Characterization of mutations in hepatitis B virus DNA isolated from Japanese HBsAg-positive blood donors in 2021 and 2022.

Missense mutations in certain small envelope proteins diminish the efficacy of antibodies. Consequently, tracking the incidence and types of vaccine-escape mutations (VEMs) was crucial both before and after the introduction of universal hepatitis B vaccination in Japan in 2016. In this study, we isolated hepatitis B virus (HBV) DNA from 58 of 169 hepatitis B surface antigen (HBsAg)-positive blood samples from Japanese blood donors and determined the nucleotide sequence encoding the small envelope protein. DNA from six (10%) of the samples had VEMs, but no missense mutations, such as G145R, were detected. Complete HBV genome sequences were obtained from 29 of the 58 samples; the viral genotype was A1 in one (3%), A2 in three (10%), B1 in nine (31%), B2 in five (17%), B4 in one (3%), and C2 in 10 (34%) samples. Tenofovir-resistance mutations were detected in two (7%) samples. In addition, several core promoter mutations, such as 1762A>T and 1764G>A, and a precore nonsense mutation, 1986G>A, which are risk factors for HBV-related chronic liver disease, were detected. These findings provide a baseline for future research and highlight the importance of ongoing monitoring of VEMs and drug resistance mutations in HBV DNA from HBsAg-positive blood donors without HBV antibodies.

Differential peripheral memory T cell subsets sensitively indicate the severity of nonalcoholic fatty liver disease.

AIM: Differential patterns of peripheral memory T cell subsets in nonalcoholic fatty liver disease (NAFLD) were assessed using flow cytometry (FCM) to elucidate their association with NAFLD severity and provide a new noninvasive method to sensitively detect the disease severity in addition to existing biomarkers. METHODS: We assessed the differential frequencies of peripheral memory T cell subsets in 103 patients with NAFLD according to the degree of liver fibrosis (FIB) using FCM analysis. We focused on the following populations: CCR7+ CD45RA+ naïve T, CCR7+ CD45RA- central memory T cells (TCM), CCR7- CD45RA- effector memory T, and CCR7- CD45RA+ terminally differentiated effector memory T (TEMRA) cells in CD4+ and CD8+ T, Th1, Th2, and Th17 cells, respectively. To evaluate the pathological progression of the disease, these frequencies were also examined according to the degree of the NAFLD activity score (NAS). RESULTS: Several significant correlations were observed between laboratory parameters and peripheral memory T lymphocyte frequencies according to the degree of liver FIB and NAS in NAFLD. In univariate and multivariate analyses, the frequency of CD8+ TEMRA cells predicted severe FIB, and the predictive power was validated in an independent cohort. Furthermore, the frequencies of several memory T cell subsets sensitively indicated the pathological progression of NAFLD (Th17 TCM: steatosis, CD4+ TCM: lobular inflammation, and CD8+ TEMRA and effector memory T cells: hepatocellular ballooning). CONCLUSIONS: Our results suggest that the analysis of peripheral memory T lymphocyte frequencies can noninvasively predict severe FIB and sensitively indicate the pathological progression of NAFLD.

Attenuation of hepatitis A antibody after immunization with hepatitis A vaccine (Aimmugen) in people living with HIV.

AIM: Hepatitis A (HA) is a vaccine-preventable disease. In regions with good sanitation, men who have sex with men (MSM) are the key affected populations. During the 2018-2019 HA outbreak among MSM in Japan, we actively vaccinated MSM living with HIV (MSM-LWHIV) with Aimmugen. As previously reported, their antibody seroconversion rate due to vaccination was lower than that of healthy individuals. However, the durability of Aimmugen in people living with HIV has not yet been reported. We evaluated attenuation after the one-series vaccination (comprising three inoculations) and the factors associated with attenuation. METHODS: We retrospectively examined anti-HA immunoglobulin G (anti-HA-IgG) titers and other clinical data from our hospital's medical records. Patients with no history of vaccination or HA infection (i.e., negative HA-IgG titers) who received one series of Aimmugen, achieved seropositivity, and anti-HA-IgG antibodies were tested ≥2 years after three doses were included. Fisher's exact test and the Mann-Whitney U-test were performed. p < 0.05 was considered statistically significant. RESULTS: Fifty-one MSM-LWHIV were included. All were seropositive after the third dose with a median HA-IgG titer of 10.1 (interquartile range, 7.2-12.2) (sample/cut-off values [s/co]). In 45 (40-49) months, seropositivity decreased to 90% (46/51) and was attenuated to a median of 4.4 (2.3-6.5) s/co. Lower baseline B cell counts (p = 0.049), lower anti-HA-IgG levels after the second dose (p = 0.002), and lower anti-HA-IgG levels after the third dose (p = 0.003) were associated with seronegativity. CONCLUSIONS: Anti-HA-IgG titers of vaccinated MSM-LWHIV may be attenuated; thus, additional immunizations should be considered.

