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BACKGROUND: Except for public health case reports, the incidence of Zika virus (ZIKV), chikungunya virus (CHIKV), and dengue virus (DENV) infection are not available to assess the potential blood transfusion safety threat in Brazil. METHODS: Pools of 6 donation samples (MP6) left over from human immunodeficiency virus, hepatitis B virus, and hepatitis C virus nucleic acid testing were combined to create MP18 pools (3 MP6 pools). Samples were tested using the Grifols triplex ZIKV, CHIKV, and DENV real-time transcription mediated amplification assay to estimate prevalence of RNAemia and incidence, and to compare these results to case reports in São Paulo, Belo Horizonte, Recife, and Rio de Janeiro, from April 2016 through June 2019. RESULTS: ZIKV, CHIKV, and DENV RNAemia were found from donors who donated without overt symptoms of infection that would have led to deferral. The highest RNAemic donation prevalence was 1.2% (95% CI, .8%–1.9%) for DENV in Belo Horizonte in May 2019. Arbovirus infections varied by location and time of year, and were not always aligned with annual arbovirus outbreak seasons in different regions of the country. CONCLUSIONS: Testing donations for arboviruses in Brazil can contribute to public health. Transfusion recipients were likely exposed to ZIKV, CHIKV, and DENV viremic blood components during the study period.

BACKGROUND: Age-specific data on anal, and corresponding cervical, human papillomavirus (HPV) infection are needed to inform female anal cancer prevention. METHODS: We centrally reanalyzed individual-level data from 26 studies reporting HPV prevalence in paired anal and cervical samples by human immunodeficiency virus (HIV) status and age. For women with HIV (WWH) with anal high-grade squamous intraepithelial lesions or worse (HSIL+), we also investigated concurrent cervical cytopathology. RESULTS: In HIV-negative women, HPV16 prevalence decreased significantly with age, both at anus (4.3% at 15–24 years to 1.0% at ≥55 years; p(trend) = 0.0026) and cervix (7.4% to 1.7%; p(trend) < 0.0001). In WWH, HPV16 prevalence decreased with age at cervix (18.3% to 7.2%; p(trend) = 0.0035) but not anus (11.5% to 13.9%; p(trend) = 0.5412). Given anal HPV16 positivity, concurrent cervical HPV16 positivity also decreased with age, both in HIV-negative women (p(trend) = 0.0005) and WWH (p(trend) = 0.0166). Among 48 WWH with HPV16-positive anal HSIL+, 27 (56%) were cervical high-risk HPV-positive, including 8 with cervical HPV16, and 5 were cervical HSIL+. CONCLUSIONS: Age-specific shifts in HPV16 prevalence from cervix to anus suggest that HPV infections in the anus persist longer, or occur later in life, than in the cervix, particularly in WWH. This is an important consideration when assessing the utility of cervical screening results to stratify anal cancer risk.

Quantitative enzyme-linked immunosorbent assays were used to measure interleukin (IL)-2, IL-10, and IL-12 in cervical secretions from female adolescents with and without sexually transmitted infections. Compared with human immunodeficiency virus [HIV]-negative patients, HIV-positive patients had higher concentrations of IL-10 (118.2 pg/mL vs. 34.5 pg/mL; P=.002) and IL-12 (175.5 pg/mL vs. 85.1; P=.03). IL-2 concentrations were not statistically different. Furthermore, genital tract infections were predictors of IL-10 and IL-12 concentrations. Coinfection with HIV and human papillomavirus predicted the highest IL-10 concentrations; coinfection with HIV, human papillomavirus, and other sexually transmitted pathogens predicted the highest IL-12 concentrations. The data indicate that concomitant infection of the genital tract with HIV and other viral, bacterial, or protozoan pathogens influences the local concentrations of some immunoregulatory cytokines.

