Why we need pre-exposure prophylaxis: incident HIV and syphilis among men, and transgender women, who have sex with men, Bangkok, Thailand, 2005-2015.

We describe incident human immunodeficiency virus (HIV) and syphilis trends in men who have sex with men (MSM) and transgender women (TGW) presenting for HIV voluntary counseling and testing (VCT) services and sexually transmitted infection (STI) management at the Silom Community Clinic, Bangkok, Thailand. Clients underwent rapid HIV testing and syphilis rapid plasma reagin (RPR) testing. For incidence analysis, we included clients with >1 follow-up visit. Initial negative HIV with subsequent positive HIV defined incident HIV infection; incident syphilis infection was defined as negative RPR followed by positive RPR (titer ≥1:8) and confirmatory anti- Treponema pallidum antibodies. Calculation of incidence using Poisson regression assumed a uniform probability distribution throughout the seroconversion interval. From 15 September 2005 to 31 December 2015, we tested 10,158 clients for HIV and 10,324 for syphilis. Overall, 7109 clients tested HIV-seronegative and contributed 7157 person-years (PY). Three-hundred forty-seven incident HIV infections resulted in an incidence rate of 4.8 per 100 PY (95% confidence interval [CI] 4.4-5.4). We found an inverted U-shape trend of HIV incidence over time with a peak of 6.4 per 100 PY in quarter 2/2011 ( p < 0.01) (Poisson with RCS function, p = 0.001). Overall, 8713 clients tested seronegative for syphilis and contributed 8623 PY. The incidence of syphilis infection was 4.4 per 100 PY (95% CI 3.9-4.8). Despite an apparent decline in HIV incidence among MSM and TGW attending VCT services, syphilis incidence rose and remained high. Evaluating temporal trends of HIV and syphilis incidence provides an opportunity to evaluate epidemic trajectories and target limited program funding. We recommend focused HIV and STI prevention interventions for MSM in Bangkok.

Feasibility of a preventive HIV-1 vaccine cohort among persons attending sexually transmitted disease clinics in Thailand.

Persons attending sexually transmitted disease clinics at three sites in Thailand were recruited to participate in a 1-year study of HIV-1 incidence. Between September 1995 and February 1996, 31% (371 of 1205) of eligible men and 24% (161 of 659) of eligible women agreed to participate. At enrollment, HIV-1 seropositivity was 3.8% among men and 2.5% among women. Follow-up of the 514 participants who were seronegative at baseline was 78% at the 12-month visit. During the study period, 53% of men reported 2 or more sexual partners, 31% reported sex with a commercial sex worker (CSW), and 33% with a casual partner. Of those visiting CSWs, 72% reported consistent condom use. Among women, 11% reported 2 or more sexual partners. Decreased HIV risk behaviors among men were observed during the study. Four incident infections occurred in men (1.4/100 person-years, 95% confidence interval [CI] = 0.4-3.6) and none among women. Based on the observed HIV-1 incidence, HIV vaccine efficacy trials in such populations would have to be larger than previously planned or more selective of high risk subgroups for recruitment.

PIP: Thailand is one of the few countries in which plans for HIV-1 vaccine efficacy trials are proceeding. The determination of cohort sample size for such trials depends upon the HIV-1 incidence among those who may enroll in the trials, participant retention, trial duration, and the frequency of risk behavior during the trial. The authors conducted a prospective cohort study of sexually transmitted disease (STD) clinic attendees at 3 sites in Thailand to determine whether a cohort in the population would be suitable for future HIV-1 vaccine efficacy trials. Between September 1995 and February 1996, 371 of 1205 (31%) eligible men and 161 of 659 (24%) eligible women agreed to participate in a 1-year study of HIV-1 incidence. At enrollment, 3.8% of the men and 2.5% of the women were infected with HIV-1. Almost all women and 54% of the men were married at the time of enrollment. 78% of the 514 participants who were seronegative at baseline were still being followed at the 12-month visit. During the study period, 53% of men reported having 2 or more sex partners, 31% reported having sex with a prostitute, and 33% with a casual partner. 72% of those frequenting prostitutes reported consistent condom use. 11% of women reported 2 or more sex partners. Decreased HIV risk behaviors among men were observed during the study. 4 incident infections occurred in men and none among the women. Based upon this observed HIV-1 infection incidence, HIV vaccine efficacy trials in such populations would have to be larger than previously planned or more selective of high-risk subgroups for recruitment.

