Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Prevalence and correlates of bacterial vaginosis in different sub-populations of women in Sub-Saharan Africa: a cross-sectional study

Background: Clinical development of vaginally applied products aimed at reducing the transmission of HIV and other sexually transmitted infections, has highlighted the need for a better characterisation of the vaginal environment. We set out to characterise the vaginal environment in women in different settings in sub-Saharan Africa. Methods: A longitudinal study was conducted in Kenya, Rwanda and South-Africa. Women were recruited into pre-defined study groups including adult, non-pregnant, HIV-negative women; pregnant women; adolescent girls; HIV-negative women engaging in vaginal practices; female sex workers; and HIV-positive women. Consenting women were interviewed and underwent a pelvic exam. Samples of vaginal fluid and a blood sample were taken and tested for bacterial vaginosis (BV), HIV and other reproductive tract infections (RTIs). This paper presents the cross-sectional analyses of BV Nugent scores and RTI prevalence and correlates at the screening and the enrolment visit. Results: At the screening visit 38% of women had BV defined as a Nugent score of 7-10, and 64% had more than one RTI (N. gonorrhoea, C. trachomatis, T. vaginalis, syphilis) and/or Candida. At screening the likelihood of BV was lower in women using progestin-only contraception and higher in women with more than one RTI. At enrolment, BV scores were significantly associated with the presence of prostate specific antigen (PSA) in the vaginal fluid and with being a self-acknowledged sex worker. Further, sex workers were more likely to have incident BV by Nugent score at enrolment. Conclusions: Our study confirmed some of the correlates of BV that have been previously reported but the most salient finding was the association between BV and the presence of PSA in the vaginal fluid which is suggestive of recent unprotected sexual intercourse

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/ mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Trends of non-vaccination, under-vaccination and missed opportunities for vaccination (2003-2014) amongst children 0-23 months in Kenya.

Vaccines are effective and cost-effective. Non-vaccination, under-vaccination, and missed opportunities for vaccination (MOV), have contributed to incomplete vaccination coverage in Kenya. Analyzing their trends is essential for targeting interventions and improvement strategies. This study aimed to assess trends of non-vaccination, under-vaccination, and MOV among children aged 0-23 months in Kenya using data obtained from the Kenya Demographic and Health Surveys (KDHS) conducted in 2003, 2008/09, and 2014. A two-stage, multi-stage, and stratified sampling technique was used. Weighted analysis was conducted to ensure generalizability to the full population. Using the KDHS sample size estimation process, the sample size was estimated for each indicator, with varying standard error estimates, level of coverage and estimated response rates. Final sample size was 2380 (2003), 2237 (2008/09) and 7380 (2014). To determine the level of non-vaccination, under-vaccination and MOV among children aged 0-23 months, a weighted descriptive analysis was used to estimate their prevalence, with 95% confidence intervals (CI) for each year. MOV was defined using an algorithm as a binary variable. Data coding and recoding were done using Stata (version 14; College Station, TX: StataCorp LP). Trends in proportions of non-vaccination, under-vaccination and MOV were compared between 2003, 2008/09, and 2014 using the Cochrane-Armitage trend test. All results with P≤0.05 were considered statistically significant. Trends in proportion of non-vaccination among children aged 0-23 months in Kenya was 13.2%, 6.1% and 3.2% in 2003, 2008/09 and 2014, respectively (P = 0.0001). Trends in proportion of under-vaccination among children aged 0-23 months in Kenya was 54.3%, 50% and 51.3% in 2003, 2008/09 and 2014, respectively (P = 0.0109). The trends in proportion of children who experienced MOV was 22.7% in 2003, 31.9% in 2008/09 and 37.6% in 2014 (P = 0.0001). In the study duration, non-vaccination decreased by 10%, under-vaccination remained relatively stable, and MOV increased by ~15%. There is need for the Government and partners to implement initiatives that improve vaccine access and coverage, particularly in regions with low coverage rates, and to address missed opportunities for vaccination

“God Didn’t Make a Mistake in Creating Me”: Intrapersonal Resilience Processes among Gay and Bisexual Male Youth in Kenya

Gay and bisexual male youth in Kenya experience human rights violations, including pervasive stigma and discrimination, and these oppressive forces are associated with elevated rates of mental health concerns. Despite these challenges, many gay and bisexual male youth in Kenya are thriving during this critical developmental period. This study explored intrapersonal processes that gay and bisexual male youth in Kisumu, Kenya, highlight as important to developing, and demonstrating resilience in the face of adversity. We conducted qualitative in-depth interviews (IDIs) with 40 gay and bisexual male youth, ages 20–30 (mean = 26.4), and an additional 20 IDIs with gay and bisexual men, ages 22–45 (mean = 26.6), who were working as peer educators (total n = 60), all in Kisumu, Kenya. A total of nine primary themes emerged which describe various intrapersonal resilience processes enacted by gay and bisexual male youth, including sexual identity acceptance, self-confidence, self-love, religious/spiritual affirmation, adaptive coping, successful navigation, legal rights awareness, economic stability, and advocacy satisfaction. These data demonstrate the range of positive personal processes that promote mental health and wellbeing among gay and bisexual male youth in Kenya. We discuss implications of these findings for community-based interventions, and call for a research paradigm shift away from deficits and toward resilience

Costs of continuing RTS,S/ASO1E malaria vaccination in the three malaria vaccine pilot implementation countries.

BackgroundThe RTS,S/ASO1E malaria vaccine is being piloted in three countries-Ghana, Kenya, and Malawi-as part of a coordinated evaluation led by the World Health Organization, with support from global partners. This study estimates the costs of continuing malaria vaccination upon completion of the pilot evaluation to inform decision-making and planning around potential further use of the vaccine in pilot areas.MethodsWe used an activity-based costing approach to estimate the incremental costs of continuing to deliver four doses of RTS,S/ASO1E through the existing Expanded Program on Immunization platform, from each government's perspective. The RTS,S/ASO1E pilot introduction plans were reviewed and adapted to identify activities for costing. Key informant interviews with representatives from Ministries of Health (MOH) were conducted to inform the activities, resource requirements, and assumptions that, in turn, inform the analysis. Both financial and economic costs per dose, cost of delivery per dose, and cost per fully vaccinated child (FVC) are estimated and reported in 2017 USD units.ResultsAt a vaccine price of $5 per dose and assuming the vaccine is donor-funded, our estimated incremental financial costs range from$1.70 (Kenya) to $2.44 (Malawi) per dose,$0.23 (Malawi) to $0.71 (Kenya) per dose delivered (excluding procurement add-on costs), and$11.50 (Ghana) to $13.69 (Malawi) per FVC. Estimates of economic costs per dose are between three and five times higher than financial costs. Variations in activities used for costing, procurement add-on costs, unit costs of per diems, and allowances contributed to differences in cost estimates across countries.ConclusionCost estimates in this analysis are meant to inform country decision-makers as they face the question of whether to continue malaria vaccination, should the intervention receive a positive recommendation for broader use. Additionally, important cost drivers for vaccine delivery are highlighted, some of which might be influenced by global and country-specific financing and existing procurement mechanisms. This analysis also adds to the evidence available on vaccine delivery costs for products delivered outside the standard immunization schedule