HIV incidence before and during the COVID-19 pandemic in Japan.

At the end of 2022, a total of 20,003 diagnoses of human immunodeficiency virus (HIV) infection and 8,983 cases of acquired immunodeficiency syndrome (AIDS) among Japanese nationals, and 3,860 HIV diagnoses and 1,575 AIDS cases among foreign residents, had been notified to the government in Japan. This study updates the estimate of HIV incidence, including during the COVID-19 pandemic. It aimed to reconstruct the incidence of HIV and understand how the disruption caused by COVID-19 affected the epidemiology of HIV. Using a median incubation period of 10.0 years, the number of undiagnosed HIV infections was estimated to be 3,209 (95% confidence interval (CI): 2,642, 3,710) at the end of 2022. This figure has declined steadily over the past 10 years. Assuming that the median incubation period was 10.0 years, the proportion of diagnosed HIV infections, including surviving AIDS cases, was 89.3% (95% CI: 87.8%, 91.0%). When AIDS cases were excluded, the proportion was 86.2% (95% CI: 84.3%, 88.3%). During the COVID-19 pandemic, the estimated annual diagnosis rate was slightly lower than during earlier time intervals, at around 16.5% (95% CI: 14.9%, 18.1%). Japan may already have achieved diagnostic coverage of 90%, given its 9% increment in the diagnosed proportion during the past 5 years. The incidence of HIV infection continued to decrease even during the COVID-19 pandemic from 2020 to 2022, and the annual rate of diagnosis decreased slightly to 16.5%. Monitoring the recovery of diagnosis along with the effective reproduction number is vital in the future.

Coronavirus disease 2019-associated thrombotic microangiopathy treated with plasma exchange and antihypertensive therapy in a patient with HIV: A case report with literature review.

RATIONALE: Coronavirus disease 2019 (COVID-19) is an infectious disease that often causes complications in multiple organs and thrombosis due to abnormal blood coagulation. This case report aimed to describe the clinical course of COVID-19-associated thrombotic microangiopathy (TMA) and reviewed the comprehensive information on TMA, thrombotic thrombocytopenic purpura (TTP), and atypical hemolytic uremic syndrome associated with COVID-19 in the past literature. PATIENT CONCERNS: A 46-year-old Japanese man was diagnosed with human immunodeficiency virus infection 10 years ago and treated with antiretroviral therapy. The patient presented with fever, malaise, hematuria, and bilateral upper abdominal discomfort for the past 4 days. DIAGNOSES: COVID-19-associated TMA was diagnosed based on a positive polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 and laboratory findings such as thrombocytopenia, acute kidney injury, and hemolytic anemia. Malignant hypertension and human immunodeficiency virus infection were also considered as differential diagnoses of TMA. INTERVENTIONS: Considering the possibility of TTP, plasma exchange was performed, and glucocorticoids were administered. Hemodialysis was performed for acute kidney injury. Antihypertensive drugs were administered to control the high blood pressure. OUTCOMES: Platelet count and renal function improved, and hemodialysis was no longer required. The patient was in good general condition and was discharged from the hospital. LESSONS: COVID-19-associated TMA should be considered as a differential diagnosis during the COVID-19 epidemic. Excessive inflammation and severe COVID-19 are not essential for TMA development. Early intervention using conventional TMA treatments, such as plasma exchange and corticosteroids, might be important in improving prognosis while differentiating between TTP and atypical hemolytic uremic syndrome. Antihypertensive therapy may be helpful in the treatment of COVID-19-associated TMA.

Successful dual antiviral therapy with remdesivir and ensitrelvir in a case of prolonged COVID-19 following B-cell depleting immunotherapy for malignant lymphoma.

