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BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection is poorly understood, partly because few studies have systematically applied genomic analysis to distinguish reinfection from persistent RNA detection related to initial infection. We aimed to evaluate the characteristics of SARS-CoV-2 reinfection and persistent RNA detection using independent genomic, clinical, and laboratory assessments.MethodsAll individuals at a large academic medical center who underwent a SARS-CoV-2 nucleic acid amplification test (NAAT) ≥45 days after an initial positive test, with both tests between 14 March and 30 December 2020, were analyzed for potential reinfection. Inclusion criteria required having ≥2 positive NAATs collected ≥45 days apart with a cycle threshold (Ct) value ResultsAmong 1569 individuals with repeat SARS-CoV-2 testing ≥45 days after an initial positive NAAT, 65 (4%) met cohort inclusion criteria. Viral genomic analysis characterized mutations present and was successful for 14/65 (22%) subjects. Six subjects had genomically supported reinfection, and 8 subjects had genomically supported persistent RNA detection. Compared to viral genomic analysis, clinical and laboratory assessments correctly distinguished reinfection from persistent RNA detection in 12/14 (86%) subjects but missed 2/6 (33%) genomically supported reinfections.ConclusionsDespite good overall concordance with viral genomic analysis, clinical and Ct value-based assessments failed to identify 33% of genomically supported reinfections. Scaling-up genomic analysis for clinical use would improve detection of SARS-CoV-2 reinfections.

A bacterial species is considered to be intrinsically resistant to an antimicrobial when nearly all of the wild-type isolates (i.e., those without acquired resistance) exhibit minimum inhibitory concentration (MIC) values that are sufficiently high such that susceptibility testing is unnecessary, and that the antimicrobial should not be considered for therapy. Accordingly, knowledge of intrinsic resistance influences both the selection of treatment regimens and the approach to susceptibility testing in the clinical laboratory, where unexpected results also facilitate the recognition of microbial identification or susceptibility testing errors.

BackgroundExtended spectrum beta-lactamase producing Enterobacterales (ESBL-PE) present a risk to public health by limiting the efficacy of multiple classes of beta-lactam antibiotics against infection. International travellers may acquire these organisms and identifying individuals at high risk of acquisition could help inform clinical treatment or prevention strategies.MethodsWe used data collected from a cohort of 528 international travellers enrolled in a multicentre US-based study to derive a clinical prediction rule (CPR) to identify travellers who developed ESBL-PE colonization, defined as those with new ESBL positivity in stool upon return to the United States. To select candidate features, we used data collected from pre-travel and post-travel questionnaires, alongside destination-specific data from external sources. We utilized LASSO regression for feature selection, followed by random forest or logistic regression modelling, to derive a CPR for ESBL acquisition.ResultsA CPR using machine learning and logistic regression on 10 features has an internally cross-validated area under the receiver operating characteristic curve (cvAUC) of 0.70 (95% confidence interval 0.69–0.71). We also demonstrate that a four-feature model performs similarly to the 10-feature model, with a cvAUC of 0.68 (95% confidence interval 0.67–0.69). This model uses traveller’s diarrhoea, and antibiotics as treatment, destination country waste management rankings and destination regional probabilities as predictors.ConclusionsWe demonstrate that by integrating traveller characteristics with destination-specific data, we could derive a CPR to identify those at highest risk of acquiring ESBL-PE during international travel.

Background Pediatric international travelers account for nearly half of measles importations in the United States. Over one third of pediatric international travelers depart the United States without the recommended measles-mumps-rubella (MMR) vaccinations: 2 doses for travelers ≥12 months and 1 dose for travelers 6 to Methods We developed a model to compare 2 strategies among a simulated cohort of international travelers (6 months to Results Compared with no PHE, PHE would avert 57 measles cases at $9.2 million/QALY among infant travelers and 7 measles cases at $15.0 million/QALY among preschool-aged travelers. Clinical benefits of PHE would be greatest for infants but cost-effective only for travelers to destinations with higher risk for measles exposure (ie, ≥160 exposures/million travelers) or if more US-acquired cases resulted from an infected traveler, such as in communities with limited MMR coverage. Conclusions Pretravel MMR vaccination provides the greatest clinical benefit for infant travelers and can be cost-effective before travel to destinations with high risk for measles exposure or from communities with low MMR vaccination coverage.

