Human papillomavirus (HPV) types among Alaska native women attending a colposcopy clinic in Anchorage, Alaska, 2009-2011.

BACKGROUND: The first HPV vaccines licensed targeted two HPV types responsible for most cervical cancers. A 9-valent vaccine (9vHPV), targeting 5 additional types, was introduced in 2016 and is currently the only HPV vaccine available in the United States. Previous studies demonstrated high rates of HPV infection in Alaska Native (AN) women. We sought to measure prevalence of high risk HPV types in AN women undergoing colposcopy and to determine those preventable by vaccination. METHODS: For this cross-sectional study, we recruited women who were undergoing colposcopy for clinical indications at Alaska Native Medical Center to obtain cervical brush biopsy samples. Specimens were shipped to Atlanta, Georgia for DNA extraction, HPV detection, and typing using L1 PCR with type-specific hybridization to detect 37 HPV types. RESULTS: Four hundred eighty eight specimens from 489 women were tested. At least one HPV type was found in 458 (94%) specimens. Of 458 participants who were HPV positive, 332 (72%) had two or more types. At least one type targeted by 9vHPV was detected in 95% of participants with CIN 3 (21/22), 82% with CIN 2 (37/45), and 65% with CIN 1 (119/184). (p < 0.001) HPV 16 or 18 were detected in 77% (17/22) with CIN 3, 53% (24/45) with CIN 2, and 36% (67/184) with CIN 1. (p < 0.001). CONCLUSIONS: A substantial proportion of AN women attending colposcopy clinic had evidence of HPV 16/18 infection, as well as other high risk types targeted by 9vHPV. At least one 9vHPV type was detected in 62% of the participants overall, and 95% of participants with CIN3. AN women are expected to benefit from vaccination against HPV 16/18, and will have greater benefit from 9vHPV. Information from this study could be used to develop public health strategies to increase vaccine uptake, or to track HPV genotype prevalence over time.

Examining self and partners for syphilis among men who have sex with men: five US cities, 2009-2011.

To increase self-examination for syphilis among men who have sex with men (MSM), we developed educational materials to increase knowledge of primary and secondary syphilis manifestations. Materials were piloted in five cities' infectious disease or MSM clinics. Self- and partner-examination behaviour was assessed with an anonymous questionnaire. Of 1459 participants, 914 men had had sex with a man in the previous three months; the 171 MSM who reported having read the materials were significantly more likely to examine themselves (anus, adjusted prevalence ratio [aPR] 1.3, 95% confidence interval [CI] 1.15-1.52), mouth, penis and skin, and their partners' anus (aPR 1.3, 95% CI 1.03-1.73) and mouth (aPR 1.6, 95% CI 1.1-2.26). Further research is needed to determine whether educational materials affect early detection and treatment of primary and secondary syphilis and reduce transmission.

HIV-1 and herpes simplex virus type-2 genital shedding among co-infected women using self-collected swabs in Chiang Rai, Thailand.

We analysed 528 genital self-collected swabs (SCS) from 67 HIV-1 and herpes simplex virus type-2 (HSV-2) co-infected women collected during the placebo month of a randomized crossover clinical trial of suppressive acyclovir in Chiang Rai, Thailand. In this first longitudinal study of HIV-1 and HSV-2 co-infected women using genital SCS specimens, we found frequent mucosal HIV-1 shedding. Overall, 372 (70%) swabs had detectable HIV-1 RNA with median HIV-1 viral load of 2.61 log(10) copies/swab. We found no statistically significant association between detectable HIV-1 RNA and HSV-2 DNA in the same SCS specimen (adjusted odds ratio [aOR] 1.40; 95% confidence intervals [CI], 0.78-2.60, P = 0.25). Only baseline HIV-1 plasma viral load was independently associated with genital HIV-1 RNA shedding (aOR, 7.6; 95% CI, 3.3-17.2, P < 0.0001). SCS may be useful for future HIV-1 and HSV-2 studies because this method allows for frequent genital sampling, and inclusion of genital sites other than the cervix.

Screening of males for Chlamydia trachomatis and Neisseria gonorrhoeae infections at STD clinics in three US cities -- Indianapolis, New Orleans, Seattle.

