Tropical Diseases in Okinawa: Overview and Emerging Infectious Diseases.

Okinawa prefecture is at risk for emerging infectious diseases due to its subtropical climate and its location within the Indo-Pacific region. Understanding the existing vectors and infectious agents contextualizes current threats, guides treatment, and informs prevention, and may be of unique concern in the setting of complex emergencies.

SARS-CoV-2 infection is associated with self-reported post-acute neuropsychological symptoms within six months of follow-up.

BACKGROUND: Chronic neuropsychological sequelae following SARS-CoV-2 infection, including depression, anxiety, fatigue, and general cognitive difficulties, are a major public health concern. Given the potential impact of long-term neuropsychological impairment, it is important to characterize the frequency and predictors of this post-infection phenotype. METHODS: The Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases with Pandemic Potential (EPICC) study is a longitudinal study assessing the impact of SARS-CoV-2 infection in U.S. Military Healthcare System (MHS) beneficiaries, i.e. those eligible for care in the MHS including active duty servicemembers, dependents, and retirees. Four broad areas of neuropsychological symptoms were assessed cross-sectionally among subjects 1-6 months post-infection/enrollment, including: depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), fatigue (PROMIS® Fatigue 7a), and cognitive function (PROMIS® Cognitive Function 8a and PROMIS® Cognitive Function abilities 8a). Multivariable Poisson regression models compared participants with and without SARS-CoV-2 infection history on these measures, adjusting for sex, ethnicity, active-duty status, age, and months post-first positive or enrollment of questionnaire completion (MPFP/E); models for fatigue and cognitive function were also adjusted for depression and anxiety scores. RESULTS: The study population included 2383 participants who completed all five instruments within six MPFP/E, of whom 687 (28.8%) had at least one positive SARS-CoV-2 test. Compared to those who had never tested positive for SARS-CoV-2, the positive group was more likely to meet instrument-based criteria for depression (15.4% vs 10.3%, p<0.001), fatigue (20.1% vs 8.0%, p<0.001), impaired cognitive function (15.7% vs 8.6%, p<0.001), and impaired cognitive function abilities (24.3% vs 16.3%, p<0.001). In multivariable models, SARS-CoV-2 positive participants, assessed at an average of 2.7 months after infection, had increased risk of moderate to severe depression (RR: 1.44, 95% CI 1.12-1.84), fatigue (RR: 2.07, 95% CI 1.62-2.65), impaired cognitive function (RR: 1.64, 95% CI 1.27-2.11), and impaired cognitive function abilities (RR: 1.41, 95% CI 1.15-1.71); MPFP/E was not significant. CONCLUSIONS: Participants with a history of SARS-CoV-2 infection were up to twice as likely to report cognitive impairment and fatigue as the group without prior SARS-CoV-2 infection. These findings underscore the continued importance of preventing SARS-CoV-2 infection and while time since infection/enrollment was not significant through 6 months of follow-up, this highlights the need for additional research into the long-term impacts of COVID-19 to mitigate and reverse these neuropsychological outcomes.

Risk of sexually transmitted infections among U.S. military service members in the setting of HIV pre-exposure prophylaxis use.

BACKGROUND: The evidence for an increased incidence of sexually transmitted infections (STIs) among patients utilizing HIV pre-exposure prophylaxis (PrEP) has been inconsistent. We assessed the risk of incident STI while on PrEP compared to periods off PrEP among military service members starting PrEP. METHODS: Incidence rates of chlamydia, gonorrhea, syphilis, hepatitis C virus, and HIV were determined among military service members without HIV prescribed daily oral tenofovir disoproxil fumarate and emtricitabine for HIV PrEP from February 1, 2014 through June 10, 2016. Hazard ratios for incident STIs were calculated using an Anderson-Gill recurrent event proportional hazard regression model. RESULTS: Among 755 male service members, 477 (63%) were diagnosed with incident STIs (overall incidence 21.4 per 100 person-years). Male service members had a significantly lower risk of any STIs (adjusted hazard ratio (aHR) 0.21, 95% CI 0.11-0.40) while using PrEP compared to periods off PrEP after adjustment for socio-demographic characteristics, reasons for initiating PrEP, surveillance period prior to PrEP initiation, and the effect of PrEP on site and type of infection in multivariate analysis. However, when stratifying for anatomical site and type of infection, the risk of extragenital gonorrhea infection (pharyngeal NG: aHR 1.84, 95% CI 0.82-4.13, p = 0.30; rectal NG: aHR 1.23, 95% CI 0.60-2.51, p = 1.00) and extragenital CT infection (pharyngeal CT: aHR 2.30, 95% CI 0.46-11.46, p = 0.81; rectal CT: aHR 1.36, 95% CI 0.81-2.31, p = 0.66) was greater on PrEP compared to off PrEP although these values did not reach statistical significance. CONCLUSIONS: The data suggest entry into PrEP care reduced the overall risk of STIs following adjustment for anatomical site of STI and treatment. Service members engaged in PrEP services also receive more STI prevention counseling, which might contribute to decreases in STI risk while on PrEP.

