RNAseq for Entaoeba histolytica
Honors & Awards
Encouraging Award in Honor of Hakoneyama, National Center for Global Health and Medicine (2021)
Academic Encouraging Award in Honor of Shibasaburo Kitasato, The Japanese Association for Infectious Diseases (2021)
Doctor of Medicine, Kanazawa University (2009)
Doctor of Philosophy, Kumamoto University (2018)
Ph.D., Kumamoto University, Medicine (2018)
Fellowship, National Center for Global Health and Medicine, AIDS Clinical Center (2017)
Senior Resident, National Center for Global Health and Medicine, General Infectious Diseases (2014)
Junior Resident, Toyama Prefectural Central Hospital (2011)
M.D.,, Kanazawa University, Medicine (2009)
- Amebiasis as a sexually transmitted infection: A re-emerging health problem in developed countries GLOBAL HEALTH & MEDICINE 2023
Effectiveness of sitafloxacin monotherapy for quinolone-resistant rectal and urogenital Mycoplasma genitalium infections: a prospective cohort study
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
Mycoplasma genitalium has a tendency to develop macrolide and quinolone resistance.We investigated the microbiological cure rate of a 7 day course of sitafloxacin for the treatment of rectal and urogenital infections in MSM.This open-label, prospective cohort study was conducted at the National Center for Global Health and Medicine, Tokyo, Japan from January 2019 to August 2022. Patients with M. genitalium urogenital or rectal infections were included. The patients were treated with sitafloxacin 200 mg daily for 7 days. M. genitalium isolates were tested for parC, gyrA and 23S rRNA resistance-associated mutations.In total, 180 patients (median age, 35 years) were included in this study, of whom 77.0% (97/126) harboured parC mutations, including 71.4% (90/126) with G248T(S83I) in parC, and 22.5% (27/120) harboured gyrA mutations. The median time to test of cure was 21 days. The overall microbiological cure rate was 87.8%. The cure rate was 100% for microbes harbouring parC and gyrA WTs, 92.9% for microbes harbouring parC G248T(S83I) and gyrA WT, and 41.7% for microbes harbouring parC G248T(S83I) and gyrA with mutations. The cure rate did not differ significantly between urogenital and rectal infection (P = 0.359).Sitafloxacin monotherapy was highly effective against infection caused by M. genitalium, except strains with combined parC and gyrA mutations. Sitafloxacin monotherapy can be used as a first-line treatment for M. genitalium infections in settings with a high prevalence of parC mutations and a low prevalence of gyrA mutations.
View details for DOI 10.1093/jac/dkad208
View details for Web of Science ID 001026348800001
View details for PubMedID 37376970
Effect of tenofovir-based HIV pre-exposure prophylaxis against HBV infection in men who have sex with men.
Hepatology (Baltimore, Md.)
2023; 77 (6): 2084-2092
Men who have sex with men (MSM) are vulnerable to contracting HBV as a sexually transmitted infection. We evaluated the incidence of HBV infection (HBI) and the prophylactic effect of tenofovir-based pre-exposure prophylaxis (PrEP) on HBI in an MSM cohort.MSM who were older than 16 years were enrolled from January 2018 and followed up until June 2021 and tested for HIV, bacterial sexually transmitted infections, and HBsAg/ HBsAb and HBcAb every 3 months based on inclusion criteria, including HBsAg, HBcAb, HBsAb, and HIV negativity at enrollment. HBI was defined as seroconversion of HBsAg or HBcAb status. The log-rank test was used to evaluate the prophylactic effect of PrEP against HBI. As a substudy, individuals excluded from the main study due to HBs Ab positivity were evaluated for HBI incidence. Among 1577 MSM, 786 participants (546 PrEP nonusers, 131 daily PrEP users, and 109 event-driven PrEP users) met the criteria and were included. The annual incidence of HBV among PrEP nonusers (3.8%, 21 infections, with 559.5 person-years) was significantly higher ( p = 0.018, log-rank test) than that among daily PrEP users [0.77%, 1 infection (admitted nonadherence), with 129.3 person-years] and event-driven PrEP users (no infection with 93.8 person-years). Although the incidence of HBI and HIV infection decreased with PrEP use, the incidence of other sexually transmitted infections was higher in both daily and event-driven PrEP users. The annual incidence of HBV among HBsAb-positive and HBcAb-negative PrEP nonusers was 1.8% (3 infections, with 167.5 person-years).Tenofovir-based PrEP prevented HBI among MSM in a real-world setting.
View details for DOI 10.1097/HEP.0000000000000384
View details for PubMedID 36960800
View details for PubMedCentralID PMC10187616
Combination of Amoxicillin 3,000 mg and Probenecid versus 1,500 mg Amoxicillin Monotherapy for Treating Syphilis in Patients with HIV: an Open-Label, Randomized, Controlled, Non-Inferiority Trial.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Amoxicillin plus probenecid is an alternative to intramuscular benzathine penicillin G for treating syphilis in the United Kingdom. Low-dose amoxicillin is an alternative treatment option used in Japan.We conducted an open-label, randomized, controlled, non-inferiority trial between August 31, 2018, and February 3, 2022, to compare 1,500 mg low-dose amoxicillin monotherapy with the combination of 3,000 mg amoxicillin and probenecid (non-inferiority margin 10%). Patients with human immunodeficiency virus (HIV) infection and syphilis were eligible. The primary outcome was the cumulative serological cure rate within 12 months post-treatment, measured using the manual rapid plasma reagin card test. Secondary outcomes included safety assessment.A total of 112 participants were randomized into two groups. Serological cure rates within 12 months were 90.6% and 94.4% with the low-dose amoxicillin and combination regimens, respectively. Serological cure rates for early syphilis within 12 months were 93.5% and 97.9% with the low-dose amoxicillin and combination regimens, respectively. Non-inferiority of low-dose amoxicillin compared with amoxicillin plus probenecid overall and for early syphilis was not confirmed. No significant side effects were detected.This is the first randomized controlled trial to demonstrate a high efficacy of amoxicillin-based regimens for treating syphilis in patients with HIV infection, and the non-inferiority of low-dose amoxicillin compared with amoxicillin plus probenecid was not seen. Therefore, amoxicillin monotherapy could be a good alternative to intramuscular benzathine penicillin G with fewer side effects. However, further studies comparing with benzathine penicillin G in different populations and with larger sample sizes are needed.University Hospital Medical Information Network (UMIN000033986).