We assessed prevalence and risk factor data for men routinely screened for Chlamydia trachomatis and Neisseria gonorrhoeae in STD clinics in four US cities from May 1995-March 1999. Data were analysed separately for 'test-visits' (self-reported symptoms, clinical signs or sexual contact to an STD) and 'screen-visits' (STD screen only) for 32,595 men with 45,390 visits. Among test-visits in Seattle, Indianapolis and New Orleans, 8.7% (807/9285), 15.3% (1305/8519), and 10.1% (1551/15,296) of men were positive for C. trachomatis, and 10.2% (773/7543), 24.9% (2108/8478), and 30.4% (4746/ 15,629) for N. gonorrhoeae. Among screen-visits, 2.1% (88/4103), 7.3% (130/1790), and 5.6% (292/5183) of men were positive for C. trachomatis, and 1.8% (46/2576), 1.7% (31/ 1786), and 5.2% (274/5235) for N. gonorrhoeae. Positivity for screen-visits was particularly high among young men (15-24 years), and those reporting > 1 sex partner in the past 60 days. Substantial variation among sites in positivity warrants local determination of prevalence and risk factors to inform screening strategies.

Amplification of the DNA polymerase I gene of Treponema pallidum from whole blood of persons with syphilis.

Previous reports suggest that Treponema pallidum bacteremia occurs in persons with syphilis exposure ('incubating syphilis') and in persons with primary or secondary syphilis. During a recent syphilis outbreak, whole blood samples from 32 persons with suspected syphilis or syphilis exposure were screened using polymerase chain reaction (PCR) to amplify the DNA polymerase I gene (polA) of T. pallidum. Of the 32 samples, polA was amplified from 13 (41%). Of these 13, three were determined to have incubating syphilis; two had primary or secondary syphilis and eight had latent syphilis. This study demonstrates that spirochetemia can occur throughout the course of T. pallidum infection.

Sexually transmitted diseases of older persons in Washington State.

BACKGROUND: Sexually transmitted diseases (STDs) in persons older than 50 years are rarely studied because STDs are more common in young people. Understanding the epidemiology of STDs in older persons is important for reducing STD morbidity and for improving STD care. GOAL: To understand the epidemiology of STDs in older persons. METHODS: Washington State's STD surveillance data from 1992 to 1998 were analyzed to describe the burden of STDs and source of care for these diseases in older persons. RESULTS: From 1992 to 1998, 1535 episodes of STDs were reported for 50- to 80-year-olds in Washington State, accounting for 1.3% of all reported STDs. The most common STDs were nongonococcal urethritis in men and genital herpes in women. As compared with younger persons, older individuals more frequently sought care at private clinics and had symptoms at the time of the clinic visit. CONCLUSIONS: Sexually transmitted diseases are reported among older persons, although at lower rates than among younger persons. Services for STD and counseling regarding safe sex should be available to persons of all ages.

Molecular subtyping of Treponema pallidum in an Arizona County with increasing syphilis morbidity: use of specimens from ulcers and blood.

A molecular-based subtyping system for Treponema pallidum was used during an investigation of increasing syphilis in Maricopa County, Arizona. Genital ulcer or whole blood specimens from patients with syphilis were assayed by a polymerase chain reaction (PCR) amplification of a T. pallidum DNA polymerase I gene. Positive specimens were typed on the basis of PCR amplification of 2 variable genes. In all, 41 (93%) of 44 of ulcer specimens and 4 (27%) of 15 blood specimens yielded typeable T. pallidum DNA. Twenty-four (53%) of 45 specimens were subtype 14f; other subtypes identified included 4f, 4i, 5f, 12a, 12f, 14a, 14d, 14e, and 14i. Only 2 specimens were from epidemiologically linked patients. This investigation demonstrates that multiple subtypes of T. pallidum can be found in an area with high syphilis morbidity, although 1 subtype (14f) was predominant. Four typeable specimens were from blood, a newly identified specimen source for subtyping.

HIV type 1 subtype E-infected patients with broadened, dual (B/E) V3 loop serology have increased cross-neutralizing antibodies.

