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Background Professional soccer athletes are at risk of acquiring SARS-CoV-2 when traveling or through domestic community transmission. The U.S. Major League Soccer (MLS) league uses protocol-based SARS-CoV-2 testing for identification of individuals with COVID-19. Methods Per MLS protocol, fully vaccinated players underwent SARS-CoV-2 RT-PCR testing weekly; unvaccinated players were tested every other day. Demographic and epidemiologic data (e.g., travel history) were collected from individuals who tested positive, and contact tracing was performed. Whole genome sequencing (WGS) was performed on positive specimens, and phylogenetic analyses were used to identify potential transmission patterns. Results In the fall of 2021, all 30 players from one MLS team underwent SARS-CoV-2 testing per protocol; 27 (90%) were vaccinated. One player who recently traveled to Africa tested positive for SARS-CoV-2; within the following two weeks, 10 additional players and 1 staff member without recent international travel history tested positive. WGS yielded full genome sequences for 10 samples, including one from the traveler. The traveler’s sample was Delta sublineage AY.36 and was closely related to a sequence from Africa. Nine samples yielded other Delta sublineages including AY.4 (n = 7), AY.39 (n = 1), and B.1.617.2 (n = 1). The seven AY.4 sequences clustered together; five were identical, suggesting a common source of infection. Transmission from a family member visiting from England to an MLS player was identified as the potential index case. The other two AY.4 sequences differed from this group by 1-3 nucleotides, as did a partial genome sequence from an additional team member. Conclusions WGS is a useful tool for understanding SARS-CoV-2 transmission dynamics in professional sports teams.

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Rationale for review Giardiasis is one of the most common human protozoal infections worldwide. First-line therapy of giardiasis includes nitroimidazole antibiotics. However, treatment failure with nitroimidazoles is increasingly reported, with up to 45% of patients not responding to initial treatment. There is no clear consensus on the approach to the management of nitroimidazole-refractory giardiasis. This systematic review aims to summarize the literature on pharmacotherapy for nitroimidazole-refractory giardiasis. Methods We conducted a systematic review of the literature to determine the optimal management strategies for nitroimidazole-refractory giardiasis. We searched Pubmed/MEDLINE, Embase and Cochrane library using the following search terms ‘Giardia’ AND ‘treatment failure’ OR ‘refractory giardia’ OR ‘resistant giardia’ with date limits of 1 January 1970 to 30 June 2021. We included all reports on humans, which described clinical outcomes of individuals with treatment refractory giardiasis, including case series and case reports. A descriptive synthesis of the data was conducted with pooling of data for interventions. Key findings Included in this review were five prospective studies, three retrospective studies, seven case series and nine case reports. Across these reports, a wide heterogeneity of treatment regimens was employed, including retreatment with an alternative nitroimidazole, combination therapy with a nitroimidazole and another agent and monotherapy with non-nitroimidazole regimens, including quinacrine, paromomycin and nitazoxanide. Retreatment with a nitroimidazole was not an effective therapy for refractory giardiasis. However, treatment with a nitroimidazole in combination with albendazole had a cure rate of 66.9%. In the included studies, quinacrine monotherapy was administered to a total of 179 patients, with a clinical cure rate of 88.8%. Overall, quinacrine was fairly well tolerated. Conclusions Reports on the treatment of nitroimidazole-refractory giardiasis demonstrate a heterogeneous approach to treatment. Of these, quinacrine appeared to be highly effective, though more data on its safety are needed.

Enteric fever, caused by Salmonella enterica serovar Typhi (S. Typhi) and S. enterica serovar Paratyphi (S. Paratyphi), is a common travel-related illness. Limited data are available on the antimicrobial resistance (AMR) patterns of these serovars among travelers. Records of travelers with a culture-confirmed diagnosis seen during or after travel from January 2007 to December 2018 were obtained from GeoSentinel. Traveler demographics and antimicrobial susceptibility data were analyzed. Isolates were classified as nonsusceptible if intermediate or resistant or as susceptible in accordance with the participating site’s national guidelines. A total of 889 travelers (S. Typhi infections, n = 474; S. Paratyphi infections, n = 414; coinfection, n = 1) were included; 114 (13%) were children of