View details for DOI 10.1093/cid/ciad278
View details for PubMedID 37157863
Diversity and Plasticity of Virulent Characteristics of Entamoeba histolytica.
Tropical medicine and infectious disease
2023; 8 (5)
The complexity of clinical syndromes of amebiasis, caused by the parasite Entamoeba histolytica, stems from the intricate interplay between the host immune system, the virulence of the invading parasite, and the surrounding environment. Although there is still a relative paucity of information about the precise relationship between virulence factors and the pathogenesis of Entamoeba histolytica, by accumulating data from clinical and basic research, researchers have identified essential pathogenic factors that play a critical role in the pathogenesis of amebiasis, providing important insights into disease development through animal models. Moreover, the parasite's genetic variability has been associated with differences in virulence and disease outcomes, making it important to fully understand the epidemiology and pathogenesis of amebiasis. Deciphering the true mechanism of disease progression in humans caused by this parasite is made more difficult through its ability to demonstrate both genomic and pathological plasticity. The objective of this article is to underscore the heterogeneous nature of disease states and the malleable virulence characteristics in experimental models, while also identifying persistent scientific issues that need to be addressed.
View details for DOI 10.3390/tropicalmed8050255
View details for PubMedID 37235303
Pharmacokinetics of Bictegravir in Older Japanese People Living with HIV-1.
2023; 11 (2): e0507922
Bictegravir (BIC) is an integrase strand transfer inhibitor widely used in the treatment of HIV-1. Although its potency and safety have been demonstrated in older patients, pharmacokinetics (PK) data remain limited in this patient population. Ten male patients aged 50 years or older with suppressed HIV RNA on other antiretroviral regimens were switched to a single-tablet regimen of BIC, emtricitabine, and tenofovir alafenamide (BIC+FTC+TAF). Four weeks later, plasma samples were collected at 9 time points for PK. Safety and efficacy were also assessed up to 48 weeks. The median age (range) of patients was 57.5 (50 to 75) years. Although 8 (80%) had lifestyle diseases requiring treatment, no participants had renal or liver failure. Nine (90%) were receiving dolutegravir-containing antiretroviral regimens at entry. The trough concentration of BIC was 2,324 (1,438 to 3,756) (geometric mean [95% confidence interval]) ng/mL, which was markedly above the 95% inhibitory concentration of the drug (162 ng/mL). All PK parameters, including area under the blood concentration-time curve and clearance, were similar to those in young HIV-negative Japanese participants in a previous study. No correlations between age and any PK parameters were observed in our study population. No participant experienced virological failure. Body weight, transaminase, renal function, lipid profiles, and bone mineral density were unchanged. Interestingly, urinary albumin was decreased after switching. PK of BIC was not affected by age, indicating that BIC+FTC+TAF may be safely used in older patients. IMPORTANCE BIC is a potent integrase strand transfer inhibitor (INSTI), widely used for the treatment of HIV-1 as part of a once-daily single-tablet regimen that includes emtricitabine and tenofovir alafenamide (BIC+FTC+TAF). Although the safety and efficacy of BIC+FTC+TAF have been confirmed in older patients with HIV-1, PK data in this patient population remain limited. Dolutegravir (DTG), an antiretroviral medication with a similar structural formula to BIC, causes neuropsychiatric adverse events. PK data for DTG have shown a higher maximum concentration (Cmax) among older patients than younger patients and are related to a higher frequency of adverse events. In the present study, we prospectively collected BIC PK data from 10 older HIV-1-infected patients and showed that PK of BIC are not affected by age. Our results support the safe use of this treatment regimen among older patients with HIV-1.
View details for DOI 10.1128/spectrum.05079-22
View details for PubMedID 36809124
View details for PubMedCentralID PMC10100687
Gene expression of axenically-isolated clinical Entamoeba histolytica strains and its impact on disease severity of amebiasis.
2022; 18 (9): e1010880
The severity of Entamoeba histolytica infection is determined by host immunology, pathogen virulence, and the intestinal environment. Conventional research for assessing pathogen virulence has been mainly performed using laboratory strains, such as a virulent HM-1: IMSS (HM-1) and an avirulent Rahman, under various artificial environmental conditions because of the difficulties of axenic isolation of the clinical strains. However, it is still unclear whether scientific knowledge based on laboratory strains are universally applicable to the true pathogenesis. Hereby, we performed transcriptomic analysis of clinical strains from patients with different degrees of disease severity, as well as HM-1 under different conditions. Even after several months of axenization, Clinical strains show the distinct profile in gene expression during in vitro passage, moreover, difference between any 2 of these strains was much greater than the changes on the liver challenge. Interestingly, 26 DEGs, which were closely related to the biological functions, were oppositely up- or down regulated between virulent Ax 19 (liver abscess) and avirulent Ax 11 (asymptomatic carrier). Additionally, RNAseq using laboratory strain (HM1) showed more than half of genes were differently expressed between continuously in vitro passaged HM1 (in vitro HM1) and periodically liver passaged HM1 (virulent HM1), which was much greater than the changes on the liver passage of virulent HM1. Also, transcriptomic analysis of a laboratory strain revealed that continuous environmental stress enhances its virulence via a shift in its gene expression profile. Changes in gene expression patterns on liver abscess formation were not consistent between clinical and laboratory strains.