Decreased Self-reported Physical Fitness Following SARS-CoV-2 Infection and the Impact of Vaccine Boosters in a Cohort Study.

Background: The long-term effects of coronavirus disease 2019 (COVID-19) on physical fitness are unclear, and the impact of vaccination on that relationship is uncertain. Methods: We compared survey responses in a 1-year study of US military service members with (n = 1923) and without (n = 1591) a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We fit Poisson regression models to estimate the association between history of SARS-CoV-2 infection and fitness impairment, adjusting for time since infection, demographics, and baseline health. Results: The participants in this analysis were primarily young adults aged 18-39 years (75%), and 71.5% were male. Participants with a history of SARS-CoV-2 infection were more likely to report difficulty exercising (38.7% vs 18.4%; P < .01), difficulty performing daily activities (30.4% vs 12.7%; P < .01), and decreased fitness test (FT) scores (42.7% vs 26.2%; P < .01) than those without a history of infection. SARS-CoV-2-infected participants were at higher risk of these outcomes after adjusting for other factors (unvaccinated: exercising: adjusted risk ratio [aRR], 3.99; 95% CI, 3.36-4.73; activities: aRR, 5.02; 95% CI, 4.09-6.16; FT affected: aRR, 2.55; 95% CI, 2.19-2.98). Among SARS-CoV-2-positive participants, full vaccination before infection was associated with a lower risk of post-COVID-19 fitness impairment (fully vaccinated: exercise: aRR, 0.81; 95% CI, 0.70-0.95; activities: aRR, 0.76; 95% CI, 0.64-0.91; FT: aRR, 0.87; 95% CI, 0.76-1.00; boosted: exercise: aRR, 0.62; 95% CI, 0.51-0.74; activities: aRR, 0.52; 95% CI, 0.41-0.65; FT: aRR, 0.59; 95% CI, 0.49-0.70). Conclusions: In this study of generally young, healthy military service members, SARS-CoV-2 infection was associated with lower self-reported fitness and exercise capacity; vaccination and boosting were associated with lower risk of self-reported fitness loss.

Hashimoto's Encephalopathy with Use of Intravenous Immunoglobulin as First-Line Therapy.

Hashimoto's encephalopathy is an uncommon cause of altered mental status in hospitalized patients and is challenging to diagnose, particularly in the presence of other psychiatric comorbidities. Corticosteroids are the primary treatment. Here, we present a patient with history of post-traumatic stress disorder and prior substance abuse admitted with profound altered mental status and agitation requiring admission to the intensive care unit and mechanical ventilation. He was treated with intravenous immunoglobulin (IVIG) instead of the standard steroid course because of concerns for worsening agitation. The patient had improvement with IVIG infusions, returned to a functional state, and has remained on IVIG therapy monthly since the initial episode without any disease recurrence.

Fatal septic shock due to disseminated coccidioidomycosis: a case series and review of the literature.

BACKGROUND: Coccidioidomycosis is a fungal infection endemic to the southwestern United States and regions of Latin America. Disseminated disease occurs in < 1% of cases. Septic shock is even rarer, with high mortality despite therapy. We describe two cases of coccidioidal septic shock. Both patients were older men of Filipino ancestry presenting with respiratory failure and vasopressor-dependent shock. Antifungal drugs were initiated after failure to improve with empiric antibiotics; in both, Coccidioides was isolated from respiratory cultures. Despite aggressive care, both patients ultimately died of their infections. We provide a review of the published literature on this topic. CONCLUSIONS: Most of the 33 reported cases of coccidioidal septic shock occurred in men (88%) of non-white race and ethnicity (78%). The overall mortality rate was 76%. All survivors received amphotericin B as part of their treatment. Coccidioidomycosis-related septic shock is a rare disease with poor outcomes; delays in diagnosis and treatment are common. Improved diagnostic testing for coccidioidomycosis could enhance recognition of this disease in the future. Although data are limited, early treatment with amphotericin B in cases of coccidioidal septic shock may reduce mortality.