Prolonged COVID-19 following B-cell depleting immunotherapy for malignant lymphoma is characterized by repeated cycles of remission followed by symptom recurrence, persistent detection of SARS-CoV-2, and profound humoral immunodeficiency. To the best of our knowledge, the present report is the first to describe dual antiviral therapy with remdesivir and ensitrelvir for prolonged COVID-19 following B-cell depleting immunotherapy for malignant lymphoma. A 59-year-old, female patient with a history of follicular lymphoma treated with obinutuzumab and bendamustine contracted COVID-19 despite receiving a single course of standard remdesivir therapy. She received dual antiviral therapy with remdesivir following a five-day course of oral ensitrelvir, which improved her clinical symptoms and chest radiology findings and cleared SARS-CoV-2 from respiratory samples. Dual antiviral therapy with remdesivir and ensitrelvir may be sufficient to stop viral replication and promote clinical resolution in prolonged COVID-19 following B-cell depleting immunotherapy for malignant lymphoma.

Changes in rapid plasma reagin titers in patients with syphilis before and after treatment: A retrospective cohort study in an HIV/AIDS referral hospital in Tokyo.

INTRODUCTION: Although the rapid plasma reagin (RPR) test is used to determine treatment efficacy for syphilis, animal studies show that it decreases gradually after an initial increase even without treatment. Pre-treatment changes in RPR titer in humans and its relationship with post-treatment changes in RPR titer are not well known. METHODS: We retrospectively analyzed the clinical records of syphilitic patients who underwent automated RPR (Mediace) testing twice before treatment (i.e., at diagnosis and treatment initiation) within 1-3 months at an HIV/AIDS referral hospital in Japan between 2006 and 2018. The RPR values were expressed as the ratio to the value at treatment initiation. The mean monthly relative change in the RPR after treatment was calculated on the log2 scale for each patient and analyzed by multivariable linear regression. RESULTS: Sixty-eight patients were identified. The median age was 45 (interquartile range [IQR], 38-50), 98.5% (67/68) were men, and 97.1% (66/68) had HIV. The median RPR titer ratio at treatment initiation/diagnosis was 0.87 (IQR, 0.48-1.30). The RPR titer decreased more than twofold in 26.5% (18/68) and more than fourfold in 10.3% (7/68) before treatment. In the multivariable analysis, higher age (predicted monthly RPR relative change on the log2 scale 0.23/10 years [95% confidence interval [CI], 0.090-0.37]), history of syphilis (0.36 [95% CI, 0.07-0.65]), and a lower ratio of RPR at treatment initiation/diagnosis (-0.52/every 10-fold increase [95% CI, -0.81 to -0.22]) were associated with a slower RPR decrease after treatment. CONCLUSIONS: In a mostly HIV patient population, RPR titer can show more than four-fold spontaneous increase or decrease within 1-3 months. Pre-treatment spontaneous decrease of RPR titer was associated with a slower decrease in post-treatment RPR titer.

Immune reconstitution inflammatory syndrome in splenic Pneumocystis jirovecii infection: A case report.

To the best of our knowledge, the present report is the first to describe immune reconstitution inflammatory syndrome (IRIS) in a case of Pneumocystis jirovecii (P. jirovecii) infection of the spleen. A 45-year-old, men who have sex with men patient presented with constipation, abdominal pain, nausea, fever, and weight loss. Human immunodeficiency virus infection and P. jirovecii pneumonia were diagnosed. Abdominal computed tomography revealed multiple, hypodense, cystic lesions in the spleen. Based on the histopathological findings of the lesion obtained from a percutaneous splenic biopsy, extrapulmonary P. jirovecii infection of the spleen was diagnosed. Trimethoprim/sulfamethoxazole was administered for 21 days, and antiretroviral therapy was initiated ten days after the former regimen was begun. Temporary enlargement of the splenic lesions and fever recurrence were observed after the trimethoprim/sulfamethoxazole regimen was completed. However, the clinical course was favorable, with no splenic rupture or splenic bleeding. Our investigation suggested that additional therapy, such as corticosteroid administration, may not be required for IRIS in a splenic P. jirovecii infection, but further research is needed for a definitive conclusion.

