Antibiotic overuse, poor antimicrobial stewardship, and low specificity of syndromic case management in a cross section of men with urethral discharge syndrome in Kampala, Uganda.

OBJECTIVE: High prevalence of sexually transmitted infections (STIs) combined with poor antimicrobial stewardship are drivers of STI antimicrobial resistance (AMR) especially in resource-limited settings where syndromic case management (SCM) is the norm. We characterized patterns of antibiotic use prior to clinic attendance and study enrollment in Ugandan men with urethral discharge syndrome (UDS), evaluated in-clinic prescribing, and the performance characteristics of SCM. METHODS: Participants were recruited from government clinics participating in an existing gonococcal surveillance program in Kampala, Uganda. Questionnaires including antimicrobial use prior to attendance, prior episodes of UDS, penile swabs, and blood samples were collected. Bivariable and multivariable logistic regression models were used to estimate odds ratios (OR) for preselected factors likely to be associated with antibiotic use. In-clinic antibiotic treatment data were extracted from clinical notes, and the performance of SCM against laboratory-based STI diagnoses was evaluated. FINDINGS: Between October 2019 and November 2020, 100(40%) of 250 men with UDS reported taking antibiotics in the 14days prior to attending the clinic. Of these 210(84%) had at least one curable STI and 20% had a reactive point-of-care HIV test. Multivariable analysis demonstrated significant associations between recent antimicrobial use and duration of UDS symptoms <6 days (OR 2.98(95%CI 1.07,8.36), p = 0.038), and sex with women only (OR 0.08(95%CI 0.01,0.82),p = 0.038). The sensitivity of SCM ranged from 80.0% to 94.4%; specificity was low between 5.6% and 33.1%. The positive predictive value of SCM ranged from 2.4(95%CI 0.7,6.0) for trichomoniasis to 63.4(95%CI 56.5,69.9) for gonorrhea. CONCLUSION: Pre-enrollment antibiotic use was common in this population at high risk of STI and HIV. Combined with the poor specificity of SCM for male UDS, extensive antibiotic use is a likely driver of STI-AMR in Ugandan men. Interventions to improve antimicrobial stewardship and deliver affordable diagnostics to augment SCM and decrease overtreatment of STI syndromes are required.

High level of HIV viral suppression in a cross-sectional study of Ugandan men with urethritis and bacterial STI.

BACKGROUND: Urethritis associated with non-viral sexually transmitted infections (STI) increases the risk of HIV acquisition and transmission in those living with HIV (LWH) without viral load suppression (VLS). Compared to women, men typically have lower rates of HIV VLS. We assessed the prevalence of VLS and drug resistance mutations in men LWH and urethral discharge syndrome (UDS) in Kampala, Uganda. METHODS: Men with UDS were recruited in Kampala October 2019-November 2020. Medical, demographic, and behavioural data were collected with biological samples. All reactive HIV results (rapid, sequential algorithm) underwent confirmatory HIV antibody- and HIV incidence-testing, and viral load (VL) measurement. The pol and gp41 regions were sequenced on samples with VLs >1000 cpm, phylogenetic trees were generated, and resistance mutations were investigated. RESULTS: 50 of 250 participants (20%) had reactive HIV rapid tests and 48/50 (96%) were aware of their HIV status and using antiretroviral therapy (ART). The median age was 38 years (IQR 32-45), 27/50 (54%) had engaged in transactional sex, and 30/50 (60%) reported alcohol before sex. VLS was present in 46/50 (92%). There were no major resistance mutations present in any samples analyzed. CONCLUSIONS: The prevalence of HIV and VLS was greater in these men than in the general Ugandan adult population. Most men LWH were on ART and thus less likely to transmit HIV despite demonstrating sexual behaviours associated with high-risk of STIs. These data emphasize that high levels of ART coverage and VLS are achievable among men with UDS in urban Kampala.