The two prevalent subtypes of HIV-1 circulating in Thailand are subtypes E and B. While the most prevalent subtype continues to be E using molecular typing assays, immunologically, a subset of subtype E-infected patients (3.4% in 1997) have binding antibodies to both the E and B V3 loops in a peptide ELISA. To assess the potential function of this dual (B/E) V3 reactivity, plasmas from patients with genetically defined HIV-1 subtype E infection and either E or B/E V3 serotypes were compared for magnitude and breadth of neutralization of seven primary and laboratory-adapted subtype B and E viruses. Dually reactive (B/E) plasmas showed significantly increased cross-neutralizing activity against subtype B viruses (p < 0.001), and increased neutralization of the panel of viruses overall (p < 0.02), as compared to monoreactive E serotype plasmas. While the total envelope binding antibody titers to both subtype B and E envelopes did not differ significantly between the E and B/E plasmas, 67% of B/E plasmas neutralized >50% of the viruses in the panel, and only 14% of E plasmas showed this broadened neutralizing activity. These data suggest that dual (B/E) V3 loop reactivity may be a marker of broader immune recognition of HIV envelope epitopes in subtype E-infected patients. V3 loop antibody, perhaps in conjunction with antibodies to additional epitopes, may play a role in neutralization of virus isolates from Thailand.

Sexually transmitted diseases during pregnancy: screening, diagnostic, and treatment practices among prenatal care providers in Georgia.

BACKGROUND: Sexually transmitted diseases (STD) during pregnancy are associated with adverse outcomes. We conducted a prenatal care provider survey to determine STD screening, diagnosis, and treatment practices. METHODS: Standard questionnaires were mailed to Georgia-licensed obstetrician/ gynecologists, family practitioners, and nurse-midwives (N = 3,082) in 1998. RESULTS: Of the 1,300 care providers who returned the survey, 565 (44%) provided prenatal care, 390 (57%) were male, and 396 (70%) were obstetrician/ gynecologists. Overall, 553 prenatal care providers (98%) reported screening all pregnant patients for syphilis, 551 (98%) for hepatitis B, 501 (89%) for trichomonas, 474 (84%) for human immunodeficiency virus (HIV), 401 (71%) for gonorrhea, 403 (71%) for chlamydia, 475 (84%) for group B streptococci, and 130 (23%) for bacterial vaginosis (BV) (high risk). Less than 10% used amplification tests for chlamydia or gonorrhea. Most providers used appropriate regimens to treat STD in pregnant women. A written office policy on testing for BV or HIV was associated with increased screening. CONCLUSIONS: Provider education is needed about diagnosis and treatment of STD during pregnancy.

Repeat Chlamydia trachomatis infection in women: analysis through a surveillance case registry in Washington State, 1993-1998.

Repeat infections with Chlamydia trachomatis are associated with increased risk for long-term sequelae. The authors analyzed the frequency and predictors of repeat chlamydial infection by using a population-based chlamydia registry in Washington State and evaluated whether women would seek care at the same clinic for repeat infections. Among 32,698 women with an appropriately treated initial chlamydial infection during 1993-1998, 15% developed one or more repeat infections during a mean follow-up time of 3.4 years. Among women less than age 20 years at the time of initial infection, 6% were reinfected by 6 months, 11% by 1 year, and 17% by 2 years. Young age was the strongest predictor for one and two or more repeat infections after controlling for the length of follow-up and other variables. Only 36% of the repeat infections were diagnosed at the same clinical setting as the initial infection, and 50% were diagnosed at the same type of clinic. Adolescent girls had the least consistency in the source of care for chlamydia. This study suggests that efforts to prevent repeat chlamydial infection in young women remain an urgent public health priority and that the burden of repeat infection may be substantially higher than estimates from clinic-based studies.

A comparative study of the impact of HIV infection on natural killer cell number and function in Thais and North Americans.

Innate immunity may play a role in preventing HIV infection and progression to AIDS. Most studies of natural killer (NK) cell function have been conducted in populations with different HLA allele frequencies and HIV subtypes than those found in Southeast Asia. NK cell number and function, defined as CD3- cells expressing CD16+/CD56+ and the ability to lyse K562 cells, were enumerated in 42 HIV-seronegative Thais and 20 HIV-seronegative North Americans. The number and percentage of NK cells were similar for both groups, but cytotoxicity function expressed as lytic units (LU20) of NK cells was significantly greater in the Thai subjects compared with the North American subjects (p = 0.004). Comparisons were also conducted between the HIV-seronegative groups and HIV-infected subjects from both Thailand and North America. NK cell number and function were not significantly different between the Thai HIV-seronegative and -seropositive groups. However, the comparison between the North American HIV-seronegative and -seropositive subjects demonstrated profound impairment of NK cell number, percentage, and function (p < 0.001). Matching the Thai and North American HIV-infected subjects on CD4+ cell count revealed higher NK number and function in the Thai subjects (p < 0.001). The study indicates that NK function in both HIV-seronegative and -seropositive Thais is elevated relative to similar groups in North America.