Challenges in Managing Gonorrhea and New Advances in Prevention.

Gonorrhea is the second most common bacterial sexually transmitted infection in the United States. Rates are increasing, and multiple challenges compound management, including worsening antimicrobial resistance. New therapeutics, enhanced screening and partner notification, and treatment through point-of-care testing and expedited partner therapy, as well as primary prevention efforts provide opportunities for success in combating these trends.

A machine learning approach identifies distinct early-symptom cluster phenotypes which correlate with hospitalization, failure to return to activities, and prolonged COVID-19 symptoms.

BACKGROUND: Accurate COVID-19 prognosis is a critical aspect of acute and long-term clinical management. We identified discrete clusters of early stage-symptoms which may delineate groups with distinct disease severity phenotypes, including risk of developing long-term symptoms and associated inflammatory profiles. METHODS: 1,273 SARS-CoV-2 positive U.S. Military Health System beneficiaries with quantitative symptom scores (FLU-PRO Plus) were included in this analysis. We employed machine-learning approaches to identify symptom clusters and compared risk of hospitalization, long-term symptoms, as well as peak CRP and IL-6 concentrations. RESULTS: We identified three distinct clusters of participants based on their FLU-PRO Plus symptoms: cluster 1 ("Nasal cluster") is highly correlated with reporting runny/stuffy nose and sneezing, cluster 2 ("Sensory cluster") is highly correlated with loss of smell or taste, and cluster 3 ("Respiratory/Systemic cluster") is highly correlated with the respiratory (cough, trouble breathing, among others) and systemic (body aches, chills, among others) domain symptoms. Participants in the Respiratory/Systemic cluster were twice as likely as those in the Nasal cluster to have been hospitalized, and 1.5 times as likely to report that they had not returned-to-activities, which remained significant after controlling for confounding covariates (P < 0.01). Respiratory/Systemic and Sensory clusters were more likely to have symptoms at six-months post-symptom-onset (P = 0.03). We observed higher peak CRP and IL-6 in the Respiratory/Systemic cluster (P < 0.01). CONCLUSIONS: We identified early symptom profiles potentially associated with hospitalization, return-to-activities, long-term symptoms, and inflammatory profiles. These findings may assist in patient prognosis, including prediction of long COVID risk.

Persistent COVID-19 Symptoms at 6 Months After Onset and the Role of Vaccination Before or After SARS-CoV-2 Infection.

Importance: Understanding the factors associated with post-COVID conditions is important for prevention. Objective: To identify characteristics associated with persistent post-COVID-19 symptoms and to describe post-COVID-19 medical encounters. Design, Setting, and Participants: This cohort study used data from the Epidemiology, Immunology, and Clinical Characteristics of Emerging Infectious Diseases With Pandemic Potential (EPICC) study implemented in the US military health system (MHS); MHS beneficiaries aged 18 years or older who tested positive for SARS-CoV-2 from February 28, 2020, through December 31, 2021, were analyzed, with 1-year follow-up. Exposures: SARS-CoV-2 infection. Main Outcomes and Measures: The outcomes analyzed included survey-reported symptoms through 6 months after SARS-CoV-2 infection and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis categories reported in medical records 6 months following SARS-CoV-2 infection vs 3 months before infection. Results: More than half of the 1832 participants in these analyses were aged 18 to 44 years (1226 [66.9%]; mean [SD] age, 40.5 [13.7] years), were male (1118 [61.0%]), were unvaccinated at the time of their infection (1413 [77.1%]), and had no comorbidities (1290 [70.4%]). A total of 728 participants (39.7%) had illness that lasted 28 days or longer (28-89 days: 364 [19.9%]; ≥90 days: 364 [19.9%]). Participants who were unvaccinated prior to infection (risk ratio [RR], 1.39; 95% CI, 1.04-1.85), reported moderate (RR, 1.80; 95% CI, 1.47-2.22) or severe (RR, 2.25; 95% CI, 1.80-2.81) initial illnesses, had more hospitalized days (RR per each day of hospitalization, 1.02; 95% CI, 1.00-1.03), and had a Charlson Comorbidity Index score of 5 or greater (RR, 1.55; 95% CI, 1.01-2.37) were more likely to report 28 or more days of symptoms. Among unvaccinated participants, postinfection vaccination was associated with a 41% lower risk of reporting symptoms at 6 months (RR, 0.59; 95% CI, 0.40-0.89). Participants had higher risk of pulmonary (RR, 2.00; 95% CI, 1.40-2.84), diabetes (RR, 1.46; 95% CI, 1.00-2.13), neurological (RR, 1.29; 95% CI, 1.02-1.64), and mental health-related medical encounters (RR, 1.28; 95% CI, 1.01-1.62) at 6 months after symptom onset than at baseline (before SARS-CoV-2 infection). Conclusions and Relevance: In this cohort study, more severe acute illness, a higher Charlson Comorbidity Index score, and being unvaccinated were associated with a higher risk of reporting COVID-19 symptoms lasting 28 days or more. Participants with COVID-19 were more likely to seek medical care for diabetes, pulmonary, neurological, and mental health-related illness for at least 6 months after onset compared with their pre-COVID baseline health care use patterns. These findings may inform the risk-benefit ratio of COVID-19 vaccination policy.