View details for DOI 10.1371/journal.ppat.1010880
View details for PubMedID 36178974
View details for PubMedCentralID PMC9555656
Evaluation of the Detection of Pathogens in Hospitalized Patients with COVID-19 at a Tertiary Hospital in Japan
JAPANESE JOURNAL OF INFECTIOUS DISEASES
2022; 75 (4): 419-422
The detection of other pathogens in patients with hospitalized coronavirus disease (COVID-19) are not frequent. Considering that data from Japan are limited, we conducted an observational study including patients with hospitalized COVID-19 at the National Center for Global Health and Medicine from January to September 2020. In total, 247 patients with COVID-19 were included in the study. Rapid diagnostic tests, such as immunochromatography, were performed in 31 patients (12.6%). The Film Array Respiratory Panel was performed in 18 (7.3%) patients, and none of the tests were positive for pathogens other than severe acute respiratory syndrome coronavirus 2. Respiratory bacterial culture was performed in 66 (26.7%) patients, with gram-positive bacteria, gram-negative bacteria and normal flora being detected in eight (12.1%), seven (10.6%), and 63 (95.5%) patients, respectively. Patients for whom cultures were performed were older, more severely ill, and more likely to have radiological evidence of pneumonia on admission. Culture was performed more frequently in the early than in the later period of the epidemic, without any differences being observed in bacterial detection rates. The proportion of viral and bacterial detection among hospitalized patients with COVID-19 in tertiary care hospitals in Japan was low. A larger cohort study is necessary to evaluate the effect of each pathogen on the clinical course of COVID-19.
View details for DOI 10.7883/yoken.JJID.2021.232
View details for Web of Science ID 000840858300017
View details for PubMedID 35228500
Unmasking latent extrapulmonary tuberculosis with newly diagnosed HIV-1 infection in a COVID-19 patient with prolonged fever.
Oxford medical case reports
2022; 2022 (7): omac079
Prolonged fever is a common symptom of COVID-19 infection. However, other febrile diseases continue during the pandemic. Herein, we report a COVID-19-infected patient with prolonged fever despite the lack of oxygen requirement, who was finally diagnosed with tuberculotic lymphadenitis and HIV-1 infection. All symptoms improved rapidly after the initiation of antituberculosis medications. Tuberculosis is an important differential diagnosis for patients with prolonged fever during the COVID-19 pandemic. It is possible that COVID-19 infection could serve to unmask latent infections via a cytokine storm.
View details for DOI 10.1093/omcr/omac079
View details for PubMedID 35903623
View details for PubMedCentralID PMC9318900
<p>A four-year observation of HIV and sexually transmitted infections among men who have sex with men before and during pre-exposure prophylaxis in Tokyo</p>
JOURNAL OF INFECTION AND CHEMOTHERAPY
2022; 28 (6): 762-766
Pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine (TDF/FTC) has been recommended worldwide. We evaluated the safety and efficacy of daily PrEP with TDF/FTC in Tokyo.This single-center, single-arm study was performed with 124 men who have sex with men (MSM) between January 2017 and March 2021. MSM who entered into an MSM cohort from January 2017 through March 2018 and had a pre-PrEP observational period of 1 year were eligible and recruited to the study between April 2018 and March 2019 and followed for 2 years. The primary outcome was the incidence of HIV infection (per 100 person-years). Secondary outcomes were the incidence of sexually transmitted infections and adverse events, and the rate of retention and adherence to PrEP.There were 309 MSM registered in the cohort (mean age, 36.6 years); 124 fulfilled the criteria and were included in the study. The remaining patients were continuously followed. There was a significant decrease in incidental HIV infection among PrEP users (0 infections, 235.5 person-years) compared to non-PrEP users (11 infections [3.4%/year], 318.9 person-years; p = 0.01). The average adherence rate was consistently greater than 95%, and the retention rate at two years was approximately 80%.The present study showed a high prophylactic effect against HIV infection, retention, and adherence to PrEP. PrEP is feasible and highly recommended in Japan.UMIN Clinical Trials Registry (UMIN000031040, www.umin.ac.jp), Japan Registry of Clinical Trials (jRCTs031180134).
View details for DOI 10.1016/j.jiac.2022.02.013
View details for Web of Science ID 000800543800008
View details for PubMedID 35248496
Identification of asymptomatic Entamoeba histolytica infection by a serological screening test: A cross-sectional study of an HIV-negative men who have sex with men cohort in Japan.
PLoS neglected tropical diseases
2022; 16 (4): e0009793
Amebiasis, caused by Entamoeba histolytica, is spreading in developing countries and in many developed countries as a sexually transmitted infection. Here, we evaluated the efficacy of serological screening to identify asymptomatic E. histolytica infection as a potential epidemiological control measure to limit its spread.This cross-sectional study was carried out between January and March 2021 in an HIV-negative men who have sex with men (MSM) cohort at the National Center for Global Health and Medicine. Serological screening was performed using a commercially available ELISA kit. For seropositive individuals, we performed stool polymerase chain reaction (PCR) to determine current E. histolytica infection. We performed E. histolytica serological screening of 312 participants. None had a history of E. histolytica infection prior to the study. The overall E. histolytica seropositivity was 6.7% (21/312), which was similar to that found by the rapid plasma reagin test (17/312). We identified current infection in 8 of 20 seropositive participants (40.0%) by stool PCR.Our serological screening approach constitutes a potentially practical epidemiological strategy. Active epidemiological surveys, in combination with an effective screening strategy for asymptomatically infected individuals, should be applied to help reduce sexually transmitted E. histolytica infections.
View details for DOI 10.1371/journal.pntd.0009793
View details for PubMedID 35468146
View details for PubMedCentralID PMC9071119
The First Reported Case of Bordetella pertussis Bacteremia in a Patient With Human Immunodeficiency Virus Infection.
Open forum infectious diseases
2022; 9 (3): ofac020
We describe a case of bacteremia in a human immunodeficiency virus-infected patient caused by a Bordetella pertussis strain lacking 2 major virulence factors, filamentous hemagglutinin and fimbriae. Although B pertussis bacteremia is uncommon, physicians should be aware that even attenuated B pertussis strains can cause invasive infection in immunocompromised patients. Bordetella pertussis is a gram-negative coccobacillus that causes a severe paroxysmal coughing disease known as whooping cough or pertussis. Bordetella pertussis colonizes the epithelial cells of the human respiratory tract, and the organisms are typically isolated from nasopharynx. We describe a case of B pertussis bacteremia in a patient with human immunodeficiency virus (HIV) infection. Interestingly, the isolate recovered from blood culture did not produce the major virulence factors, filamentous hemagglutinin (FHA) and fimbriae (FIM). Previously, 3 cases of B pertussis bacteremia were reported in the literature. We discuss the features of B pertussis bacteremia.
