Neisseria gonorrhoeae antimicrobial susceptibility trends in Bangkok, Thailand, 2015-21: Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP).

Objectives: Rising antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a global public health concern. Many ceftriaxone-resistant cases have been linked to Asia. In the WHO/CDC global Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP), we conducted AMR surveillance at two clinical sites in Bangkok, Thailand, 2015-21. Methods: Urethral discharge samples, from males with urethral discharge and/or dysuria, were Gram-stained and cultured. ETEST was performed to determine AMR. EGASP MIC alert values, CLSI and EUCAST breakpoints were used. Results: In 2015-21, gonococcal isolates were cultured from 1928 cases; most (64.1%) were males reporting having sex with females. The sensitivity and specificity of Gram-stained microscopy compared with culture for detection of gonococci were 97.5% and 96.6%, respectively. From 2015 to 2021, the azithromycin MIC90 increased from 0.125 to 1 mg/L, and the MIC90 of ceftriaxone and cefixime increased from 0.008 and ≤0.016 mg/L to 0.032 and 0.064 mg/L, respectively. Eight EGASP MIC alert values (in seven isolates) were identified. Five alert values were for cefixime (all resistant according to EUCAST breakpoints) and three for azithromycin (all resistant according to EUCAST breakpoints). The average annual resistance to ciprofloxacin during 2015-21 was 92%. Conclusions: A continuous high susceptibility to ceftriaxone, Thailand's first-line gonorrhoea treatment, was found. However, the increasing MICs of ceftriaxone, cefixime and azithromycin are a substantial threat, especially considering these are the last remaining options for the treatment of gonorrhoea. To monitor AMR, continuous and quality-assured gonococcal AMR surveillance such as the Thai WHO/CDC EGASP, ideally including WGS, is imperative globally.

Neisseria Meningitidis Urethritis in a Thai Male.

Although Neisseria meningitidis (N. meningitidis) urogenital infections have been reported widely, meningococcal urethritis has not been reported previously in Thailand. A 42-year-old Thai male presented at a sexual health clinic with dysuria and urethral discharge following oral and insertive anal intercourse. N. meningitidis, serogroup C was cultured from a urethral discharge specimen and the patient was treated successfully with standard treatment for gonococcal urethritis. This case reflects a growing trend of reports describing meningococcal urethritis, likely resulting from sexual contact.

The first year of the global Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) in Bangkok, Thailand, 2015-2016.

Antimicrobial-resistant Neisseria gonorrhoeae (NG) infection is a global public health threat, and there is a critical need to monitor patterns of resistance and risk factors. In collaboration with the World Health Organization (WHO), the U.S. Centers for Disease Control and Prevention (CDC), and the Thailand Department of Disease Control (DDC), Ministry of Public Health (MoPH) implemented the first Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) in November 2015. Men presenting with urethritis at two clinical settings in Bangkok, Thailand (Bangrak Hospital [BH] and Silom Community Clinic @TropMed [SCC @TropMed]) provided demographic and behavioral information and had a urethral swab for Gram's stain and NG culture collected. The NG isolates were evaluated for antimicrobial susceptibility by the Epsilometer test (Etest) to determine minimum inhibitory concentrations (MICs) for cefixime (CFM), ceftriaxone (CRO), azithromycin (AZI), gentamicin (GEN), and ciprofloxacin (CIP). From November 2015 -October 2016, 1,102 specimens were collected from 1,026 symptomatic men; 861 (78.1%) specimens were from BH and 241 (21.9%) specimens were from SCC @TropMed. Among the 1,102 specimens, 582 (52.8%) had intracellular Gram-negative diplococci and 591 (53.6%) had NG growth (i.e., NG infection); antimicrobial susceptibility testing (AST) was performed on 590 (99.8%) NG isolates. Among all symptomatic men, 293 (28.6%) had sex with men only, 430 (41.9%) were ages 18-29 years, 349 (34.0%) had antibiotic use in the last 2 weeks, and 564 (55.0%) had NG infection. Among 23 men with repeat NG infection during this first year of surveillance, 20 (87.0%) were infected twice, 2 (8.7%) were infected three times, and 1 (4.3%) was infected more than four times. All NG isolates were susceptible to CFM and CRO, and had MICs below 2 µg/mL for AZI and below 16 µg/mL for GEN. Overall, 545 (92.4%) isolates were resistant to CIP. This surveillance activity assessed individual patients, and included demographic and behavioral data linked to laboratory data. The inclusion of both individual and laboratory information in EGASP could help identify possible persistent infection and NG treatment failures. Expansion of EGASP to additional global settings is critical to assess trends and risk factors for NG, and to monitor for the emergence of resistance.