Recent technological and computational advances have made metagenomic assembly a viable approach to achieving high-resolution views of complex microbial communities. In previous benchmarking, short-read (SR) metagenomic assemblers had the highest accuracy, long-read (LR) assemblers generated the most contiguous sequences and hybrid (HY) assemblers balanced length and accuracy. However, no assessments have specifically compared the performance of these assemblers on low-abundance species, which include clinically relevant organisms in the gut. We generated semi-synthetic LR and SR datasets by spiking small and increasing amounts of Escherichia coli isolate reads into fecal metagenomes and, using different assemblers, examined E. coli contigs and the presence of antibiotic resistance genes (ARGs). For ARG assembly, although SR assemblers recovered more ARGs with high accuracy, even at low coverages, LR assemblies allowed for the placement of ARGs within longer, E. coli-specific contigs, thus pinpointing their taxonomic origin. HY assemblies identified resistance genes with high accuracy and had lower contiguity than LR assemblies. Each assembler type’s strengths were maintained even when our isolate was spiked in with a competing strain, which fragmented and reduced the accuracy of all assemblies. For strain characterization and determining gene context, LR assembly is optimal, while for base-accurate gene identification, SR assemblers outperform other options. HY assembly offers contiguity and base accuracy, but requires generating data on multiple platforms, and may suffer high misassembly rates when strain diversity exists. Our results highlight the trade-offs associated with each approach for recovering low-abundance taxa, and that the optimal approach is goal-dependent.

Purpose of review Antimicrobial resistance (AMR) in bacteria poses a major risk to global public health, with many factors contributing to the observed increase in AMR. International travel is one recognized contributor. The purpose of this review is to summarize current knowledge regarding the acquisition, carriage and spread of AMR bacteria by international travelers. Recent findings Recent studies have highlighted that travel is an important risk factor for the acquisition of AMR bacteria, with approximately 30% of studied travelers returning with an acquired AMR bacterium. Epidemiological studies have shown there are three major risk factors for acquisition: travel destination, antimicrobial usage and travelers' diarrhea (TD). Analyses have begun to illustrate the AMR genes that are acquired and spread by travelers, risk factors for acquisition and carriage of AMR bacteria, and local transmission of imported AMR organisms. Summary International travel is a contributor to the acquisition and dissemination of AMR organisms globally. Efforts to reduce the burden of AMR organisms should include a focus on international travelers. Routine genomic surveillance would further elucidate the role of international travel in the global spread of AMR bacteria.

Background To assess the implications of coronavirus disease 2019 (COVID-19)–related travel disruptions, we compared demographics and travel-related circumstances of US travelers seeking pretravel consultation regarding international travel at US Global TravEpiNet (GTEN) sites before and after the initiation of COVID-19 travel warnings. Methods We analyzed data in the GTEN database regarding traveler demographics and travel-related circumstances with standard questionnaires in the pre-COVID-19 period (January–December 2019) and the COVID-19 period (April 2020–March 2021), excluding travelers from January to March 2020. We conducted descriptive analyses of differences in demographics, travel-related circumstances, routine and travel-related vaccinations, and medications. Results Compared with 16 903 consultations in the pre-COVID-19 period, only 1564 consultations were recorded at GTEN sites during the COVID-19 period (90% reduction), with a greater proportion of travelers visiting friends and relatives (501/1564 [32%] vs 1525/16 903 [9%]), individuals traveling for >28 days (824/1564 [53%] vs 2522/16 903 [15%]), young children (6 mo– Conclusions Compared with the pre-COVID-19 period, a greater proportion of travelers during the COVID-19 period were young children, were planning to visit friends and relatives, were traveling for >28 days, or were traveling to Africa, which are circumstances that contribute to high risk for travel-related infections. Fewer vaccine-eligible travelers were administered travel-related vaccines at pretravel consultations. Counseling and vaccination focused on high-risk international travelers must be prioritized during the COVID-19 pandemic.