Background. Human papillomavirus type 58 (HPV-58) accounts for a much higher proportion of cervical cancers in East Asia than other types. A classification system of HPV-58, which is essential for molecular epidemiological study, is lacking. Methods and results. This study analyzed the sequences of 401 isolates collected from 15 countries and cities. The 268 unique concatenated E6-E7-E2-E5-L1-LCR sequences that comprised 57% of the whole HPV-58 genome showed 4 distinct clusters. L1 and LCR produced tree topologies that best resembled the concatenated sequences and thus are the most appropriate surrogate regions for lineage classification. Moreover, short fragments from L1 (nucleotides 6014–6539) and LCR (nucleotides 7257–7429 and 7540–52) were found to contain sequence signatures informative for lineage identification. Lineage A was the most prevalent lineage across all regions. Lineage C was more frequent in Africa than elsewhere, whereas lineage D was more prevalent in Africa than in Asia. Among lineage A variants, sublineage A2 dominated in Africa, the Americas, and Europe, but not in Asia. Sublineage A1, which represents the prototype that originated from a patient with cancer, was rare worldwide except in Asia. Conclusions. HPV-58 can be classified into 4 lineages that show some degree of ethnogeographic predilection in distribution. The evolutionary, epidemiological, and pathological characteristics of these lineages warrant further study.

Background. The risk of developing the human papillomavirus (HPV)- associated precancer high-grade squamous intraepithelial lesion (HSL) in human immunodeficiency virus (HIV)-infected adolescents is unknown. We examined the risk of developing HSIL among adolescents with and without HIV infection. Methods. HIV-infected (n = 172) and -uninfected (n = 84) girls aged 13-18 years who were participating in a multicenter study of primarily horizontally acquired HIV infections in adolescents (Reaching for Excellence in Adolescent Health Care) and who did not have HSIL on cytologic examination at study entry or at the first follow-up visit were followed at 6-month intervals. HIV-uninfected girls were recruited for comparison in a 2:1 ratio (HIV infected:HIV uninfected) The primary outcome was cytologic diagnosis of HSIL confirmed by expert review. Results. Incidence of HSIL by the end of follow-up was higher for HIV-infected girls than for HIV-uninfected girls (21.5% vs. 4.8% respectively). In multivariate analysis use of hormonal (either estrogen/progesterone oral combination or medroxyprogesterone acetate intramuscular) contraceptives high cervical mucous concentrations of interleukin (IL)-12 a positive HPV test and persistent low-grade squamous intraepithelial lesion (LSIL) were significantly associated with the development of HSIL. Conclusions. The incidence of HSIL was alarmingly high in HIV-infected adolescent girls. However when other predictors were considered in multivariate analysis HIV status was not retained in the model. The heightened risk for HSIL associated with persistent LSIL underscores the need to closely monitor HIV-infected adolescents with LSIL. The risk for HSIL associated with high concentrations of IL-12 may be suggestive of a local immune dysregulation. The role of hormonal contraception as a risk factor deserves further investigation. (authors)

Background. High rates of persistence of human papillomavirus (HPV) infection have been reported for adult women with human immunodeficiency virus (HIV) infection. Although most women are first infected with HPV during adolescence, persistence of specific HPV types has not been carefully examined among HIV-infected adolescents. The objective of this study was to examine the rates of and risk factors for persistence of HPV types among HIV-infected and -uninfected adolescent girls. Methods. This is a prospective cohort study of female adolescents, aged 13-18 years, participating in the Reaching for Excellence in Adolescent Care and Health project, a national study of HIV-infected and -uninfected adolescents. The main outcome measured was type-specific loss of initial HPV DNA detected. Loss of HPV DNA was defined for the following categories of HPV DNA types: low risk, which included types 6, 11, 42, 44, 54, 40, 13, 32, 62, 72, 2, 57, and 55; and high risk, which included types 16-like (16, 31, 33, 35, 52, 58, and 67), 18-like (18, 39, 45, 59, 68, 70, 26, 69, and 51), and 56-like (56, 53, and 66). Results. Prevalent or incident HPV infection was detected in 334 girls. When type-specific loss of HPV was examined, HIV-uninfected girls had a shorter mean time to loss of initial infection than did HIV-infected girls (403 days vs. 689 days, respectively; P