Cost of providing sexually transmitted disease services in Bangkok.

OBJECTIVE: The main purpose of this study was to assess the economic costs of sexually transmitted disease (STD) treatment and to identify opportunities for sustaining Bangkok's STD clinics. DESIGN: A cost analysis was used to assess the resources required to provide (i) STD services, (ii) additional services at STD clinics during the evening, and (iii) outreach activities with commercial sex workers. The cost analysis included a review of opportunities to increase sustainability through cost recovery and institutional restructuring. RESULTS: The study revealed that the cost of providing services does differ significantly across the five clinics analysed, with recurrent costs of day-clinic STD care varying from US$13-37 per patient reached. An analysis of expanded evening hours at STD clinics suggested that an investment of US$62 000 per year allowed an additional 2000 patients to receive STD treatment and that evening hours appear to offer greater convenience to patients. It was also found that outreach activities initiated by the STD clinics and carried out in brothels have been used inexpensively (US$0.20 per woman reached) to reach commercial sex workers with critical information on STDs, including HIV. An analysis of opportunities for cost recovery at public STD clinics indicated that although some resources can be recovered, government support will continue to be required. The cost recovery option believed to be most feasible for promoting sustainability was a proposed charge of US$2-4 for STD clinic attenders. This charge was projected to allow each clinic to recover between 11% and 22% of their recurrent costs. CONCLUSION: This study concluded that there are numerous opportunities for promoting the financial sustainability of STD services at public clinics. It was also concluded that the existing outreach program is extremely inexpensive and is reaching people who are in need of the services that are being offered. However, this study was not able to determine if it would be worthwhile to reopen public STD clinics during evening hours.

PIP: Findings are presented from an assessment of the economic costs of treating STDs and sustaining 5 STD clinics in the Bangkok metropolitan area. The cost analysis was done in June 1995 using a composite of costing guidelines. Costs were evaluated for 1994, and are therefore in 1994 dollars. The analysis determined that the cost of providing services differs significantly across the 5 clinics analyzed, with recurrent costs of day-clinic STD care at US$13-37 per patient reached. An analysis of expanded evening hours at the clinics suggests that an investment of US$62,000 per year would allow an additional 2000 patients to receive STD treatment and that evening hours seem to be more convenient for patients. Inexpensive outreach activities initiated by the clinics and conducted in brothels have reached prostitutes with important information on STDs, including HIV. An analysis of opportunities for cost recovery found that although some resources can be recovered, government support will continue to be required. The most feasible cost recovery option for promoting sustainability is a proposed charge of US$2-4 per STD clinic attender. This charge was projected to allow each clinic to recover 11-22% of their recurrent costs.

Azithromycin in non-gonococcal urethritis.

The efficacy and safety of a single 1 g oral dose of azithromycin was evaluated in 100 male patients with non-gonococcal urethritis (NGU). Enrolled were men with > or = 5 polymorphonuclear leukocytes (PMNL)/high power field (HPF) (x 1000 magnification) in a Gram-stained smear of urethral discharge with or without symptoms and signs of NGU. Of the 66 evaluable patients, Chlamydia trachomatis was isolated from 18 cases (27.3%) and Ureaplasma urealyticum from 12 cases (18.2%). After treatment, signs and symptoms disappeared from 59 cases (89.4%). Forty-four cases (66.7%) showed reduced PMNL/HPF. C. trachomatis was eradicated in 18 cases (100%) and U. urealyticum in 12 cases (83.3%). One patient complained of mild dizziness, moderate nausea, and palpitations. Single 1 g oral dose of azithromycin appears to be effective and safe for treating chlamydial, non-chlamydial, and ureaplasmal NGU. In addition, its ease of use encourages patient compliance.

Azithromycin in the treatment of chlamydial cervicitis and eradication of Ureaplasma urealyticum in female lower genital tract.