Background Extensively drug-resistant (XDR) typhoid fever is a threat to travelers to Pakistan. We describe a multicontinental case series of travel-acquired XDR typhoid fever to demonstrate the global spread of the problem and encourage preventive interventions as well as appropriate empiric antimicrobial use. Methods Cases were extracted from the GeoSentinel database, microbiologic laboratory records of two large hospitals in Toronto, Canada, and by invitation to TropNet sites. All isolates were confirmed XDR Salmonella enterica serovar Typhi (Salmonella typhi), with resistance to ampicillin, ceftriaxone, ciprofloxacin and trimethoprim–sulfamethoxazole. Results Seventeen cases were identified in Canada (10), USA (2), Spain (2), Italy (1), Australia (1) and Norway (1). Patients under 18 years represented 71% (12/17) of cases, and all patients travelled to Pakistan to visit friends or relatives. Only one patient is known to have been vaccinated. Predominant symptoms were fever, abdominal pain, vomiting and diarrhoea. Antimicrobial therapy was started on Day 1 of presentation in 75% (12/16) of patients, and transition to a carbapenem or azithromycin occurred a median of 2 days after blood culture was drawn. Antimicrobial susceptibilities were consistent with the XDR S. typhi phenotype, and whole genome sequencing on three isolates confirmed their belonging to the XDR variant of the H58 clade. Conclusions XDR typhoid fever is a particular risk for travelers to Pakistan, and empiric use of a carbapenem or azithromycin should be considered. Pre-travel typhoid vaccination and counseling are necessary and urgent interventions, especially for visiting friends and relatives travelers. Ongoing sentinel surveillance of XDR typhoid fever is needed to understand changing epidemiology.

Vibriocidal antibodies are the best characterized correlate of protection against cholera and are used to gauge immunogenicity in vaccine trials. However, there is no vibriocidal titer threshold associated with absolute protection against infection with Vibrio cholerae or with symptomatic disease in infected individuals. While other circulating antibody responses have also been associated with a decreased risk of V. cholerae infection, there has been no comprehensive comparison of correlates of protection against cholera. To address this, we analyzed 58 serum antibody biomarkers as correlates of protection against both V. cholerae infection and against cholera diarrhea in infected individuals. The study was performed in two cohorts: (1) household contacts of patients with cholera in Bangladesh, and (2) North American volunteers who were vaccinated with a single dose of CVD 103-HgR live oral cholera vaccine and then challenged with virulent V. cholerae O1 El Tor Inaba. In household contacts, we identified 20 antibody markers that were correlated with protection against V. cholerae infection, though there was overlap between distributions. Conditional random forest models identified serum antibody-dependent complement deposition, targeting the V. cholerae O1 antigen, as the most predictive individual correlate of protection from infection, while vibriocidal antibody titers were less predictive. The model that most accurately predicted protection from infection included five biomarkers, with a cross-validated area under the curve (cvAUC) of 79% (95% CI 73-85). Similarly, in North American volunteers who were challenged with V. cholerae after vaccination, a different five-biomarker model predicted protection from the development of cholera diarrhea with a cvAUC of 78% (95% CI 66-91). Thus, while several new biomarkers predict protection better than vibriocidal titers, it remains difficult to consistently predict whether an individual will be protected from future mucosal infection or symptoms using current serologic markers.

As U.S. healthcare systems plan for future physician workforce needs, the systemic impacts of climate change, a worldwide environmental and health crisis, have not been factored in. The current foc...

Highlights • Serum IgG antibody responses developed in 95% of mildly symptomatic individuals by day 14 and all subjects had seroconverted by day 30. • Serum IgM and IgA antibody responses were lower and less frequent than corresponding IgG responses, and peaked and declined earlier 100% of mild symptomatic individuals developed an IgG antibody response by day 30. • Fewer than 45% of asymptomatic infected individuals had seroconverted by day 30 post-PCR diagnosis. • Impact on modeling of herd immunity., Objectives Studies on serologic responses following COVID-19 have been published primarily in individuals who are moderately or severely symptomatic, but there are few data from individuals who are mildly symptomatic or asymptomatic. Methods We measured IgG, IgM, and IgA to the receptor-binding domain of SARS-CoV-2 by ELISA in mildly symptomatic (n = 108) and asymptomatic (n = 63) on days 1, 7, 14, and 30 following RT-PCR confirmation in Bangladesh, and compared with pre-pandemic samples, including healthy controls (n = 73) and individuals infected with other viruses (n = 79). Results Mildly symptomatic individuals developed IgM and IgA responses by day 14 in 72% and 83% of individuals, respectively, while 95% of individuals developed IgG response, and rose to 100% by day 30. In contrast, individuals infected with SARS-CoV-2 but who remained asymptomatic developed antibody responses significantly less frequently, with only 20% positive for IgA and 22% positive for IgM by day 14, and 45% positive for IgG by day 30 after infection. Conclusions These results confirm immune responses are generated following COVID-19 who develop a mildly symptomatic illness. However, those with the asymptomatic infection do not respond or have lower antibody levels. These results will impact modeling needed for determining herd immunity generated by natural infection or vaccination.