The objective of this study was to examine factors, including human immunodeficiency virus (HIV) infection, associated with ectopy among adolescent girls aged 12‐20 years who were participating in an ongoing study of HIV infection in adolescents. Samples for detection of bacterial vaginosis, Chlamydia trachomatis, and Neisseria gonorrhoeae and a high-resolution photograph of the cervix for ectopy measurement were collected. Ectopy data for 189 and 92 HIV-positive and -negative adolescents, respectively, were examined. Although univariate analysis found HIV infection and oral contraceptive use to be associated with the amount of ectopy, multivariate logistic regression analysis showed that only number of lifetime sex partners was a significant predictor, with more partners associated with less ectopy (odds ratio, 0.47; 95% confidence interval, 0.22‐1.00; ). In summary, adolescent girls with greater P p .05 numbers of lifetime sex partners were more likely to have mature cervixes (less ectopy). HIV infection was not independently associated with ectopy. “Ectopy” refers to the area of the ectocervix lined by columnar epithelium. Columnar epithelium lines the endocervix and, in many women, extends onto the proximal portion of the cervix immediately adjacent to the multilayer squamous epithelium, forming a visible squamocolumnar junction. Because of its thin, vascularized epithelium, the area of ectopy is fragile, and blood vessels lie in close contact with the vaginal environment [1]. This creates easy access to blood and lymphatic systems, possibly diminishing mucosal barriers to sexually transmitted infections. Several studies have shown that the area of cervical ectopy, or cervical immaturity, is associated with increased risk for human

Our cross-sectional study suggested that cytotoxic T lymphocyte (CTL) responses have a protective effect in squamous intraepithelial lesion (SIL) development. More CTL responses in women with human papillomavirus type 16 (HPV 16) infection without SILs than with SILs were detected. In the current longitudinal study, the role of CTL in clearing HPV 16 infection in women without SILs was investigated. Women with HPV 16 infection (n=51) were enrolled, along with HPV 16-negative control women (n=3). Twenty-two (55%) of 40 women who cleared HPV 16 infection had an E6 CTL response at least once, compared with none of 9 women who had HPV 16 persistence (P=.003). Such a difference was not demonstrated for E7; 25 (63%) of 40 women who cleared HPV 16 infection responded, versus 5 (56%) of 9 women with persistence (P=.720). It appears that lack of response to E6 is important in the persistence of HPV 16 infection.

Cytotoxic T lymphocyte (CTL) responses to the human papillomavirus (HPV) type 16 E6 and E7 proteins were measured in 20 women with known HPV and cervical disease status. CTL assays were performed after stimulation with E6 or E7 fusion proteins using autologous B lymphoblastoid cells infected with vaccinia viruses expressing E6 or E7. CTL responses to E6 and E7 were detected in 6 (75%) of 8 and 5 (56%) of 9 HPV-16-positive women without cervical intraepithelial neoplasia (CIN), respectively. Responses to E6 or E7 were each detected in only 2 (29%) of 7 HPV-16-positive women with CIN. Responses to both antigens were found in 63% of women without CIN and 14% of those with CIN. CTL responses to E6 or E7 are more commonly detectable in HPV-16-positive women without CIN than in HPV-16-positive women with CIN, suggesting that CTL response may play a role in disease protection.

This study examined the accuracy of samples obtained by women with Dacron swabs for testing for human papillomavirus (HPV). A total of 114 women obtained samples with the swabs and then had routine pelvic examinations done by nurse practitioners during which endocervical and exocervical samples were obtained by speculum-assisted technique. These samples were used for HPV DNA testing and cytology. The results of both sets of samples were compared. A total of 104 samples (91%) obtained by self-sampling were concordant with those obtained by speculum-assisted technique. Thus, self-sampling with a Dacron swab appears to be an accurate and noninvasive method for obtaining samples for HPV DNA testing.