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Background 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. Methods We conducted an open-label, randomized, controlled, non-inferiority trial between 31 August 2018, and 3 February 2022, to compare 1500 mg low-dose amoxicillin monotherapy with the combination of 3000 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. Results A total of 112 participants were randomized into 2 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. Conclusions 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. Trials Registration (UMIN000033986). [ABSTRACT FROM AUTHOR]

Background Mycoplasma genitalium has a tendency to develop macrolide and quinolone resistance. Objectives We investigated the microbiological cure rate of a 7 day course of sitafloxacin for the treatment of rectal and urogenital infections in MSM. Patients and methods 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. Results 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). Conclusions 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. [ABSTRACT FROM AUTHOR]

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. Author summary: Various genotypes of Entamoeba histolytica are prevalent in the field. Some papers suggest the association between genotypes and disease severity. However, most studies for assessing pathogen virulence were performed using laboratory strains, such as virulent HM1: IMSS (HM1) and avirulent Rahman, because axenic isolation from clinical specimen is technically complex and time consuming. This transcriptomic analysis using clinical strains from the patients with different clinical severity, as well as the laboratory strain HM1 under different conditions showed unique gene expression patterns. Following things were confirmed; 1. Virulent clinical strain maintains its virulence with unique gene expression pattern after axenic isolation, 2. Continuous environmental stress enhances its virulence via the accumulation of altered gene expressions, and 3. Changes in gene expression on the liver abscess formation are not always the same amongst strains. For an accurate understanding the pathogenesis, comprehensive analyses of various clinical strains under different environmental conditions should be promoted. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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. Methodology/Principal findings: 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. Conclusions/Significance: 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. Author summary: Amebiasis, caused by Entamoeba histolytica, is now spreading not only in developing countries, but also in many of developed countries. Unlike the situation in developing countries, transmission occurs directly from one infected person to another via sexual contact, called sexually transmitted E. histolytica infection. Furthermore, most cases of E. histolytica infection are asymptomatic, who can be a reservoir for sexual transmission in the community. Cost-effective epidemiological strategy is urgently needed. Hereby, we performed a serological test for 312 "asymptomatic" HIV-negative men who have sex with men to assess the effective screening method for E. histolytica infection. We identified 21 seropositive samples (6.7% of seropositivity, 21/312), in which relatively high seropositivity to E. histolytica was seen among the participants with positive serology for Treponema pallidum hemagglutination (TPHA) or hepatitis B core antibody (HBcAb). Finally, we identified current infection (asymptomatic E. histolytica infection) in 8 out of 20 stool sampling cases (40.0%) by polymerase chain reaction. Our serological screening assay provides a potentially practical epidemiological strategy. Active epidemiological survey, in combination with the effective screening strategy for asymptomatically infected individuals are considered for the future control of sexually transmitted E. histolytica infection. [ABSTRACT FROM AUTHOR]

Background 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. Methods 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. Results 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. Conclusions These results indicate that the encystation and attenuation of E. histolytica are highly affected by the intestinal contents, including the gut microbiome. [ABSTRACT FROM AUTHOR]

Background Evidence on efficacy of high-dose ceftriaxone monotherapy for extragenital Neisseria gonorrhoeae (NG) infection is lacking. Methods 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. Results 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). Conclusions High-dose ceftriaxone monotherapy is as effective as dual therapy for extragenital NG among MSM. [ABSTRACT FROM AUTHOR]

Objectives: 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.Methods: 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.Results: 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.Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objectives: 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.Methods: 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.Results: 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).Conclusions: 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. [ABSTRACT FROM AUTHOR]

Patient 1 who was a 43-year-old male was first referred to our institute because of an allergic reaction to metronidazole with oral mucosal erosions during his sixth treatment for amebic colitis. Graph: Fig 1 Macroscopic findings during colonoscopy.(A) Sporadic ulcerative lesions with edema were identified in the cecum of patient 1 before treatment. [[7]] These results raise the unresolved issue that monotherapy by a lumen-active agent can be inadequate treatment for asymptomatically infected patients with I E i . Successful treatment with paromomycin monotherapy due to metronidazole intolerance was microbiologically and endoscopically confirmed in 2 patients with mild symptoms of I E i . [Extracted from the article]