The earth is rapidly warming, driven by increasing atmospheric carbon dioxide and other gases that result primarily from fossil fuel combustion. In addition to causing arctic ice melting and extreme weather events, climatologic factors are linked strongly to the transmission of many infectious diseases. Changes in the prevalence of infectious diseases not only reflect the impacts of temperature, humidity, and other weather-related phenomena on pathogens, vectors, and animal hosts but are also part of a complex of social and environmental factors that will be affected by climate change, including land use, migration, and vector control. Vector- and waterborne diseases and coccidioidomycosis are all likely to be affected by a warming planet; there is also potential for climate-driven impacts on emerging infectious diseases and antimicrobial resistance. Additional resources for surveillance and public health activities are urgently needed, as well as systematic education of clinicians on the health impacts of climate change.

SARS-CoV-2 reinfection is poorly understood, partly because few studies have systematically applied genomic analysis to distinguish reinfection from persistent RNA detection related to initial infection. We aimed to evaluate the characteristics of SARS-CoV-2 reinfection and persistent RNA detection using independent genomic, clinical, and laboratory assessments.All individuals at a large academic medical center who underwent a SARS-CoV-2 nucleic acid amplification test (NAAT) ≥ 45 days after an initial positive test, with both tests between March 14th and December 30th, 2020, were analyzed for potential reinfection. Inclusion criteria required having ≥2 positive NAATs collected ≥45 days apart with a cycle threshold (Ct) value35 at repeat testing. For each included subject, likelihood of reinfection was assessed by viral genomic analysis of all available specimens with a Ct value35, structured Ct trajectory criteria, and case-by-case review by infectious diseases physicians.Among 1,569 individuals with repeat SARS-CoV-2 testing ≥45 days after an initial positive NAAT, 65 (4%) met cohort inclusion criteria. Viral genomic analysis characterized mutations present, and was successful for 14/65 (22%) subjects. Six subjects had genomically-supported reinfection and eight subjects had genomically-supported persistent RNA detection. Compared to viral genomic analysis, clinical and laboratory assessments correctly distinguished reinfection from persistent RNA detection in 12/14 (86%) subjects but missed 2/6 (33%) genomically-supported reinfections.Despite good overall concordance with viral genomic analysis, clinical and Ct value-based assessments failed to identify 33% of genomically-supported reinfections. Scaling-up genomic analysis for clinical use would improve detection of SARS-CoV-2 reinfections.

Recent studies indicate that the human intestinal microbiota could impact the outcome of infection by Vibrio cholerae, the etiological agent of the diarrheal disease cholera. A commensal bacterium, Paracoccus aminovorans, was previously identified in high abundance in stool collected from individuals infected with V. cholerae when compared to stool from uninfected persons. However, if and how P. aminovorans interacts with V. cholerae has not been experimentally determined; moreover, whether any association between this bacterium alters the behaviors of V. cholerae to affect the disease outcome is unclear. Here, we show that P. aminovorans and V. cholerae together form dual-species biofilm structure at the air–liquid interface, with previously uncharacterized novel features. Importantly, the presence of P. aminovorans within the murine small intestine enhances V. cholerae colonization in the same niche that is dependent on the Vibrio exopolysaccharide and other major components of mature V. cholerae biofilm. These studies illustrate that multispecies biofilm formation is a plausible mechanism used by a gut microbe to increase the virulence of the pathogen, and this interaction may alter outcomes in enteric infections.

To evaluate severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific antibody responses after Covishield vaccination for 6 months after vaccination.SARS-CoV-2-specific antibody responses were assessed by enzyme-linked immunosorbent assay of the recombinant receptor-binding domain of SARS-CoV-2 in 381 adults given the Covishield vaccine at baseline (Over 51% of participants were seropositive at baseline (before vaccination with Covishield), and almost all participants (159/161) became seropositive 1 month after the second dose. Antibody levels peaked 1 month after receipt of the second dose of vaccine, and decreased by 4 months after the first dose; the lowest responses were found 6 months after the first dose, although antibody responses and responder frequencies remained significantly higher compared with baseline (These findings help to elucidate the longevity of vaccine-specific antibody responses following vaccination with Covishield, and provide information relevant to the planning of booster doses after the initial two doses of vaccine.

