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Background Enteric fever, caused by Salmonella enterica serovars Typhi and Paratyphi A, is a major public health problem in low- and middle-income countries. Moderate sensitivity and scalability of current methods likely underestimate enteric fever burden. Determining the serological responses to organism-specific antigens may improve incidence measures. Methods Plasma samples were collected from blood culture-confirmed enteric fever patients, blood culture-negative febrile patients over the course of 3 months, and afebrile community controls. A panel of 17 Salmonella Typhi and Paratyphi A antigens was purified and used to determine antigen-specific antibody responses by indirect ELISAs. Results The antigen-specific longitudinal antibody responses were comparable between enteric fever patients, patients with blood culture-negative febrile controls, and afebrile community controls for most antigens. However, we found that IgG responses against STY1479 (YncE), STY1886 (CdtB), STY1498 (HlyE), and the serovar-specific O2 and O9 antigens were greatly elevated over a 3-month follow up period in S. Typhi/ S. Paratyphi A patients compared to controls, suggesting seroconversion. Conclusions We identified a set of antigens as good candidates to demonstrate enteric fever exposure. These targets can be used in combination to develop more sensitive and scalable approaches to enteric fever surveillance and generate invaluable epidemiological data for informing vaccine policies. Clinical Trial Registration ISRCTN63006567. [ABSTRACT FROM AUTHOR]

Shigella represents a paraphyletic group of enteroinvasive Escherichia coli. More than 40 Shigella serotypes have been reported. However, most cases within the men who have sex with men (MSM) community are attributed to 3 serotypes: Shigella sonnei unique serotype and Shigella flexneri 2a and 3a serotypes. Using the zebrafish model, we demonstrate that Shigella can establish persistent infection in vivo. Bacteria are not cleared by the immune system and become antibiotic tolerant. Establishment of persistent infection depends on the O-antigen, a key constituent of the bacterial surface and a serotype determinant. Representative isolates associated with MSM transmission persist in zebrafish, while representative isolates of a serotype not associated with MSM transmission do not. Isolates of a Shigella serotype establishing persistent infections elicited significantly less macrophage death in vivo than isolates of a serotype unable to persist. We conclude that zebrafish are a valuable platform to illuminate factors underlying establishment of Shigella persistent infection in humans. [ABSTRACT FROM AUTHOR]

Patients with suspected enteric (typhoid and paratyphoid) fever are predominantly managed as outpatients in endemic regions. Nonspecific clinical presentation, lack of accurate diagnostic tools, and widespread antimicrobial resistance makes management challenging. Resistance has been described for all antimicrobials including chloramphenicol, amoxycillin, trimethoprim-sulfamethoxazole, ciprofloxacin, ceftriaxone, and azithromycin. No significant differences have been demonstrated between these antimicrobials in their ability to treat enteric fever in systematic reviews of randomized controlled trials (RCTs). Antimicrobial choice should be guided by local resistance patterns and national guidance. Extensively drug-resistant typhoid isolates require treatment with azithromycin and/or meropenem. Combining antimicrobials that target intracellular and extracellular typhoid bacteria is a strategy being explored in the Azithromycin and Cefixime in Typhoid Fever (ACT-SA) RCT, in progress in South Asia. Alternative antimicrobials, such as the oral carbapenem, tebipenem, need clinical evaluation. There is a paucity of evidence to guide the antimicrobial management of chronic fecal carriers. [ABSTRACT FROM AUTHOR]

The global response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic demonstrated the value of timely and open sharing of genomic data with standardized metadata to facilitate monitoring of the emergence and spread of new variants. Here, we make the case for the value of Salmonella Typhi (S. Typhi) genomic data and demonstrate the utility of freely available platforms and services that support the generation, analysis, and visualization of S. Typhi genomic data on the African continent and more broadly by introducing the Africa Centres for Disease Control and Prevention's Pathogen Genomics Initiative, SEQAFRICA, Typhi Pathogenwatch, TyphiNET, and the Global Typhoid Genomics Consortium. [ABSTRACT FROM AUTHOR]

Typhoid is an enteric disease caused by Salmonella Typhi. Like many febrile illnesses, typhoid presents with nonspecific symptoms. In routine healthcare settings in low- and middle-income countries, typhoid fever is suspected and treated empirically. Though many diagnostic tests are available for typhoid diagnosis, there are currently no diagnostic tests that meet ideal requirements for sensitivity, specificity, speed, and cost-effectiveness. With introduction of typhoid conjugate vaccine, it is essential to explore the current and future typhoid approach in the context of use case and access to ensure their utilization for disease control. [ABSTRACT FROM AUTHOR]

Airborne severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in a coronavirus disease 19 (COVID-19) ward before activation of HEPA-air filtration but not during filter operation; SARS-CoV-2 was again detected following filter deactivation. Airborne SARS-CoV-2 was infrequently detected in a COVID-19 intensive care unit. Bioaerosol was also effectively filtered. [ABSTRACT FROM AUTHOR]

We report the persistent circulation of third-generation cephalosporin resistant Salmonella Typhi in Mumbai, linked to the acquisition and maintenance of a previously characterized IncX3 plasmid carrying the ESBL gene bla SHV-12 and the fluoroquinolone resistance gene qnrB7 in the genetic context of a triple mutant also associated with fluoroquinolone resistance. [ABSTRACT FROM AUTHOR]