Understanding "Hybrid Immunity": Comparison and Predictors of Humoral Immune Responses to Severe Acute Respiratory Syndrome Coronavirus 2 Infection (SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19) Vaccines.

BACKGROUND: Comparison of humoral responses in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinees, those with SARS-CoV-2 infection, or combinations of vaccine/ infection ("hybrid immunity") may clarify predictors of vaccine immunogenicity. METHODS: We studied 2660 US Military Health System beneficiaries with a history of SARS-CoV-2 infection-alone (n = 705), vaccination-alone (n = 932), vaccine-after-infection (n = 869), and vaccine-breakthrough-infection (n = 154). Peak anti-spike-immunoglobulin G (IgG) responses through 183 days were compared, with adjustment for vaccine product, demography, and comorbidities. We excluded those with evidence of clinical or subclinical SARS-CoV-2 reinfection from all groups. RESULTS: Multivariable regression results indicated that vaccine-after-infection anti-spike-IgG responses were higher than infection-alone (P < .01), regardless of prior infection severity. An increased time between infection and vaccination was associated with greater post-vaccination IgG response (P < .01). Vaccination-alone elicited a greater IgG response but more rapid waning of IgG (P < .01) compared with infection-alone (P < .01). BNT162b2 and mRNA-1273 vaccine-receipt was associated with greater IgG responses compared with JNJ-78436735 vaccine-receipt (P < .01), regardless of infection history. Those with vaccine-after-infection or vaccine-breakthrough-infection had a more durable anti-spike-IgG response compared to infection-alone (P < .01). CONCLUSIONS: Vaccine-receipt elicited higher anti-spike-IgG responses than infection-alone, although IgG levels waned faster in those vaccinated (compared to infection-alone). Vaccine-after-infection elicits a greater humoral response compared with vaccine or infection alone; and the timing, but not disease severity, of prior infection predicted these post-vaccination IgG responses. While differences between groups were small in magnitude, these results offer insights into vaccine immunogenicity variations that may help inform vaccination timing strategies.

Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history.

The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with a single infection or multiple vaccine exposures, or both. We measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diversity. Antigenic maps of primary infection sera showed that Omicron sublineages BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and more similar to Beta/Gamma/Mu variants. Three mRNA COVID-19 vaccinations increased neutralization of BA.1 more than BA.4/BA.5 or BA.2.12.1. BA.1 post-vaccination infection elicited higher neutralization titers to all variants than three vaccinations alone, although with less neutralization to BA.2.12.1 and BA.4/BA.5. Those with BA.1 infection after two or three vaccinations had similar neutralization titer magnitude and antigenic recognition. Accounting for antigenic differences among variants when interpreting neutralization titers can aid the understanding of complex patterns in humoral immunity that informs the selection of future COVID-19 vaccine strains.

COVID-19 Patient-Reported Symptoms Using FLU-PRO Plus in a Cohort Study: Associations With Infecting Genotype, Vaccine History, and Return to Health.