From May 1995 to May 1996, thirty-six females with chlamydial cervicitis were enrolled at Bangrak Hospital's Venereal Disease Clinic in an open study to assess the efficacy and safety of a single, 1-gram oral dose of azithromycin. Thirty-five had positive C. trachomatis and one had a positive Gen-probe test. Twenty-two returned for their first and second follow-ups and 18 came back for their final follow-up (visit 4). Eradication rate was 100 per cent on all visits. Fourteen patients were excluded from the final analysis- three had dropped out from the beginning, ten had sexual intercourse without a condom and one had a positive Gen-probe test but negative C. trachomatis culture. U. urealyticum was isolated from the vaginal wall of 15 of the 36 cases and eradication rate was 0 per cent at visit 2 and visit 4. In conclusion, this study shows that a single, 1-gram oral dose of azithromycin is an effective and well-tolerated alternative therapy for chlamydial cervicitis.

Antimicrobial susceptibilities of strains of Neisseria gonorrhoeae in Bangkok, Thailand: 1994-1995.

BACKGROUND AND OBJECTIVES: Failure of uncomplicated gonococcal infections acquired in the Far East to respond to doses of ciprofloxacin and ofloxacin recommended by the Centers for Disease Control and Prevention have been identified in Australia, the United Kingdom, and the United States. In the Republic of the Philippines, 54.3% of strains exhibited decreased susceptibility to fluoroquinolones; 12% of strains were resistant to ciprofloxacin. This study was undertaken to compare the antimicrobial susceptibilities of gonococcal isolates in Bangkok, Thailand, with those in the Republic of the Philippines. GOAL: To determine the frequency and diversity of antimicrobial resistance, particularly to fluoroquinolones, in gonococcal strains in Bangkok, Thailand. STUDY DESIGN: Strains of Neisseria gonorrhoeae isolated from 101 patients with uncomplicated gonorrhea in Bangkok, Thailand, in July, 1994 (46 strains) and November, 1994 to July, 1995 (55 strains), were characterized by auxotype/serovar class, antimicrobial susceptibilities, and plasmid profile. Susceptibilities were determined to penicillin G, tetracycline, ceftriaxone, cefixime, cefoxitin, ciprofloxacin, ofloxacin, norfloxacin, erythromycin, kanamycin, and thiamphenicol. RESULTS: Of 101 strains, 89.1% (90/101) were resistant to penicillin or tetracycline. Plasmid-mediated resistance to penicillin or tetracycline was identified in 33.7% (34/101) of the isolates: penicillinase-producing Neisseria gonorrhoeae (17.8%; 18/101), tetracycline-resistant Neisseria gonorrhoeae (7.9%; 8/101), and penicillinase-producing/tetracycline-resistant Neisseria gonorrhoeae (7.9%; 8/101). Most penicillinase-producing strains (96.2%; 25/26) possessed the 4.4-megadalton (Md) beta-lactamase plasmid; one strain possessed the 3.2-Md beta-lactamase plasmid. Chromosomally mediated resistance to penicillin and tetracycline was exhibited by 51.5% (52/101) of strains, and 4.0% (4/101) were tetracycline resistant. All strains were susceptible to spectinomycin. Of 21.8% (22/101) strains exhibiting decreased susceptibility to ciprofloxacin (minimal inhibitory concentration [MIC] > or = 0.125 microgram/ml), one strain (ciprofloxacin MIC, 0.5 microgram/ml; ciprofloxacin inhibition zone diameter of 23 mm) had MICs of 2.0 and 8.0 micrograms/ml for ofloxacin and norfloxacin, respectively, indicating resistance to these agents. Decreased susceptibility to ciprofloxacin was identified in strains with chromosomally mediated resistance to penicillin or tetracycline and in penicillinase-producing strains. CONCLUSIONS: In Bangkok, Thailand, gonococcal isolates exhibit resistance to penicillin, tetracycline, kanamycin, and thiamphenicol. Decreased susceptibility to fluoroquinolones is emerging in a variety of strains of N. gonorrhoeae. Thus, all gonococcal infections should be treated with antimicrobial therapies known to be active against all gonococcal strains to reduce the spread of strains exhibiting decreased susceptibilities to fluoroquinolones.