Association between HIV genotype, viral load and disease progression in a cohort of Thai men who have sex with men with estimated dates of HIV infection.

BACKGROUND: Differences between HIV genotypes may affect HIV disease progression. We examined infecting HIV genotypes and their association with disease progression in a cohort of men who have sex with men with incident HIV infection in Bangkok, Thailand. METHODS: We characterized the viral genotype of 189 new HIV infections among MSM identified between 2006-2014 using hybridization and sequencing. Plasma viral load (PVL) was determined by PCR, and CD4+ T-cell counts were measured by flow cytometry. We used Generalized Estimating Equations to examine factors associated with changes in CD4+ T-cell counts. Factors associated with immunologic failure were analyzed using Cox proportional hazard models. RESULTS: Among 189 MSM, 84% were infected with CRF01_AE, 11% with recombinant B/CRF01_AE and 5% with subtype B. CD4+ T-cell decline rates were 68, 65, and 46 cells/µL/year for CRF01_AE, recombinants, and subtype B, respectively, and were not significantly different between HIV subtypes. CD4+ T-cell decline rate was significantly associated with baseline PVL and CD4+ T-cell counts (p <0.001). Progression to immunologic failure was associated with baseline CD4+ T-cell ≤ 500 cells/µL (AHR 1.97; 95% CI 1.14-3.40, p = 0.015) and PVL > 50,000 copies/ml (AHR 2.03; 1.14-3.63, p = 0.017). There was no difference in time to immunologic failure between HIV subtypes. CONCLUSION: Among HIV-infected Thai MSM, low baseline CD4+ T-cell and high PVL are associated with rapid progression. In this cohort, no significant difference in CD4+ T-cell decline rate or time to immunologic failure was seen between CRF01_AE and other infecting HIV subtypes.

The finding of casual sex partners on the internet, methamphetamine use for sexual pleasure, and incidence of HIV infection among men who have sex with men in Bangkok, Thailand: an observational cohort study.

BACKGROUND: The finding of casual sex partners on the internet and methamphetamine use have been described as risk factors for HIV infection in men who have sex with men (MSM). However, the interplay between these factors has not been studied prospectively in one design. This study aims to determine the associations between finding casual sex partners on the internet and incident methamphetamine use and HIV infection. METHODS: In this observational cohort study of Thai MSM, we recruited Bangkok residents aged 18 years or older with a history of penetrative male-to-male sex in the past 6 months. Baseline and follow-up visits were done at a dedicated study clinic in central Bangkok. Men were tested for HIV infection at every study visit and for sexually transmitted infections at baseline. Baseline demographics and HIV risk behaviour information were collected at every visit by audio computer-assisted self-interview. We used a descriptive model using bivariate odds ratios to elucidate the order of risk factors in the causal pathway to HIV incidence and methamphetamine use. We used Cox proportional hazard regression analysis to evaluate covariates for incident methamphetamine use and HIV infection. FINDINGS: From April 6, 2006, to Dec 31, 2010, 1977 men were screened and 1764 were found eligible. 1744 men were enrolled, of whom 1372 tested negative for HIV and were followed up until March 20, 2012. Per 100 person-years of follow-up, incidence of methamphetamine use was 3·8 (128 events in 3371 person-years) and incidence of HIV infection was 6·0 (212 events in 3554 person-years). In our descriptive model, methamphetamine use, anal sex, and various other behaviours cluster together but their effect on HIV incidence was mediated by the occurrence of ulcerative sexually transmitted infections. Dual risk factors for both incident methamphetamine use and HIV infection were younger age and finding casual sex partners on the internet. Having ever received money for sex was predictive for incident methamphetamine use; living alone or with a housemate, recent anal sex, and ulcerative sexually transmitted infections at baseline were predictive for incident HIV infection. INTERPRETATION: In MSM in Bangkok, casual sex partner recruitment on the internet, methamphetamine use, and sexually transmitted infections have important roles in sustaining the HIV epidemic. Virtual HIV prevention education, drug use harm reduction, and biomedical HIV prevention methods, such as pre-exposure prophylaxis, could help to reduce or revert the HIV epidemic among MSM in Bangkok. FUNDING: US Centers for Disease Control and Prevention and the Johns Hopkins Fogarty AIDS International Training and Research Program.