Background: Patient-reported outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are an important measure of the full burden of coronavirus disease (COVID). Here, we examine how (1) infecting genotype and COVID-19 vaccination correlate with inFLUenza Patient-Reported Outcome (FLU-PRO) Plus score, including by symptom domains, and (2) FLU-PRO Plus scores predict return to usual activities and health. Methods: The epidemiology, immunology, and clinical characteristics of pandemic infectious diseases (EPICC) study was implemented to describe the short- and long-term consequences of SARS-CoV-2 infection in a longitudinal, observational cohort. Multivariable linear regression models were run with FLU-PRO Plus scores as the outcome variable, and multivariable Cox proportional hazards models evaluated effects of FLU-PRO Plus scores on return to usual health or activities. Results: Among the 764 participants included in this analysis, 63% were 18-44 years old, 40% were female, and 51% were White. Being fully vaccinated was associated with lower total scores (ß = -0.39; 95% CI, -0.57 to -0.21). The Delta variant was associated with higher total scores (ß = 0.25; 95% CI, 0.05 to 0.45). Participants with higher FLU-PRO Plus scores were less likely to report returning to usual health and activities (health: hazard ratio [HR], 0.46; 95% CI, 0.37 to 0.57; activities: HR, 0.56; 95% CI, 0.47 to 0.67). Fully vaccinated participants were more likely to report returning to usual activities (HR, 1.24; 95% CI, 1.04 to 1.48). Conclusions: Full SARS-CoV-2 vaccination is associated with decreased severity of patient-reported symptoms across multiple domains, which in turn is likely to be associated with earlier return to usual activities. In addition, infection with the Delta variant was associated with higher FLU-PRO Plus scores than previous variants, even after controlling for vaccination status.

An Analysis of SARS-CoV-2 Vaccine Reactogenicity: Variation by Type, Dose, and History, Severity, and Recency of Prior SARS-CoV-2 Infection.

Background: There is limited information on the functional consequences of coronavirus disease 2019 (COVID-19) vaccine side effects. To support patient counseling and public health messaging, we describe the risk and correlates of COVID-19 vaccine side effects sufficient to prevent work or usual activities and/or lead to medical care ("severe" side effects). Methods: The EPICC study is a longitudinal cohort study of Military Healthcare System beneficiaries including active duty service members, dependents, and retirees. We studied 2789 adults who were vaccinated between December 2020 and December 2021. Results: Severe side effects were most common with the Ad26.COV2.S (Janssen/Johnson and Johnson) vaccine, followed by mRNA-1273 (Moderna) then BNT162b2 (Pfizer/BioNTech). Severe side effects were more common after the second than first dose (11% vs 4%; P < .001). First (but not second) dose side effects were more common in those with vs without prior severe acute respiratory syndrome coronavirus 2 infection (9% vs 2%; adjusted odds ratio [aOR], 5.84; 95% CI, 3.8-9.1), particularly if the prior illness was severe or critical (13% vs 2%; aOR, 10.57; 95% CI, 5.5-20.1) or resulted in inpatient care (17% vs 2%; aOR, 19.3; 95% CI, 5.1-72.5). Side effects were more common in women than men but not otherwise related to demographic factors. Conclusions: Vaccine side effects sufficient to prevent usual activities were more common after the second than first dose and varied by vaccine type. First dose side effects were more likely in those with a history of COVID-19-particularly if that prior illness was severe or associated with inpatient care. These findings may assist clinicians and patients by providing a real-world evaluation of the likelihood of experiencing impactful postvaccine symptoms.

SARS-CoV-2 BA.1 variant is neutralized by vaccine booster-elicited serum but evades most convalescent serum and therapeutic antibodies.

