Data quality assessment of the Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP), Thailand, 2015-2021.

BACKGROUND: Quality assessments of gonococcal surveillance data are critical to improve data validity and to enhance the value of surveillance findings. Detecting data errors by systematic audits identifies areas for quality improvement. We designed and implemented an internal audit process to evaluate the accuracy and completeness of surveillance data for the Thailand Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP). METHODS: We conducted a data quality audit of source records by comparison with the data stored in the EGASP database for five audit cycles from 2015-2021. Ten percent of culture-confirmed cases of Neisseria gonorrhoeae were randomly sampled along with any cases identified with elevated antimicrobial susceptibility testing results and cases with repeat infections. Incorrect and incomplete data were investigated, and corrective action and preventive actions (CAPA) were implemented. Accuracy was defined as the percentage of identical data in both the source records and the database. Completeness was defined as the percentage of non-missing data from either the source document or the database. Statistical analyses were performed using the t-test and the Fisher's exact test. RESULTS: We sampled and reviewed 70, 162, 85, 68, and 46 EGASP records during the five audit cycles. Overall accuracy and completeness in the five audit cycles ranged from 93.6% to 99.4% and 95.0% to 99.9%, respectively. Overall, completeness was significantly higher than accuracy (p = 0.017). For each laboratory and clinical data element, concordance was >85% in all audit cycles except for two laboratory data elements in two audit cycles. These elements significantly improved following identification and CAPA implementation. DISCUSSION: We found a high level of data accuracy and completeness in the five audit cycles. The implementation of the audit process identified areas for improvement. Systematic quality assessments of laboratory and clinical data ensure high quality EGASP surveillance data to monitor for antimicrobial resistant Neisseria gonorrhoeae in Thailand.

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.

Complete Genome Sequence of Neisseria gonorrhoeae Multilocus Sequence Type ST7363 Isolated from Thailand.

A Neisseria gonorrhoeae multilocus sequence type (MLST) ST7363 strain was isolated from a patient at the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, in 2010 and completely sequenced. This strain is susceptible to ceftriaxone and cefixime. A complete circular chromosome and circular plasmids were assembled from combined Oxford Nanopore Technologies (ONT) and Illumina sequencing.

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.

Complete Genome Sequences of Three Neisseria gonorrhoeae Isolates from Thailand with Multidrug Resistance and Multilocus Sequence Type 1903.

Multilocus sequence typing (MLST) sequence type 1903 (ST1903) is the most common ST of ceftriaxone-resistant Neisseria gonorrhoeae Here, we report three completed genome sequences of MLST ST1903 N. gonorrhoeae isolates collected from patients at Faculty of Medicine Siriraj Hospital, a university hospital in Bangkok, Thailand, in 2009 to 2011.

HIV-1 genetic diversity to estimate time of infection and infer adherence to preexposure prophylaxis.

OBJECTIVE: To estimate time of HIV infection in participants from the Bangkok Tenofovir Study (BTS) with daily oral tenofovir disoproxil fumarate (TDF) for preexposure prophylaxis (PrEP) and relate infection with adherence patterns. DESIGN: We used the diversity structure of the virus population at the first HIV RNA-positive sample to estimate the date of infection, and mapped these estimates to medication diaries obtained under daily directly observed therapy (DOT). METHODS: HIV genetic diversity was investigated in all 17 PrEP breakthrough infections and in 16 placebo recipients. We generated 10-25 HIV env sequences from each participant by single genome amplification, and calculated time since infection (and 95% confidence interval) using Poisson models of early virus evolution. Study medication diaries obtained under daily DOT were then used to compute the number of missed TDF doses at the approximate date of infection. RESULTS: Fifteen of the 17 PrEP breakthrough infections were successfully amplified. Of these, 13 were initiated by a single genetic variant and generated reliable estimates of time since infection (median = 47 [IQR = 35] days). Eleven of these 13 were under daily DOT at the estimated time of infection. Analysis of medication diaries in these 11 participants showed 100% adherence in five, 90-95% adherence in two, 55% adherence in one, and nonadherence in three. CONCLUSION: We estimated time of infection in participants from BTS and found several infections when high levels of adherence to TDF were reported. Our results suggest that the biological efficacy of daily TDF against parenteral HIV exposure is not 100%.

Hepatitis C virus infection among people who inject drugs in Bangkok, Thailand, 2005-2010.