Background Frequent observation of increasing fever and rising inflammatory markers late after onset of COVID-19 suggests Cytokine Release Syndrome (CRS, “Cytokine Storm”) may contribute to pathophysiology. Tocilizumab (TCZ), a monoclonal antibody targeting the receptor for the pro-inflammatory cytokine, IL-6, is effective in suppressing pathological inflammation in several rheumatological diseases. After administering TCZ to COVID-19 patients with suspected CRS, we observed a sharp fall in inflammatory indices. We analyzed this effect using results from the first 19 COVID-19 patients receiving TCZ at our hospital. Methods Data for all patients with confirmed COVID-19 who received TCZ at our center, a 200 bed community hospital in New England, were extracted from the Electronic Medical Record, including demographics, body temperature, C-Reactive Protein (CRP), IL-6 levels, clinical severity on the Ordinal Scale for Clinical Improvement (OSCI), and clinical outcome (recovery/discharge home, partial recovery/discharge rehab, death). Results were tabulated and statistical significance of changes in indices pre- and post- TCZ assessed by Wilcoxon Signed-Rank Test. Results 19 patients received TCZ: 16 got 400mg x1, 2 got 400 mg x2, 1 got 660 mg x1. Median age was 64 years (range: 44–94), 68% male. Mean interval from symptom onset to receiving TCZ was 11.5 days. Mean IL-6 was 145 pg/mL. Demographics, OSCI scores, and discharge status are shown in Table 1. Average daily peak temperatures (Tmax) pre- and post- TCZ were 100.7 and 98.9°F, p< 0.001. Mean CRP pre- and post- were 234 and 84.6 mg/L, p=0.001 (Fig.1). Decrease in Tmax and CRP was rapid and sustained (Fig. 2, 1st 8 patients shown for clarity.). 58% had improved clinical improvement by OSCI by day 7, 68% by day 14. 7 of 19 of patients were discharged home, 6 to rehab or acute care facility, and 6 died. Table 1: Patient Demographics, Clinical Severity Score, and Discharge Status Conclusion In this cohort of patients with moderate-to-severe COVID-19 and evidence of Cytokine Release Syndrome, tocilizumab was associated with rapid resolution of fever and marked decline in CRP. Most patients showed improvement in clinical severity scores and no adverse reactions were noted. Tocilizumab may be useful in control of pathological inflammation in COVID-19. Controlled trials will be needed to assess overall clinical benefit. Disclosures All Authors: No reported disclosures

An episode of cholera provides better protection against reinfection than oral cholera vaccines, and the reasons for this are still under study. To better understand this, we compared the immune responses of human cells exposed to live Vibrio cholerae with those of cells exposed to heat-killed V. cholerae (similar to the contents of oral cholera vaccines). We also compared the effects of active cholera toxin and the inactive cholera toxin B subunit (which is included in some cholera vaccines). One key immune signaling molecule, IL-23, was uniquely produced in response to the combination of live bacteria and active cholera holotoxin. Stimulation with V. cholerae that did not produce the active toxin or was killed did not produce an IL-23 response. The stimulation of IL-23 production by cholera toxin-producing V. cholerae may be important in conferring long-term immunity after cholera., Vibrio cholerae infection provides long-lasting protective immunity, while oral, inactivated cholera vaccines (OCV) result in more-limited protection. To identify characteristics of the innate immune response that may distinguish natural V. cholerae infection from OCV, we stimulated differentiated, macrophage-like THP-1 cells with live versus heat-inactivated V. cholerae with and without endogenous or exogenous cholera holotoxin (CT). Interleukin 23A gene (IL23A) expression was higher in cells exposed to live V. cholerae than in cells exposed to inactivated organisms (mean change, 38-fold; 95% confidence interval [95% CI], 4.0 to 42; P

International travel continues to steadily increase, including leisure travel, travel to one’s country of origin to visit friends and relatives, travel for service work, and business travel. Travelers with HIV may have an increased risk for travel-associated infections. The pre-travel medical consultation is an important means of assessing one’s risk for travel-related health issues. The aim of this review is to provide an update on key health considerations for the HIV-infected traveler. Like all travelers, the HIV-infected traveler should adhere to behavioral precautions, including safety measures with food and water consumption, safe sexual practices, and arthropod bite avoidance. HIV is a risk factor for venous thromboembolism and patients should be educated regarding this risk. Most pre-travel vaccines are safe and immunogenic in HIV-infected individuals, though live vaccines should be avoided in patients with low CD4 counts. Malaria chemoprophylaxis is strongly recommended in patients with HIV traveling to endemic areas and no significant interactions exist between the commonly used prophylactic anti-malarial agents and anti-retroviral therapy (ART). Travelers with HIV, particularly those who are not on ART or who have low CD4 cell counts, may have increased risk for tuberculosis, malaria, enteric infections, visceral leishmaniasis, American trypanosomiasis, and endemic mycoses such as histoplasmosis, talaromycosis, and coccidioidomycosis. The immune status of the HIV-infected traveler should be assessed prior to travel along with the duration, itinerary, and activities planned during travel in order to carefully consider individual risk for travel-related health issues.

