ResearchPad - sexually-transmitted-diseases https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Serum and cervicovaginal IgG immune responses against α7 and α9 HPV in non-vaccinated women at risk for cervical cancer: Implication for catch-up prophylactic HPV vaccination]]> https://www.researchpad.co/article/elastic_article_15726 Cervical cancer associated with high risk-human papillomavirus (HR-HPV) infection is becoming the one of the most common female cancer in many sub-Saharan African countries. First-generation immigrant African women living in Europe are at-risk for cervical cancer, in a context of social vulnerability, with frequent lack of cervical cancer screening and HPV vaccination.ObjectiveOur objective was to address immunologically the issue of catch-up prophylactic HPV vaccination in first-generation African immigrant women living in France.MethodsIgG immune responses and cross-reactivities to α7 (HPV-18, -45 and -68) and α9 (HPV-16, -31, -33, -35, -52 and -58) HPV types, including 7 HR-HPV targeted by the Gardasil-9® prophylactic vaccine, were evaluated in paired serum and cervicovaginal secretions (CVS) by HPV L1-virus-like particles-based ELISA. Genital HPV were detected by multiplex real time PCR (Seegene, Seoul, South Korea).ResultsFifty-one immigrant women (mean age, 41.7 years; 72.5% HIV-infected) were prospectively included. More than two-third (68.6%) of them carried genital HPV (group I) while 31.4% were negative (group II). The majority (90.2%) exhibited serum IgG to at least one α7/α9 HR-HPV. Serum HPV-specific IgG were more frequently detected in group I than group II (100% versus 68.7%; P = 0.002). The distribution of serum and genital HPV-specific IgG was similar, but mean number of IgG reactivities to α7/α9 HR-HPV was higher in serum than CVS (5.6 IgG per woman in serum versus 3.2 in CVS; P<0.001). Rates of IgG cross-reactivities against HPV different from detected cervicovaginal HPV were higher in serum and CVS in group I than group II. Finally, the majority of groups I and II women (68.6% and 68.7%, respectively) exhibited serum or cervicovaginal IgG to Gardasil-9® HR-HPV, with higher mean rates in group I than group II (6.1 Gardasil-9® HR-HPV per woman versus 1.4; P<0.01). One-third (31.2%) of group II women did not show any serum and genital HPV-specific IgG.ConclusionsAround two-third of first-generation African immigrant women living in France showed frequent ongoing genital HPV infection and high rates of circulating and genital IgG to α7/α9 HPV, generally cross-reacting, avoiding the possibility of catch-up vaccination. Nevertheless, about one-third of women had no evidence of previous HPV infection, or showed only low levels of genital and circulating HR-HPV-specific IgG and could therefore be eligible for catch-up vaccination. ]]> <![CDATA[Modulation of T helper 1 and T helper 2 immune balance in a murine stress model during <i>Chlamydia muridarum</i> genital infection]]> https://www.researchpad.co/article/elastic_article_14727 A murine model to study the effect of cold-induced stress (CIS) on Chlamydia muridarum genital infection and immune response has been developed in our laboratory. Previous results in the lab show that CIS increases the intensity of chlamydia genital infection, but little is known about the effects and mechanisms of CIS on the differentiation and activities of CD4+ T cell subpopulations and bone marrow-derived dendritic cells (BMDCs). The factors that regulate the production of T helper 1 (Th1) or T helper 2 (Th2) cytokines are not well defined. In this study, we examined whether CIS modulates the expressions of beta-adrenergic receptor (β-AR), transcription factors, hallmark cytokines of Th1 and Th2, and differentiation of BMDCs during C. muridarum genital infection in the murine model. Our results show that the mRNA level of the beta2-adrenergic receptor (β2-AR) compared to β1-AR and β3-AR was high in the mixed populations of CD4+ T cells and BMDCs. Furthermore, we observed decreased expression of T-bet, low level of Interferon-gamma (IFN-γ) production, increased expression of GATA-3, and Interleukin-4 (IL-4) production in CD4+ T cells of stressed mice. Exposure of BMDCs to Fenoterol, β2-AR agonist, or ICI118,551, β2-AR antagonist, revealed significant β2-AR stimulation or inhibition, respectively, in stressed mice. Moreover, co-culturing of mature BMDCs and naïve CD4+ T cells increased the production of IL-4, IL-10, L-17, and IL-23 cytokines, suggesting that stimulation of β2-AR leads to the increased production of Th2 cytokines. Overall, our results show for the first time that CIS promotes the switching from a Th1 to Th2 cytokine environment. This was evidenced in the murine stress model by the overexpression of GATA-3 concurrent with elevated IL-4 production, reduced T-bet expression, and IFN-γ secretion.