The co-occurrence of the 2020 Atlantic hurricane season and the ongoing coronavirus disease 2019 (COVID-19) pandemic creates complex dilemmas for protecting populations from these intersecting threats. Climate change is likely contributing to stronger, wetter, slower-moving, and more dangerous hurricanes. Climate-driven hazards underscore the imperative for timely warning, evacuation, and sheltering of storm-threatened populations – proven life-saving protective measures that gather evacuees together inside durable, enclosed spaces when a hurricane approaches. Meanwhile, the rapid acquisition of scientific knowledge regarding how COVID-19 spreads has guided mass anti-contagion strategies, including lockdowns, sheltering at home, physical distancing, donning personal protective equipment, conscientious handwashing, and hygiene practices. These life-saving strategies, credited with preventing millions of COVID-19 cases, separate and move people apart. Enforcement coupled with fear of contracting COVID-19 have motivated high levels of adherence to these stringent regulations. How will populations react when warned to shelter from an oncoming Atlantic hurricane while COVID-19 is actively circulating in the community? Emergency managers, health care providers, and public health preparedness professionals must create viable solutions to confront these potential scenarios: elevated rates of hurricane-related injury and mortality among persons who refuse to evacuate due to fear of COVID-19, and the resurgence of COVID-19 cases among hurricane evacuees who shelter together.

Many studies have examined the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on neutralizing antibody activity after they have become dominant strains. Here, we evaluate the consequences of further viral evolution. We demonstrate mechanisms through which the SARS-CoV-2 receptor binding domain (RBD) can tolerate large numbers of simultaneous antibody escape mutations and show that pseudotypes containing up to seven mutations, as opposed to the one to three found in previously studied variants of concern, are more resistant to neutralization by therapeutic antibodies and serum from vaccine recipients. We identify an antibody that binds the RBD core to neutralize pseudotypes for all tested variants but show that the RBD can acquire an N-linked glycan to escape neutralization. Our findings portend continued emergence of escape variants as SARS-CoV-2 adapts to humans.

BackgroundOral cholera vaccines (OCVs) are an important tool for reduction of the worldwide cholera burden, but some individuals who receive an OCV do not develop protective immune responses. The gut microbiota is a potential explanation for these differences. Components of the gut microbiota associated with differences in OCV response have not been identified.ResultsWe used metagenomic sequencing to identify predicted protein-coding genes in the gut microbiota at the time of OCV administration, and then measured immune responses to vaccination. Vaccine recipients were classified as OCV “responders” if they developed a post­vaccination increase in memory B cell populations that produce IgA or IgG specific for cholera toxin and the V. cholerae O-specific polysaccharide. We next analyzed microbial genes seen at similar abundances across individual samples and classified these into co-abundant gene groupings (CAGs), and correlated CAGs with OCV responses. Next, to identify specific bacterial strains associated with OCV responses, we mapped CAGs to bacterial genomes and generated a “priority score” for each strain detected in the study population. This score reflects both the number of CAGs aligning to a specific bacterial genome and the strength of the association between the CAGs and the vaccine response. This strain-level analysis revealed relationships between the gut microbiota and immune response to OCV that were not detected at the genus or species level. Bacterial strains which produce short-chain fatty acids and those with sphingolipid-containing cell membranes were correlated with more robust immune responses to vaccination.ConclusionOur study demonstrates a method for translating metagenomic sequencing data into strain-specific results associated with a biological outcome. Using this approach, we identified strains for the study of bacterial-derived molecules or metabolites associated with immune responses; such agents might have potential utility as vaccine adjuvants.

Early detection of SARS-CoV-2 infection is crucial to prevent the spread of the virus. In this study, we evaluated the performance of a commercial rapid antigen detection test, BD Veritor, and compared this (and another rapid test, Standard Q) against a gold-standard of nasopharyngeal (NP) swab tested by reverse transcription-polymerase chain reaction (RT-PCR) in prospectively-recruited adults in Dhaka, Bangladesh. We compared the sensitivity and specificity of the two rapid antigen tests against RT-PCR results in 130 symptomatic and 130 asymptomatic adults. In addition, we evaluated the suitability and ease-of-use of the BD Veritor test in a subsample of study participants (n=42) and implementers (n=5). The sensitivity of the BD Veritor rapid antigen test was 70% in symptomatic (95% confidence interval [CI]: 51-85%) and 87% (95% CI: 69-96%) in asymptomatic individuals with positive SARSCoV-2 RT-PCR, for overall sensitivity of 78% (95% CI: 66-88%). The sensitivity of the Standard Q rapid antigen test was 63% (95% CI: 44-80%) in symptomatic and 73% (95% CI: 54-87%) in asymptomatic individuals. One false positive in BD Veritor test (specificity 99.5) and no false positive in Standard Q tests were observed (specificity 100%). The BD Veritor rapid antigen test was 78% sensitive when compared with RT-PCR irrespective of the cycle threshold (Ct) levels in this evaluation in Bangladesh. The implementation evaluation data showed good acceptability in the field settings. This warrants large field evaluation as well as use of the rapid antigen test for quick assessment of SARS-CoV-2 for containment of epidemics in the country.