[Outcomes of COVID-19 due to omicron variant infection complicated with hematological disorders].

When the omicron variant became the most dominant severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) variant causing coronavirus disease 2019 (COVID-19) in Japan, 11 patients with hematological diseases infected with this new variant were treated at our institution. Among them, four of the five patients who had been treated with chemotherapy progressed to moderate-II COVID-19, and two of them died. In contrast, five of the six patients who did not receive the treatment remained at mild to moderate-I stage of COVID-19, except for a single case progressing to moderate-II COVID-19. While all four patients infused with anti-coronavirus monoclonal antibodies within 8 days after the onset survived, the other two patients, being withheld from treatment or treated later, died. In these two cases, anti-SARS-Cov-2 immunoglobulin G antibodies remained at low titers. Although the omicron variant is considered a less harmful SARS-Cov-2 variant, patients with hematological disorders, particularly those who are immunosuppressed caused by chemotherapy, should be continuously cared for as they remain at a higher risk of severe COVID-19 due to insufficient or delayed anti-viral humoral immunity development. Thus, the rapid introduction of antiviral monoclonal antibodies together with anti-viral reagents may rescue these patients.

Nationwide Descriptive Epidemiological Study of Patients with COVID-19 Evacuated from Wuhan, China to Japan from January to February, 2020.

We investigated the epidemiological findings regarding the route of coronavirus disease 2019 (COVID-19) and infection prevention and control (IPC) measures among returnees in the emergency evacuation from Wuhan, China to Japan during the COVID-19 outbreak in 2020. A total of 12 of the 14 returnees (median age [range]: 49.5 years [29-65 years]; 9 men [75%]) had confirmed COVID-19. The proportion of returnees with COVID-19 was 12/566 (2.1%) in Flights 1-3 and 2/263 (0.8%) in Flights 4 and 5. Six patients were asymptomatic on admission, while 3 patients developed symptoms thereafter. None of the participants reported a specific history of contact with animals, going to seafood markets, or visiting medical facilities. Two patients were in contact with an individual who was confirmed or suspected of having COVID-19. Most patients resided in hotels in the center of Wuhan City, taking taxis and trains for commute. Patients relatively adhered to IPC measures such as wearing a mask and hand hygiene. However, emphasis on IPC measures such as universal masking and more rigorous avoidance of exposure risk might have been necessary to prevent infection. In addition, forced social distancing due to lockdown might have contributed to the lower infection rates in Flights 4 and 5, compared to Flights 1-3.

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.

Assessing countermeasures during a hepatitis A virus outbreak among men who have sex with men.

BACKGROUND: A hepatitis A epidemic occurred among men who have sex with men (MSM) in Japan in 2017-2018. In this study, we employ a parsimonious mathematical model to epidemiologically investigate the dynamics of infection, aiming to evaluate the effectiveness of campaign-based interventions among MSM to raise awareness of the situation. METHODS: A mathematical model describing a mixture of human-to-human transmission and environmental transmission was fitted to surveillance data. Taking seasonally varying environmental transmission into account, we estimated the reproduction number of hepatitis A virus during the course of epidemic, and, especially, the abrupt decline in this reproduction number following campaign-based interventions. RESULTS: The reproduction number prior to the countermeasures ranged from 2.6 to 3.1 and then began to decrease following campaign-based interventions. After the first countermeasure, the reproduction number decreased, but the epidemic remained supercritical (i.e., Rt > 1). The value of Rt dropped well below one following the second countermeasure, which used web articles to widely disseminate information about the epidemic risk. CONCLUSIONS: Although the effective reproduction number, Rt, changes because of both intrinsic and extrinsic factors, the timing of the examined countermeasures against hepatitis A in the MSM population was consistent with the abrupt declines observed in Rt. Even without vaccination, the epidemic was brought under control, and risky behaviors may have been changed by the increase in situation awareness reached through web articles.