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<![CDATA[Confidential, accessible point-of-care sexual health services to support the participation of key populations in biobehavioural surveys: Lessons for Papua New Guinea and other settings where reach of key populations is limited]]> https://www.researchpad.co/article/elastic_article_14720 To achieve the UNAIDS 90-90-90 targets at a national level, many countries must accelerate service coverage among key populations. To do this, key population programs have adopted methods similar to those used in respondent-driven sampling (RDS) to expand reach. A deeper understanding of factors from RDS surveys that enhance health service engagement can improve key population programs. To understand the in-depth lives of key populations, acceptance of expanded point-of-care biological testing and determine drivers of participation in RDS surveys, we conducted semi-structured interviews with 111 key population participants (12–65 years) were purposefully selected from six biobehavioral surveys (BBS) in three cities in Papua New Guinea. Key populations were female sex workers, men who have sex with men, and transgender women. Four reasons motivated individuals to participate in the BBS: peer referrals; private, confidential, and stigma-free study facilities; “one-stop shop” services that provided multiple tests and with same-day results, sexually transmitted infection treatment, and referrals; and the desire to know ones’ health status. Biobehavioral surveys, and programs offering key population services can incorporate the approach we used to facilitate key population engagement in the HIV cascade.

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<![CDATA[Vulnerability profiles and prevalence of HIV and other sexually transmitted infections among adolescent girls and young women in Ethiopia: A latent class analysis]]> https://www.researchpad.co/article/elastic_article_14613 Adolescent girls and young women (AGYW) aged 15–24 years have among the highest risk for HIV and other sexually transmitted infections (STI) across sub-Saharan Africa. A latent class analysis (LCA) was conducted to identify intersecting social- and structural-level determinants of HIV/STI acquisition among AGYW in Ethiopia.MethodsAGYW were recruited from venues using time-location sampling, completing an interviewer-administered behavioral survey and biological testing for HIV, syphilis, and chlamydia. LCA was used to identify distinct groups, defined by social- and structural-level determinants of HIV/STI risk, among AGYW. Prevalence ratios (PR) and 95% confidence intervals (CI) compared differences in HIV/STI prevalence by group.ResultsA total of 1,501 AGYW were enrolled across Addis Ababa (March–May 2018) and Gambella (June–July 2019). We identified three patterns of vulnerability defined by schooling status, migration history, food insecurity, orphan status, social support, and employment. We labeled these groups as “highly vulnerable” (representing ~21% of the population), “stable, out-of-school, migrated” (~42%), and “stable, in-school, never migrated” (~37%). STI prevalence was nearly two-fold higher among AGYW in the “highly vulnerable” group compared to AGYW in the “stable, in-school, never migrated” group (PR 1.93; 95% CI 1.33, 2.80).ConclusionsCharacterizing patterns of vulnerability among AGYW that reflect higher-level social and structural factors can help facilitate early identification of AGYW at the highest risk of HIV/STI acquisition, thus differentiating groups of AGYW who may most benefit from targeted HIV prevention interventions during adolescence and early adulthood. ]]> <![CDATA[Feasibility of establishing an HIV vaccine preparedness cohort in a population of the Uganda Police Force: Lessons learnt from a prospective study]]> https://www.researchpad.co/article/Ne890bb8a-5661-4c39-82f7-6f40a2e69675

Background

Members of uniformed armed forces are considered to be at high risk for HIV infection and have been proposed as suitable candidates for participation in HIV intervention studies. We report on the feasibility of recruitment and follow up of individuals from the community of the Uganda Police Force (UPF) for an HIV vaccine preparedness study.

Methods

HIV-negative volunteers aged 18–49 years, were identified from UPF facilities situated in Kampala and Wakiso districts through community HIV counselling and testing. Potential volunteers were referred to the study clinic for screening, enrolment and quarterly visits for one year. HIV incidence, retention rates were estimated and expressed as cases per 100 person years of observation (PYO). Rate ratios were used to determine factors associated with retention using Poisson regression models.