The rapid spread of the highly contagious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along with its high number of mutations in the spike gene has raised alarms about the effectiveness of current medical countermeasures. To address this concern, we measured the neutralization of the Omicron BA.1 variant pseudovirus by postvaccination serum samples after two and three immunizations with the Pfizer/BioNTech162b2 SARS-CoV-2 mRNA (Pfizer/BNT162b2) vaccine, convalescent serum samples from unvaccinated individuals infected by different variants, and clinical-stage therapeutic antibodies. We found that titers against the Omicron variant were low or undetectable after two immunizations and in many convalescent serum samples, regardless of the infecting variant. A booster vaccination increased titers more than 30-fold against Omicron to values comparable to those seen against the D614G variant after two immunizations. Neither age nor sex was associated with the differences in postvaccination antibody responses. We also evaluated 18 clinical-stage therapeutic antibody products and an antibody mimetic protein product obtained directly from the manufacturers. Five monoclonal antibodies, the antibody mimetic protein, three antibody cocktails, and two polyclonal antibody preparations retained measurable neutralization activity against Omicron with a varying degree of potency. Of these, only three retained potencies comparable to the D614G variant. Two therapeutic antibody cocktails in the tested panel that are authorized for emergency use in the United States did not neutralize Omicron. These findings underscore the potential benefit of mRNA vaccine boosters for protection against Omicron and the need for rapid development of antibody therapeutics that maintain potency against emerging variants.

Real World Impact of Remdesivir and Dexamethasone on Clinical Outcomes of Severe Coronavirus Disease 2019 in a Community Hospital.

BACKGROUND: Evidence has emerged showing potential benefit of Remdesivir and dexamethasone in severe coronavirus disease 2019 (COVID-19) but results from large randomized control trials are conflicting. While initial data for dexamethasone indicated a mortality benefit, the impact of Remdesivir was best demonstrated in decreased time to recovery. Despite extensive disease burden throughout the world efficacy data of individual interventions is lacking in part due to extensive concurrent use of confounding investigational therapeutics. MATERIALS AND METHODS: We performed a retrospective analysis of the impact of Remdesivir and dexamethasone on real-world outcomes in severe COVID-19. All patients admitted to our community hospital between March 2020 and December 31, 2020 were included, and all patients admitted before national guidelines endorsed Remdesivir and dexamethasone outside of clinical trials were treated with only supportive care and used as historical controls. No other investigational therapeutics were utilized. This study was reviewed and approved by the Fort Belvoir Community Hospital IRB. RESULTS: 58 hospitalized patients met criteria for severe COVID-19 as confirmed by RT-PCR, and 14 (25%) were used as historical controls. Baseline demographics and overall mortality rate (7.1%) did not significantly differ between the groups. The median length of stay was 7 days and 6 days in the historical control group and interventional group, respectively (P = 0.55). CONCLUSIONS: We did not observe an appreciable impact on the duration of hospitalization when Remdesivir and dexamethasone were added to supportive care in a community hospital. This study was not sufficiently powered to detect the previously described mortality benefit of dexamethasone.

SARS-CoV-2 Omicron neutralization by therapeutic antibodies, convalescent sera, and post-mRNA vaccine booster.

The rapid spread of the highly contagious Omicron variant of SARS-CoV-2 along with its high number of mutations in the spike gene has raised alarm about the effectiveness of current medical countermeasures. To address this concern, we measured neutralizing antibodies against Omicron in three important settings: (1) post-vaccination sera after two and three immunizations with the Pfizer/BNT162b2 vaccine, (2) convalescent sera from unvaccinated individuals infected by different variants, and (3) clinical-stage therapeutic antibodies. Using a pseudovirus neutralization assay, we found that titers against Omicron were low or undetectable after two immunizations and in most convalescent sera. A booster vaccination significantly increased titers against Omicron to levels comparable to those seen against the ancestral (D614G) variant after two immunizations. Neither age nor sex were associated with differences in post-vaccination antibody responses. Only three of 24 therapeutic antibodies tested retained their full potency against Omicron and high-level resistance was seen against fifteen. These findings underscore the potential benefit of booster mRNA vaccines for protection against Omicron and the need for additional therapeutic antibodies that are more robust to highly mutated variants. ONE SENTENCE SUMMARY: Third dose of Pfizer/BioNTech COVID-19 vaccine significantly boosts neutralizing antibodies to the Omicron variant compared to a second dose, while neutralization of Omicron by convalescent sera, two-dose vaccine-elicited sera, or therapeutic antibodies is variable and often low.

Antibiotic resistance, molecular characterizations, and clinical manifestations of Campylobacteriosis at a military medical center in Hawaii from 2012-2016: a retrospective analysis.