Highlights • West Nile Virus can lead to various neurological presentation. • It is important to identify Acute Transverse Myelitis with the help of imaging. • It should be in our differentials in patients presenting with muscular weakness in endemic regions., Introduction West Nile Virus varies in presentation from asymptomatic to a febrile illness often associated with malaise, weakness and maculopapular rash. West Nile neuro-invasive disease often manifests as meningitis, encephalitis, and less commonly acute flaccid paralysis in a "polio-like" presentation. Acute transverse myelitis (ATM) is a rare manifestation. We present a case of neuro-invasive West Nile Virus infection with radiographic evidence of longitudinally extensive transverse myelitis (LETM), a subset of ATM, Case narration A 42-year-old male from Massachusetts presented with progressive asymmetric paralysis of 4 days duration after developing a prodrome of fever, neck stiffness and urinary retention. Physical examination demonstrated asymmetric lower extremity weakness Lumbar puncture revealed lymphocytic pleocytosis with normal protein and glucose and a positive West Nile IgM in CSF (4.89, reference

International travel, adventure travel, and eco-tourism are increasing over the past few decades. This review aims to summarize the spectrum of infections associated with recreational freshwater activities and international travel. Recreational water activities can be associated with a wide range of infections. Acute febrile illnesses due to leptospirosis and schistosomiasis are not uncommon in travelers following extensive freshwater exposure. Aeromonas and other water-associated pathogens are important to consider in a traveler presenting with a skin and soft tissue infection. Recreational water activities are often associated with diarrheal illnesses, especially in children, and the range of enteric pathogens includes bacterial pathogens such as Escherichia coli O157:H7 and Shigella species and the protozoan parasites Cryptosporidium and Giardia duodenalis. Infections due to free-living amebas though rare can lead to fulminant central nervous system infections. A diverse range of infections may be associated with freshwater exposure, and it is important that these entities are considered in a returning traveler presenting with an acute illness.

To better understand the innate immune response to Vibrio cholerae infection, we tracked gene expression in the duodenal mucosa of 11 Bangladeshi adults with cholera, using biopsy specimens obtained immediately after rehydration and 30 and 180 days later. We identified differentially expressed genes and performed an analysis to predict differentially regulated pathways and upstream regulators. During acute cholera, there was a broad increase in the expression of genes associated with innate immunity, including activation of the NF-κB, mitogen-activated protein kinase (MAPK), and Toll-like receptor (TLR)-mediated signaling pathways, which, unexpectedly, persisted even 30 days after infection. Focusing on early differences in gene expression, we identified 37 genes that were differentially expressed on days 2 and 30 across the 11 participants. These genes included the endosomal Toll-like receptor gene TLR8 , which was expressed in lamina propria cells. Underscoring a potential role for endosomal TLR-mediated signaling in vivo , our pathway analysis found that interferon regulatory factor 7 and beta 1 and alpha 2 interferons were among the top upstream regulators activated during cholera. Among the innate immune effectors, we found that the gene for DUOX2, an NADPH oxidase involved in the maintenance of intestinal homeostasis, was upregulated in intestinal epithelial cells during cholera. Notably, the observed increases in DUOX2 and TLR8 expression were also modeled in vitro when Caco-2 or THP-1 cells, respectively, were stimulated with live V. cholerae but not with heat-killed organisms or cholera toxin alone. These previously unidentified features of the innate immune response to V. cholerae extend our understanding of the mucosal immune signaling pathways and effectors activated in vivo following cholera.

Leptotrichiaspecies are normal constituents of the oral cavity and the genitourinary tract microbiota that are known to provoke disease in immunocompromised patients and rarely in immunocompetent individuals. Following the description ofLeptotrichia goodfellowiisp. nov., two cases of endocarditis by this species have been reported. Here, we report a case ofLeptotrichia goodfellowiiendocarditis in an immunocompetent patient with a valvular allograft. The isolation and identification ofLeptotrichiacan be challenging, and it is likely that infection with this pathogen is significantly underdiagnosed. A definitive identification, as in this case, most often requires 16S rRNA gene sequencing, highlighting the increasingly important role of this diagnostic modality among immunocompetent patients with undetermined anaerobic bacteremia.

Objective To investigate the susceptibilities to and consequences of HIV-1 dual infection. Design We compared clinical, virologic, and immunologic factors between participants who were dually infected with HIV-1 subtype B and monoinfected controls who were matched by ongoing HIV risk factor. Methods The viral load and CD4 progressions of dually and singly infected participant groups were compared with linear mixed-effects models, and individual dynamics before and after superinfection were assessed with a structural change test (Chow test). Recombination breakpoint analysis (GARD), HLA frequency analysis, and cytotoxic T-lymphocyte (CTL) epitope mapping were also performed (HIV LANL Database). Results The viral loads of dually infected participants increased more over 3 years of follow-up than the viral loads of monoinfected controls, whereas CD4 progressions of the two groups did not differ. Viral escape from CTL responses following superinfection was observed in two participants whose superinfecting strain completely replaced the initial strain. This pattern was not seen among participants whose superinfecting virus persisted in a recombinant form with the initial virus or was only detected transiently. Several HLA types were over-represented in dually infected participants as compared to monoinfected controls. Conclusions These results identify potential factors for dual infection susceptibility and further define its clinical consequences.

This article presents a case report of nonhepatic hyperammonemia, i.e., elevated serum ammonia secondary to a nonhepatic etiology. It then discusses the importance of broadening one's differential diagnosis to include such nonhepatic causes of elevated ammonia levels, and provides a short review of rarer causes of hyperammonemia in the adult population. Treating the underlying condition is the best way to prevent recurrence of hyperammonemia. However, symptomatic treatment should not be delayed while investigating the underlying source.