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.

Evolution of cervical cancer screening and prevention in United States and Canada: implications for public health practitioners and clinicians.

OBJECTIVE: Declines in cervical cancer incidence and mortality in Canada and in the United States have been widely attributed to the introduction of the Papanicolaou (Pap) test. This article reviews changes in screening and introduction of HPV vaccination. METHOD: Sentinel events in cervical cancer screening and primary prevention through HPV vaccination in the US and Canada are described. RESULTS: Despite commonalities, cervical cancer screening and prevention differ between the two countries. Canada has a combination of opportunistic and organized programs at the provincial and territorial level, while the US has opportunistic screening and vaccination systems. In the US, the HPV test along with the Pap test (co-testing) is part of national recommendations for routine cervical cancer screening for women age 30 and older. Co-testing is not being considered anywhere in Canada, but primary HPV testing is currently recommended (but not implemented) in one province in Canada. CONCLUSION: Many prevention strategies are available for cervical cancer. Continued public health efforts should focus on increasing vaccine coverage in the target age groups and cervical cancer screening for women at appropriate intervals. Ongoing evaluation will be needed to ensure appropriate use of health resources, as vaccinated women become eligible for screening.

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.

Human papillomavirus and HPV vaccines: a review.

Cervical cancer, the most common cancer affecting women in developing countries, is caused by persistent infection with "high-risk" genotypes of human papillomaviruses (HPV). The most common oncogenic HPV genotypes are 16 and 18, causing approximately 70% of all cervical cancers. Types 6 and 11 do not contribute to the incidence of high-grade dysplasias (precancerous lesions) or cervical cancer, but do cause laryngeal papillomas and most genital warts. HPV is highly transmissible, with peak incidence soon after the onset of sexual activity. A quadrivalent (types 6, 11, 16 and 18) HPV vaccine has recently been licensed in several countries following the determination that it has an acceptable benefit/risk profile. In large phase III trials, the vaccine prevented 100% of moderate and severe precancerous cervical lesions associated with types 16 or 18 among women with no previous infection with these types. A bivalent (types 16 and 18) vaccine has also undergone extensive evaluation and been licensed in at least one country. Both vaccines are prepared from non-infectious, DNA-free virus-like particles produced by recombinant technology and combined with an adjuvant. With three doses administered, they induce high levels of serum antibodies in virtually all vaccinated individuals. In women who have no evidence of past or current infection with the HPV genotypes in the vaccine, both vaccines show > 90% protection against persistent HPV infection for up to 5 years after vaccination, which is the longest reported follow-up so far. Vaccinating at an age before females are exposed to HPV would have the greatest impact. Since HPV vaccines do not eliminate the risk of cervical cancer, cervical screening will still be required to minimize cancer incidence. Tiered pricing for HPV vaccines, innovative financing mechanisms and multidisciplinary partnerships will be essential in order for the vaccines to reach populations in greatest need.

Transgenic overexpression of neuromedin U promotes leanness and hypophagia in mice.

Recent work has shown that neuromedin U (NmU), a peptide initially identified as a smooth muscle contractor, may play a role in regulating food intake and energy homeostasis. To further evaluate this putative function, we measured food intake, body weight, energy expenditure and glucose homeostasis in transgenic mice that ubiquitously overexpress murine proNmU. NmU transgenic mice were lighter and had less somatic and liver fat, were hypophagic, and had improved insulin sensitivity as judged by an intraperitoneal insulin tolerance test. Transgenic mice had higher levels of hypothalamic NPY, POMC and MCH mRNA. There was no difference in O2 consumption between genotypes; however, NmU transgenic mice displayed a modest increase in respiratory quotient during food deprivation and refeeding. There were no behavioral disturbances in the NmU transgenic mice that could account for the results (e.g. changes in locomotor activity). When placed on a high-fat diet, transgenic mice remained lighter than wild-type mice and ate less, but gained weight at a rate similar to wild-type mice. Despite the increased weight gain with high-fat feeding, glucose tolerance was significantly improved in the transgenic mice. These findings support the hypothesized role of NmU as an endogenous anorexigenic peptide.

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.

Evaluation of an early two-dose measles vaccination schedule.

Vaccination at 6 months of age followed by routine revaccination is recommended when exposure of infants to measles is likely. Dade County, Florida, began this early two-dose schedule during a large epidemic in 1986-1987 (i.e., 22% of cases occurred in infants aged 6-11 months). This schedule was continued routinely in high-risk areas. The effect of an early two-dose schedule on measles prevention in the county was examined by comparing measles vaccination coverage and epidemiology before (1985-1987) and after (1988-1996) the schedule became routine. To assess serologic response, seroprevalence of measles antibody among children aged 4-6 years in 1995 was examined. To evaluate vaccine effectiveness, a case-control study was conducted among preschool-aged children. Among those aged 2 years, vaccination coverage with > or =1 dose increased from 75% to 94% in 1996. The number of annual cases declined, and endemic measles transmission reportedly ended after 1993. Seroprevalence of plaque reduction neutralization antibody (titer > 1:120) among those receiving vaccination according to an early two-dose schedule and a single dose at age > or =12 months was 94% (95% confidence interval: 89, 98) and 98% (95% confidence interval: 95, 100). In these groups, vaccine effectiveness was comparably high. Early two-dose measles vaccination is associated with improved coverage and a comparably high level of humoral immunity and clinical protection as a single dose at age > or =12 months. This strategy can be useful in areas at high risk for measles among infants.