Diversity of envelope glycoprotein from human immunodeficiency virus type 1 of recent seroconverters in Thailand.

The envelope-coding sequence of human immunodeficiency virus type 1 (HIV-1) was determined for 11 Thai seroconverters between 1995 and 1996. On the basis of the env sequences, all subjects were infected with HIV subtype E. Compared with the interpatient protein diversity among HIV-1 Thai reference sequences from 1990 to 1992 (4.4%), the diversity among the 1995-1996 seroconverters was approximately double (9.5%). The tetrapeptide tip of the V3 loop was invariant for 10 of the 11 seroconverters, and identical to that observed in sequences derived from the 1990-1992 group. However, in the V3 region, sequences from 2 of the 11 subjects demonstrated more than 5 amino acid changes relative to the reference strains. This may represent the "aging" of the HIV epidemic seen in other endemic regions. These findings may have substantial implications for vaccine development and evaluation for both HIV antibody and cytotoxic T lymphocyte repertoire recognition.

A phase I/II trial of HIV SF2 gp120/MF59 vaccine in seronegative thais.AFRIMS-RIHES Vaccine Evaluation Group. Armed Forces Research Institute of Medical Sciences and the Research Institute for Health Sciences.

Fifty-two human immunodeficiency virus type 1, seronegative Thai adults from the community were enrolled in a double-blind, placebo controlled, phase I/II trial of HIV SF2 gp120/MF59 vaccine to determine the safety and immunogenicity of this recombinant, B clade, HIV envelope protein vaccine. Twenty-six subjects were enrolled at each of two sites in Thailand, Bangkok and Chiang Mai. Twelve subjects received placebo and 40 subjects received vaccine (50 microg). Subjects were immunized according to one of two schedules, 0, 1 and 4 or 0, 1 and 6 months. The frequency of adverse reactions was not different between placebo and vaccine subjects, nor between immunization schedules. Of vaccinees, all developed high-titer binding antibody to the immunogen (rgp120), 39 developed neutralizing antibody (NA) responses against homologous virus (HIV-1(SF2)), and 22 developed NA against heterologous virus (HIV-1(MN)). No subject demonstrated intercurrent HIV infection, however screening EIA reactivity occurred in 27% of recipients. Thus, this candidate HIV vaccine was found to be safe and immunogenic in Thai adults, laying the foundation for development of a subtype E construct in this population.

Willingness to participate in HIV-1 vaccine trials among young Thai men.

OBJECTIVES: Willingness to participate in HIV-1 vaccine trials and associated factors were investigated in a sample of 2670 Royal Thai Army conscripted recruits. METHODS: Self administered questionnaires were used. Data were collected during the final visit of a longitudinal cohort study of HIV-1 epidemiology. Cross sectional analysis of data from this visit was performed. RESULTS: 32% of the respondents reported they would "definitely" join an HIV-1 vaccine trial. Greater willingness was associated with perceived risk of HIV-1 infection and a desire to help Thai society, although tangible incentives and intentions to reduce condom use in a vaccine trial also were associated with increased willingness. Concerns about physical harm and anticipated social pressure from family not to join were the most substantial impediments to willingness. Concerns about "social harm" (for example, participation would give appearance of having AIDS virus, a partner might refuse sex) also appeared to inhibit interest in joining trials and approached significance. CONCLUSIONS: Willingness to participate was somewhat greater than in other investigations of non-injection drug user (IDU) cohorts in Thailand, with fewer concerns expressed about physical harm. Motivations appear to involve tradeoffs among perceived risk, anticipated social pressure, altruism, and tangible rewards. The absence of significant problems associated with vaccine trials to date, along with the presence of educational interventions in the study may help explain the lower level of concerns here relative to other Thai studies.

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.

Nationwide surveillance of HIV-1 prevalence and subtype in young Thai men.

As part of routine surveillance, an HIV-1 serosurvey of 366,074 members of successive cohorts of young Thai men entering service with the Royal Thai Army (RTA) was conducted between November 1989 and November 1995. We analyzed regional and temporal trends in HIV-1 seroprevalence in young men in Thailand and determined the proportion of infections resulting from subtypes E and B in this population in 1992 and 1995. The prevalence in 1992 was compared with that in 1995 by region and demographic group. The HIV-1 subtype was determined in a random sample of HIV-1-positive specimens in 1992 and 1995 using a V3 peptide enzyme immunoassay. From a peak of 3.7% in 1993, overall seroprevalence declined to 3.0% in 1994 and further in 1995 to 2.5%. Between 1992 and 1995, the absolute decrease in seroprevalence was greatest in the upper North (from 12.5% to 5.3%), where the prevalence has been the highest. Overall, 96.9% and 95.9% of typable specimens were determined to be subtype E in 1992 and 1995, respectively. Decline in HIV-1 seroprevalence among young men in Thailand has continued, which suggests that HIV control programs in Thailand may have been successful in decreasing spread of HIV-1. Almost all HIV-1 infections resulted from subtype E.

