Pregnancy and contraceptive use among women participating in an HIV prevention trial in Tanzania.

OBJECTIVES: Information on pregnancy rates and factors associated with pregnancy and contraceptive use is important for clinical trials in women in sub-Saharan Africa where withdrawal of investigational products may be required in the event of pregnancy with a consequent effect on sample size and trial power. METHODS: A prospective cohort analysis of pregnancy and contraceptive use was conducted in Tanzanian women enrolled in a randomised placebo-controlled trial of herpes simplex virus-suppressive therapy with acyclovir to measure the effect on HIV incidence in HIV-negative women and on genital and plasma HIV viral load in HIV-positive women. The cohort was followed every 3 months for 12-30 months. Women at each visit were categorised into users or non-users of contraception. Pregnancy rates and factors associated with pregnancy incidence and contraceptive use were measured. RESULTS: Overall 254 of 1305 enrolled women became pregnant at least once during follow-up (pregnancy rate: 12.0/100 person-years). Younger age, being unmarried, higher baseline parity and changes in contraceptive method during follow-up were independently associated with pregnancy. Having paid sex and being HIV positive were associated with lower risk of pregnancy. Uptake of contraception was associated with young age, being unmarried, occupation, parity and the number and type of sexual partners. CONCLUSIONS: Data on use of contraceptive methods and risk factors for pregnancy can help to guide decisions on trial eligibility and the need for additional counselling. Mandatory reliable contraceptive use in study participants may be required to reduce pregnancy rates in studies where pregnancy is contraindicated

Why do people not attend for treatment for trachomatous trichiasis in Ethiopia? A study of barriers to surgery.

BACKGROUND: Trachomatous trichiasis (TT) surgery is provided free or subsidised in most trachoma endemic settings. However, only 18-66% of TT patients attend for surgery. This study analyses barriers to attendance among TT patients in Ethiopia, the country with the highest prevalence of TT in the world. METHODOLOGY/PRINCIPAL FINDINGS: Participants with previously un-operated TT were recruited at 17 surgical outreach campaigns in Amhara Region, Ethiopia. An interview was conducted to ascertain why they had not attended for surgery previously. A trachoma eye examination was performed by an ophthalmologist. 2591 consecutive individuals were interviewed. The most frequently cited barriers to previous attendance for surgery were lack of time (45.3%), financial constraints (42.9%) and lack of an escort (35.5% in females, 19.6% in males). Women were more likely to report a fear of surgery (7.7% vs 3.2%, p<0.001) or be unaware of how to access services (4.5% vs 1.0% p<0.001); men were more frequently asymptomatic (19.6% vs 10.1%, p<0.001). Women were also less likely to have been previously offered TT surgery than men (OR = 0.70, 95%CI 0.53-0.94). CONCLUSIONS/SIGNIFICANCE: The major barriers to accessing surgery from the patients' perspective are the direct and indirect costs of surgery. These can to a large extent be reduced or overcome through the provision of free or low cost surgery at the community level. TRIAL REGISTRATION: ClinicalTrials.gov NCT00522860 and NCT00522912

Safety and immunogenicity of boosting BCG vaccinated subjects with BCG: comparison with boosting with a new TB vaccine, MVA85A.