Incidence of sexually transmitted hepatitis C virus infection among men who have sex with men in Japan from 2009 to 2023.

Although the prevalence of hepatitis C virus (HCV) infection has decreased significantly with the advent of direct-acting antiviral agents, HCV is known to spread as a sexually transmitted disease among men who have sex with men (MSM), and this study aims to provide a perspective on the future prevalence of HCV in Japan. We examined incidence in two groups of MSM with HIV attending our institution in this retrospective cohort study, from 2009 to 2019 and from 2020 to May 2023 and investigated their background factors. Twenty-two cases were newly confirmed to be HCV infection in 2009-2019 and a total of 9 cases in 2020-2023, with an incidence rate of 5.04 per 1000 person-years in 2009-2019 and 5.55 per 1000 person-years in 2020-2023. All of them were diagnosed at routine outpatient visits for HIV, and few cases were considered to have symptoms of suspected hepatitis that led to a visit to the hospital and a diagnosis of HCV. Although HCV is still prevalent among MSM in Japan, it is possible that it would not have been diagnosed without testing at regular visits as in the case of people with HIV, and that the true prevalence rate among MSM, including non-HIV-infected persons, may be much higher.

Injection drug use and sexually transmitted infections among men who have sex with men: A retrospective cohort study at an HIV/AIDS referral hospital in Tokyo, 2013-2022.

Men who have sex with men (MSM) who use injection drugs (MSM-IDU) are at high risk of sexually transmitted infections (STIs), but the long-term incidence is unclear. We conducted a single-centre retrospective cohort study using the clinical records of non-haemophilia men with human immunodeficiency virus (HIV) who visited the Institute of Medical Science, the University of Tokyo (IMSUT) Hospital, located in Tokyo, Japan, from 2013 to 2022. We analysed 575 patients including 62 heterosexual males and 513 MSM patients, of whom 6.8% (35/513) were injection drug use (IDU). Compared to non-IDU MSM, MSM-IDU had a higher incidence of hepatitis C virus (HCV) (44.8 vs 3.5 /1,000 person-years (PY); incidence rate ratio (IRR) [95% confidence interval (95% CI)], 12.8 [5.5-29.3], p < 0.001) and syphilis (113.8 vs 53.3 /1,000 PY; IRR, 2.1 [1.4-3.1], p < 0.001). The incidence of other symptomatic STIs (amoebiasis, chlamydia, and gonorrhoea infections) was <4/1,000 PY. In multivariable Poisson regression analysis, HCV incidence was associated with MSM (IRR, 1.8 × 106 [9.9 × 105-3.4 × 106], p < 0.001), IDU (IRR, 10.1 [4.0-25.6], p < 0.001), and syphilis infection during the study period (IRR, 25.0 [1.2-518.3]/time/year, p < 0.001). Among men with HIV, the prevalence of IDU in MSM and the long-term incidence of STIs in MSM-IDU were high. IDU and sexual contact are important modes of transmission of HCV among HIV-infected MSM in Tokyo.

Triglyceride level and soft drink consumption predict nonalcoholic fatty liver disease in nonobese male adolescents.