Sexual behavior of young men in Thailand: regional differences and evidence of behavior change.

An anonymous, self-administered behavioral survey was conducted in Royal Thai Army (RTA) conscripts from 19 provinces throughout Thailand in May 1996. All (to a maximum of 350) Thai men who entered the RTA in each province were selected. Data from 5474 men were included in this analysis. High-risk behaviors were reported nationwide; however, some regional differences were found. Men from the upper North were more likely to have had a commercial sex worker (CSW) as their first sexual partner (42%) than men from any other region. However, in the past year, reported sex with CSWs in the upper North (41%) was similar to or lower than those in other regions. Consistent condom use with CSWs was higher in the North than in any other region. Condom use at first sex with CSWs increased with later years at first sex in all regions. These data suggest that past higher-risk behavior among young men in the upper northern part of Thailand may have contributed to the concentration of the HIV epidemic in that region. Risk behaviors, particularly unprotected sex, appear to be decreasing nationwide.

PIP: The HIV behavioral risk factors associated with temporal and regional trends in HIV prevalence were investigated in a 1996 survey of 5474 Royal Thai Army conscripts from 19 provinces. 89% of respondents were 21 years of age and 77% were single. HIV prevalence was highest among men from the upper north (4.3%), followed by 2.6% in the central region, 2.4% in Bangkok, and 1.2% in the southeast. The median age at first intercourse was 17 years. Among sexually experienced men, a significantly higher proportion of those from the upper north (42%) had their first such encounter with a commercial sex worker (CSW). However, sex with CSWs during the year preceding the survey was similar or less frequent among men from the upper north (41%) compared with other regions. Also, significantly more men from the upper north (62%) used condoms every time with a CSW. Overall, 10% (range, 8-12%) reported having had sex with a man and 13% reported symptoms of a sexually transmitted disease (STD). Men whose sexual initiation occurred after 1990 were more likely to use condoms with a CSW partner. The decrease in sexual risk factors documented in this survey is consistent with national declines in HIV prevalence, especially in the upper northern region, after 1992. The increase in condom use with CSWs coincides with the 100% condom campaign initiated in 1991, intensified STD control efforts, and the emergence of AIDS deaths. Sex with non-CSW female partners, where condoms are rarely used, and homosexual sex require attention as situations where HIV risk may persist.

Correlation of genetic and serologic approaches to HIV-1 subtyping in Thailand.

The aim of this study was to compare the performance of differential polymerase chain reaction (PCR) typing and peptide enzyme-linked immunosorbent assay (V3-EIA) for human immunodeficiency virus type 1 (HIV-1) subtyping in Thailand using heteroduplex mobility assay (HMA) as the reference standard. Paired peripheral blood mononuclear cells (PBMC) and sera were collected from 38 HIV-1 seropositive persons in Thailand. HMA was done by standard methods; differential PCR employs primer pairs that differentially amplify either subtype E or B. V3-EIA used peptides specific for subtypes E or B. Thirty-two cases (84%) were found by HMA to be infected with subtype E: and six with (16%) subtype B. The results obtained with differential PCR were 100% concordant with those of HMA; V3 EIA correctly predicted the subtype in 95% (36 of 38). Six samples that molecularly subtyped as E were repeatedly dual reactive by screening V3-EIA, but these resolved to subtype E using an antigen-limiting EIA. Two samples were serologically nontypeable because of overall low levels of V3 antibody. Using HMA as the standard, differential PCR was shown to subtype HIV-1 reliably from patient PBMC samples. V3-EIA correctly predicted HIV-1 subtype in most (95%) of our cases. Because of the less rigorous sampling requirements, specimen processing, and logistical and technical requirements of serotyping compared with molecular techniques, it appears to be practical for screening purposes in a field environment. Samples that cannot be definitively subtyped serologically should undergo differential PCR and antigen-limiting V3 EIA. These approaches to HIV-1 subtyping should be used in complementary fashion in Thailand, where subtypes B and E are currently known to cocirculate.