OBJECTIVES: To investigate the safety and immunogenicity of a booster BCG vaccination delivered intradermally in healthy, BCG vaccinated subjects and to compare with a previous clinical trial where BCG vaccinated subjects were boosted with a new TB vaccine, MVA85A. DESIGN: Phase I open label observational trial, in the UK. Healthy, HIV-negative, BCG vaccinated adults were recruited and vaccinated with BCG. The primary outcome was safety; the secondary outcome was cellular immune responses to antigen 85, overlapping peptides of antigen 85A and tuberculin purified protein derivative (PPD) detected by ex vivo interferon-gamma (IFN-gamma) ELISpot assay and flow cytometry. RESULTS AND CONCLUSIONS: BCG revaccination (BCG-BCG) was well tolerated, and boosting of pre-existing PPD-specific T cell responses was observed. However, when these results were compared with data from a previous clinical trial, where BCG was boosted with MVA85A (BCG-MVA85A), MVA85A induced significantly higher levels (>2-fold) of antigen 85-specific CD4+ T cells (both antigen and peptide pool responses) than boosting with BCG, up to 52 weeks post-vaccination (p = 0.009). To identify antigen 85A-specific CD8+ T cells that were not detectable by ex vivo ELISpot and flow cytometry, dendritic cells (DC) were used to amplify CD8+ T cells from PBMC samples. We observed low, but detectable levels of antigen 85A-specific CD8+ T cells producing IFNgamma (1.5% of total CD8 population) in the BCG primed subjects after BCG boosting in 1 (20%) of 5 subjects. In contrast, in BCG-MVA85A vaccinated subjects, high levels of antigen 85A-specific CD8+ T cells (up to 14% total CD8 population) were observed after boosting with MVA85A, in 4 (50%) of 8 subjects evaluated. In conclusion, revaccination with BCG resulted in modest boosting of pre-existing immune responses to PPD and antigen 85, but vaccination with BCG-MVA85A induced a significantly higher response to antigen 85 and generated a higher frequency of antigen 85A-specific CD8+ T cells. TRIAL REGISTRATION: ClinicalTrials.gov NCT00654316 NCT00427830

Effect of vaccine dose on the safety and immunogenicity of a candidate TB vaccine, MVA85A, in BCG vaccinated UK adults.

PURPOSE: A non-randomised, open-label, Phase I safety and immunogenicity dose-finding study to assess the safety and immunogenicity of the candidate TB vaccine Modified Vaccinia virus Ankara expressing Antigen 85A (MVA85A) from Mycobacterium tuberculosis (MTB) in healthy adult volunteers previously vaccinated with BCG. METHODS: Healthy BCG-vaccinated volunteers were vaccinated with either 1×10(7) or 1×10(8)PFU of MVA85A. All adverse events were documented and antigen specific T cell responses were measured using an ex vivo IFN-γ ELISPOT assay. Safety and immunogenicity were compared between the 2 dose groups and with a previous trial in which a dose of 5×10(7)PFU MVA85A had been administered. RESULTS: There were no serious adverse events recorded following administration of either 1×10(7) or 1×10(8)PFU of MVA85A. Systemic adverse events were more frequently reported following administration of 1×10(8)PFU of MVA85A when compared to either 5×10(7) or 1×10(7)PFU of MVA85A but were mild or moderate in severity and resolved completely within 7 days of immunisation. Antigen specific T cell responses as measured by the IFN-γ ELISPOT were significantly higher following immunisation in adults receiving 1×10(8)PFU compared to the 5×10(7) and 1×10(7) doses. Additionally, a broader range of Ag85A epitopes are detected following 1×10(8)PFU of MVA85A. CONCLUSION: A higher dose of 1×10(8)PFU of MVA85A is well-tolerated, increases the frequency of IFN-γ secreting T cells detected following immunisation and broadens the range of Ag85A epitopes detected

Mindfulness- Based Functional Therapy: a preliminary open trial of an integrated model of care for people with persistent low back pain

Objectives: This pilot study investigated the feasibility and clinical utility of implementing a novel, evidence-informed, interdisciplinary group intervention—Mindfulness Based Functional Therapy (MBFT)—for the management of persistent low back pain (LBP) in primary care. MBFT aimed to improve physical and psychological functioning in patients with persistent LBP. Design: A single-group repeated measures design was utilized to gather data about feasibility, effect sizes, clinically significant changes and patient satisfaction. Setting: A community sample of 16 adults (75% female), mean (SD) age 47.00 (9.12) years (range 26–65 years), with mean (SD) LBP duration of 8.00 (9.00) years participated, using a simulated primary care setting at Curtin University in Australia. Intervention: MBFT is an 8-week group intervention co-facilitated by psychology and physiotherapy disciplines. Content includes: mindfulness meditation training, cognitive-functional physiotherapeutic movement retraining, pain education, and group support.Main outcome measures: Several validated self-report measures were used to assess functional disability, emotional functioning, mindfulness, pain catastrophizing, health-related quality of life at baseline, post-intervention, and 6 months follow-up. Results: Adherence and satisfaction was high, with 85% of participants highly satisfied with MBFT. Clinical significance analysis and effect size estimates showed improvements in a number of variables, including pain catastrophizing, physical functioning, role limitations due to physical condition, and depression, although these may have occurred due to non-intervention effects. Conclusions: MBFT is feasible to implement in primary care. Preliminary findings suggest that a randomized controlled trial is warranted to investigate its efficacy in improving physical and emotional functioning in people with disabling persistent LBP

Increased ocular lens density in HIV-infected individuals with low nadir CD4 counts in South Africa: evidence of accelerated aging.