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.

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.

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.

HIV viral load in Thai men and women with subtype E infections.

The assessment of potential "breakthrough infections" in HIV vaccine trials requires knowledge of viral load in unvaccinated persons. Therefore, HIV-1 RNA was quantitated in plasma from Thai adults with subtype E infections. RNA was detectable (> or =500 copies/ml) in 93% of 255 specimens, with a mean (standard deviation) value of 4.09 (0.88) log copies/ml. The concentration of RNA was directly related to the presence of AIDS-defining illnesses, inversely related to CD4 count, and independent of gender after adjustment for CD4 count.

Incidence of herpes simplex virus type 2 infection in the United States.

Between the time that two large, national surveys were conducted, the Second National Health and Nutrition Examination Survey (1976-1980) and the Third National Health and Nutrition Examination Survey (1988-1994), prevalence of herpes simplex virus type 2 (HSV-2) infection in the United States increased by 30%. From these survey data, the authors estimated the incidence of HSV-2 infection in the civilian, noninstitutionalized population aged > or = 12 years by means of a mathematical model that allowed overall incidence to increase linearly with time but required the shape of the age-specific incidence curve to remain constant. From 1970 to 1985, annual incidence of HSV-2 infection in HSV-2-seronegative persons increased by 82%, from 4.6 per 1,000 (95% confidence interval: 4.2, 5.0) to 8.4 per 1,000 (95% confidence interval: 7.7, 9.1). Incidence in 1985 was higher in women than in men (9.9 vs. 6.9 per 1,000), higher in Blacks than in Whites (20.4 vs. 6.3 per 1,000), and highest in the group aged 20-29 years (14.6 and 22.5 per 1,000 in men and women, respectively). Thus, by 1985, approximately 1,640,000+/-150,000 persons (730,000 men and 910,000 women) were being infected annually with HSV-2.

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.

DTH responsiveness of HIV-infected Thai adults.

A study was carried out in Thailand to determine the frequency of reactivity to delayed-type hypersensitivity (DTH) skin tests used for the staging of HIV patients in the United States. A four-antigen panel which included tetanus toxoid (1:10), Candida (1:10), mumps and Trichophyton antigens was assessed in 221 adult subjects from across the full immunological spectrum of HIV disease. Complete anergy was found in 38 per cent of 73 subjects with CD4 counts of 0-200 cells/ml and in 6 per cent of 78 subjects with 201-400 cells/ml. Partial anergy (response to 1 of 4 antigens) was found in 26 per cent of the 0-200 cell/ml group and decreased progressively with increasing CD4 cell count. Results suggested that a 3-member recall antigen panel would provide nearly all the clinically useful information gained by the more standard 4-member panel. In conclusion, DTH skin testing was confirmed to provide a method of assessing the integrity of cellular immune function of HIV-infected Thai adults which correlated with disease progression.

Duration of untreated genital infections with chlamydia trachomatis: a review of the literature.

BACKGROUND: Estimates of the duration of untreated genital infections with Chlamydia trachomatis vary. Accurately estimating the distribution of the duration of infection would be useful in the counseling patients, and is essential when modeling the burden of chlamydial disease and the potential impact of prevention programs. GOAL: The authors review the scientific literature to summarize what is known about the duration of genital chlamydial infection and the factors that affect it. STUDY DESIGN: Literature review of animal and human studies. RESULTS: Animal studies document a longer duration of infection in primates than in mice or guinea pigs. Although animals spontaneously become culture negative over time, numerous studies document persistent nonculture evidence of chlamydiae in the upper genital tract. Studies in which women have been serially cultured suggest that most untreated infections remain culture positive for more than 60 days. Small series report that some infections may persist for years. Most infections eventually become culture negative; however, non-culture evidence of chlamydiae often persist in women with negative cultures. The duration of chlamydial infection is reduced in animals previously exposed to chlamydiae and in older humans, suggesting that partial immunity may result from exposure. Data are inadequate to define the median duration of untreated infection or to derive a curve that describes the natural history of untreated genital chlamydial infections. CONCLUSION: Current data do not allow one to reliably estimate the duration of genital infections with C trachomatis. Systematic retesting could help to better define the duration of infection in patients who, against medical advice, delay treatment for genital chlamydial infections.