Background: Approximately 1% of adults in Thailand are infected with hepatitis C virus (HCV). New direct-acting antiviral agents achieve sustained virologic responses in >95% of HCV-infected patients and are becoming available in countries around the world. To prepare for new HCV treatment options in Thailand, this study characterized HCV infections among people who inject drugs (PWID) in Bangkok. Methods: The Bangkok Tenofovir Study (BTS) was a pre-exposure prophylaxis trial conducted among PWID, 2005-2013. Blood specimens were randomly selected from PWID screened for the BTS, to test for anti-HCV antibody and HCV RNA. The HVR1 region was amplified by polymerase chain reaction, using multiplex primer sets with unique identifier sequences; amplification products were pooled in sets of 25; and consensus sequencing was performed to characterize individual HCV genotypes. Results: The median age of 3679 participants tested for anti-HCV antibody was 31 years, 3016 (82.0%) were male and 447 (12.2%) were HIV infected. The prevalence of anti-HCV antibody was 44.3%. The adjusted odds of testing positive for anti-HCV antibody were higher in men (adjusted odds ratio [aOR] 3.2, 95% confidence interval [CI] 2.4-4.3), those aged 40 years or older (aOR 2.7, 95% CI 2.1-3.5), those who had more than a primary school education (aOR 1.7, 95% CI 1.4-2.1), and those who tested HIV positive (aOR 5.2, 95% CI 3.7-7.4). HCV RNA was detected in 644 (81.3%) of the 792 anti-HCV antibody-positive specimens, yielding an HCV RNA-positive prevalence of 36.0% (95% CI 33.8-38.2). Among a random sample of 249 of the 644 specimens, 218 could be characterized, and the most common HCV subtypes were 1a (30.3%), 1b (12.8%), 3a (35.8%), 3b (6.9%) and 6n (8.7%). Conclusion: The prevalence of anti-HCV antibody among PWID was 44.3% and more than one third (36.0%) were HCV RNA positive. Genotypes 1, 3 and 6 accounted for all typable infections. As the government of Thailand considers introduction of direct-acting antiviral medications for people with hepatitis C, it will be important to ensure that the medications target these subtypes.

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.

Assessment of Oral Fluid HIV Test Performance in an HIV Pre-Exposure Prophylaxis Trial in Bangkok, Thailand.

BACKGROUND: Rapid easy-to-use HIV tests offer opportunities to increase HIV testing among populations at risk of infection. We used the OraQuick Rapid HIV-1/2 antibody test (OraQuick) in the Bangkok Tenofovir Study, an HIV pre-exposure prophylaxis trial among people who inject drugs. METHODS: The Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial. We tested participants' oral fluid for HIV using OraQuick monthly and blood using a nucleic-acid amplification test (NAAT) every 3 months. We used Kaplan-Meier methods to estimate the duration from a positive HIV NAAT until the mid-point between the last non-reactive and first reactive oral fluid test and proportional hazards to examine factors associated with the time until the test was reactive. RESULTS: We screened 3678 people for HIV using OraQuick. Among 447 with reactive results, 436 (97.5%) were confirmed HIV-infected, 10 (2.2%) HIV-uninfected, and one (0.2%) had indeterminate results. Two participants with non-reactive OraQuick results were, in fact, HIV-infected at screening yielding 99.5% sensitivity, 99.7% specificity, a 97.8% positive predictive value, and a 99.9% negative predictive value. Participants receiving tenofovir took longer to develop a reactive OraQuick (191.8 days) than participants receiving placebo (16.8 days) (p = 0.02) and participants infected with HIV CRF01_AE developed a reactive OraQuick earlier than participants infected with other subtypes (p = 0.04). DISCUSSION: The oral fluid HIV test performed well at screening, suggesting it can be used when rapid results and non-invasive tools are preferred. However, participants receiving tenofovir took longer to develop a reactive oral fluid test result than those receiving placebo. Thus, among people using pre-exposure prophylaxis, a blood-based HIV test may be an appropriate choice. TRIAL REGISTRATION: ClinicalTrials.gov NCT00119106.

Renal function of participants in the Bangkok tenofovir study--Thailand, 2005-2012.

BACKGROUND: Tenofovir disoproxil fumarate (tenofovir) has been associated with renal dysfunction in people infected with human immunodeficiency virus (HIV) receiving combination antiretroviral therapy. We reviewed data from an HIV preexposure prophylaxis trial to determine if tenofovir use was associated with changes in renal function in an HIV-uninfected population. METHODS: During the trial, 2413 HIV-uninfected people who inject drugs were randomized to receive tenofovir or placebo. We assessed the renal function of trial participants with the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations using t tests for cross-sectional analysis and linear regression for longitudinal analysis. RESULTS: Creatinine clearance and glomerular filtration rate (GFR) results were lower at 24, 36, 48, and 60 months in the tenofovir group compared with the placebo group. Results declined more in the tenofovir group than in the placebo group during follow-up using the Cockcroft-Gault (P < .001) and CKD-EPI (P = .007) equations, but not MDRD (P = .12). Creatinine clearance measured when study drug was stopped was lower in the tenofovir group than the placebo group (P < .001), but the difference resolved when tested a median of 20 months later (P = .12). CONCLUSIONS: We found small but significant decreases in cross-sectional measures of creatinine clearance and GFR in the tenofovir group compared with the placebo group and modest differences in downward trends in longitudinal analysis using the Cockcroft-Gault and CKD-EPI equations. These results suggest that with baseline assessments of renal function and routine monitoring of creatinine clearance during follow-up, tenofovir can be used safely for HIV preexposure prophylaxis. Clinical Trials Registration. NCT00119106.