BACKGROUND: HIV infection is thought to be associated with an increased risk of age-related morbidity and premature aging. Lens density increases with age and may function as a biomarker of aging. The relationship of lens density measurements with clinical and demographic characteristics in HIV-infected individuals in comparison with a matched population of HIV-seronegative individuals was investigated. METHODS: Case-control study of 490 adults aged greater than or equal to 30 years composed of 242 HIV-infected adults and 248 age- and sex-matched HIV-seronegative individuals. Lens density was assessed using lens densitometry (Pentacam) imaging. Measurements were divided into quartiles, and comparison of HIV status and HIV-related factors was assessed by multivariate and multinomial logistic regression. RESULTS: The mean age was 41.2 years in HIV-infected adults and 42.3 years in HIV-seronegative individuals (P = 0.14). Of the HIV-infected adults, 88% were receiving antiretroviral therapy (ART) (median duration, 58 months), and within this group, their median CD4 count was 468 cells per microliter and 84% had undetectable viral load. Although adjusted lens densities were similar by HIV serostatus, participants on ART and who had nadir CD4 counts less than 200 cells per microliter had a higher risk of high lens density compared with HIV-seronegative individuals (P trend = 0.04). Lens density was weakly associated with detectable HIV viremia despite ART, but not with current CD4 count. CONCLUSIONS: HIV-infected individuals on ART with nadir CD4 counts <200 cells per microliter had increased risk of higher lens density. Lens density may represent a novel biomarker of aging, providing insight into accelerated aging trajectories in HIV infection

Absorbable versus silk sutures for surgical treatment of trachomatous trichiasis in Ethiopia: a randomised controlled trial.

BACKGROUND: Trachoma causes blindness through an anatomical abnormality called trichiasis (lashes touching the eye). Trichiasis can recur after corrective surgery. We tested the hypothesis that using absorbable sutures instead of silk sutures might reduce the risk of recurrent disease among patients with major trichiasis in a randomised trial. METHODS AND FINDINGS: 1,300 individuals with major trichiasis from rural villages in the Amhara Region of Ethiopia were recruited and assigned (1:1) by computer-generated randomisation sequence to receive trichiasis surgery using either an absorbable suture (polyglactin-910) or silk sutures (removed at 7-10 days) in an otherwise identical surgical technique. Participants were examined every 6 months for 2 years by clinicians masked to allocation. The primary outcome measure was recurrent trichiasis (≥one lash touching the eye) at 1 year. There was no difference in prevalence of recurrent trichiasis at 1 year (114 [18.2%] in the absorbable suture group versus 120 [19.7%] in the silk suture group; odds ratio = 0.90, 95% CI 0.68-1.20). The two groups also did not differ in terms of corneal opacification, visual acuity, conjunctival inflammation, and surgical complications. CONCLUSIONS: There was no evidence that use of absorbable polyglactin-910 sutures was associated with a lower prevalence of trichiasis recurrence at 1 year postsurgery than silk sutures. However, from a programmatic perspective, polyglactin-910 offers the major advantage that patients do not have to be seen soon after surgery for suture removal. The postoperative review after surgery using absorbable polyglactin-910 sutures can be delayed for 3-6 months, which might allow us to better determine whether a patient needs additional surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT00522860

Digital clinical communication for families and caregivers of children or young people with short- or long-term conditions : rapid review