Hawaii has one of the highest incidences of Campylobacteriosis in the United States, but there remains little published data on circulating strains or antimicrobial resistance. We characterized 110 clinical Campylobacter isolates (106 C. jejuni, 4 C. coli) processed at Tripler Army Medical Center in Honolulu, HI from 2012-2016. Twenty-five percent of C. jejuni isolates exhibited fluoroquinolone (FQ) resistance, compared with 16% for tetracycline (TET), and 0% for macrolides. Two of the four C. coli isolates were resistant to FQ, TET, and macrolides. C. jejuni isolates further underwent multilocus sequence typing, pulsed-field gel electrophoresis, and molecular capsular typing. Nineteen capsule types were observed, with two capsule types (HS2 and HS9) being associated with FQ resistance (p < 0.001 and p = 0.006, respectively). HS2 FQ-resistant isolates associated with clonal complex 21, possibly indicating clonal spread in FQ resistance. Macrolides should be considered for treatment of suspect cases due to lack of observed resistance.

Concurrent Systemic Chemoimmunotherapy and Sofosbuvir-Based Antiviral Treatment in a Hepatitis C Virus-Infected Patient With Diffuse Large B-Cell Lymphoma.

Hepatitis C virus (HCV) infection is associated with the development of non-Hodgkin lymphomas. For aggressive lymphomas, such as diffuse large B-cell lymphoma (DLBCL), treatment of HCV infection is typically deferred in treatment-naive patients until after completion of lymphoma therapy [1, 2]. We report a case of HCV-associated stage IV DLBCL successfully treated concurrently using chemoimmunotherapy and a sofosbuvir-based antiviral regimen.

Natural History of Aerosol Exposure with Marburg Virus in Rhesus Macaques.

Marburg virus causes severe and often lethal viral disease in humans, and there are currently no Food and Drug Administration (FDA) approved medical countermeasures. The sporadic occurrence of Marburg outbreaks does not allow for evaluation of countermeasures in humans, so therapeutic and vaccine candidates can only be approved through the FDA animal rule-a mechanism requiring well-characterized animal models in which efficacy would be evaluated. Here, we describe a natural history study where rhesus macaques were surgically implanted with telemetry devices and central venous catheters prior to aerosol exposure with Marburg-Angola virus, enabling continuous physiologic monitoring and blood sampling without anesthesia. After a three to four day incubation period, all animals developed fever, viremia, and lymphopenia before developing tachycardia, tachypnea, elevated liver enzymes, decreased liver function, azotemia, elevated D-dimer levels and elevated pro-inflammatory cytokines suggesting a systemic inflammatory response with organ failure. The final, terminal period began with the onset of sustained hypotension, dehydration progressed with signs of major organ hypoperfusion (hyperlactatemia, acute kidney injury, hypothermia), and ended with euthanasia or death. The most significant pathologic findings were marked infection of the respiratory lymphoid tissue with destruction of the tracheobronchial and mediastinal lymph nodes, and severe diffuse infection in the liver, and splenitis.

Immunoproliferative Small Intestinal Disease Associated with Overwhelming Polymicrobial Gastrointestinal Infection with Transformation to Diffuse Large B-cell Lymphoma.

Immunoproliferative small intestinal disease (IPSID) is an extra-nodal B-cell lymphoma most commonly described in the Mediterranean, Africa, and Asia. It is associated with poverty and poor sanitation, and is rarely encountered in developed countries. A 26-year-old previously healthy, Marshallese male was transferred to our facility with a 6-month history of watery diarrhea, weakness, and cachexia refractory to multiple short courses of oral antibiotics. Stool cultures grew Campylobacter jejuni and Vibrio fluvialis. Endoscopic evaluation showed histologic evidence of Helicobacter pylori gastritis and gross evidence of whipworm infection found in the colon. Mesenteric lymph node biopsy cultures grew Escherichia coli. Histopathology and immunohistochemical stains of the small intestine were consistent with IPSID. He subsequently transformed to diffuse large B-cell lymphoma (DLBCL) with tonsillar involvement despite treatment with rituximab and an extended course of antibiotics. Systemic chemotherapy with six cycles of rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone, and lenalidomide, resulted in remission of his diffuse B cell lymphoma. This case is illustrative of IPSID developing in a previously healthy individual due to overwhelming polymicrobial gastrointestinal infection by C. jejuni and other enteric pathogens with subsequent transformation to an aggressive DLBCL. IPSID should be considered in residents of developing countries presenting with refractory chronic diarrhea, weight loss, and mesenteric lymphadenopathy.