AIM: Differential metabolic risk factors of nonalcoholic fatty liver disease (NAFLD) in nonobese male adolescents were analyzed examining relationships between NAFLD and clinical parameters of metabolic syndrome, including exercise and soft drink consumption, in male adolescents. METHODS: In total, 134 male university students (nonobese, n = 78; obese, n = 56) who underwent the first-year health checkup were divided into the NAFLD and non-NAFLD groups based on abdominal ultrasonography (AUS) findings. Relationships between NAFLD and metabolic parameters, including body mass index (BMI) and AUS score, were examined in nonobese students. RESULTS: Metabolic factors associated with hypertension, abdominal fat, liver damage, dyslipidemia, and impaired glucose tolerance were significantly less common in nonobese students than in obese students. The aforementioned factors and soft drink consumption were significantly more common in the NAFLD group than in the non-NAFLD group. The univariate and multivariate analyses of nonobese students showed that the triglyceride level (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.01-1.10, p = 0.001) was higher and soft drink consumption (OR, 36.8; 95% CI, 3.69-368, p < 0.001) was more common in the NAFLD group than the non-NAFLD group. CONCLUSIONS: Triglyceride level and soft drink consumption could aid in the detection of NAFLD in nonobese male adolescents. Our findings could provide useful information related to NAFLD and metabolic syndrome in nonobese adolescents.

Background factors in people living with HIV in Japan who switch to cabotegravir plus rilpivirine: A pilot study.

Long-acting therapy of cabotegravir and rilpivirine is expected to free people from the negative emotions of living with HIV associated with taking drugs, but problems such as increased number of hospital visits, lack of anti-HBV activity, and limited convenience in people with concomitant drugs have been noted. In this single-center, prospective, cross-sectional study, we investigated background factors of people living with HIV in Japan who chose cabotegravir plus rilpivirine. Forty-seven percent (36 of 76) of individuals chose this regimen, but many people living with HIV who visited the hospital once every 3 months or needed concomitant medications due to complications chose this regimen and there were no significant differences in background factors that could affect convenience between the groups of those who switched and those who did not.

Mpox associated with Panton-Valentin leucocidin-producing methicillin-resistant Staphylococcus aureus among people with HIV.

We report three cases of mpox (disease caused by the monkeypox virus) that developed in people with HIV co-infected with Panton-Valentin leucocidin-producing methicillin-resistant Staphylococcus aureus (PVL-MRSA), diagnosed in mid-February 2023. All three cases had preserved HIV immune status, and their mpox was mild and resolved without antiviral medications, but the trigger for their visit was the presence and history of skin and soft tissue infections. Our cases suggest that mpox is already prevalent among sexually active MSM in Tokyo, Japan. PVL-MRSA has been extremely rare in the general population of Japan, but several literatures reported widespread prevalence of PVL-MRSA among sexually active MSM-HIV. Mpox will become prevalent in the future in a population of sexually active MSM at high risk for PVL-MRSA infection, requiring an understanding of the interaction and pathogenesis of the two diseases.

Clinical efficacy and tolerability of 1.5 g/day oral amoxicillin therapy without probenecid for the treatment of syphilis.

OBJECTIVES: Intramuscular benzathine penicillin G is not available in certain countries. In a previous report, 3 g/day amoxicillin with probenecid was shown to be effective in treating syphilis in patients with HIV; however, 7.3% of patients changed their therapy owing to adverse events. The objective of this study was to assess the clinical efficacy and tolerability of 1.5 g/day amoxicillin without probenecid for the treatment of syphilis. METHODS: The routine clinical records of patients diagnosed with syphilis and treated with 1.5 g/day amoxicillin at a tertiary care hospital between 2006 and 2018 were retrospectively analysed. Syphilis was diagnosed if serum rapid plasma reagin (RPR) titres were ≥8 RU and the Treponema pallidum latex-agglutination test was positive. Serological cure was defined as a ≥fourfold decrease in the RPR titre within 12 months in symptomatic early syphilis and within 24 months in latent syphilis. RESULTS: Overall, 138 patients (112 with HIV) were analysed. The percentages of primary, secondary, early latent, late latent and latent syphilis of unknown duration were 8.0%, 50.0%, 25.4%, 5.8% and 10.9%, respectively. The median treatment duration was 4.5 weeks (IQR 4-8 weeks), which was not related to the stage of syphilis. Two patients (1.5%) changed treatment due to skin rash. The rate of serological cure was 94.9% (131/138; 95% CI 89.8% to 97.9%) overall; 93.8% (105/112; 95% CI 87.5% to 97.5%) in patients with HIV and 100% (26/26; 95% CI 86.8% to 100%) in patients without HIV. Treatment duration was not related to the treatment efficacy. CONCLUSION: The regimen of 1.5 g/day amoxicillin without probenecid is highly effective with a low switch rate in patients with and without HIV.