Screening for Chlamydia trachomatis and Neisseria gonorrhoeae infection among asymptomatic men who have sex with men in Bangkok, Thailand.

We report positivity rates of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection at each anatomic site among asymptomatic men who have sex with men (MSM). We calculated the number needed to screen (NNS) to detect CT and NG infection at each anatomic site. From 2006 to 2010, we enrolled Thai MSM, age ≥ 18 years into the Bangkok MSM Cohort Study. Participants underwent physical examination and had rectal, urethral, and pharyngeal screening for CT and NG infection using nucleic acid amplification tests (NAATs). Of 1744 enrollees, 1696 (97.2%) had no symptoms of CT and NG infection. The positivity rates of CT and NG infection at any site were 14.3% (rectum, urethra, pharynx) and 6.4% (rectum, urethra), respectively. The NNS to detect rectal CT and rectal NG infections was 10 and 16, respectively (p < 0.05). For urethral infection, the NNS of CT was lower than the NNS of NG (22, 121: p < 0.05). The lowest NNS found for rectal CT infection was in HIV-infected MSM (6, 5-8). Asymptomatic CT and NG infection were common among MSM in Bangkok, Thailand and frequently detected in the rectum. In setting where screening in all specimens using NAAT is not feasible, rectal screening should be a priority.

Analysis of False-Negative Human Immunodeficiency Virus Rapid Tests Performed on Oral Fluid in 3 International Clinical Research Studies.

BACKGROUND.: The OraQuick Advance Rapid HIV-1/2 Test is a point-of-care test capable of detecting human immunodeficiency virus (HIV)-specific antibodies in blood and oral fluid. To understand test performance and factors contributing to false-negative results in longitudinal studies, we examined results of participants enrolled in the Botswana TDF/FTC Oral HIV Prophylaxis Trial, the Bangkok Tenofovir Study, and the Bangkok MSM Cohort Study, 3 separate clinical studies of high-risk, HIV-negative persons conducted in Botswana and Thailand. METHODS.: In a retrospective observational analysis, we compared oral fluid OraQuick (OFOQ) results among participants becoming HIV infected to results obtained retrospectively using enzyme immunoassay and nucleic acid amplification tests on stored specimens. We categorized negative OFOQ results as true-negative or false-negative relative to nucleic acid amplification test and/or enzyme immunoassay, and determined the delay in OFOQ conversion relative to the estimated time of infection. We used log-binomial regression and generalized estimating equations to examine the association between false-negative results and participant, clinical, and testing-site factors. RESULTS.: Two-hundred thirty-three false-negative OFOQ results occurred in 80 of 287 seroconverting individuals. Estimated OFOQ conversion delay ranged from 14.5 to 547.5 (median, 98.5) days. Delayed OFOQ conversion was associated with clinical site and test operator (P < .05), preexposure prophylaxis (P = .01), low plasma viral load (P < .02), and time to kit expiration (P < .01). Participant age, sex, and HIV subtype were not associated with false-negative results. Long OFOQ conversion delay time was associated with antiretroviral exposure and low plasma viral load. CONCLUSIONS.: Failure of OFOQ to detect HIV-1 infection was frequent and multifactorial in origin. In longitudinal trials, negative oral fluid results should be confirmed via testing of blood samples.

Hepatitis B vaccination uptake and correlates of serologic response among HIV-infected and uninfected men who have sex with men (MSM) in Bangkok, Thailand.