View details for DOI 10.1093/ofid/ofac020
View details for PubMedID 35146052
View details for PubMedCentralID PMC8825563
Clinical Features and Gut Microbiome of Asymptomatic Entamoeba histolytica Infection.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
2021; 73 (9): e3163-e3171
Entamoeba histolytica infection is a sexually transmitted disease in some developed countries. Asymptomatic infection often occurs and can be a source of transmission; however, limited data are available regarding the pathogenesis of E. histolytica.This was a single-center, cross-sectional study. Specimens were prospectively collected from patients with clinically suspected cases. Entamoeba histolytica infection was defined as a case in which the identification of E. histolytica was confirmed by polymerase chain reaction (PCR) of a clinical specimen. Data from asymptomatic cases were compared with those from symptomatic invasive cases.Sixty-four E. histolytica-infected cases, including 13 asymptomatic cases, were identified during the study period. Microbiological diagnosis was made by endoscopic sampling in 26.6% of these cases (17/64). Endoscopy identified macroscopically visible lesions in all cases; however, the sensitivity of histopathology on biopsy samples was low (45.5%) compared with PCR (94.7%). In asymptomatic cases, infection sites were limited around the proximal colon; moreover, trophozoites were frequently identified at infection sites whereas cystic forms were commonly detected in stools. Gut microbiome analyses showed more uniform composition in asymptomatic cases than in symptomatic invasive cases, which were represented by a relatively high abundance of Ruminococcaceae, Coriobacteriaceae, and Clostridiaceae, and a low abundance of Streptococcaceae.These results indicate that the encystation and attenuation of E. histolytica are highly affected by the intestinal contents, including the gut microbiome.
View details for DOI 10.1093/cid/ciaa820
View details for PubMedID 32564059
View details for PubMedCentralID PMC8563208
Efficacy of 1 g Ceftriaxone Monotherapy Compared to Dual Therapy With Azithromycin or Doxycycline for Treating Extragenital Gonorrhea Among Men Who Have Sex With Men.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
2021; 73 (8): 1452-1458
Evidence on efficacy of high-dose ceftriaxone monotherapy for extragenital Neisseria gonorrhoeae (NG) infection is lacking.A cohort of men who have sex with men (MSM) were tested for NG/Chlamydia trachomatis (CT) every 3 months, in a single-center observational study in Tokyo, Japan. MSM aged > 19 years diagnosed with extragenital NG infection between 2017 and 2020 were included. A single dose of 1 g ceftriaxone monotherapy was provided, while dual therapy with a single oral dose of 1 g azithromycin or 100 mg doxycycline administered orally twice daily for 7 days were given, for those coinfected with CT, according to infected sites. Efficacy of these treatments was calculated by the number of NG-negative subjects at test-of-cure divided by the number of subjects treated. Fisher exact tests were used to compare the efficacy between the 2 groups.Of 320 cases diagnosed with extragenital NG, 208 were treated with monotherapy and 112 were treated with dual therapy. The efficacy against total, pharyngeal, and rectal infections was 98.1% (204/208, 95% confidence interval [CI]: 95.2-99.3%), 97.8% (135/138, 95% CI: 93.8-99.4%), and 98.6% (69/70, 95% CI: 92.3-99.9%), respectively, in the monotherapy group, whereas the corresponding efficacy in the dual therapy was 95.5% (107/112, 95% CI: 90.0-98.1%), 96.1% (49/51, 95% CI: 86.8-99.3%), and 95.1% (58/61, 95% CI: 86.5-98.7%), respectively. No significant difference in the corresponding efficacy was observed between the two groups (P = .29, P = .61, P = .34, respectively).High-dose ceftriaxone monotherapy is as effective as dual therapy for extragenital NG among MSM.
View details for DOI 10.1093/cid/ciab455
View details for PubMedID 34000039
Anal human papillomavirus infection and its relationship with abnormal anal cytology among MSM with or without HIV infection in Japan.
2021; 11 (1): 19257
Anal high-risk human papillomavirus (hr-HPV) infection is widely considered a cause of anal cancer. However, epidemiological data are quite limited in Japan. This study investigated anal HPV infections and cytological abnormalities among MSM with or without HIV infection. Anal swabs were obtained, and cytological results were examined. Hybrid capture-based methodology was used for hr-HPV genotyping. The exclusion criterion was a history of vaccination against HPV. 644 subjects participated, and the overall prevalence of hr-HPV was 59.7% (95% CI 54.7-62.3), HIV-infected had higher prevalence than HIV-uninfected (68.9% vs 40.6%) p < .001. Among hr-HPV-infected participants, 82.8% (312/377) were infected with at least one of 9 valent vaccine-covered hr-HPV genotypes. From regression analysis, detection of abnormal cytology correlated positively with HIV infection (OR 2.17 [95% CI 1.51-3.13]), number of hr-HPV genotypes infected (OR 1.83 [1.59-2.10]), history of STI (OR 1.58 [1.14-2.22]) and No. of lifetime sexual partners (OR 1.56 [1.10-2.21]), albeit multivariate analysis identified the number of detected hr-HPV genotypes (adjusted OR 1.78 [1.54-2.06]) as the independent risk factor for abnormal cytology. High rates of anal hr-HPV infection, especially 9-valent HPV vaccine-preventable hr-HPV were detected among our MSM participants in Japan. HPV vaccination should also be encouraged for MSM in Japan.
View details for DOI 10.1038/s41598-021-98720-3
View details for PubMedID 34584174
View details for PubMedCentralID PMC8479121
Modified self-obtained pooled sampling to screen for Chlamydia trachomatis and Neisseria gonorrhoeae infections in men who have sex with men.