Prevalence of HIV infection among non-elderly individuals with hepatitis C in Japan: a population-based cohort study using a health insurance claim data.

BACKGROUND: Hepatitis C virus (HCV) has been mainly transmitted through injection drug use, but recently, sexual transmission among men who have sex with men (MSM), which is also a major route of HIV transmission, is increasing. However, the prevalence of HIV and the incidence of other sexually transmitted infections (STIs) among HCV patients have been rarely reported. METHODS: Using a healthcare insurance claim data of employees and their dependents covering seven-million people in Japan, we evaluated HIV prevalence among HCV patients aged 20-59 years. Hemophilia patients were excluded. HIV and HCV were defined by registered diagnoses and receiving viral RNA testing. The time course of HCV and HIV infections was analyzed. Incidences of syphilis, amebiasis, chlamydia, gonorrhea, hepatitis A, and hepatitis B were assessed. RESULTS: From April 2012 to August 2018, 6,422 HCV patients were identified. HIV prevalence was 0.48% (31/6422, 95% CI [confidence interval]: 0.33-0.68%). HIV was diagnosed after HCV in 3.2% (1/31), before HCV in 58.1% (18/31), and concurrently in 38.7% (12/31). Compared with HCV patients without HIV infection, HCV/HIV co-infected patients were younger (median age, 37 vs 51 years, p < 0.001), more likely to be male (30/31 [96.8%] vs 3059/6391 [47.9%], p < 0.001), more likely to have other STIs (38.7% [12/31] vs 0.9% [56/6391], p < 0.001), and live in Tokyo, the most populous capital city in Japan (67.7% [21/31] vs 11.6% [742/6391], p < 0.001). In Tokyo, the HIV prevalence among 20-30 s male with HCV was 18.6% (13/70; 95% CI, 10.3-29.7%). CONCLUSIONS: HIV prevalence among young male HCV patients was very high in Tokyo. HCV/HIV co-infected patients were more likely to acquire HIV before HCV, which is a known feature of MSM. They also had a higher incidence of STIs. These findings suggest that HCV might be prevalent as an STI among MSM particularly in Tokyo.

Predictors associated with a better response to the Japanese aluminum-free hepatitis A vaccine, Aimmugen® , for people living with HIV.

AIM: After the hepatitis A virus (HAV) outbreak among men who have sex with men (MSM) around 2018, the importance of HAV vaccination was emphasized, especially for MSM-living with human immunodeficiency virus (MSM-LWHIV). Aimmugen® is licensed and distributed exclusively in Japan. While administration of three doses is recommended, 85% of recipients in the general population were reported to acquire seroprotection after the second dose. In this study, we evaluated the efficacy of two or three vaccine doses along with predictors associated with the response to Aimmugen® in MSM-LWHIV. METHODS: We retrospectively examined anti-HA-IgG titers of MSM-LWHIV vaccinated with Aimmugen® in our hospital. Patients' data were collected from medical records. RESULTS: Between January 2018 and October 2019, 141 subjects whose median age was 46 years old, were examined. All the subjects were on antiretroviral therapy (ART) and the median CD4 count was 615/µL. The acquisition rate of protectable anti-HA-IgG titers after the second and third dose was 71.1% and 98.6%, respectively. In 114 subjects whose anti-HA-IgG titers were tested after the second-dose, factors significantly associated with better response were prolonged ART duration and higher CD4 count. The titers of anti-HA-IgG after the third dose were higher in those who became seropositive after the second-dose than those who did not. CONCLUSIONS: Three-dose of Aimmugen® for MSM-LWHIV was effective while two-dose was less effective compared to non-HIV-infected people. People-LWHIV with shorter duration of ART and lesser CD4 cell count achieved lower titers of anti-HA-IgG and might require an additional vaccination.

An Outbreak of USA300 Methicillin-Resistant Staphylococcus aureus Among People With HIV in Japan.