High burden of untreated syphilis, drug resistant Neisseria gonorrhoeae, and other sexually transmitted infections in men with urethral discharge syndrome in Kampala, Uganda.

OBJECTIVES: Prompt diagnosis and treatment of sexually transmitted infections (STIs) are essential to combat the STI epidemic in resource-limited settings. We characterized the burden of 5 curable STIs chlamydia, gonorrhea, trichomoniasis, Mycoplasma genitalium, syphilis, and HIV infection in Ugandan men with urethritis. METHODS: Participants were recruited from a gonococcal surveillance program in Kampala, Uganda. Questionnaires, penile swabs were collected and tested by nucleic acid amplification. Gonococcal isolates were tested for antimicrobial sensitivity. Sequential point-of-care tests on blood samples were used to screen for syphilis and HIV. Bivariable and multivariable multinomial logistic regression models were used to estimate odds ratios for preselected factors likely to be associated with STIs. Adherence to STI treatment guidelines were analyzed. RESULTS: From October 2019 to November 2020, positivity (95% CI) for gonorrhea, chlamydia, trichomoniasis, and Mycoplasma genitalium, were 66.4% (60.1%, 72.2%), 21.7% (16.8%, 27.4%), 2.0% (0.7%, 4.9%), and 12.4% (8.7%, 17.3%) respectively. All Neisseria gonorrhoeae isolates were resistant to ciprofloxacin, penicillin, and tetracycline, but susceptible to extended spectrum cephalosporins and azithromycin. HIV and syphilis prevalence was 20.0% (50/250) and 10.0% (25/250), and the proportion unaware of their infection was 4.0% and 80.0% respectively. Most participants were treated per national guidelines. Multivariable analysis demonstrated significant associations between curable STI coinfections and younger age, transactional sex, but not HIV status, nor condom or alcohol use. CONCLUSIONS: STI coinfections including HIV their associated risk factors, and gonococcal AMR were common in this population. The majority with syphilis were unaware of their infection and were untreated. Transactional sex was associated with STI coinfections, and > 80% of participants received appropriate treatment.

Retrospective Analysis of Ugandan Men with Urethritis Reveals Mycoplasma genitalium and Associated Macrolide Resistance.

The rising rates of antimicrobial resistance (AMR) in Mycoplasma genitalium globally and the association of this sexually transmitted infection (STI) with cervicitis, urethritis, and HIV are potentially of great public health concern. Data on the epidemiology of M. genitalium in men in sub-Saharan Africa are limited. We sought to determine the prevalence of M. genitalium and macrolide resistance in men with urethritis in Kampala, Uganda. Self-collected penile-meatal swabs and/or urine samples from men with symptomatic urethritis (n = 250) were retrospectively analyzed for the presence of M. genitalium and macrolide resistance markers with the Aptima M. genitalium and ResistancePlus M. genitalium assays. Additionally, demographic and STI coinfection data were used to investigate associations with M. genitalium infection. M. genitalium was detected in 12.8% (32/250) of individuals; 40.6% (n = 13) had M. genitalium monoinfection. Mutations associated with macrolide resistance were detected in 10.7% (3/28) of participants. Coinfection with Neisseria gonorrhoeae was common (41.0%), but M. genitalium was more prevalent in participants without N. gonorrhoeae coinfection (P = 0.001). M. genitalium is common in Ugandan men with urethritis both as a monoinfection and as a coinfection with other curable STIs. Macrolide resistance was present and warrants further research on treatment outcomes and the association between untreated M. genitalium and subsequent morbidity. IMPORTANCE Mycoplasma genitalium is a common sexually transmitted infection associated with urethritis in men. Little is known about M. genitalium infection in men with urethritis in Uganda. We report that 12% of participants in this study were positive for M. genitalium and that resistance to azithromycin, a macrolide antibiotic, is present. Furthermore, we show that either self-collected penile-meatal swabs or urine can be used for detection of M. genitalium.

A portable magnetofluidic platform for detecting sexually transmitted infections and antimicrobial susceptibility.