BACKGROUND: Vaccination against hepatitis B virus (HBV) is recommended for all HBV-susceptible men who have sex with men (MSM). There is limited information on correlates of immunity to HBV vaccination in this group. We present serologic response rates to hepatitis B vaccine and identify factors associated with impaired response among HIV-uninfected and HIV-infected Thai MSM. METHODOLOGY: HBV-susceptible volunteers were offered hepatitis B vaccination at months zero, one, and six. We measured baseline (pre-vaccination) total serum IgG and IgG subclasses (all participants), baseline CD4 count, and plasma HIV-1 viral load (PVL) (HIV+ participants). HBV serologies were retested at 12 months. Serologic responses were compared between all groups in men receiving three vaccine doses. RESULTS: 511/651 HIV-negative and 64/84 HIV-positive participants completed the three-dose series. Response rates in HIV-uninfected and -infected participants were 90.1% vs. 50.0% (p<0.0001). Median pre-vaccination IgG was higher among non-responders than responders overall (1238.9.0 vs. 1057.0mg/dL, p=0.003) and among HIV-infected participants (1534.0 vs. 1244.5mg/dL, p=0.005), but not significantly among HIV-uninfected participants (1105.5 vs. 1054.3mg/dL, p=0.96). Pre-vaccination IgG1 and IgG3 levels were higher among HIV-positive than HIV-negative participants (median 866.0 vs. 520.3, and 105.8 vs. 83.1mg/dL, respectively, p<0.0001). Among HIV-infected participants, median CD4 count in non-responders was 378 cells/µL vs. 431 cells/µL in responders (p=0.20). Median PVL in non-responders was 64,800 copies/mL vs. 15500 copies/mL in responders (p=0.04). Participants with pre-vaccination plasma IgG >1550 mg/dL and PVL >10,000 copies/mL were almost always non-responsive (p<0.01). CONCLUSIONS: HIV infection was associated with poor vaccine responses. High plasma viral load, elevated pre-vaccination total serum IgG and elevated pre-vaccination IgG1 are associated with poorer response to vaccination among HIV-infected MSM. In this group, the combination of high PVL and pre-vaccination total IgG is highly predictive of vaccine failure.

Loss to follow-up and bias assessment among a cohort of Thai men who have sex with men in Bangkok, Thailand.

Minimising loss to follow-up is essential to obtain unbiased results. This study aimed to assess factors associated with loss to follow-up and effects on biasing exposure-outcome associations in a cohort of men who have sex with men in Bangkok. We enrolled sexually-active Thai men who have sex with men, at least 18 years old, in a study with four-monthly follow-up visits. At each visit, men answered HIV risk behaviour questions using audio computer-assisted self-interview. Logistic regression was used to evaluate factors associated with loss to follow-up and bias between exposures and prevalent HIV infection were estimated using adjusted relative odds ratios. From 2006 to 2010, we enrolled 1744 men who have sex with men; as of April, 2014, 1256 (72%) had completed at least the month-36 visit; loss to follow-up was 9.6%. Factors independently associated with loss to follow-up were age (18-21 years), education (primary level or less, secondary or vocational education), living outside Bangkok and vicinity, sexual orientation (bisexual, heterosexual), previous HIV testing, HIV infection, and behaviour in the past 4 months (recreational drug use, reporting group sex). An effect of loss to follow-up on factors of prevalent HIV infection was found by sexual orientation (transgender) and unprotected anal intercourse (receptive/insertive). These findings highlight the need to strengthen post-HIV test counselling. Directed counselling for HIV care should be given to young men who have sex with men and recreational drug users.

Prevalence and Correlates of Chlamydia trachomatis and Neisseria gonorrhoeae by Anatomic Site Among Urban Thai Men Who Have Sex With Men.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection are prevalent among men who have sex with men (MSM) and may infect multiple anatomic sites. We measured site-specific prevalence and correlates of CT and NG infection among Bangkok MSM Cohort Study participants. METHODS: In April 2006 to November 2010, 1744 men enrolled in the Bangkok MSM Cohort Study. Participants provided historical information and underwent physical examination. Rectal, urethral, and pharyngeal CT and NG screening were performed by nucleic acid amplification and/or culture. Logistic regression was used to identify correlates of site-specific CT, NG, and coinfection. RESULTS: Among 1743 participants, 19.2% were infected with CT and/or NG. CT, NG, and CT-NG coinfection were detected in 11.6%, 4.6%, and 2.9%, of participants, respectively. Rectal, urethral, and pharyngeal CT infections were detected in 9.5%, 4.5%, and 3.6% of cases. N. gonorrhoeae was present at these sites in 6.1%, 1.8%, and 0.5% of cases. Most infections were asymptomatic (CT: 95.3%, NG: 83.2%). Rectal CT and NG infections were mutually associated (CT: adjusted odds ratio [AOR], 5.4; 95% confidence interval [CI], 3.4-8.7; NG: AOR, 2.4; 95% CI, 1.1-5.2) and independently associated with HIV infection (CT: AOR, 1.6, 95% CI, 1.0-2.4; NG: AOR, 2.0, 95% CI, 1.3-3.1). Numerous behavioral correlates of infection were observed. CONCLUSIONS: CT and NG infections are highly prevalent among MSM in Bangkok, most frequently affect the rectum, and are most often asymptomatic. Routine screening of asymptomatic MSM for CT and NG infection should include rectal sampling and focus on men with HIV and a history of other sexually transmitted infections.