Antimicrobials are a key group of therapeutic agents. Given the animal/human population density and high antimicrobial consumption rate in Southeast Asia, the region is a focal area for monitoring antimicrobial resistance (AMR). Hypothesizing that the gastrointestinal tract of healthy individuals in Vietnam is a major source of AMR genes that may be transferred to pathogens, we performed shotgun metagenomic sequencing on fecal samples from 42 healthy Vietnamese people (21 children and 21 adults). We compared their microbiome profiles by age group and determined the composition of AMR genes. An analysis of the taxonomic profiles in the gut microbiome showed a clear differentiation by age, with young children (age <2 years) exhibiting a unique structure in comparison to adults and older children. We identified a total of 132 unique AMR genes, with macrolide, lincosamide, and streptogramin class resistance genes (ermB and lnuC) and tetracycline resistance genes being almost ubiquitous across the study population. Notably, samples from younger children were significantly associated with a greater number of AMR genes than other age groups, including key signature genes associated with AMR pathogens (eg, blaCTX-M, mphA). Our data suggest that the gut microbiome of those living in Vietnam, particularly young children, is a substantial reservoir of AMR genes, which can be transferred to circulating enteric pathogens. Our data support the generation of longitudinal cohort studies of those living in urban and rural areas of developing countries to understand the behavior of these AMR reservoirs and their role in generating multidrug-resistant and extensively drug-resistant pathogens. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial therapy is essential for the treatment of enteric fever, the infection caused by Salmonella serovars Typhi and Paratyphi A. However, an increase in resistance to key antimicrobials and the emergence of MDR and XDR in Salmonella Typhi poses a major threat for efficacious outpatient treatments.Objectives: We recently identified tebipenem, an oral carbapenem licensed for use for respiratory tract infections in Japan, as a potential alternative treatment for MDR/XDR Shigella spp. Here, we aimed to test the in vitro antibacterial efficacy of this drug against MDR and XDR typhoidal Salmonella.Methods: We determined the in vitro activity of tebipenem in time-kill assays against a collection of non-XDR and XDR Salmonella Typhi and Salmonella Paratyphi A (non-XDR) isolated in Nepal and Bangladesh. We also tested the efficacy of tebipenem in combination with other antimicrobials.Results: We found that both XDR and non-XDR Salmonella Typhi and Salmonella Paratyphi A are susceptible to tebipenem, exhibiting low MICs, and were killed within 8-24 h at 2-4×MIC. Additionally, tebipenem demonstrated synergy with two other antimicrobials and could efficiently induce bacterial killing.Conclusions: Salmonella Paratyphi A and XDR Salmonella Typhi display in vitro susceptibility to the oral carbapenem tebipenem, while synergistic activity with other antimicrobials may limit the emergence of resistance. The broad-spectrum activity of this drug against MDR/XDR organisms renders tebipenem a good candidate for clinical trials. [ABSTRACT FROM AUTHOR]

Background: The clinical response to ceftriaxone in patients with typhoid fever is significantly slower than with ofloxacin, despite infection with Salmonella enterica serovar Typhi (S. Typhi) isolates with similar susceptibilities (MIC 0.03-0.12 mg/L). The response to ofloxacin is slower if the isolate has intermediate susceptibility (MIC 0.25-1.0 mg/L).Objectives: To determine the bactericidal activity and post-antibiotic effect (PAE) of ceftriaxone and ofloxacin against S. Typhi.Methods: The mean time to reach a 99.9% reduction in log10 count (bactericidal activity) and PAE of ceftriaxone and ofloxacin were determined for 18 clinical isolates of S. Typhi in time-kill experiments (MIC range for ofloxacin 0.06-1.0 mg/L and for ceftriaxone 0.03-0.12 mg/L).Results: The mean (SD) bactericidal activity of ofloxacin was 33.1 (15.2) min and 384.4 (60) min for ceftriaxone. After a 30 min exposure to ofloxacin, the mean (SD) duration of PAE was 154.7 (52.6) min. There was no detectable PAE after 1 h of exposure to ceftriaxone. For ofloxacin, bactericidal activity and PAE did not significantly differ between isolates with full or intermediate susceptibility provided ofloxacin concentrations were maintained at 4×MIC.Conclusions: Infections with S. Typhi with intermediate ofloxacin susceptibility may respond to doses that maintain ofloxacin concentrations at 4×MIC at the site of infection. The slow bactericidal activity of ceftriaxone and absent PAE may explain the slow clinical response in typhoid. [ABSTRACT FROM AUTHOR]

Background: Plastic surgeons increasingly use social media as a means for patient engagement, trainee education, and research dissemination. Appropriate patient diversity on these platforms is critical to promote interaction with all patients and ensure adequate training of plastic surgeons to work with diverse populations.Objectives: This study aimed to assess patient representation, particularly of racial and ethnic groups, among plastic surgery Instagram accounts.Methods: Nine Instagram accounts of plastic surgery journals and professional organizations were analyzed for posts containing patient images between April 2015 and June 2020. Each unique patient image was assessed for demographic factors. Skin tone was analyzed as a proxy for racial diversity, with Fitzpatrick scale scores of 1 to 3 indicating white and 4 to 6 indicating nonwhite. Univariate analysis was performed to determine differences in representation.Results: A total of 6719 posts from 5 journal and 4 professional organization accounts were found to contain 2547 unique patient images. Overall, 88.14% of patient images had white skin tone, whereas only 11.86% displayed nonwhite skin tone. Cosmetic procedure patient images had a higher frequency of white skin tone than reconstruction images (89.93% vs 81.98%, P < 0.001). When compared with US Census data and the ASPS Annual Report data on race of patients undergoing plastic surgery, our data revealed significant underrepresentation of patients of color on social media (P < 0.001).Conclusions: This study highlights the underrepresentation of patients of color within social media imagery. Equitable representation of patients on social media is important to decrease patient barriers to healthcare and improve physician training to engage with diverse populations. [ABSTRACT FROM AUTHOR]