Susceptibility of Trichomonas vaginalis to metronidazole and other compounds.

Ph. D. University of KwaZulu-Natal, Durban 2015.Trichomonas vaginalis is the most common sexually transmitted infection caused by a single known organism worldwide; and has been associated with an increased risk of HIV acquisition and transmission. Despite its high prevalence in South Africa, limited information is available on the extent of T. vaginalis metronidazole resistance and genotypic variation in this setting. We therefore tested the susceptibility of local T. vaginalis isolates against metronidazole and drugs prescribed in combination in the context of syndromic management of vaginal discharge syndrome. Susceptibility testing of 40 isolates demonstrated that metronidazole as well as some of the other drugs tested showed inhibiting effect on T. vaginalis. We recommend that these drugs be tested for synergistic effect with metronidazole. In a different set of 160 isolates the minimum inhibitory concentrations (MIC) of metronidazole ranged from 1.1 μg/ml to > 34.2 μg/ml (6.25 μM to > 200 μM) in the aerobic assay. Interpretation of these MICs differed based on the different resistance breakpoints applied. There was no correlation between MIC and treatment outcome in the subset of 56 patients that returned for follow-up. The expected association between MIC and clinical outcome was only observed in one of eight patients with unsatisfactory treatment outcome. This patient‘s isolate had the highest MIC. In the remaining seven patients with unsatisfactory treatment outcome, no relation with the susceptibility test result was found. A possible reason for the poor correlation may be inadequate concentration of metronidazole at the site of infection. In view of this, we assessed a self-administered and collected vaginal tampon specimen for the investigation of metronidazole concentration in the vagina of five healthy volunteers, using high performance liquid chromatography (HPLC). Maximum values of metronidazole concentrations detected in both serum and vaginal fluid were obtained at two hours following oral administration of 2 g of the drug. This method can be applied in future clinical studies to correlate treatment outcome and MICs with metronidazole concentration at the site of infection. This may lead to the development of susceptibility assays and interpretation criteria that are better able to predict treatment outcome than the current methods. Another reason for the poor correlation between treatment outcome and in vitro resistance may be early reinfection. We used PCR-RFLP, targeting a 650-bp repeat region in the T. vaginalis genome, to genotype T. vaginalis isolates. Four genotypes were found in 100 T. vaginalis isolates using this method. Both the vaginal secretion of metronidazole and the strain typing methodology needs to be further investigated before a comprehensive study as outlined above can be executed

Prevalent Herpes Simplex Virus-2 Increases the Risk of Incident Bacterial Vaginosis in Women from South Africa.

Studies have shown that women diagnosed with herpes simplex virus-2 (HSV-2) have a higher risk for bacterial vaginosis (BV) infection. We investigated the presence of HSV-2 infections as a risk factor for incident BV infections in high risk, Human immunodeficiency virus (HIV) uninfected women enrolled in a HIV prevention trial in Durban, South Africa. The Vaginal and Oral Interventions to Control the Epidemic trial was a multicentre, double blinded, randomized controlled trial which was designed to estimate the effectiveness of daily treatment with vaginal tenofovir gel, oral tenofovir disoproxil fumarate and oral Truvada in preventing HIV-1 infection in women. Women provided samples for the diagnosis of HSV-2 and BV. The presence of HSV-2 antibodies was detected using HerpeSelect™ ELISA IgG. Bacterial vaginosis was diagnosed using the Nugent scoring system. To assess the risk of BV incidence, modelled as a time-dependent variable, we used the Andersen-Gill model with robust variance estimation and Efron methods for ties. Overall, 2750 women were enrolled in the VOICE trial at our study sites. Women who had a HSV-2 infection at enrolment were shown to be at increased risk for incident BV infections (adjusted hazard ratio 1.17, 95% CI 1.08, 1.27, p ≤ 0.001). In addition, being of a young age, being unmarried and having a partner that has other partners were significantly associated with subsequent BV infection. Our findings therefore advocate the need for strengthening STI prevention efforts among women in high burden STI settings

Experiences in conducting multiple community-based HIV prevention trials among women in KwaZulu-Natal, South Africa