Results

We screened 560 to enroll 500 volunteers between November 2015 and May 2016. One HIV seroconversion occurred among 431 PYO, for an incidence rate of 0.23/100 PYO (95% confidence interval [CI]: 0.03–1.64). Overall, retention rate was 87% at one year, and this was independently associated with residence duration (compared to <1 year, 1 to 5 years adjusted rate ratio (aRR) = 1.19, 95%CI: 1.00–1.44); and >5 years aRR = 1.34, 95%CI: 0.95–1.37); absence of genital discharge in the last 3 months (aRR = 1.97, 95% CI: 1.38–2.83, absence of genital ulcers (aRR = 1.90, 95%CI: 1.26–2.87, reporting of new sexual partner in the last month (aRR = 0.57, 95%CI: 0.45–0.71, being away from home for more than two nights (aRR = 1.27, 95%CI: 1.04–1.56, compared to those who had not travelled) and absence of knowledge on HIV prevention (aRR = 2.67, 95%CI: 1.62–4.39).

Conclusions

While our study demonstrates the feasibility of recruiting and retaining individuals from the UPF for HIV research, we did observe lower than anticipated HIV incidence, perhaps because individuals at lower risk of HIV infection may have been the first to come forward to participate or participants followed HIV risk reduction measures. Our findings suggest lessons for recruitment of populations at high risk of HIV infection.

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<![CDATA[Antibiotic use for Australian Aboriginal children in three remote Northern Territory communities]]> https://www.researchpad.co/article/N999fa4e6-a15c-456a-862e-2e1ce88316a9

Objective

To describe antibiotic prescription rates for Australian Aboriginal children aged <2 years living in three remote Northern Territory communities.

Design

A retrospective cohort study using electronic health records.

Setting

Three primary health care centres located in the Katherine East region.

Participants

Consent was obtained from 149 mothers to extract data from 196 child records. There were 124 children born between January 2010 and July 2014 who resided in one of the three chosen communities and had electronic health records for their first two years of life.

Main outcome measures

Antibiotic prescription rates, factors associated with antibiotic prescription and factors associated with appropriate antibiotic prescription.

Results

There were 5,675 Primary Health Care (PHC) encounters for 124 children (median 41, IQR 25.5, 64). Of the 5,675 PHC encounters, 1,542 (27%) recorded at least one infection (total 1,777) and 1,330 (23%) had at least one antibiotic prescription recorded (total 1,468). Children had a median five (IQR 2, 9) prescriptions in both their first and second year of life, with a prescription rate of 5.99/person year (95% CI 5.35, 6.63). Acute otitis media was the most common infection (683 records, 38%) and Amoxycillin was the most commonly prescribed antibiotic (797 prescriptions, 54%). Of the 1,468 recorded prescriptions, 398 (27%) had no infection recorded and 116 (8%) with an infection recorded were not aligned with local treatment guidelines.

Conclusion

Prescription rates for Australian Aboriginal children in these communities are significantly higher than that reported nationally for non-Aboriginal Australians. Prescriptions predominantly aligned with treatment guidelines in this setting where there is a high burden of infectious disease.

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<![CDATA[Urea-mediated dissociation alleviate the false-positive Treponema pallidum-specific antibodies detected by ELISA]]> https://www.researchpad.co/article/5c8823e2d5eed0c484639234

The serological detection of antibodies to Treponema pallidum is essential to the diagnosis of syphilis. However, for the presence of cross-reaction, the specific antibody tests [e.g., enzyme-linked immunosorbent assay (ELISA)] always have false-positive results. In this study, we derived and validated the dissociation of urea in an attempt to alleviate the situation of false-positive antibodies to T. pallidum detected by ELISA. Six serum samples that were false-positive antibodies to T. pallidum detected by ELISA, and 16 control serum samples (8 sera positive for both specific IgG and IgM, and 8 IgG-positive and IgM-negative sera) were collected to select the appropriate dissociated concentration and time of urea. Our goal was to establish improved an ELISA method based on the original detection system of ELISA. The sensitivity of the improved ELISA was evaluated by 275 serum samples with class IgM-positive antibodies to T. pallidum. At 6 mol/L with 10 minutes dissociation of urea, 6 samples with false-positive antibodies to T. pallidum were converted to negative, and compared with true-positive antibodies to T. pallidum. The sensitivity of the improved ELISA was 100% by detecting the class IgM-positive antibodies to T. pallidum in sera of patients with syphilis. Considering the importance at the diagnosis of syphilis, antibodies to T. pallidum in serum samples should be retested by the improved ELISA method to avoid false-positive results.