Proactive Engagement of the Expert Meeting in Managing the Early Phase of the COVID-19 Epidemic, Japan, February-June 2020.

To deal with the risk of emerging diseases with many unknowns, close and timely collaboration and communication between science experts and policymakers are crucial to developing and implementing an effective science-based intervention strategy. The Expert Meeting, an ad hoc medical advisory body, was established in February 2020 to advise Japan's COVID-19 Response Headquarters. The group played an important role in the policymaking process, promoting timely situation awareness and developing science-based proposals on interventions that were promptly reflected in government actions. However, this expert group may have been overly proactive in taking on the government's role in crisis management. For the next stage of managing the coronavirus disease pandemic and future pandemics, the respective roles of the government and its advisory bodies need to be clearly defined. Leadership and strategic risk communication by the government are key.

Number of Patients with Influenza and COVID-19 Coinfection in a Single Japanese Hospital during the First Wave.

An individual may contract coronavirus disease 2019 (COVID-19) and influenza simultaneously; hence, adequate measures must be undertaken for the next winter in Japan. In preparation for the future, this study aimed to clarify the incidence of influenza coinfection in patients with COVID-19 during the previous winter. We conducted a retrospective study of the medical records of 193 patients diagnosed with COVID-19 between January 31, 2020, and April 23, 2020, in a single hospital. We evaluated the incidence of COVID-19 and influenza coinfection. Using rapid diagnostic testing, we found that no patient with COVID-19 was coinfected with influenza. Coinfection with influenza and COVID-19 was rare during the past winter in Japan.

An analysis of the radiological factors associated with respiratory failure in COVID-19 pneumonia and the CT features among different age categories.

PURPOSE: To investigate CT patterns of COVID-19 pneumonia associated with respiratory failure (RF) focused on the distribution of lesions. MATERIALS AND METHODS: Eighty-five patients with COVID-19 pneumonia were reviewed. CT findings were classified as follows: Type A; patchy ground glass attenuation (GGA) with/without air-space consolidation, Type B; non-segmental GGA with/without air-space consolidation in both the central and peripheral lung portions especially with subpleural spare, and Type C; non-segmental GGA with/without air-space consolidation predominantly distributed in the peripheral lung portion without subpleural spare. We analyzed CT patterns and clinical factors associated with RF, including age categories. RESULTS: The number of patients with Type A, B and C was 31 (37%), 24 (28%) and 30 (35%), respectively. Type C and hypertension were independently associated with RF. On comparing between Types B and C, the frequency of traction bronchiectasis was higher in Type C than in Type B (P < 0.001). The ratio of Type C in patients ≥ 65 years old (66%) was higher than in patients < 40 years old (P < 0.001) and 40-49 years old (P = 0.001). CONCLUSION: The Type C, increasing with age, was associated with RF. Traction bronchiectasis in the lesion was more frequent in Type C than in Type B. Secondary abstract A lesion adjacent to the pleura and hypertension is associated with respiratory failure in patients with COVID-19. The frequency of a lesion adjacent to the pleura increased with age. The distribution of lesions is a useful parameter to predict respiratory failure.

Prevalence of thromboembolic events and status of prophylactic anticoagulant therapy in hospitalized patients with COVID-19 in Japan.

