Effectiveness of sitafloxacin monotherapy for quinolone-resistant rectal and urogenital Mycoplasma genitalium infections: a prospective cohort study.

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.

Diversity and Plasticity of Virulent Characteristics of Entamoeba histolytica.

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.

Combination of Amoxicillin 3000 mg and Probenecid Versus 1500 mg Amoxicillin Monotherapy for Treating Syphilis in Patients With Human Immunodeficiency Virus: An Open-Label, Randomized, Controlled, Non-Inferiority Trial.

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).

Effect of tenofovir-based HIV pre-exposure prophylaxis against HBV infection in men who have sex with men.

BACKGROUND AND AIMS: 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. METHODS AND RESULTS: 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). CONCLUSIONS: Tenofovir-based PrEP prevented HBI among MSM in a real-world setting.

Pharmacokinetics of Bictegravir in Older Japanese People Living with HIV-1.

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.

Amebiasis as a sexually transmitted infection: A re-emerging health problem in developed countries.

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.

Gene expression of axenically-isolated clinical Entamoeba histolytica strains and its impact on disease severity of amebiasis.

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.

Unmasking latent extrapulmonary tuberculosis with newly diagnosed HIV-1 infection in a COVID-19 patient with prolonged fever.

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.

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.

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.

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.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%. CONCLUSIONS: The present study showed a high prophylactic effect against HIV infection, retention, and adherence to PrEP. PrEP is feasible and highly recommended in Japan. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN000031040, www.umin.ac.jp), Japan Registry of Clinical Trials (jRCTs031180134).

Evaluation of the Detection of Pathogens in Hospitalized Patients with COVID-19 at a Tertiary Hospital in Japan.

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.

The First Reported Case of Bordetella pertussis Bacteremia in a Patient With Human Immunodeficiency Virus Infection.

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.

Progressive Cytopenia Developing during Treatment of Cryptococcosis in a Patient with HIV Infection and Bone Marrow Cryptococcal Infection.

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.

Anal human papillomavirus infection and its relationship with abnormal anal cytology among MSM with or without HIV infection in Japan.

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.

High prevalence of circulating dual-class resistant Mycoplasma genitalium in asymptomatic MSM in Tokyo, Japan.

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.

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.

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.

External validation and update of prediction models for unfavorable outcomes in hospitalized patients with COVID-19 in Japan.

INTRODUCTION: 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. METHODS: 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 ß2-microglobulin (ß2MG) to the model and recalculating the intercept and the coefficient of ß2MG. RESULTS: 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 ß2MG. CONCLUSIONS: 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.

Performance of an enzyme-linked immunosorbent-based serological assay for Entamoeba histolytica: Comparison with an indirect immunofluorescence assay using stored frozen samples.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Clinical Features and Gut Microbiome of Asymptomatic Entamoeba histolytica Infection.

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.