Sexually transmitted infections
2021; 97 (5): 324-328
To assess whether pooled sample testing with nucleic acid amplification tests was a potential alternative to three single-site sample testing to screen for Chlamydia trachomatis and Neisseria gonorrhoeae infections in asymptomatic men who have sex with men.We prospectively compared pooled sample testing with single-site sample testing in asymptomatic MSM. Self-obtained paired rectal samples, one gargle sample and one first-void urine sample were collected from participants to generate two sets of samples: one for pooled sample testing and the other for single-site testing. We used modified pooled sampling, which is defined as the use of gargle samples, instead of swabs, for the pooled sample to test for pharyngeal infection.This study included 513 MSM. The positive rates of C. trachomatis and N. gonorrhoeae were 20.3% and 11.7%, respectively, for single-site sample testing. Compared with the sensitivity of single-site testing as the gold standard, the sensitivities of pooled sample testing for C. trachomatis and N. gonorrhoeae were 94.2% (95% CI 88.0% to 97.3%) and 98.3% (95% CI 90.9% to 99.9%), respectively. The concordance rate and kappa coefficient were 98.3% (95% CI 96.7% to 99.2%) and 0.945 (95% CI 0.859 to 1.000), respectively, for C. trachomatis and 98.8% (95% CI 90.1% to 100%) and 0.943 (95% CI 0.857 to 1.000), respectively, for N. gonorrhoeae.The modified pooled sampling had a comparably high consistency with single-site sample testing. The results strongly suggest that the gargle sample is suitable as a part of pooled sample for STI screening of C. trachomatis and N. gonorrhoeae.
View details for DOI 10.1136/sextrans-2020-054666
View details for PubMedID 33082236
External validation and update of prediction models for unfavorable outcomes in hospitalized patients with COVID-19 in Japan.
Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy
2021; 27 (7): 1043-1050
Most of the currently used prognostic models for COVID-19 are based on Western cohorts, but it is unknown whether any are applicable to patients with COVID-19 in Japan.This retrospective cohort study included 160 patients with COVID-19 who were admitted to the National Center for Global Health and Medicine between January 26, 2020 and July 25, 2020. We searched PubMed for prognostic models for COVID-19. The predicted outcome was initiation of respiratory support or death. Performance of the candidate models was evaluated according to discrimination and calibration. We recalibrated the intercept of each model with our data. We also updated each model by adding β2-microglobulin (β2MG) to the model and recalculating the intercept and the coefficient of β2MG.Mean patient age was 49.8 years, 68% were male, 88.7% were Japanese. The study outcomes occurred in 15 patients, including two deaths. Two-hundred sixty-nine papers were screened, and four candidate prognostic models were assessed. The model of Bartoletti et al. had the highest area under receiver operating characteristic curve (AUC) (0.88; 95% confidence interval 0.81-0.96). All four models overestimated the probability of occurrence of the outcome. None of the four models showed statistically significant improvement in AUCs by adding β2MG.Our results suggest that the existing prediction models for COVID-19 overestimate the probability of occurrence of unfavorable outcomes in a Japanese cohort. When applying a prediction model to a different cohort, it is desirable to evaluate its performance according to the prevalent health situation in that region.
View details for DOI 10.1016/j.jiac.2021.04.008
View details for PubMedID 33865699
View details for PubMedCentralID PMC8041181
High prevalence of circulating dual-class resistant Mycoplasma genitalium in asymptomatic MSM in Tokyo, Japan.
2021; 3 (2): dlab091
To assess the prevalence and antibiotic resistance profile of Mycoplasma genitalium detected from urogenital/rectal swab samples obtained from MSM in Tokyo, Japan.We performed PCR-based screening for M. genitalium urogenital/rectal infection in 982 asymptomatic MSM between 1 January 2019 and 5 November 2020. Mutations in the antibiotic resistance-associated genes gyrA and parC and the 23S rRNA of M. genitalium were analysed.The prevalence of M. genitalium infection was 6.1%: the prevalence of rectal and urogenital infection was 4.7% and 1.4%, respectively. Among the cases, 48 were successfully analysed for 23S rRNA, 41 for parC mutations and 37 for gyrA mutations. Macrolide- and quinolone-resistance associated mutations (23S rRNA and parC mutations) were observed in 43 (89.6%) and 28 (68.3%) cases, respectively. The quinolone-resistance associated mutation-harbouring variants also harboured macrolide-resistance associated mutations. The S83I mutation in the parC gene was most commonly identified (24 cases, 58.5%), and its combination with M95I or D99N mutation in the gyrA gene was observed in 9 of 36 successfully analysed cases (25.0%). No significant association was observed between the presence of antibiotic resistance and antibiotic exposure for either macrolides or fluoroquinolones (P = 0.785 and 0.402, respectively).In Tokyo, there is an alarmingly high prevalence of M. genitalium harbouring macrolide and/or quinolone resistance-associated mutations in MSM, irrespective of antibiotic exposure. The high prevalence of M. genitalium strains with both parC and gyrA mutations limits the efficacy of sitafloxacin. Therefore, suitable alternatives are required to treat such M. genitalium infections.
View details for DOI 10.1093/jacamr/dlab091
View details for PubMedID 34223146
View details for PubMedCentralID PMC8242132
Performance of an enzyme-linked immunosorbent-based serological assay for Entamoeba histolytica: Comparison with an indirect immunofluorescence assay using stored frozen samples.
Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy
2021; 27 (5): 736-739
Entamoeba histolytica infections are increasingly diagnosed as sexually transmitted infections in Japan. However, the stool ova-parasite examination (O&P) test has been the only approved diagnostic method used in Japan since production of the indirect immunofluorescence assay (IFA) serum antibody test was discontinued at the end of 2017. Herein, we assessed whether an enzyme-linked immunosorbent assay (ELISA)-based serological test could substitute for IFA.This cross-sectional study used stored frozen serum samples from the Biobank of the National Center for Global Health and Medicine. A serological ELISA-based test was performed on these samples and their titers were compared with those previously measured by IFA based on the medical record data.Sixty seven stored frozen serum samples with differing recorded IFA antibody titers (16 samples with titers < ×100, 13 samples × 100, 16 samples × 200, 11 samples × 400, and 11 samples ≥ × 800) were analyzed. The sensitivity and specificity values for ELISA vs. IFA were 92.2% [95% confidential interval: 81.5-96.9] and 87.5% [64.0-97.8], respectively. A strong correlation between the antibody titers was confirmed by a one-way ANOVA (R square 0.83, p value < 0.0001) for the two diagnostic methods.The ELISA and IFA antibody titers for E. histolytica were well correlated, and results from these methods were highly concordant. Introduction of an ELISA-based serological test for E. histolytica should be considered to improve E. histolytica infection diagnosis in Japan.