Vibrio cholerae can cause a range of symptoms, from severe diarrhea to asymptomatic infection. Previous studies using whole-genome sequencing (WGS) of multiple bacterial isolates per patient showed that V. cholerae can evolve modest genetic diversity during symptomatic infection. To further explore the extent of V. cholerae within-host diversity, we applied culture-based WGS and metagenomics to a cohort of both symptomatic and asymptomatic cholera patients from Bangladesh. While metagenomics allowed us to detect more mutations in symptomatic patients, WGS of cultured isolates was necessary to detect V. cholerae diversity in asymptomatic carriers, likely due to their low V. cholerae load. Using both metagenomics and isolate WGS, we report three lines of evidence that V. cholerae hypermutators evolve within patients. First, we identified nonsynonymous mutations in V. cholerae DNA repair genes in 5 out of 11 patient metagenomes sequenced with sufficient coverage of the V. cholerae genome and in 1 of 3 patients with isolate genomes sequenced. Second, these mutations in DNA repair genes tended to be accompanied by an excess of intrahost single nucleotide variants (iSNVs). Third, these iSNVs were enriched in transversion mutations, a known hallmark of hypermutator phenotypes. While hypermutators appeared to generate mostly selectively neutral mutations, nonmutators showed signs of convergent mutation across multiple patients, suggesting V. cholerae adaptation within hosts. Our results highlight the power and limitations of metagenomics combined with isolate sequencing to characterize within-patient diversity in acute V. cholerae infections, while providing evidence for hypermutator phenotypes within cholera patients. IMPORTANCE Pathogen evolution within patients can impact phenotypes such as drug resistance and virulence, potentially affecting clinical outcomes. V. cholerae infection can result in life-threatening diarrheal disease or asymptomatic infection. Here, we describe whole-genome sequencing of V. cholerae isolates and culture-free metagenomic sequencing from stool of symptomatic cholera patients and asymptomatic carriers. Despite the typically short duration of cholera, we found evidence for adaptive mutations in the V. cholerae genome that occur independently and repeatedly within multiple symptomatic patients. We also identified V. cholerae hypermutator phenotypes within several patients, which appear to generate mainly neutral or deleterious mutations. Our work sets the stage for future studies of the role of hypermutators and within-patient evolution in explaining the variation from asymptomatic carriage to symptomatic cholera.

Cholera is a diarrheal disease caused by Vibrio cholerae that continues to be a major public health concern in populations without access to safe water. IgG- and IgA-secreting memory B cells (MBC) targeting the V. cholerae O-specific polysaccharide (OSP) correlate with protection from infection in persons exposed to V. cholerae and may be a major determinant of long-term protection against cholera. Shanchol, a widely used oral cholera vaccine (OCV), stimulates OSP MBC responses in only some people after vaccination, and the gut microbiota is a possible determinant of variable immune responses observed after OCV. Using 16S rRNA sequencing of feces from the time of vaccination, we compared the gut microbiota among adults with and without MBC responses to OCV. Gut microbial diversity measures were not associated with MBC isotype or OSP-specific responses, but individuals with a higher abundance of Clostridiales and lower abundance of Enterobacterales were more likely to develop an MBC response. We applied protein-normalized fecal supernatants of high and low MBC responders to THP-1-derived human macrophages to investigate the effect of microbial factors at the time of vaccination. Feces from individuals with higher MBC responses induced significantly different IL-1β and IL-6 levels than individuals with lower responses, indicating that the gut microbiota at the time of vaccination may “prime” the mucosal immune response to vaccine antigens. Our results suggest the gut microbiota could impact immune responses to OCVs, and further study of microbial metabolites as potential vaccine adjuvants is warranted.