INTRODUCTION: One of the most prominent and concerning complications associated with coronavirus disease 2019 (COVID-19) is venous and arterial thromboembolisms. The aim of the present study was to delineate the prevalence of thromboembolic events and the current status of prophylactic anticoagulation therapy in patients with COVID-19 in Japan. METHODS: Between February 1 and August 31, 2020, we performed a dual-center, retrospective cohort study based on data obtained from the medical charts of COVID-19 patients admitted to healthcare facilities in Japan. The primary outcome was any thromboembolic event including pulmonary embolism (PE), deep vein thrombosis (DVT), myocardial infarction, ischemic stroke and other systemic thromboemboli. RESULTS: During the study period, we extracted 628 consecutive patients admitted for COVID-19. Prophylactic anticoagulant therapy was administered in 63 (10%) patients of whom 20 (31.7%) were admitted to the intensive care unit (ICU). Thromboembolic events occurred in 18 (2.9%) patients (14.3% of patients in ICU and 2.2% of patients in the general wards). DVT were detected in 13 (2.1%) patients, PE in 11 (1.8%), and both DVT and PE in 6 (0.96%) patients. An increasing prevalence in thromboembolic events was noted with progressive clinical severity. Overall in-hospital mortality was 4.8%. CONCLUSIONS: Prophylactic anticoagulation therapy was administered in only 10% of all hospitalized COVID-19 patients. The prevalence of any thromboembolic events was 2.9% in COVID-19 patients with most events occurring in severe and critical patients. Therefore, prophylactic anticoagulation therapy may be warranted in severe and critical patients but in asymptomatic to moderate patients the practice remains controversial.

Development of a Risk Prediction Score to Identify High-Risk Groups for the Critical Coronavirus Disease 2019 (COVID-19) in Japan.

Coronavirus disease 2019 (COVID-19) emerged in mid-December 2019 and has rapidly spread worldwide. We conducted a retrospective analysis of data from patients with COVID-19 to construct a simple risk prediction score to be implemented in prehospital settings. Patients were classified into critical and non-critical groups based on disease severity during hospitalization. Multivariate analysis was performed to identify independent risk factors and develop a risk prediction score. A total of 234 patients were included in the study. The median age of the critical group was significantly older than that of the non-critical group (68.0 and 44.0 years, respectively), and the percentage of males in the critical group was higher than that in the non-critical group (90.2% and 60.6%, respectively). Multivariate analysis revealed that factors such as age ≥ 45 years, male sex, comorbidities such as hypertension and cancer, and having fever and dyspnea on admission were independently associated with the critical COVID-19 infection. No critical events were noted in patients with a total risk factor score of ≤ 2. Contrastingly, patients with a total risk factor score ≥ 4 were more likely to have critical COVID-19 infection. This risk prediction score may be useful in identifying critical COVID-19 infections.

Characteristics and outcomes of coronavirus disease 2019 (COVID-19) patients with cancer: a single-center retrospective observational study in Tokyo, Japan.

BACKGROUND: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an international outbreak of coronavirus disease 2019 (COVID-19), data on the clinical characteristics of COVID-19 patients with cancer are limited. This study aimed to evaluate the clinical characteristics and outcomes including mortality and viral shedding period in COVID-19 patients with cancer in Japan. METHODS: We retrospectively analyzed 32 patients with a history of cancer who were referred to our hospital between January 31, 2020 and May 25, 2020. We evaluated the association between clinical outcomes and potential prognostic factors using univariate analyses. RESULTS: The median age was 74.5 (range 24-90) years and 22 patients (69%) were men. A total of 11 patients (34%) died. Our analyses demonstrated that the mortality was significantly associated with lymphocyte count, albumin, lactate dehydrogenase, serum ferritin, and C-reactive protein on admission. The median period between illness onset and the first effective negative SARS-CoV-2 PCR result was 22 days (interquartile range 18-25) in survivors. Of four patients with hematological malignancy who developed COVID-19 within the rest period of chemotherapy, three died and the other patient, who received bendamustine plus rituximab therapy, had the longest duration of viral shedding (56 days). CONCLUSION: Our study suggested that the risk factors for mortality previously reported in general COVID-19 patients, including lymphocytopenia, were also effective in cancer patients. Patients who received cytotoxic chemotherapy recently or were treated with chemotherapy, which can lead to lymphocyte reduction, had poor prognosis and prolonged periods of viral shedding.

SARS-CoV-2 Screening Test for Japanese Returnees From Wuhan, China, January 2020.