View details for DOI 10.1016/j.jiac.2020.12.026
View details for PubMedID 33483275
Effectiveness of doxycycline 100 mg twice daily for 7 days and azithromycin 1 g single dose for the treatment of rectal Chlamydia trachomatis infection among men who have sex with men.
The Journal of antimicrobial chemotherapy
2021; 76 (2): 495-498
To compare the effectiveness of doxycycline 100 mg twice daily for 7 days and azithromycin 1 g single dose for the treatment of rectal Chlamydia trachomatis infection among MSM in a real clinical setting.A prospective study was performed to compare the effectiveness of doxycycline and azithromycin for the treatment of rectal C. trachomatis among MSM in Tokyo, Japan. Subjects diagnosed with rectal C. trachomatis infection were treated and test-of-cure examination (TOC) was performed at least 3 weeks after the treatment. Treatment of rectal C. trachomatis infection was decided prospectively in a time-dependent manner; in the period between January 2017 and October 2018, azithromycin was administered to all subjects, whereas from October 2018 through March 2020, doxycycline was administered to all subjects. Effectiveness of these treatments was calculated by the number of rectal C. trachomatis-negative subjects at TOC divided by the number of subjects treated.Two hundred and ninety-six MSM with rectal C. trachomatis infection were treated with azithromycin (80 patients) and doxycycline (216 patients) in a time-dependent manner. Of the 296 MSM, 274 (92.6%) were treated successfully [67 (83.7%, 95% CI = 79.6%-87.9%) in the azithromycin group versus 207 (95.8%, 95% CI = 94.5%-97.2%) in the doxycycline group, P < 0.001]. To evaluate factors associated with treatment failure, we performed logistic regression analysis. In univariate and multivariate analysis, only doxycycline treatment was inversely associated with treatment failure (OR = 0.29, 95% CI = 0.084-0.976, P = 0.046).The treatment with doxycycline 100 mg twice daily for 7 days was superior to that with azithromycin 1 g single dose for rectal C. trachomatis among MSM in a real-world setting.
View details for DOI 10.1093/jac/dkaa437
View details for PubMedID 33147327
- A case of SARS-CoV-2 infection in an untreated HIV patient in Tokyo, Japan. Journal of medical virology 2021; 93 (1): 40-42
Near-chromosome level genome assembly reveals ploidy diversity and plasticity in the intestinal protozoan parasite Entamoeba histolytica.
2020; 21 (1): 813
Amoebozoa is a eukaryotic supergroup composed of unicellular and multicellular amoebic protozoa (e.g. Acanthamoeba, Dictyostelium, and Entamoeba). They are model organisms for studies in cellular and evolutionary biology and are of medical and veterinary importance. Despite their importance, Amoebozoan genome organization and genetic diversity remain poorly studied due to a lack of high-quality reference genomes. The slime mold Dictyostelium discoideum is the only Amoebozoan species whose genome is available at the chromosome-level.Here, we provide a near-chromosome-level assembly of the Entamoeba histolytica genome, the second semi-completed Amoebozoan genome. The availability of this improved genome allowed us to discover inter-strain heterogeneity in ploidy at the near-chromosome or sub-chromosome level among 11 clinical isolates and the reference strain. Furthermore, we observed ploidy-independent regulation of gene expression, contrary to what is observed in other organisms, where RNA levels are affected by ploidy.Our findings offer new insights into Entamoeba chromosome organization, ploidy, transcriptional regulation, and inter-strain variation, which will help to further decipher observed spectrums of virulence, disease symptoms, and drug sensitivity of E. histolytica isolates.
View details for DOI 10.1186/s12864-020-07167-9
View details for PubMedID 33225881
View details for PubMedCentralID PMC7681961
Utility of the Rapid Antigen Detection Test E. histolytica Quik Chek for the Diagnosis of Entamoeba histolytica Infection in Nonendemic Situations.
Journal of clinical microbiology
2020; 58 (11)
Entamoeba histolytica infection is an increasingly common sexually transmitted infection in Japan. Currently, stool ova and parasite examination (O&P) is the only approved diagnostic method. Here, we assessed the utility of the commercially available rapid antigen detection test (Quik Chek) for E. histolytica A multicenter cross-sectional study was conducted. Stool samples that had been submitted for O&P were included. The samples were subjected to both Quik Chek and PCR, and the Quik Chek results were assessed in comparison with PCR as the reference standard. E. histolytica infection was confirmed in 5.8% (38/657) of the samples and comprised 20 diarrheal and 18 nondiarrheal cases. The overall sensitivity and specificity of Quik Chek were 44.7% (95% confidence interval, 30.1 to 60.3) and 99.8% (99.1 to 100), respectively. The sensitivity of Quik Chek was higher for diarrheal cases (60.0%) than for nondiarrheal cases (27.8%). Furthermore, the combined use of Quik Chek with O&P increased the sensitivity (78.9%), especially for diarrheal cases (up to 90%). The E. histolytica burden assessed by quantitative PCR was similar between Quik Chek-positive and -negative samples. The Quik Chek assay sensitivity was lower for cyst-containing stools than for trophozoite-containing stools, although it was shown that cultured E. histolytica clinical strains from Quik Chek-negative cyst-containing stools exhibited antigenicity in vitro The present study confirmed the high specificity of Quik Chek for E. histolytica infection. Combined use with O&P increased the sensitivity of detection, facilitating the use of Quik Chek in point-of-care settings in nonendemic situations.