<p>Abstract</p> <p>Background</p> <p>South Africa, with its scientific capacity, good infrastructure and high HIV incidence rates, is ideally positioned to conduct large-scale HIV prevention trials. The HIV Prevention Research Unit of the South African Medical Research Council conducted four phase III and one phase IIb trials of women-initiated HIV prevention options in KwaZulu-Natal between 2003 and 2009. A total of 7046 women participated, with HIV prevalence between 25% and 45% and HIV incidence ranging from 4.5-9.1% per year. Unfortunately none of the interventions tested had any impact on reducing the risk of HIV acquisition; however, extremely valuable experience was gained, lessons learned and capacity built, while the communities gained associated benefits.</p> <p>Experience</p> <p>Our experience in conducting these trials ranged from setting up community partnerships to developing clinical research sites and dissemination of trial results. Community engagement included setting up community-based research sites with approval from both political and traditional leaders, and developing community advisory groups to assist with the research process. Community-wide education on HIV/sexually transmitted infection prevention, treatment and care was provided to over 90 000 individuals. Myths and misconceptions were addressed through methods such as anonymous suggestion boxes in clinic waiting areas and intensive education and counselling. Attempts were made to involve male partners to foster support and facilitate recruitment of women. Peer educator programmes were initiated to provide ongoing education and also to facilitate recruitment of women to the trials. Recruitment strategies such as door-to-door recruitment and community group meetings were initiated. Over 90% of women enrolled were retained.</p> <p>Community benefits from the trial included education on HIV prevention, treatment and care and provision of ancillary care (such as Pap smears, reproductive health care and referral for chronic illnesses). Social benefits included training of home-based caregivers and sustainable ongoing HIV prevention education through peer educator programmes.</p> <p>Challenges</p> <p>Several challenges were encountered, including manipulation by participants of their eligibility criteria in order to enroll in the trial. Women attempted to co-enroll in multiple trials to benefit from financial reimbursements and individualised care. The trials became ethically challenging when participants refused to take up referrals for care due to stigma, denial of their HIV status and inadequate health infrastructure. Lack of disclosure of HIV status to partners and family members was particularly challenging. Some of the ethical dilemmas put to the test our responsibility as researchers and our obligation to provide health care to research participants.</p> <p>Conclusion</p> <p>Conducting these five trials in a period of six years provided us with invaluable insights into trial implementation, community participation, recruitment and retention, provision of care and dissemination of trial results. The critical mass of scientists trained as clinical trialists will continue to address the relentless HIV epidemic in our setting and ensure our commitment to finding a biomedical HIV prevention option for women in the future.</p

Clinical and socio-behavioral correlates of tooth loss: a study of older adults in Tanzania

BACKGROUND: Focusing 50 year olds and above, this study assessed the frequency, extent and correlates of tooth loss due to various reasons. Frequency and correlates of posterior occluding support was also investigated. METHOD: A cross-sectional household survey was conducted in Pwani region and in Dar es Salaam in 2004/2005. One thousand and thirty-one subjects, mean age 62.9 years participated in a clinical examination and completed interviews. RESULTS: The prevalence of tooth loss due to any reason was 83.5 %, due to caries 63.4% and due to other reasons than caries, 32.5%. A total of 74.9% had reduced number of posterior occluding units. Compared to subjects having less than 5 teeth lost due to caries, those with 5 or more lost teeth were more likely to be females, having decayed teeth, confirming dental attendance and to be among the least poor residents. Compared to subjects who had lost less than 5 teeth due to reasons other than caries, those who had lost 5 or more teeth were more likely to be of higher age, having mobile teeth, being males, being very poor and to disconfirm dental attendance when having problems. Predictors of prevalence of tooth loss (1 or more lost tooth) due to various reasons and reduced number of occluding units followed similar patterns of relationships. CONCLUSION: The results are consistent with prevalence and extent of tooth loss due to caries and due to reasons other than caries being differently related to disease- and socio- behavioral risk indicators. Caries was the principle cause of tooth loss and molar teeth were the teeth most commonly lost

Participants as community-based peer educators: Impact on a clinical trial site in KwaZulu-Natal