PIP: To assess the frequency and diversity of antimicrobial resistant strains of Neisseria gonorrhoeae in Thailand, endocervical or urethral strains were isolated from 101 patients at a Bangkok sexually transmitted disease clinic. Of the 101 strains, 90 (89.1%) were resistant to penicillin or tetracycline. Plasmid-mediated resistance to penicillin or tetracycline was found in 33.7% of isolates; this included penicillinase-producing N gonorrhoeae (17.8%), tetracycline-resistant N gonorrhoeae (7.9%), and penicillinase-producing/tetracycline-resistant N gonorrhoeae (7.9%). Moreover, 51.5% of all strains exhibited chromosomally mediated resistance to penicillin and tetracycline. All strains were susceptible to spectinomycin. 22 strains (21.8%) showed decreased susceptibility to ciprofloxacin, while another fifth demonstrated resistance to both fluoroquinolones and norfloxacin. Finally, more than 75% of strains exhibited decreased susceptibility to kanamycin and thiamphenicol. The penicillin/tetracycline resistance phenotypes identified in Bangkok were more similar to those of isolates in the US than in the Philippines, where decreased susceptibility to fluoroquinolones predominates. Given evidence of antimicrobial resistance to penicillin, tetracycline, kanamycin, thiamphenicol, and fluoroquinolones in Thailand, the choice of agents for the treatment of uncomplicated gonococcal infection should be considered carefully and periodic surveillance of antimicrobial resistance is recommended to permit timely revision of treatment protocols.

Treatment of acute gonococcal infections in Bangkok with a dose range of the new cephalosporin, cefodizime.

In this randomized dose range study conducted in Bangkok, 326 patients with presumed acute uncomplicated gonorrhoea were treated with a single intramuscular dose of either 0.25 g, 0.5 g, or 1.0 g of a new aminothiazole cephalosporin, cefodizime. One hundred and eighty men and 110 women were evaluable for efficacy. Pathogens were eliminated in all but 4 of these patients resulting in a cure rate of 99%, irrespective of dose, sex, or multiplicity of infected sites. A high percentage of the 290 strains of Neisseria gonorrhoeae isolated from the evaluable patients showed resistance to penicillin, and 40% were penicillinase producing (PPNG). The minimum inhibitory concentration of cefodizime for 90% of the PPNG strains was less than 0.04 mg/l. No clinically relevant adverse drug reactions were reported. This study demonstrates that a single 0.25 g dose of cefodizime is effective against both PPNG and non-PPNG strains in a geographic region characterized by high endemic antibiotic resistance.

Etiology of urethritis in Thai men.

The etiology of urethritis was determined for 303 Thai men with urethral discharge containing 5 or more polymorphonuclear cells (PMN)/high power field (hpf) and 132 men with a discharge containing less than 5 PMN/hpf. Neisseria gonorrhoeae was isolated significantly more often from men with greater than or equal to 5 PMN/hpf than from men with less than 5 PMN/hpf (42% vs 1%, P less than .0001). Chlamydia trachomatis was also isolated more often from patients with greater than or equal to 5 PMN/hpf than from men with less than 5 PMN/hpf (16% vs 8%, P less than .03). Ureaplasma urealyticum was isolated with nearly equal frequency from both groups of patients (45% vs 37%). Among men with a urethral exudate containing greater than or equal to 5 PMN/hpf, N. gonorrhoeae was isolated as the only pathogen from 19% and in combination with C. trachomatis or U. urealyticum in 23% of these men. C. trachomatis or U. urealyticum, but not N. gonorrhoeae, was isolated from 30%, and no pathogen was isolated from 28% of these men. Among men with urethral exudate containing less than 5 PMN/hpf, N. gonorrhoeae was isolated from only 1%, C. trachomatis or U. urealyticum from 41%, and no pathogen from 58%. These findings suggest that all Thai men with urethral discharge containing greater than or equal to 5 PMN/hpf should be treated for non-gonococcal urethritis and for gonococcal urethritis if gram-negative diplococci are demonstrated on gram stain of the urethral discharge. Men with urethritis with less than 5 PMN/hpf should be treated for only non-gonococcal urethritis.

Rapid Plasma Reagin test (RPR) compared to Venereal Diseases Research Laboratory test (VDRL) for the diagnosis of syphilis in pregnancy.