BACKGROUND: USA300 produces Panton-Valentin leucocidin (PVL) and is known as a predominant community-associated methicillin-resistant Staphylococcus aureus (MRSA) strain in the United States, but it was extremely rare in Japan. We report here an outbreak of USA300 in people with HIV (PWH) in Tokyo, Japan. METHODS: We analyzed the cases of PVL-MRSA infection between 2010 and 2020 and screened for nasal colonization of PVL-MRSA in PWH who visited an HIV/AIDS referral hospital from December 2019 to March 2020. Whole-genome sequencing-based single nucleotide polymorphism (SNP) analysis was performed on these isolates. RESULTS: During the study period, a total of 21 PVL-MRSA infections in 14 patients were identified after 2014. The carriage prevalence was 4.3% (12/277) and PVL-MRSA carriers were more likely to have sexually transmitted infections (STIs) within a year compared with patients who had neither a history of PVL-MRSA infection nor colonization (33.3% [4/12] vs 10.1% [26/258]; P = .03). SNP analysis showed that all 26 isolates were ST8-SCCmecIVa-USA300. Twenty-four isolates were closely related (≤100 SNP differences) and had the nonsynonymous SNPs associated with carbohydrate metabolism and antimicrobial tolerance. CONCLUSIONS: An outbreak of USA300 has been occurring among PWH in Tokyo and a history of STI was a risk of colonization.

Change in hepatitis C virus positivity among needle-stick injury source patients: a 10-year experience in a Japanese tertiary hospital.

BACKGROUND: As a blood-borne pathogen, hepatitis C virus (HCV) has long been a major threat associated with needle-stick injuries (NSIs) mainly because no vaccine is available for HCV. Following an NSI, we usually test the source patient for HCV antibody (HCV-Ab). Since HCV-Ab positivity does not necessarily indicate current infection, HCV RNA is further examined in patients positive for HCV-Ab. Direct-acting antivirals (DAAs) have enabled us to treat most HCV-infected patients; therefore, we speculate that the rate of HCV RNA positivity among HCV-Ab-positive patients decreased after the emergence of DAAs. This cross-sectional study was performed to investigate the change in the actual HCV RNA positivity rate in source patients before and after the interferon (IFN)-free DAA era. METHODS: This was a cross-sectional study of NSI source patients at a tertiary academic hospital in Japan from 2009 to 2019. IFN-free DAA regimens were first introduced in Japan in 2014. Accordingly, we compared HCV status of NSI source patients that occurred between 2009 and 2014 (the era before IFN-free DAAs) with those that occurred between 2015 and 2019 (the era of IFN-free DAAs) in a tertiary care hospital in Japan. RESULTS: In total, 1435 NSIs occurred, and 150 HCV-Ab-positive patients were analyzed. The proportion of HCV RNA-positive patients significantly changed from 2009 through 2019 (p = 0.005, Cochran-Armitage test). Between 2009 and 2014, 102 source patients were HCV-Ab-positive, 78 of whom were also positive for HCV RNA (76.5%; 95%CI, 67.4-83.6%). Between 2015 and 2019, 48 patients were HCV-Ab-positive, 23 of whom were also positive for HCV RNA (47.9%; 95%CI, 34.5-61.7%; p = 0.0007 compared with 2009-2014). In the era of IFN-free DAAs, 9 of 23 HCV RNA-negative patients (39.1%) and 2 of 22 HCV RNA-positive patients (9.1%) were treated with an IFN-free combination of DAAs (p = 0.0351). Regarding the departments where NSIs occurred, HCV RNA-negative patients were predominant in departments not related to liver diseases in the era of IFN-free DAAs (p = 0.0078, compared with 2009-2014). CONCLUSIONS: Actual HCV RNA positivity in source patients of NSIs decreased after the emergence of IFN-free DAAs. IFN-free DAAs might have contributed to this reduction, and HCV RNA-negative patients were predominant in departments not related to liver diseases in the era of IFN-free DAAs.

Association of coagulopathy with liver dysfunction in patients with COVID-19.