BACKGROUND: Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) was found to be the causative microorganism of coronavirus disease 2019 (COVID-19), which started to spread in Wuhan, China. This study was to evaluate the effectiveness of questionnaire, symptoms-based screening, and polymerase chain reaction (PCR) screening of returnees from COVID-19-endemic areas on a chartered flight, to examine the proportion of infected persons and the proportion of asymptomatic persons among infected persons who returned from Wuhan. METHODS: A retrospective cohort study was done in 7 tertiary medical institutions in Japan. A total of 566 Japanese who returned from Wuhan participated in the study. RESULTS: Overall, 11 of the 566 passengers had a positive SARS-CoV-2 PCR result for pharyngeal swabs and 6 were asymptomatic. Only fever differed between SARS-CoV-2-positive and -negative individuals (P < .043). Six of the 11 PCR-positive individuals were asymptomatic; 4 remained positive on day 10, and 1 asymptomatic person tested positive up to day 27. Two of the 11 were negative on the first PCR test and positive on the second. CONCLUSIONS: Our results will be important insights on screening returnees from locked-down cities, as well as providing important data on the proportion of asymptomatic individuals infected with SARS-CoV-2. A 13-day observation period and a second round of PCR may be effective to screen patients, including asymptomatic infections.

Estimating the syphilis incidence and diagnosis rate in Japan: a mathematical modelling study.

OBJECTIVES: The reported number of syphilis cases is increasing in Japan. In this study, we aimed to estimate both the incidence of infection and diagnosis-and-reporting rate using a mathematical model that captures the time course of infection. METHODS: We analysed yearly notification data from 1961 to 2016 and stratified according to clinical stage and sex. We built a compartmental ordinary differential equations model to describe the natural epidemiological course of syphilis in which the incidence of infection and diagnosis-and-reporting rate were included as time-varying parameters that we estimated via the maximum likelihood method. RESULTS: From 2008 to 2016, the estimated number of new syphilis cases among men and women was 1070 (95% CI 1037 to 1104) and 302 (95% CI 287 to 318), respectively, which was increased from the previous period (1999-2007) with 269 (95% CI 256 to 282) and 71 (95% CI 64 to 78) cases, respectively. The diagnosis-and-reporting rate did not vary greatly over time. We estimated the number of undiagnosed syphilis cases from either incubating or early clinical (ie, primary or secondary) infections in 2016 to be 262 (95% CI 249 to 275) and 79 (95% CI 74 to 84) for men and women, respectively. CONCLUSIONS: The recent increase in reported cases of syphilis is owing to an increase in the number of infections. We found no evidence of time-dependent improvement in detection or reporting.

Investigation of the Proportion of Diagnosed People Living with HIV/AIDS among Foreign Residents in Japan.

Foreign residents represent an increasing proportion of newly diagnosed human immunodeficiency virus (HIV) infections and acquired immunodeficiency syndrome (AIDS) cases in Japan, though scant research has addressed this. This study aimed to estimate the diagnosed proportion of people living with HIV/AIDS (PLWHA) among foreign residents in Japan, covering 1990-2017 and stratifying by geographic region of the country of origin. A balance equation model was employed to statistically estimate the diagnosed proportion as a single parameter. This used published estimates of HIV incidence and prevalence, population size, visit duration, travel volume, as well as surveillance data on HIV/AIDS in Japan. The proportion varied widely by region: People from Western Europe, East Asia and the Pacific, Australia and New Zealand, and North America were underdiagnosed, while those from sub-Saharan Africa, South and South-East Asia, and Latin America were more frequently diagnosed. Overall, the diagnosed proportion of PLWHA among foreign residents in Japan has increased, but the latest estimate in 2017 was as low as 55.3%; lower than the estimate among Japanese on the order of 80% and far below the quoted goal of 90%. This finding indicates a critical need to investigate the underlying mechanisms, including disparate access to HIV testing.