Obstetric departments which provide service for a large number of patients from different parts of the country and socioeconomic backgrounds like the Obstetric Department of Chulalongkorn hospital, need to develop rapid laboratory tests which can cope with the volume of work and yet provide sound laboratory data for management decisions. We, therefore, undertook a study of the suitable Rapid Plasma Reagin (RPR) test as a diagnostic tool for syphilis in 9,347 pregnant women who attended antenatal clinics at this institute from August 1984 to May 1985. The RPR test was used in addition to the routine serological tests for syphilis namely the VDRL, TPHA and/or FTA-ABS. Analysis of results confirmed that the RPR test fulfilled all laboratory results for clinical requirements. The results from RPR and VDRL were not significantly different. Their sensitivities were 90.86 and 89.95 per cent, their specificities were 99.57 and 99.68 per cent, their positive predictive values were 82.11 and 85.92 per cent, their negative predictive values were 99.8 and 99.78 per cent, and their accuracy was 99.39 and 99.47 per cent respectively. In our study it was found that the RPR test could provide a laboratory diagnosis in 60-90 minutes; in the same morning period when 15-20 prenatal patients were seen for the first time. The above results suggest that the RPR test is a rapid and reliable tool which is particularly suitable for syphilis screening in a busy antenatal clinic. The test enabled all 197 patients with syphilis in pregnancy to be treated promptly and without any loss of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of sexual contacts of syphilitic pregnant women.

Between August 1984 and May 1985, 197 syphilitic pregnant women were diagnosed at the antenatal clinic, Department of Obstetrics & Gynaecology, Faculty of Medicine, Chulalongkorn University. One hundred and sixty-nine male sexual contacts were serologically tested for syphilis and seventy-eight cases were found positive. Twenty-eight cases refused to be tested. Thirty-two syphilitic male contacts had cerebrospinal fluid tests and four were found to be abnormal. Fifty-three cases or 67.9 per cent of 78 syphilitic male consorts did not complete a full diagnostic and treatment protocol. They preferred to be treated with benzathine penicillin G 2.4 million units intramuscularly for 3 consecutive weeks. After this treatment no patient agreed to a repeat spinal tap. This behavioral attitude concurred with their socioeconomic background. All were from a low socioeconomic group and lacked health knowledge. This made it difficult to work with them and contributed to inadequate management of their disease.

Effectiveness of benzathine penicillin regimen in the treatment of syphilis in pregnancy.

The intramuscular injection of benzathine penicillin G 2.4 million units weekly for 3 consecutive weeks to syphilitic pregnant women was again confirmed to be clinically effective for prevention of their neonates from congenital syphilis and well accepted as treatment for syphilis in pregnancy. It was administered to 184 cases, or 93.5 per cent, of 197 syphilitic gravidas. It was found that pregnancy outcomes in terms of abortion, stillbirth, prematurity, full term delivery, neonatal birth weight, macroscopic examination of the placenta and general physical examination of the neonate were clinically useful as a parameter to evaluate the effectiveness of the therapy for the infant. Clinical symptoms and signs in the mother, serological tests for syphilis in the gravida and cord blood of the newborn, and placental weight were not useful in the evaluation of adequacy of treatment of our study group.

Evaluation of 500- and 1,000-mg doses of ciprofloxacin for the treatment of chancroid.

A randomized, double-blind study was performed comparing ciprofloxacin in a 500-mg single dose with 1,000 mg (500-mg doses given 12 h apart) for the treatment of chancroid in Thailand. Haemophilus ducreyi was isolated from 87 (48%) of 180 men with a clinical diagnosis of chancroid. For men with ulcers that were culture positive for H. ducreyi, rates of cure were 100% in the 500-mg group and 98% in the 1,000-mg group. For men with ulcers that were culture negative for H. ducreyi, rates of cure were 93% in the 500-mg group and 96% in the 1,000-mg group. The MIC of ciprofloxacin for 50% of isolates among 85 isolates of H. ducreyi was 0.007 micrograms/ml (range, 0.002 to 0.03 micrograms/ml). No significant adverse effects were detected in either group. These data indicate that both of these treatment regimens are equally effective therapies for chancroid in Thailand.

Clinical and microbiological efficacy of a single dose of norfloxacin in the treatment of chancroid.