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<![CDATA[Profile of the tprK gene in primary syphilis patients based on next-generation sequencing]]> https://www.researchpad.co/article/5c784fecd5eed0c484007915

Background

The highly variable tprK gene of Treponema pallidum has been acknowledged to be one of the mechanisms that causes persistent infection. Previous studies have mainly focused on the heterogeneity in tprK in propagated strains using a clone-based Sanger approach. Few studies have investigated tprK directly from clinical samples using deep sequencing.

Methods/Principal findings

We conducted a comprehensive analysis of 14 primary syphilis clinical isolates of T. pallidum via next-generation sequencing to gain better insight into the profile of tprK in primary syphilis patients. Our results showed that there was a mixture of distinct sequences within each V region of tprK. Except for the predominant sequence for each V region as previously reported using the clone-based Sanger approach, there were many minor variants of all strains that were mainly observed at a frequency of 1–5%. Interestingly, the identified distinct sequences within the regions were variable in length and differed by only 3 bp or multiples of 3 bp. In addition, amino acid sequence consistency within each V region was found among the 14 strains. Among the regions, the sequence IASDGGAIKH in V1 and the sequence DVGHKKENAANVNGTVGA in V4 showed a high stability of inter-strain redundancy.

Conclusions

The seven V regions of the tprK gene in primary syphilis infection demonstrated high diversity; they generally contained a high proportion sequence and numerous low-frequency minor variants, most of which are far below the detection limit of Sanger sequencing. The rampant variation in each V region was regulated by a strict gene conversion mechanism that maintained the length difference to 3 bp or multiples of 3 bp. The highly stable sequence of inter-strain redundancy may indicate that the sequences play a critical role in T. pallidum virulence. These highly stable peptides are also likely to be potential targets for vaccine development.

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<![CDATA[Infectious human adenoviruses are shed in urine even after disappearance of urethral symptoms]]> https://www.researchpad.co/article/5c8977a3d5eed0c4847d322b

Background

Urethritis is a common sexually transmitted disease, and human adenoviruses (HAdVs) have been found to be associated with nonchlamydial nongonococcal urethritis. However, the level and viability of HAdV in the urine of patients with urethritis remain unclear.

Methods

Male patients with urethritis and an asymptomatic group were screened using their First-void urine (FVU) for urethritis-related pathogens to identify those with HAdV DNA. FVU and gargle fluid were collected from all patients including from those in the asymptomatic group. A swab of eye discharge was also collected from patients with eye symptoms. The pharyngeal and/ or ocular fluid was also screened only in cases in which FVU was positive for HAdV DNA. HAdVs were isolated using A549 cell lines and typed by sequencing, and viral shedding during 2 years was quantified using real-time PCR. The prevalence of HAdV was assessed in the urethritis and asymptomatic groups, and viral load, isolated HAdV types, and urethral symptoms were compared between the groups.

Results

The positive detection rate of HAdV DNA was significantly higher in the urethritis group than in the asymptomatic group. Of 398 patients with urethritis, HAdV was isolated in all 32 cases (23 cases in which only HAdV DNA was detected with a mean of 2 × 109 copies/mL in urine samples). Of 124 control cases, one had HAdV monoinfection. The most frequently detected HAdV type was 56, followed by types 37 and 64. Regarding the relationship between symptoms and isolated HAdVs, the virus was isolated for up to 12 days after urethritis symptoms disappeared.

Conclusions

HAdVs were significantly detected and isolated from the FVU of patients with urethritis. Furthermore, high levels of infectious HAdVs are excreted in urine for a long period even after urethritis symptoms disappear.

