with larval stages of a dog and cat intestinal nematode and causes human morbidity. The current United States estimate of Toxocara exposure is 13.9% (National Health and Nutrition Examination Survey [NHANES] III [1988-1994]). Methods We used a multiplex bead-based assay (Tc-CTL-1MBA) with purified Toxocara canis antigen to estimate Toxocara antibody seroprevalence in serum of 13 509 persons aged ≥6 years from NHANES 2011-2014 and identified seropositivity risk factors. We tested a subset of 500 samples with the T. canis enzyme immunoassay used in NHANES III to estimate prior seroprevalence had samples from NHANES III been tested by Tc-CTL-1MBA. Results The age-standardized estimate of Toxocara seroprevalence was 5.0% (95% confidence interval [CI], 4.2%-5.8%), lower than previously reported even after adjusting for increased Tc-CTL-1MBA specificity. Risk factors for seropositivity from multiple logistic regression were older age, non-Hispanic black/Hispanic origin, male sex, living below poverty level, households with ≥0.5 persons per room, less than college education, and birth outside of the United States. Conclusions Toxocara seroprevalence estimates in 2011-2014 were lower than in a study from NHANES III (1988-1994), but seropositivity risk factors remained the same and should continue to be the focus of prevention efforts.

(See the Editorial Commentary by Barbut and Rupnik, on pages 1669–72.) An increase in the incidence and severity of Clostridium difficile infection (CDI) throughout the United States, Canada, and Europe coincided with the emergence of a previously rare genotype [1]. This genotype, known as polymerase chain reaction (PCR) ribotype 027, North American Pulsed-field type 1 (NAP1), or restriction endonuclease analysis (REA) type BI, was reported to harbor an intrinsic ability to cause more severe disease compared to other pathogenic isolates [1, 2]. At least one other C. difficile lineage, ribotype 078, has been referred to as “hypervirulent” [3]. Laboratory studies identified numerous microbiologic properties to explain the increased virulence of 027 and/or 078 isolates, including antibiotic resistance [4], increased toxin production [5], enhanced ability for toxin B isoforms to bind target cells [6], and increased sporulation ability [7]. More recent data do not support the hypervirulent hypothesis [8–12], although the clinical definition of severe CDI or the methods used for data analysis are not consistent across all studies. Because institutions are often limited to retrospective review of patient records, it is important to define severe CDI using commonly recorded information. Such a definition has been recommended [13] but not universally used. We sought to quantify the prevalence of C. difficile ribotypes at a single institution and to determine whether specific ribotypes were associated with severe disease. In particular, we tested the hypothesis that C. difficile ribotype predicts severe CDI cases even after adjustment for other clinical and laboratory variables. To do so, we developed models using an initial (derivation) data set and then validated our results with the same model fitted to a validation data set.