Forty-one men with a clinically and bacteriologically verified diagnosis of chancroid were given a single dose of 800 mg of norfloxacin and were examined clinically and bacteriologically four, seven and 14 days after treatment. Five patients were excluded from evaluation of efficacy due to concomitant infections or incomplete follow-up. Of the remaining 36 patients, 34 were cured and culture negative at follow-up controls. Another 15 men with culture-negative ulcers treated with 800 mg of norfloxacin as a single dose, were all cured clinically. The high cure rate and the good tolerability make norfloxacin a convenient and cheap alternative to intramuscular single dose therapy of chancroid.

Efficacy of ofloxacin in uncomplicated gonorrhoea.

A randomised double blind trial comparing single oral dose therapy with 200 mg and 400 mg of ofloxacin, respectively was conducted at the Bangrak Hospital, Bangkok during the period December 6, 1985 to January 24, 1986. We treated 234 male patients diagnosed as having uncomplicated gonococcal urethritis with ofloxacin. Ofloxacin, at a single dose of 200 mg or 400 mg, was given to each of them. Fourteen patients were excluded for efficacy assessment. There were 223 patients left for safety assessment. The cure rates were 100% in both groups. Among 233 isolates tested, 48.5% were penicillinase producing Neisseria gonorrhoeae. The range of minimum inhibitory concentrations of ofloxacin was 0.008 to 0.063 mg/l. No adverse drug experiences were reported.

Treating gonococcal infections resistant to penicillin in Bangkok: comparison of cefuroxime and spectinomycin.

Gonococcal organisms have become resistant to antimicrobials throughout the world. Such resistance is common in Thailand, where 40% of gonococci produce penicillinase (PPNG strains) and over half the remainder have MICs of penicillin greater than or equal to 1 mg/l. To evaluate the effectiveness of cefuroxime against such resistant organisms, a controlled clinical trial comparing spectinomycin and cefuroxime was conducted at Bangrak Hospital, Bangkok, in 1982-3. Of 472 patients who were randomly assigned to treatment, 365 (77%) yielded positive cultures before treatment and returned for follow up evaluation three to 13 days after treatment. Of the 365 patients, 359 (98%) were cured, and no difference between the two treatment regimens was found either by the sex of the patient or by the presence of PPNG strains. The MIC of cefuroxime against all organisms was less than or equal to 1 mg/l. In vitro susceptibilities of gonococci in Bangkok have not changed appreciably during the past two years. Regimens of cefuroxime and spectinomycin are highly effective even for the relatively resistant gonococci in Bangkok. The pharmacokinetics, in vitro susceptibilities, and effectiveness of cefuroxime encourage evaluation of lower doses of the drug.

Randomised comparative study of ceftriaxone and spectinomycin in gonorrhoea.

From 26 April to 30 June 1983 a total of 200 men with uncomplicated gonococcal urethritis were randomly treated with either 2 g spectinomycin or 250 mg ceftriaxone, both administered intramuscularly. Of 197 isolates tested for the presence of the enzyme beta lactamase, 91 (46.2%) were positive (PPNG) and 106 (53.8%) were non-PPNG strains. All 93 patients treated with spectinomycin and followed up and 97 treated with ceftriaxone and followed up were cured. Ceftriaxone 250 mg administered by intramuscular injection is highly effective in treating gonococcal infections caused by both PPNG and non-PPNG strains and is an appropriate alternative to spectinomycin.

Single-dose treatment of uncomplicated gonorrhea in men with intramuscular and oral thiamphenicol.

Each of 200 men with uncomplicated gonococcal urethritis was randomly assigned to a group receiving one of two therapeutic regimens. Group A received 2 g of spectinomycin intramuscularly. Group B received 2.5 g of thiamphenicol, with 500 mg administered intramuscularly just after oral administration of 2 g. Of the 89 patients in group A who completed the study, 32 were infected with penicillinase-producing Neisseria gonorrhoeae, 49 with non-penicillinase-producing N. gonorrhoeae, and eight with gonococcal strains not tested for penicillinase production. Infection was cured in all 89 patients. Of the 91 patients in group B who completed the study, 33 were infected with penicillinase-producing N. gonorrhoeae, 54 with non-penicillinase-producing N. gonorrhoeae, and four with gonococcal strains not tested for penicillinase production. Infection was cured in 86 (94.5%) of the 91 patients. Thus, the single-dose regimen of thiamphenicol was effective against uncomplicated infections caused by either penicillinase-producing or non-penicillinase-producing strains of N. gonorrhoeae.