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<![CDATA[PML nuclear body-residing proteins sequentially associate with HPV genome after infectious nuclear delivery]]> https://www.researchpad.co/article/5c7d95e9d5eed0c484734f7e

Subnuclear promyelocytic leukemia (PML) nuclear bodies (NBs) are targeted by many DNA viruses after nuclear delivery. PML protein is essential for formation of PML NBs. Sp100 and Small Ubiquitin-Like Modifier (SUMO) are also permanently residing within PML NBs. Often, large DNA viruses disassemble and reorganize PML NBs to counteract their intrinsic antiviral activity and support establishment of infection. However, human papillomavirus (HPV) requires PML protein to retain incoming viral DNA in the nucleus for subsequent efficient transcription. In contrast, Sp100 was identified as a restriction factor for HPV. These findings suggested that PML NBs are important regulators of early stages of the HPV life cycle. Nuclear delivery of incoming HPV DNA requires mitosis. Viral particles are retained within membrane-bound transport vesicles throughout mitosis. The viral genome is released from transport vesicles by an unknown mechanism several hours after nuclear envelope reformation. The minor capsid protein L2 mediates intracellular transport by becoming transmembranous in the endocytic compartment. Herein, we tested our hypothesis that PML protein is recruited to incoming viral genome prior to egress from transport vesicles. High-resolution microscopy revealed that PML protein, SUMO-1, and Sp100 are recruited to incoming viral genomes, rather than viral genomes being targeted to preformed PML NBs. Differential immunofluorescent staining suggested that PML protein and SUMO-1 associated with transport vesicles containing viral particles prior to egress, implying that recruitment is likely mediated by L2 protein. In contrast, Sp100 recruitment to HPV-harboring PML NBs occurred after release of viral genomes from transport vesicles. The delayed recruitment of Sp100 is specific for HPV-associated PML NBs. These data suggest that the virus continuously resides within a protective environment until the transport vesicle breaks down in late G1 phase and imply that HPV might modulate PML NB assembly to achieve establishment of infection and the shift to viral maintenance.

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<![CDATA[Antiretroviral adherence and virologic suppression in partnered and unpartnered HIV-positive individuals in southern Brazil]]> https://www.researchpad.co/article/5c803c70d5eed0c484ad896d

Background

An undetectable serum HIV-1 load is key to effectiveness of antiretroviral (ARV) therapy, which depends on adherence to treatment. We evaluated factors possibly associated with ARV adherence and virologic response in HIV-infected heterosexual individuals.

Methods

A cross-sectional study was conducted in 200 HIV-1 serodiscordant couples and 100 unpartnered individuals receiving ARV treatment at a tertiary hospital in southern Brazil. All subjects provided written informed consent, answered demographic/behavioral questionnaires through audio computer-assisted self-interviews (ACASI), and collected blood and vaginal samples for biological markers and assessment of sexually transmitted infections (STIs). HIV-negative partners were counseled and tested for HIV-1.

Results

The study population mean age was 39.9 years, 53.6% were female, 62.5% were Caucasian, 52.6% had incomplete or complete elementary education, 63.1% resided in Porto Alegre. Demographic, behavioral and biological marker characteristics were similar between couples and single individuals. There was an association between adherence reported on ACASI and an undetectable serum viral load (P<0.0001). Logistic regression analysis demonstrated that single-tablet ARV-regimens were independently associated with adherence (OR = 2.3; 95CI%: 1.2–4.4; P = 0.011) after controlling for age, gender, education, marital status, personal income, ARV regimen, and median time of ARV use. A positive correlation between genital secretion PCR results and serum viral load was significant in the presence of STIs (r = 0.359; P = 0.017). Although HIV PCR detection in vaginal secretions was more frequent in women with detectable viremia (9/51, 17.6%), it was also present in 7 of 157 women with undetectable serum viral loads (4.5%), p = 0.005.

Conclusions

ARV single tablet regimens are associated with adherence. Detectable HIV-1 may be present in the genital secretions of women with undetectable viremia which means there is potential for HIV transmission in adherent individuals with serologic suppression.

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<![CDATA[Chlamydia trachomatis infection among patients attending sexual and reproductive health clinics: A cross-sectional study in Bao'an District, Shenzhen, China]]> https://www.researchpad.co/article/5c75ac92d5eed0c484d08a5a

This study aimed to estimate the prevalence of chlamydial trachomatis (CT) infection and explore its risk factors among patients attending sexual and reproductive health clinics in Shenzhen, China. We collected demographic and clinical information from attendees (aged 18–49). CT and Neisseria gonorrhoeae (NG) infection was determined by nucleic acid amplification test (NAAT) on self-collected urine specimens. Of 1,938 participants recruited, 10.3% (95% confidence interval [CI]: 9.6%-11.0%) tested positive for CT. Prevalence was similar between men (10.6% [85/804]; 95% CI, 9.5%–11.7%) and women (10.1% [115/1134]; 95% CI: 9.2%–11.0%). Being 18–25 years old (adjusted odds ratio [aOR] = 2.52; 95%CI:1.35–4.71), never tested for CT before (aOR = 2.42; 95%CI: 1.05–5.61) and infected with NG(aOR = 3.87; 95%CI: 2.10–7.10) were independently associated with CT infection. We found that CT infection is prevalent among patients attending sexual and reproductive health clinics in Shenzhen, China. A comprehensive program including CT screening, surveillance and treatment is urgently needed.