Longitudinal analysis of key HIV-risk behavior patterns and predictors in men who have sex with men, Bangkok, Thailand.

The HIV incidence among Thai men who have sex with men (MSM) enrolled in the Bangkok MSM Cohort Study (BMCS) has remained high since its inception in 2006. The purpose of this BMCS analysis was to determine: (1) changes in three HIV-risk behaviors (unprotected anal intercourse (UAI), recreational drug use, and multiple sexual partners i.e., more than four male/transgender partner) over time; and (2) factors associated with each one separately. Thai MSM aged 18 years or older and living in Bangkok were eligible to participate in the BMCS. At each follow-up visit, participants were asked to report their sexual and drug behaviors in the previous 4 months. We conducted a longitudinal analysis using generalized estimating equations logistic regression that included 1,569 MSM who were enrolled from 2006 to 2010 and contributed at least one follow-up visit. For each four-month visit increase, we found a 2, 1, and 1 % decrease in odds for reported UAI, recreational drug use, and multiple sexual partners, respectively. We found significant predictors associated with three HIV-risk behaviors such as binge drinking, participation in group sex, and use of erectile dysfunction drugs. The statistically significant decrease in odds of HIV-risk behaviors among the participants is encouraging; however, continued vigilance is required to address the factors associated with HIV-risk behaviors through currently available interventions reaching MSM.

Point-of-care glucose testing: on-site competency assessment.

PURPOSE: The purpose of this pilot paper is to use on-site assessment to determine common non-compliance in point-of-care (POC) glucose testing, deficiencies that should be improved by the POC team or emphasized in further training. DESIGN/METHODOLOGY/APPROACH: Assessment forms for POC site and staff competency were developed and used for direct observation in four POC sites. Nurses were sampled in these sites. FINDINGS: The on-site assessment demonstrated that initial operator training was insufficient. Only three of 15 nurses achieved a satisfactory score on the first assessment. In all nine participants who had been assessed at least twice improved their performance. In total, 16 (30 percent) of 53 competency items were not achieved, so these should be addressed during refresher training. Improved compliance with the checklist was observed in two of four POC sites. RESEARCH LIMITATIONS/IMPLICATIONS: Medical students and residents also perform the test, so more representative samples are needed. PRACTICAL IMPLICATIONS: The assessment of staff performance in the workplace with constructive input and POC site inspections to identify common deficiencies are recommended. Refresher trainings should be focussed on the deficiencies identified. SOCIAL IMPLICATIONS: Assessing staff performance in the workplace with constructive input and POC site inspections to identify common deficiencies are recommended. Refresher trainings should focus on deficiencies. ORIGINALITY/VALUE: This study involved directly observing POC site staff during glucose testing. The assessment forms were based on ISO 22870:2006 technical requirements.

Hepatitis A and hepatitis B infection prevalence and associated risk factors in men who have sex with men, Bangkok, 2006-2008.

Despite the availability of safe and effective vaccines, little is known about prevalence and risk factors for hepatitis A (HAV) and hepatitis B virus (HBV) infection among Thai men who have sex with men. The prevalence of HAV and HBV infection among men who have sex with men cohort in Bangkok was assessed. Baseline blood specimens were drawn and demographic and behavioral data were collected. Bivariate and multivariate logistic regression analysis was used to analyze risk factors for prevalent HAV and HBV infection. One thousand two hundred ninety-nine Thai men who have sex with men 18 years and older were enrolled. Among those with results, 349/1,291 (27.0%) had evidence of past or current hepatitis A infection. Of the 1,117 (86.5%) men with unambiguous HBV test results, 442 (39.6%) had serologic evidence of past/current infection, 103 (9.2%) were immune due to hepatitis B vaccination, 572 (51.2%) had no evidence of immunological exposure to HBV or vaccine. Of those with past/current HBV infection, 130 (29.4%) were HIV positive. Age >35 years was independently associated with both HAV and HBV infection. University education was protective against both HAV and HBV infection. Increased alcohol consumption, number of lifetime male sexual partners ≥10, and prevalent HIV infection were also independently associated with HBV infection. The prevalence of past/current HAV and HBV infection was high in Bangkok men who have sex with men. Age-cohorts with a higher prevalence of hepatitis B vaccine induced immunity may be expected in the future. Hepatitis A and B vaccination is recommended.