View details for DOI 10.1128/JCM.01991-20
View details for PubMedID 32878955
View details for PubMedCentralID PMC7587111
Evaluation of Coronavirus Disease 2019 Severity Using Urine Biomarkers.
Critical care explorations
2020; 2 (8): e0170
Early detection of coronavirus disease 2019 in patients likely to develop severe manifestations enables appropriate interventions, including rapid ICU admission. This study was conducted to determine whether noninvasive urine biomarkers can predict the clinical severity of coronavirus disease 2019.Not applicable.This is single-center study, national center hospital designated for infectious disease. Fifty-eight patients who tested positive for severe acute respiratory syndrome coronavirus 2 in respiratory specimens through real-time reverse transcription-polymerase chain reaction were retrospectively studied. Urinary β2-microglobulin, liver-type fatty acid-binding protein were serially measured. Serum interferon-γ and monocyte chemotactic protein-1 were also evaluated. The 58 patients were assigned into three groups. Patients requiring intensive care were assigned to the severe group (n = 12). Patients treated with oxygen were assigned to the moderate group (n = 13). Other patients were assigned to the mild group (n = 33). Urine tests revealed that low β2-microglobulin and liver-type fatty acid-binding protein levels were associated with mild disease, whereas high levels were associated with severe disease. In severe cases, liver-type fatty acid-binding protein tended to be persistently high. The resulting cutoff values were β2-microglobulin; severe versus moderate + mild: 2,457 μg/dL (specificity 76.9% and sensitivity 90.0%, area under the receiver operating characteristic curve 85.9%), liver-type fatty acid-binding protein; severe versus moderate + mild: 22.0 μg/gCre (specificity 84.6% and sensitivity 90%, area under the receiver operating characteristic curve 91.8%). Urinary β2-microglobulin and serum interferon-γ/monocyte chemotactic protein-1 showed a similar trend.Evaluating urinary biomarkers such as β2-microglobulin and liver-type fatty acid-binding protein may allow determination of coronavirus disease 2019 patients with active cytokines and recognition of patients likely to become critically ill and requiring careful observation and early intervention.
View details for DOI 10.1097/CCE.0000000000000170
View details for PubMedID 32766565
View details for PubMedCentralID PMC7402421
Phylogenetic position of Nyctotherus teleacus isolated from a tortoise (Astrochelys radiata) and its electron microscopic features.
The Journal of veterinary medical science
2020; 82 (6): 699-703
A commensal ciliate was isolated from the stool of a tortoise (Astrochelys radiata). The ciliate was classified as Nyctotherus teleacus, according to its basic morphological features. Electron microscopic observations using cultured N. teleacus (NictoT1 strain) revealed many spherical hydrogenosomes and methanogen-suspected bacteria, together with a characteristic triangular macronucleus containing many spherical chromosomes in the cytoplasm of NictoT1. The results of phylogenetic analysis showed that NictoT1 was included in the cluster of Nyctotheroides spp. (family Nyctotheridae). Nyctotheroides spp. commonly infest amphibians, which are taxonomically closely related to reptiles, including the tortoises evaluated in the present study.
View details for DOI 10.1292/jvms.20-0004
View details for PubMedID 32336700
View details for PubMedCentralID PMC7324835
- Two cases of endoscopically diagnosed amebic colitis treated with paromomycin monotherapy. PLoS neglected tropical diseases 2020; 14 (3): e0008013
Seroprevalence of Entamoeba histolytica at a voluntary counselling and testing centre in Tokyo: a cross-sectional study.
2020; 10 (2): e031605
Amebiasis, which is caused by Entamoeba histolytica, is a re-emerging public health issue owing to sexually transmitted infection (STI) in Japan. However, epidemiological data are quite limited.To reveal the relative prevalence of sexually transmitted E. histolytica infection to other STIs, we conducted a cross-sectional study at a voluntary counselling and testing (VCT) centre in Tokyo. Seroprevalence of E. histolytica was assessed according to positivity with an ELISA for E. histolytica-specific IgG in serum samples collected from anonymous VCT clients.Among 2083 samples, seropositive rate for E. histolytica was 2.64%, which was higher than that for HIV-1 (0.34%, p<0.001) and comparable to that for syphilis (rapid plasma reagin (RPR) 2.11%, p=0.31). Positivity for Chlamydia trachomatis in urine by transcription-mediated amplification (TMA) was 4.59%. Seropositivity for E. histolytica was high among RPR/Treponema pallidum hemagglutination (TPHA)-positive individuals and it was not different between clients with and without other STIs. Both seropositivity of E. histolytica and RPR were high among male clients. The seropositive rate for anti-E. histolytica antibody was positively correlated with age. TMA positivity for urine C. trachomatis was high among female clients and negatively correlated with age. Regression analysis identified that male sex, older age and TPHA-positive results are independent risk factors of E. histolytica seropositivity.Seroprevalence of E. histolytica was 7.9 times higher than that of HIV-1 at a VCT centre in Tokyo, with a tendency to be higher among people at risk for syphilis infection. There is a need for education and specific interventions against this parasite, as a potentially re-emerging pathogen.
View details for DOI 10.1136/bmjopen-2019-031605
View details for PubMedID 32102805
View details for PubMedCentralID PMC7044870
High prevalence and incidence of rectal Chlamydia infection among men who have sex with men in Japan.