AIM: Liver dysfunction is sometimes observed in patients with coronavirus disease 2019 (COVID-19), but most studies are from China, and the frequency in other countries is unclear. In addition, previous studies suggested several mechanisms of liver damage, but precise or additional mechanisms are not clearly elucidated. Therefore, we examined COVID-19 patients to explore the proportion of patients with liver dysfunction and also the factors associated with liver dysfunction. METHODS: We retrospectively examined 60 COVID-19 patients hospitalized at the Hospital affiliated with The Institute of Medical Science, The University of Tokyo (Tokyo, Japan). Patients who presented ≥40 U/L alanine aminotransferase (ALT) levels at least once during their hospitalization were defined as high-ALT patients, and the others as normal-ALT patients. The worst values of physical and laboratory findings during hospitalization for each patient were extracted for the analyses. Univariable and multivariable logistic regression models with bootstrap (for 1000 times) were carried out. RESULTS: Among 60 patients, there were 31 (52%) high-ALT patients. The high-ALT patients were obese, and had significantly higher levels of D-dimer and fibrin/fibrinogen degradation products, as well as white blood cell count, and levels of C-reactive protein, ferritin, and fibrinogen. Multivariable analysis showed D-dimer and white blood cells as independent factors. CONCLUSIONS: Considering that higher D-dimer level and white blood cell count were independently associated with ALT elevation, liver dysfunction in COVID-19 patients might be induced by microvascular thrombosis in addition to systemic inflammation.

First human case of catheter-related blood stream infection caused by Staphylococcus schleiferi subspecies coagulans: a case report and literature review.

BACKGROUND: Staphylococcus schleiferi is a gram-positive pathogenic coccus which causes canine skin and ear infections. Only four cases of human infection caused by Staphylococcus schleiferi subspecies coagulans have been reported. Herein, we present the first case of catheter-related bloodstream infection caused by S. schleiferi subspecies coagulans. CASE PRESENTATION: A 62-year-old Japanese man was admitted to our hospital for examination of sigmoid colon tumor. During hospitalization, he had fever, shaking chills, and swelling at the peripheral venous catheter insertion site. Two sets of blood cultures were positive for S. schleiferi subspecies coagulans which was confirmed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), 16S ribosomal RNA sequencing and the coagulase test. The patient was successfully treated without relapse. CONCLUSION: To our knowledge, this is the first report of catheter-related bloodstream infection caused by S. schleiferi subspecies coagulans. S. schleiferi subsp. coagulans can be pathogenic in humans, and MALDI-TOF MS can contribute to accurate identification of S. schleiferi subspecies coagulans.

Changes in survival and causes of death among people living with HIV: Three decades of surveys from Tokyo, one of the Asian metropolitan cities.

INTRODUCTION: Survival among people living with HIV (PLWH) has dramatically improved in the antiretroviral therapy (ART) era. This is the first study in Asia to describe three decades of surveys on survival and causes of death among PLWH. METHODS: We included 1121 HIV-infected patients, categorized into three period groups according to date of first visit: 1986-1996 (Pre-ART); 1997-2007 (Early-ART); and 2008-2018 (Late-ART). RESULTS: Ten-year all-cause mortality has reduced from Pre-ART (49.6/1000 person-years) to Late-ART (6.3/1000 person-years). Mortality for AIDS-defining illnesses (ADIs) has also reduced from Pre-ART (34.4/1000 person-years) to Late-ART (2.9/1000 person-years), and mortality for non-ADIs has reduced from Pre-ART (11.7/1000 person-years) to Late-ART (2.9/1000 person-years). In the ART-era, deaths from non-AIDS-defining malignancies and unnatural events including suicide represented the majority of non-ADI-related deaths and mortality rates of non-AIDS defining malignancies and unnatural cause event were not different between each group (3.4, 1.9 and 2.5/1000 person-years). Crude cumulative survival improved over the study period, and 10-year survival ratios of HIV-infected patients to the general Japanese population approached 1.00, from Pre-ART (0.66) to Late-ART (0.99). Even in the Late-ART period, survival remained lower in patients with a history of ADIs than in those without, but the difference in 5-year mortality between these groups has shrunk in the Late-ART compared to the Pre-ART. CONCLUSIONS: Mortality for ADIs and non-ADIs in PLWH has reduced in the Early-ART and Late-ART. To improve survival for PLWH further, early HIV detection and treatment and good management of non-AIDS-defining malignancies and mental disorders are needed. (248/250).

Relative Bradycardia in Patients with Mild-to-Moderate Coronavirus Disease, Japan.

Coronavirus disease is reported to affect the cardiovascular system. We showed that relative bradycardia was a common characteristic for 54 patients with PCR-confirmed mild-to-moderate coronavirus disease in Japan. This clinical sign could help clinicians to diagnose this disease.