Recent studies indicate that the human intestinal microbiota could impact the outcome of infection by

[This corrects the article DOI: 10.1371/journal.pntd.0006399.].

A Woman with Fever, Headache, and Progressive Encephalopathy A 70-year-old woman with a history of migraines was admitted to the hospital in autumn because of fever, headache, and encephalopathy. M...

Community Health Centers (CHCs) are a critical source of care for low-income and non-privately insured populations. During the pandemic, CHCs have leveraged their infrastructure and role as a trusted source of care to engage the communities they serve in COVID-19 testing.To directly address the impact that COVID-19 has had on historically marginalized populations in Massachusetts, we designed a study of community-engaged COVID-19 testing expansion: (1) leveraging existing partnerships to accelerate COVID-19 testing and rapidly disseminate effective implementation strategies; (2) incorporating efforts to address key barriers to testing participation in communities at increased risk for COVID-19; (3) further developing partnerships between communities and CHCs to address testing access and disparities; (4) grounding the study in the development of a shared ethical framework for advancing equity in situations of scarcity; and (5) developing mechanisms for communication and science translation to support community outreach. We use a controlled interrupted time series design, comparing number of COVID-19 tests overall and among people identified as members of high-risk groups served by intervention CHCs compared with six matched control CHCs in Massachusetts, followed by a stepped wedge design to pilot test strategies for tailored outreach by CHCs.Here, we describe a community-partnered strategy to accelerate COVID-19 testing in historically marginalized populations that provides ongoing resources to CHCs for addressing testing needs in their communities. The study aligns with principles of community-engaged research including shared leadership, adequate resources for community partners, and the flexibility to respond to changing needs over time.

Interventional studies targeting environment enteropathy (EE) are impeded by the lack of appropriate, validated, non-invasive biomarkers of EE. Thus, we aimed to validate the association of potential biomarkers for EE with enteric infections and nutritional status in a longitudinal birth cohort study. We measured endotoxin core antibody (EndoCab) and soluble CD14 (sCD14) in serum, and myeloperoxidase (MPO) in feces using commercially available enzyme-linked immunosorbent assay (ELISA) kits. We found that levels of serum EndoCab and sCD14 increase with the cumulative incidence of enteric infections. We observed a significant correlation between the fecal MPO level in the children at 24 months of age with the total number of bacterial and viral infections, the total number of parasitic infections, and the total number of diarrheal episodes and diarrheal duration. We observed that the levels of serum EndoCab, sCD14, and fecal MPO at 3 months of age were significantly associated with whether children were malnourished at 18 months of age or not. Biomarkers such as fecal MPO, serum EndoCab and sCD14 in children at an early age may be useful as a measure of cumulative burden of preceding enteric infections, which are predictive of subsequent malnutrition status and may be useful non-invasive biomarkers for EE.

Recent studies indicate that the human intestinal microbiota could impact the outcome of infection byVibrio cholerae, the etiological agent of the diarrheal disease cholera. A commensal bacterium,Paracoccus aminovorans, was previously identified in high abundance in stool collected from individuals infected withV. choleraewhen compared to stool from uninfected persons. However, if and howP. aminovoransinteracts withV. choleraehas not been experimentally determined; moreover, whether any association between this bacterium alters the behaviors ofV. choleraeto affect the disease outcome is unclear. Here we show thatP. aminovoransandV. choleraetogether form dual-species biofilm structures at the air-liquid interface, with previously uncharacterized novel features. Importantly, the presence ofP. aminovoranswithin the murine small intestine enhancesV. choleraecolonization in the same niche that is dependent on theVibrioexopolysaccharide (VPS) and other major components of matureV. choleraebiofilm. These studies illustrate that dual-species biofilm formation is a plausible mechanism used by a gut microbe to increase the virulence of the pathogen, and this interaction may alter outcomes in enteric infections.Significance StatementWhile ample evidence suggests that the outcome of some enteric infections can be affected by the intestinal microbiota, how specific gut microbes change the behaviors of a pathogen is unclear. Here we characterize the interaction betweenVibrio choleraeandParacoccus aminovorans, a gut microbe known to increase in abundance in the intestines during activeV. choleraeinfection in humans. These two bacteria form a dual-species biofilm structure at the air-liquid interface, and the gut microbe increases the host colonization efficiency ofV. cholerae. Importantly, our study identifies a previously unknown mechanism of gut microbe-pathogen interaction that has the potential to alter the disease outcome.