Background The communication relationship between parents of children or young people with health conditions and health professionals is an important part of treatment, but it is unclear how far the use of digital clinical communication tools may affect this relationship. Objective The objective of our study was to describe, assess the feasibility of, and explore the impact of digital clinical communication between families or caregivers and health professionals. Methods We searched the literature using 5 electronic databases. We considered all types of study design published in the English language from January 2009 to August 2015. The population of interest included families and caregivers of children and young people aged less than 26 years with any type of health condition. The intervention was any technology permitting 2-way communication. Results We included 31 articles. The main designs were randomized controlled trials (RCTs; n=10), cross-sectional studies (n=9), pre- and postintervention uncontrolled (pre/post) studies (n=7), and qualitative interview studies (n=2); 6 had mixed-methods designs. In the majority of cases, we considered the quality rating to be fair. Many different types of health condition were represented. A breadth of digital communication tools were included: videoconferencing or videoconsultation (n=14), and Web messaging or emails (n=12). Health care professionals were mainly therapists or cognitive behavioral therapists (n=10), physicians (n=8), and nurses (n=6). Studies were very heterogeneous in terms of outcomes. Interventions were mainly evaluated using satisfaction or acceptance, or outcomes relating to feasibility. Clinical outcomes were rarely used. The RCTs showed that digital clinical communication had no impact in comparison with standard care. Uncontrolled pre/post studies showed good rates of satisfaction or acceptance. Some economic studies suggested that digital clinical communication may save costs. Conclusions This rapid review showed an emerging body of literature on the use of digital clinical communication to improve families’ and caregivers’ involvement in the health management of children or young people. Further research with appropriate study designs and longer-term outcome measures should be encouraged. Trial Registration: PROSPERO CRD42016035467; http://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD 42016 035467(Archived by WebCite at http://www.webcitation.org/6vpgZU1FU

Associations of Human Papillomavirus (HPV) genotypes with high-grade cervical neoplasia (CIN2+) in a cohort of women living with HIV in Burkina Faso and South Africa.

OBJECTIVE: To describe associations of high-risk human papillomavirus (HR-HPV) with high-grade cervical intraepithelial neoplasia (CIN2+) in women living with HIV (WLHIV) in Burkina Faso (BF) and South Africa (SA). METHODS: Prospective cohort of WLHIV attending HIV outpatient clinics and treatment centres. Recruitment was stratified by ART status. Cervical HPV genotyping using INNO-LiPA and histological assessment of 4-quadrant cervical biopsies at enrolment and 16 months later. RESULTS: Among women with CIN2+ at baseline, the prevalence of any HR-HPV genotypes included in the bi/quadrivalent (HPV16/18) or nonavalent (HPV16/18/31/35/45/52/58) HPV vaccines ranged from 37% to 90%. HPV58 was most strongly associated with CIN2+ (aOR = 5.40, 95%CI: 2.77-10.53). At 16-months follow-up, persistence of any HR-HPV was strongly associated with incident CIN2+ (aOR = 7.90, 95%CI: 3.11-20.07), as was persistence of HPV16/18 (aOR = 5.25, 95%CI: 2.14-12.91) and the additional HR types in the nonavalent vaccine (aOR = 3.23, 95%CI: 1.23-8.54). CONCLUSION: HR-HPV persistence is very common among African WLHIV and is linked to incident CIN2+. HPV vaccines could prevent between 37-90% of CIN2+ among African WLHIV

Patterns of herpes simplex virus shedding over 1 month and the impact of acyclovir and HIV in HSV-2-seropositive women in Tanzania

Objectives Few studies have examined the frequency and duration of genital herpes simplex virus (HSV) shedding in sub-Saharan Africa. This study describes HSV shedding patterns among a sample of HSV-2-seropositive women enrolled in a placebo-controlled trial of HSV suppressive therapy (acyclovir 400 mg twice a day) in Tanzania.Methods Trial participants were invited to participate in a substudy involving 12 clinic visits over 4 weeks. At each visit, cervical, vaginal and external skin swabs were taken and analysed for HSV DNA using inhouse real-time PCR.Results HSV shedding was mainly subclinical (90%; 57/63 shedding days in the placebo arm). The most frequent shedding site was the external skin, but HSV DNA was detected from all three sites on 42% (27/63) of shedding days. In HIV-negative women, HSV DNA was detected on 3% (9/275) of days in the acyclovir versus 11% (33/309) in the placebo arm, while in HIV-positive women, detection was on 14% (23/160) versus 19% (30/155) of days, respectively.Conclusions HSV shedding was common, varying greatly by individual. Shedding rates were similar to studies in African and non-African settings. Among HIV-negative women, shedding rates were lower in the acyclovir arm; however, acyclovir did not substantially impact on HSV shedding in HIV-positive women