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<![CDATA[Visual cues that predict intuitive risk perception in the case of HIV]]> https://www.researchpad.co/article/5c76fe53d5eed0c484e5b8b2

Field studies indicate that people may form impressions about potential partners’ HIV risk, yet lack insight into what underlies such intuitions. The present study examined which cues may give rise to the perception of riskiness. Towards this end, portrait pictures of persons that are representative of the kinds of images found on social media were evaluated by independent raters on two sets of data: First, sixty visible cues deemed relevant to person perception, and second, perceived HIV risk and trustworthiness, health, and attractiveness. Here, we report correlations between cues and perceived HIV risk, exposing cue-criterion associations that may be used to infer intuitively HIV risk. Second, we trained a multiple cue-based model to forecast perceived HIV risk through cross-validated predictive modelling. Trained models accurately predicted how ‘risky’ a person was perceived (r = 0.75) in a novel sample of portraits. Findings are discussed with respect to HIV risk stereotypes and implications regarding how to foster effective protective behaviors.

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<![CDATA[Perceptions of nurses on human papillomavirus vaccinations in the Republic of Korea]]> https://www.researchpad.co/article/5c648cc6d5eed0c484c81769

Background

In June 2016, the Republic of Korea included free human papillomavirus (HPV) vaccinations for all 12-year-old girls in its national immunization program.

Purpose

This study investigated perceptions of nurses on HPV vaccination and their intent to vaccinate preteens at the best ages.

Methods

Recruited for the survey were 514 health teachers (181, 35.2%), public health nurses (168, 32.7%), and clinical nurses (165, 32.1%). Factor-analysis was conducted to validate the Vaccine-Hesitancy Scale for Korean nurses. Related variables associated with vaccine-acceptance were examined using the Kruskal–Wallis test and Spearman’s rho coefficients, due to lack of normalization.

Results

Factor-analysis results showed that two factors of positive acceptance (7 items) and negative acceptance (3 items) accounted for 67.46% of the total variance, and explained 47.4% and 20.1%, respectively. Nurses who positively accepted HPV vaccine differed significantly in agreement to vaccinate girls or boys. For the proper vaccination age, a significant difference emerged between answers for girls and vaccine-acceptance scores, whereas no difference emerged between answers for boys and the scores. The vaccinated status of respondents significantly related to higher HPV vaccine acceptance, although age, religion, marital status, education, and working duration did not.

Conclusions

This study showed that vaccine-acceptance levels reflect nurses’ attitudes and opinions about HPV vaccination for girls and boys.

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<![CDATA[Neglected tropical diseases in children: An assessment of gaps in research prioritization]]> https://www.researchpad.co/article/5c59fef6d5eed0c484135851

Background

Despite the known burden of neglected tropical diseases (NTDs) on child health, there is limited information on current efforts to increase pediatric therapeutic options. Our objective was to quantify and characterize research activity and treatment availability for NTDs in children in order to inform the prioritization of future research efforts.

Methodology/Principal findings

We conducted a review of the World Health Organization’s (WHO) International Clinical Trials Registry Platform to assess research activity for NTDs. The burden of disease of each NTD was measured in terms of disability adjusted life years (DALYs), which was extracted from the Global Health Data Exchange. First- and second-line medications for each NTD were identified from WHO guidelines. We reviewed FDA drug labels for each medication to determine whether they were adequately labeled for use in children. Descriptive statistics, binomial tests, and Spearman’s rank order correlations were calculated to assess research activity compared to burden of disease. Children comprised 34% of the 20 million DALYs resulting from NTDs, but pediatric trials contributed just 17% (63/369) of trials studying these conditions (p<0.001 for binomial test). Conditions that were particularly under-represented in pediatric populations compared to adults included rabies, leishmaniasis, scabies, and dengue. Pediatric drug trial activity was poorly correlated with pediatric burden of disease across NTDs (Spearman’s rho = 0.41, p = 0.12). There were 47 medications recommended by the WHO for the treatment of NTDs, of which only 47% (n = 22) were adequately labeled for use in children. Of the 25 medications lacking adequate pediatric labeling, three were under study in pediatric trials.