Participant recruitment, retention and product adherence are necessary to measure the efficacy or effectiveness of an intervention in a clinical trial. As part of a Phase III HIV prevention trial in a rural area in Kwazulu-Natal, South Africa, a peer educator programme was initiated to aid in recruitment and retention of trial participants from the community. Enrolled trial participants who had completed at least 6 months of trial participation and who had honoured all of their scheduled trial visits within that period were approached to be peer educators. Following additional selection criteria, 24 participants were eligible to be trained as peer educators. Training topics included HIV/AIDS, sexually transmitted infections, nutrition, antiretrovirals, clinical trials, and methods of disseminating this information to the community. The role of peer educators was to bring interested women from their community to the trial site for comprehensive education and information about the trial and possibly trial participation. A total of 1879 women were educated by peer educators between July 2004 and December 2006. Of these, 553 women visited the trial site for further education and screening for participation in the trial. Peer educators provided continuous education and support to women enrolled in the trial which also promoted retention, ultimately contributing to the site’s 94% retention rate. Recruitment and retention efforts of trial participants are likely to be enhanced by involving trial participants as peer educators. Such trial participants are in a better position to understand cultural dynamics and hence capable of engaging the community with appropriate HIV prevention and trial-related messaging

Ethical considerations in implementing a biometric coenrolment prevention system in clinical trials in South Africa

Preventing co-enrolment in clinical trials ensures participant safety and data integrity. To facilitate co-enrolment checks, a novel biometric coenrolment prevention system (BCEPS) was developed and implemented in 2010 by the HIV Prevention Research Unit (HPRU) in collaboration with the South African Medical Research Council’s (SAMRC) Information Technology Services Division. The use of this web-based system to capture participant’s identification details in real time was approved by the SAMRC Ethics Committee. BCEPS was implemented at 13 other research organisations conducting clinical trials in South Africa (SA). Participants who screened at the clinical research sites (CRSs) had their names, SA identity or passport number and fingerprints captured onto BCEPS after comprehensive education and discussion. This information was verified at all study visits. If a participant attempted to screen or co-enrol at multiple CRSs, the system flagged this as a potential coenrolment.By addressing the ethical concerns around participant consent and rights, participant confidentiality and privacy, data securityand access, and data management and storage, we were able to successfully implement BCEPS within the clinical trials conducted at HPRU,while adhering to the principles of good clinical practice (GCP), including respect for persons, beneficence and justice

Disclosure of pharmacokinetic drug results to understand nonadherence

Objectives: In VOICE, a phase IIB trial of daily oral and vaginal tenofovir for HIV prevention, at least 50% of women receiving active products had undetectable tenofovir in all plasma samples tested. MTN-003D, an ancillary study using in-depth interviews (IDIs) and focus group discussions (FGDs), together with retrospective disclosure of plasma tenofovir pharmacokinetic results, explored adherence challenges during VOICE. Methods: We systematically recruited participants with pharmacokinetic data (median six plasma samples), categorized as low (0%, N = 79), inconsistent (1–74%, N = 28) or high (≥75%; N = 20) on the basis of frequency of tenofovir detection. Following disclosure of pharmacokinetic results, reactions were captured and adherence challenges systematically elicited; IDIs and FGDs were audio-recorded, transcribed, coded and thematically analysed. Results: We interviewed 127 participants from South Africa, Uganda and Zimbabwe. The most common reactions to pharmacokinetic results included surprise (41%; low pharmacokinetic), acceptance (39%; inconsistent pharmacokinetic) and happiness (65%; high pharmacokinetic). On the basis of participants’ explanations, we developed a typology of adherence patterns: noninitiation, discontinuation, misimplementation (resulting from visit-driven use, variable taking, modified dosing or regimen) and adherence. Fear of product side effects/harm was a frequent concern, fuelled by stories shared among participants. Although women with high pharmacokinetic levels reported similar concerns, several described strategies to overcome challenges. Women at all pharmacokinetic levels suggested real-time drug monitoring and feedback to improve adherence and reporting. Conclusion: Retrospective provision of pharmacokinetic results seemingly promoted candid discussions around nonadherence and study participation. The effect of real-time drug monitoring and feedback on adherence and accuracy of reporting should be evaluated in trials