2019; 14 (12): e0220072
Rectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections have been neglected and epidemiological data are unavailable in Japan. Thus, we evaluated the prevalence and incidence of rectal CT/NG in a cohort of HIV-negative men who have sex with men (MSM), which was established at the National Center for Global Health and Medicine (NCGM), in Tokyo, Japan, in January 2017.HIV-negative MSM aged ≥16 years old were included. The prevalence of rectal CT/NG among HIV-negative MSM was compared with that among an existing HIV-positive MSM cohort at NCGM. The HIV-negative MSM cohort was examined for rectal and pharyngeal CT/NG every 3 months. Urethral CT/NG was evaluated at the physician's discretion. The incidences of CT/NG were evaluated in December 2018.Of 502 MSM initially included in this study, 13 men were diagnosed with HIV infection at enrollment and were subsequently excluded from the analysis. We evaluated 561 HIV-positive MSM for rectal CT/NG. The mean ages of the two cohorts were 33.6 and 46.2 years old, respectively (p<0.001). The prevalences of rectal CT were 16.4% and 15.9% (p = 0.707) and the prevalences of rectal NG were 4.1% and 2.3% (p = 0.101), for the HIV-negative and HIV-positive MSM cohorts, respectively. Of 489 HIV-negative MSM, 328 were followed at least twice, with 261.1 person-years during the study period. The incidences of rectal CT/NG were 17.2 and 3.8/100 person-years and the incidences of pharyngeal CT/NG were 2.0 and 11.0/100 person-years for the two cohorts, respectively. Approximately 37.9% of incident cases were attributed to recurrent infection.The prevalence and incidence of rectal CT/NG were high among MSM in Tokyo, Japan, suggesting that urgent countermeasures for early diagnosis and treatment are necessary.
View details for DOI 10.1371/journal.pone.0220072
View details for PubMedID 31821348
View details for PubMedCentralID PMC6903740
Case Report: Acute Amebic Colitis Triggered by Colonoscopy: Exacerbation of Asymptomatic Chronic Infection with Entamoeba histolytica Accompanied by Dysbiosis.
The American journal of tropical medicine and hygiene
2019; 101 (6): 1384-1387
Recent data show that the gut microbiome plays a role in determining the clinical outcome of Entamoeba histolytica infection. We report the case of a patient who developed recurrent acute amebic colitis (second episode of acute colitis) after colonoscopy. Genotyping of E. histolytica revealed that she developed a second episode of acute amebic colitis with the same genotype as that of the first episode, indicating chronic infection had persisted asymptomatically for > 10 months between the first and second episodes. Analysis of the gut microbiome, in addition to the clinical findings, suggested that dysbiosis at colonoscopy induced the change in the clinical form of E. histolytica infection from asymptomatic chronic infection to symptomatic colitis.
View details for DOI 10.4269/ajtmh.19-0396
View details for PubMedID 31595870
View details for PubMedCentralID PMC6896890
Growth-promoting effects of the hydrogen-sulfide compounds produced by Desulfovibrio desulfuricans subsp. desulfuricans co-cultured with Escherichia coli (DH5α) on the growth of Entamoeba and Endolimax species isolates from swine.
2019; 13 (5): 402-410
Certain Desulfovibrio sp. (anaerobic sulfate-reducing bacteria) are indigenous to swine cecum and colon, which are also common habitats for parasitic amoebae such as Entamoeba polecki and Entamoeba suis. In this study, we evaluated the growth-promoting effects of D. desulfuricans co-cultured with Escherichia coli (DH5α) and its products [e.g., hydrogen sulfide (H2S) and certain iron-sulfide (FeS) compounds] using Robinson's medium, on the 4 amoeba isolates from swine-Entamoeba polecki subtype (ST)-1, E. polecki ST-3, Entamoeba suis, and Endolimax sp., and, consequently, a continuous culture system for these amoebae was established. However, this novel culture system was required to regulate the excess H2S dissolved in the medium by increasing air space as amoeba isolates thrive only in large air spaces (30-40%). The effects of air space and H2S and FeS compounds on the growth of E. polecki ST-1 (TDP-5) were determined. E. polecki ST-1 (TDP-5) thrived well in culture bottles with an air space of 30-40% (aerobic) (H2S: ~250-400 μmoles/L), but did not grow at all in an air space < 5% (microaerobic) ( H2S:~800 μmoles/L) and in anaerobic vessels (H2S: 20-30 μmoles/L). In both H2S-depleted and FeS compound-depleted conditions, the amoebae sp. could not thrive either. It was hypothesized that an appropriate concentration of H2S and FeS compounds might function as important physiologically active components of electron carriers such as FeS and ferredoxin.
View details for DOI 10.5582/bst.2019.01233
View details for PubMedID 31597818
Increases in Entamoeba histolytica Antibody-Positive Rates in Human Immunodeficiency Virus-Infected and Noninfected Patients in Japan: A 10-Year Hospital-Based Study of 3,514 Patients.
The American journal of tropical medicine and hygiene
2016; 95 (3): 604-609
Serological evidence of the epidemiological trends in Entamoeba histolytica infection is scarce, especially in nonendemic countries. We aimed to determine the antibody-positive rates over a 10-year period, and compare the trends between human immunodeficiency virus (HIV)-infected and -noninfected patients. We reviewed 3,514 patients who underwent antibody testing during the study periods, which were divided into five annual categories: 2004-2005, 2006-2007, 2008-2009, 2010-2011, and 2012-2013. Anti-E. histolytica antibody was assessed by indirect immunofluorescence assay. The antibody-positive rate increased yearly from 2004-2005 to 2012-2013 (P < 0.001), although there was no increase in the annual number of antibody tests. This trend was seen among males (18.6-28.3%; P < 0.01), females (5.4-28.2%; P < 0.01), HIV-infected patients (18.4-26.9%; P < 0.001), and non-HIV-infected patients (14.6-36.8%; P < 0.001), and HIV-infected men who have sex with men (19.4-29.1%; P < 0.001). Among antibody-positive patients, there was a significant increase in the proportion of patients with high (≥ 1,600) titers (0.7-12.9%; P < 0.001), whereas this trend was not seen in patients with low (100) or intermediate (200-800) titers (P = 0.282 and 0.409, respectively). This large hospital-based study demonstrated that positive anti-E. histolytica antibody rates increased over 10 years, even though the annual number of antibody tests remained constant. Moreover, this trend was identified in non-high-risk patients (females and non-HIV-infected patients) as well as in high-risk patients. The proportion of patients with high antibody titers significantly increased among the antibody-positive patients.
View details for DOI 10.4269/ajtmh.16-0134
View details for PubMedID 27296390
View details for PubMedCentralID PMC5014266