Conclusions/Significance

There is a substantial gap between the burden of disease for NTDs in children and research devoted to this population. Most medications lack adequate pediatric prescribing information, highlighting the urgency to increase pediatric research activity for NTDs with high burden of disease and limited treatment options.

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<![CDATA[A mobile-phone based high-resolution microendoscope to image cervical precancer]]> https://www.researchpad.co/article/5c648ce0d5eed0c484c819d1

Nearly 90% of cervical cancer cases and deaths occur in low- and middle-income countries that lack comprehensive national HPV immunization and cervical cancer screening programs. In these settings, it is difficult to implement screening programs due to a lack of infrastructure and shortage of trained personnel. Screening programs based on visual inspection with acetic acid (VIA) have been successfully implemented in some low-resource settings. However, VIA has poor specificity and up to 90% of patients receiving treatment based on a positive VIA exam are over-treated. A number of studies have suggested that high-resolution cervical imaging to visualize nuclear morphology in vivo can improve specificity by better distinguishing precancerous and benign lesions. To enable high-resolution imaging in low-resource settings, we developed a portable, low-cost, high-resolution microendoscope that uses a mobile phone to detect and display images of cervical epithelium in vivo with subcellular resolution. The device was fabricated for less than $2,000 using commercially available optical components including filters, an LED and triplet lenses assembled in a 3D-printed opto-mechanical mount. We show that the mobile high-resolution microendoscope achieves similar resolution and signal-to-background ratio as previously reported high-resolution microendoscope systems using traditional cameras and computers to detect and display images. Finally, we demonstrate the ability of the mobile high-resolution microendoscope to image normal and precancerous squamous epithelium of the cervix in vivo in a gynecological referral clinic in Barretos, Brazil.

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<![CDATA[Community-level chlamydial serology for assessing trachoma elimination in trachoma-endemic Niger]]> https://www.researchpad.co/article/5c58d649d5eed0c484031a9e

Background

Program decision-making for trachoma elimination currently relies on conjunctival clinical signs. Antibody tests may provide additional information on the epidemiology of trachoma, particularly in regions where it is disappearing or elimination targets have been met.

Methods

A cluster-randomized trial of mass azithromycin distribution strategies for trachoma elimination was conducted over three years in a mesoendemic region of Niger. Dried blood spots were collected from a random sample of children aged 1–5 years in each of 24 study communities at 36 months after initiation of the intervention. A multiplex bead assay was used to test for antibodies to two Chlamydia trachomatis antigens, Pgp3 and CT694. We compared seropositivity to either antigen to clinical signs of active trachoma (trachomatous inflammation—follicular [TF] and trachomatous inflammation—intense [TI]) at the individual and cluster level, and to ocular chlamydia prevalence at the community level.

Results

Of 988 children with antibody data, TF prevalence was 7.8% (95% CI 6.1 to 9.5) and TI prevalence was 1.6% (95% CI 0.9 to 2.6). The overall prevalence of antibody positivity to Pgp3 was 27.2% (95% CI 24.5 to 30), and to CT694 was 23.7% (95% CI 21 to 26.2). Ocular chlamydia infection prevalence was 5.2% (95% CI 2.8 to 7.6). Seropositivity to Pgp3 and/or CT694 was significantly associated with TF at the individual and community level and with ocular chlamydia infection and TI at the community level. Older children were more likely to be seropositive than younger children.

Conclusion

Seropositivity to Pgp3 and CT694 correlates with clinical signs and ocular chlamydia infection in a mesoendemic region of Niger.

Trial registration

ClinicalTrials.gov NCT00792922.