Background: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is ongoing and spreading worldwide after cases of COVID-19 were reported in Wuhan, China in December 2019.1 Older age, diabetes, hypertension, and smoking have been reported as aggravating factors,2 and human immunodeficiency virus (HIV) infection is considered to be a potentially aggravating factor. There are very few reports of COVID-19 in untreated HIV patients3-5 HIV patients are known to be susceptible to respiratory viruses and to have more severe symptoms, but the clinical course and prognosis of COVID-19 in HIV patients are not known yet. COVID-19 pneumonia in untreated HIV patients requires careful follow-up for IRIS with ART. [Extracted from the article]

Background: The epidemiology of incident syphilis infection among HIV-1-infected men who have sex with men (MSM) largely remains unknown. Methods: The incidence and risk factors for incident syphilis (positive TPHA and RPR> = 1:8) among HIV-1-infected MSM who visited a large HIV clinic in Tokyo for the first time between 2008 and 2013 were determined, using clinical data and stored blood samples taken every three months for screening and determination of the date of incident syphilis. Poisson regression compared the incidence of syphilis at different observation periods. Results: Of 885 HIV-1-infected MSM with baseline data, 34% either presented with active syphilis at baseline (21%) or became infected with syphilis during follow-up (13%). After excluding 214 patients (MSM with syphilis at baseline (n = 190) and no follow-up syphilis test (n = 24)), of 671 men, 112 (17%) developed incident syphilis with an incidence of 43.7/1,000 person-years [95% CI, 36.5–52.3]. The incidence decreased slightly during observation period although the trend was not significant (2008–2009: 48.2/1,000 person-years, 2010–2011: 51.1/1,000 person-years, 2012–2013: 42.6/1,000 person-years, 2014 to 2015: 37.9/1,000 person-years, p = 0.315). Multivariable analysis identified young age (<33 years versus >40, HR 4.0, 95%CI 2.22–7.18, p<0.001), history of syphilis at baseline (HR 3.0, 95%CI 2.03–4.47, p<0.001), positive anti-amoeba antibody (HR 1.8, 95%CI 1.17–2.68, p = 0.006), and high baseline CD4 count (CD4 ≥350 /μL versus CD4 <200, HR 1.6, 95%CI 1.00–2.53, p = 0.050) as risk factors for incident syphilis. Incidence of syphilis was particularly high among young patients (age <33 years: 60.1/1,000 person-years). Interestingly, 37% of patients with incident syphilis were asymptomatic. Conclusions: Although incidence of syphilis did not increase during the observation period, it was high among HIV-1-infected MSM, especially among young HIV-1-infected MSM and those with history of syphilis, in Tokyo. Regular screening for syphilis needs to be strictly applied to this population. [ABSTRACT FROM AUTHOR]

Summary: Spondylodiscitis caused by Parvimonas micra, a rarely reported infection, might be under-detected using conventional methods. This report of the detection and treatment of two cases of spondylodiscitis due to P. micra and review of the literature indicates that the use of gene sequencing methods might improve the accuracy of diagnosing this infection. [ABSTRACT FROM AUTHOR]

Amebiasis, which is caused by Entamoeba histolytica ( E. histolytica ), is the second leading cause of parasite-related death worldwide. It manifests from asymptomatic carriers to severe clinical conditions, like colitis and liver abscesses. Amebiasis is commonly seen in developing countries, where water and food are easily contaminated by feces because of the poor sanitation. However, a recently challenge in many developed countries is the increase in domestic cases of invasive amebiasis as a sexually transmitted infection (STI amebiasis). In contrast to food-/ waterborne transmission of E. histolytica in developing countries, transmission of STI amebiasis occurs directly through human-to-human sexual contact ( e.g. , men who have sex with men and people who engage in oral-anal sex); in this setting, asymptomatic infected individuals are the main reservoir of E. histolytica . The Development of screening methods for the early diagnosis of asymptomatic E. histolytica infection is the key to epidemiologic control. Moreover, delay in diagnosis of severe cases ( e.g. , fulminant amebiasis) leads to death even in developed countries. It is also important to increase clinical awareness of domestically transmitted STI amebiasis in the clinical settings. This review considers the changing epidemiology and clinical manifestations of STI amebiasis, and finally discusses the future strategies for the better practice., Competing Interests: The authors have no conflicts of interest to disclose., (2023, National Center for Global Health and Medicine.)