Unusual manifestation of disseminated herpes simplex virus type 2 infection associated with pharyngotonsilitis, esophagitis, and hemophagocytic lymphohisitocytosis without genital involvement.

BACKGROUND: Herpes simplex virus (HSV) has various presentations, depending on the patient's immune status, age, and the route of transmission. In adults, HSV type 1 is found predominantly in the oral area, and HSV type 2 (HSV-2) is commonly found in the genital area. HSV-2 infection without genital lesions is uncommon. Herein we report a unique case of pharyngotonsillitis as an initial manifestation of disseminated HSV-2 infection without genital involvement. CASE PRESENTATION: A 46-year-old male was admitted to our hospital with a 1-week history of fever and sore throat. His past medical history included hypereosinophilic syndrome diagnosed at age 45 years. Physical examination revealed throat congestion, bilaterally enlarged tonsils with exudates, tender cervical lymphadenopathy in the left posterior triangle, and mild epigastric tenderness. The laboratory data demonstrated bicytopenia, elevated liver enzyme levels, and hyperferritinemia. A bone marrow smear showed hypocellular marrow with histiocytes and hemophagocytosis. The diagnosis of HLH was confirmed, and the patient was treated with methylprednisolone pulse therapy on days 1-3. On day 5, despite initial improvement of the fever and sore throat, multiple, new, small bullae developed on the patient's face, trunk, and extremities. Additional testing showed that he was positive for HSV-specific immunoglobulin M and immunoglobulin G. Disseminated HSV infection was suspected, and intravenous acyclovir (10 mg/kg every 8 h) was begun. A subsequent direct antigen test of a bulla sample was positive for HSV-2. Moreover, tonsillar and esophageal biopsies revealed viral inclusion bodies. Immunohistochemical staining and a quantitative real-time polymerase chain reaction (PCR) assay confirmed the presence of HSV-2. Disseminated HSV-2 infection with multiple bullae, tonsillitis, esophagitis, and suspected hepatic involvement was diagnosed. After a 2-week course of intravenous acyclovir, his hematological status and liver function normalized, and his cutaneous skin lesions resolved. He was discharged on day 22 in good general health and continued taking oral valacyclovir for viral suppression due to his immunosuppressed status. CONCLUSION: Disseminated HSV-2 infection should be considered as one of the differential diagnoses in patients with pharyngotonsillitis and impaired liver function of unknown etiology even if there are no genital lesions.

Bacterial peritonitis in a patient with malignant ascites caused by pancreatic carcinoma: Case report and review of literature.

Bacterial peritonitis, an infection of the ascitic fluid, can be classified etiologically as spontaneous or secondary bacterial peritonitis. The former is mainly caused by portal hypertension and its subsequent effects, whereas the latter is caused by the direct dissemination of bacteria into the peritoneal cavity. Previous reports have described some distinguishing features of these two entities. Here, we report the first known case of bacterial peritonitis with Aeromonas hydrophilia and Escherichia coli in a patient with malignant ascites associated with pancreatic carcinoma who exhibited features of both spontaneous and secondary peritonitis. Our report suggests that clinicians should also consider bacterial peritonitis in patients with malignant ascites who present with ostensibly cancer-related symptoms.

Odd and Even Modes of Neutron Spin Resonance in the Bilayer Iron-Based Superconductor CaKFe_{4}As_{4}.

We report an inelastic neutron scattering study on the spin resonance in the bilayer iron-based superconductor CaKFe_{4}As_{4}. In contrast to its quasi-two-dimensional electron structure, three strongly L-dependent modes of spin resonance are found below T_{c}=35 K. The mode energies are below and linearly scale with the total superconducting gaps summed on the nesting hole and electron pockets, essentially in agreement with the results in cuprate and heavy fermion superconductors. This observation supports the sign-reversed Cooper pairing mechanism under multiple pairing channels and resolves the long-standing puzzles concerning the broadening and dispersive spin resonance peak in iron pnictides. More importantly, the triple resonant modes can be classified into odd and even symmetries with respect to the distance of Fe-Fe planes within the Fe-As bilayer unit. Thus, our results closely resemble those in the bilayer cuprates with nondegenerate spin excitations, suggesting that these two high-T_{c} superconducting families share a common nature.