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<![CDATA[Prevalence of high-risk human papilloma virus in women with high-grade squamous cell intraepithelial lesions in Botswana using Abbott RealTime HPV assay]]> https://www.researchpad.co/article/5c5b52a6d5eed0c4842bcd6b

Background

High-risk human papillomavirus (HR-HPV) has been demonstrated to be the necessary cause of cervical carcinoma. High-risk HPV detection has a prognostic significance for the women who are at increased risk of disease progression. HPV genotyping in cervical cancer precursor lesions is crucial for prevention and management of cervical cancer. This study was designed to investigate the distribution of HR-HPV genotypes among a group of patients with high-grade squamous intraepithelial lesions and higher, of the cervix, in Botswana.

Materials and methods

185-archived residual formalin-fixed paraffin-embedded cervical biopsies collected between the years, 2006 and 2008 were studied. These tissues were diagnosed with HSIL (n = 146) and squamous cell carcinoma (n = 39). DNA was extracted using the Abbott m2000 analyser (Abbott Laboratories, Illinois) using reagents provided by the manufacturer. HPV genotyping was done using the Abbott RealTime HR-HPV PCR, which qualitatively detects 14 HR-HPV (reported as HPV 16, 18 & Other HR-HPV).

Results

DNA was successfully extracted from 162/185 (87.6%) tissues as indicated by a positive β-globin test. 132/162 (82%) tested positive for HR-HPV The HPV 16 prevalence was 50% (66/132), HPV 18 at 15.2% (20/132) and other Group 1 HR-HPV plus HPV 66 and 68 had a prevalence of 56.1% (74/132). Other HR-HPV types were common in HSIL than in carcinoma, while HPV 16 was more prevalent in carcinomas than other HR-HPV genotypes.

Conclusion

In this study, HPV 16 and other HR-HPV genotypes were commonly associated with HSIL but HPV 18 was uncommon among Botswana women. Our data highlights the need for multivalent HPV vaccines with cross coverage for other high risk HPV other than HPV 16 and 18.

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<![CDATA[An efficient and cost-effective method for purification of small sized DNAs and RNAs from human urine]]> https://www.researchpad.co/article/5c633929d5eed0c484ae611f

Urine holds great promise as a non-invasive sampling method for molecular diagnostics. The cell-free nucleic acids of urine however are small, labile, and difficult to purify. Here an efficient method for the purification of these nucleic acids is presented. An empirically derived protocol was devised by first identifying conditions that allowed recovery of a 100 base pair (bp) DNA, followed by optimization using a quantitative polymerase chain reaction (qPCR) assay. The resulting method efficiently purifies both small sized DNAs and RNAs from urine, which when combined with quantitative reverse transcription PCR (qRTPCR), demonstrably improves detection sensitivity. Fractionation experiments reveal that nucleic acids in urine exist both in the cell-free and cellular fraction, roughly in equal proportion. Consistent with previous studies, amplicons > 180bp show a marked loss in PCR sensitivity for cell-free nucleic acids. Finally, the lysis buffer developed here also doubles as an effective preservative, protecting against nucleic acid degradation for at least two weeks under simulated field conditions. With this method, volumes of up to 25ml of whole urine can be purified in a high-throughput and cost-effective manner. Coupled with its ability to purify both DNA and RNA, the described method may have broad applicability for improving the diagnostic utility of urine, particularly for the detection of low abundant targets.

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<![CDATA[HPV-driven oropharyngeal squamous cell cancer in Croatia — Demography and survival]]> https://www.researchpad.co/article/5c5df339d5eed0c484580f3c

Objectives

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Main HNSCC risk factors are tobacco, alcohol, and high-risk human papillomavirus (HPV). HPV+ oropharyngeal squamous cell cancer (OPSCC) usually have different etiology, increasing incidence and often show an improved survival when compared to HPV-negative cases. The objective of the current study was to retrospectively examine the influence of HPV on the survival of OPSCC patients in a non-Western population setting.

Materials and methods

We determined the presence of HPV DNA and/or RNA in 99 formalin-fixed paraffin embedded (FFPE) tissue samples of OPSCC patients treated between 2002 and 2015. Patients were compared based on laboratory, demographic, clinical, life style characteristics and survival.

Results

HPV RNA was found in 29.3% cases. However, groups based on HPV data (either RNA, DNA or retrospectively collected p16 staining) did not show significant differences. Overall, 5-year survival was 30% with minimal influence of the HPV positivity.

Conclusions

The HPV influence on survival of OPSCC patients is not identical between populations probably due to other factors overshadowing the HPV effect. This should be taken into account when treatment or policy decisions are made in each particular setting.

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