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 ( C max ) 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.

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.

Cytopenia is a common complication in patients with human immunodeficiency virus (HIV) infection. Identifying the cause is demanding because of the wide range of possible diagnoses. We herein report an HIV-infected patient with disseminated cryptococcosis involving multiple organs including the blood, brain, lungs, and bone marrow, who developed progressive pancytopenia after initiation of anti-fungal treatment with liposomal amphotericin-B (L-AMB) and flucytosine (5FC). The pancytopenia persisted despite early 5FC discontinuation. A bone marrow biopsy revealed cryptococcal infiltration and the blood examination findings recovered quickly after resuming L-AMB. Thus, this HIV-infected patient's pathological findings and clinical course suggested that the primary cause of the pancytopenia was bone marrow cryptococcosis.

Objectives: 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., Methods: 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., Results: 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 ., Conclusions: 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 ., Competing Interests: Competing interests: SO has received research grants/materials from Gilead Sciences, MSD KK, CSL Behring and ViiV Healthcare, Co., and has received honorarium for lectures from MSD KK, Gilead Sciences, ViiV Healthcare and Janssen Pharmaceutical, KK., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To assess the prevalence and antibiotic resistance profile of Mycoplasma genitalium detected from urogenital/rectal swab samples obtained from MSM in Tokyo, Japan., Methods: 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., Results: 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)., Conclusions: 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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)

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., (Copyright © 2020 Yanagawa et al.)

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.

Background: 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., Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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 (H 2 S) 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 H 2 S 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 H 2 S 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) (H 2 S: ~250-400 μmoles/L), but did not grow at all in an air space < 5% (microaerobic) ( H 2 S:~800 μmoles/L) and in anaerobic vessels (H 2 S: 20-30 μmoles/L). In both H 2 S-depleted and FeS compound-depleted conditions, the amoebae sp. could not thrive either. It was hypothesized that an appropriate concentration of H 2 S and FeS compounds might function as important physiologically active components of electron carriers such as FeS and ferredoxin.

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., (© The American Society of Tropical Medicine and Hygiene.)

Background: Sputum conversion defined as 3 consecutive smear-negative sputum samples collected on different days is one of standard requirements for discontinuation of isolation for patients with smear-positive pulmonary tuberculosis (SPpTB). Sputum smear conversion is usually seen prior to culture conversion. However, in some patients, sputum smear tests are continuously positive for a long time. To discontinue isolation of the patients, culture conversion is required instead of smear conversion. Culture testing requires a long incubation period, which results in longer patient stay and isolation., Objectives: To identify a more efficient definition of culture conversion, which will enable treating physicians to take the decision to discontinue isolation., Methods: The charts of patients with SPpTB admitted from September 2007 to March 2011 were reviewed. The recent definition of culture conversion is 3 subsequent culture-negative sputum specimens incubated for 6 weeks (3 CNs for 6 weeks) in liquid media. Treatment days and admission days were calculated based on the application of the new 3 definitions (3 CNs for 4 weeks, 2 CNs for 6 weeks, 2 CNs for 4 weeks)., Results: Of 301 patients, 224 were discharged after smear conversion; 77 were continuously smear-positive and were discharged after culture conversion. The median hospital stay was 56 days in patients discharged due to smear conversion and 107 days in patients discharged due to culture conversion, based on the recent definition. The numbers of treatment days needed for culture conversion were identical in most patients, regardless of definitions. At the time of reporting, all patients conformed to the new definitions and all the patients' sputum specimens were 3 CNs for 6 weeks except for one patient happened to be with 2 consecutive smear-negative specimens at an early phase of chemotherapy. The most efficient definition of culture conversion in this study was 2 CNs for 4 weeks. This enabled to shorten each patient's stay by 31 days and to lessen each patient's cost of hospitalization by about 4,900 dollars., Conclusion: Two subsequent CNs for 4 weeks of smear-positive sputum samples is enough to enable discontinuation of patient isolation and may thus shorten hospital stay.