Effective treatment of sexually transmitted infections (STIs) is limited by diagnostics that cannot deliver results rapidly while the patient is still in the clinic. The gold standard methods for identification of STIs are nucleic acid amplification tests (NAATs), which are too expensive for widespread use and have lengthy turnaround times. To address the need for fast and affordable diagnostics, we have developed a portable, rapid, on-cartridge magnetofluidic purification and testing (PROMPT) polymerase chain reaction (PCR) test. We show that it can detect Neisseria gonorrhoeae, the pathogen causing gonorrhea, with simultaneous genotyping of the pathogen for resistance to the antimicrobial drug ciprofloxacin in <15 min. The duplex test was integrated into a low-cost thermoplastic cartridge with automated processing of penile swab samples from patients using magnetic beads. A compact instrument conducted DNA extraction, PCR, and analysis of results while relaying data to the user via a smartphone app. This platform was tested on penile swab samples from sexual health clinics in Baltimore, MD, USA (n = 66) and Kampala, Uganda (n = 151) with an overall sensitivity and specificity of 97.7% (95% CI, 94.7 to 100%) and 97.6% (95% CI, 94.1 to 100%), respectively, for N. gonorrhoeae detection and 100% concordance with culture results for ciprofloxacin resistance. This study paves the way for delivering accessible PCR diagnostics for rapidly detecting STIs at the point of care, helping to guide treatment decisions and combat the rise of antimicrobial resistant pathogens.

The Potential Teratogenicity Alert for Women Conceiving on Dolutegravir-Based Regimens: An Assessment of Risk Communication by an Urban HIV Clinic in Uganda and Choices made by Women.

INTRODUCTION AND OBJECTIVE: In May 2018, the World Health Organization and other regulatory authorities released a safety alert for dolutegravir related to a risk of neural tube defects among women exposed to dolutegravir at the time of conception. Models of how drug safety information can be shared effectively in the shortest time are necessary to prevent interruptions of public health programs. We sought to describe an implementation process to inform and support women already on dolutegravir-based regimens at the time of conception to make informed choices following the safety alert of a potential teratogenicity risk. We describe the choices made by women, as well as determine the factors associated with women's choices to switch off dolutegravir. METHODS: A clinic response plan was developed in the first week following the alert and clinic staff were trained on safety guidance. All women aged < 55 years taking dolutegravir were identified from the clinic database and contacted by phone for earlier appointments. Non-menopausal and non-surgically sterilized women were referred for urine pregnancy testing and evaluation of pregnancy intentions in the following 12 months and effective family planning was offered. We describe the coverage of women who received the communication as well as the fidelity to the outlined plan from 21 May to 12 September, 2018. We used modified a Poisson regression analysis to determine factors associated with switching off dolutegravir. RESULTS: Of all active patients in the clinic, 9% (690/7963) were identified as female aged < 55 years taking dolutegravir. Ninety-five percent (656/690) were reviewed by September 2018 and informed of the safety alert, implying a high level of uptake. Fidelity to standard operating procedures was also high at 72%. Twenty-two percent (146/656) of patients were menopausal or surgically sterilized. Five hundred and ten women were of reproductive potential with a median age (interquartile range) of 37 years (30-42 years). Five percent (23/510) were human chorionic gonadotrophin positive and all initial ultrasound reports revealed no deformities. Twenty-one percent (108/510) had intentions to conceive and opted to stop taking dolutegravir with 90% (97/108) switching to efavirenz. Seventy-nine percent (402/510) opted to remain taking dolutegravir. However, only 40% (160/402) chose effective contraceptive methods and 60% (242/402) opted for condoms only/no contraceptive method. CONCLUSIONS: A rapid well-coordinated response ensured prompt communication of the dolutegravir safety warning. The process developed by the clinic can act as a model for response during drug safety alerts. Women made informed decisions with most opting to remain taking dolutegravir; however, effective contraception uptake was low.