Do topical repellents divert mosquitoes within a community? Health equity implications of topical repellents as a mosquito bite prevention tool.

OBJECTIVES: Repellents do not kill mosquitoes--they simply reduce human-vector contact. Thus it is possible that individuals who do not use repellents but dwell close to repellent users experience more bites than otherwise. The objective of this study was to measure if diversion occurs from households that use repellents to those that do not use repellents. METHODS: The study was performed in three Tanzanian villages using 15%-DEET and placebo lotions. All households were given LLINs. Three coverage scenarios were investigated: complete coverage (all households were given 15%-DEET), incomplete coverage (80% of households were given 15%-DEET and 20% placebo) and no coverage (all households were given placebo). A crossover study design was used and coverage scenarios were rotated weekly over a period of ten weeks. The placebo lotion was randomly allocated to households in the incomplete coverage scenario. The level of compliance was reported to be close to 100%. Mosquito densities were measured through aspiration of resting mosquitoes. Data were analysed using negative binomial regression models. FINDINGS: Repellent-users had consistently fewer mosquitoes in their dwellings. In villages where everybody had been given 15%-DEET, resting mosquito densities were fewer than half that of households in the no coverage scenario (Incidence Rate Ratio [IRR]=0.39 (95% confidence interval [CI]: 0.25-0.60); p<0.001). Placebo-users living in a village where 80% of the households used 15%-DEET were likely to have over four-times more mosquitoes (IRR=4.17; 95% CI: 3.08-5.65; p<0.001) resting in their dwellings in comparison to households in a village where nobody uses repellent. CONCLUSIONS: There is evidence that high coverage of repellent use could significantly reduce man-vector contact but with incomplete coverage evidence suggests that mosquitoes are diverted from households that use repellent to those that do not. Therefore, if repellents are to be considered for vector control, strategies to maximise coverage are required

Use of a Semi-field System to Evaluate the Efficacy of Topical Repellents under user Conditions Provides a Disease Exposure free Technique Comparable with Field Data.

Before topical repellents can be employed as interventions against arthropod bites, their efficacy must be established. Currently, laboratory or field tests, using human volunteers, are the main methods used for assessing the efficacy of topical repellents. However, laboratory tests are not representative of real life conditions under which repellents are used and field-testing potentially exposes human volunteers to disease. There is, therefore, a need to develop methods to test efficacy of repellents under real life conditions while minimizing volunteer exposure to disease. A lotion-based, 15% N, N-Diethyl-3-methylbenzamide (DEET) repellent and 15% DEET in ethanol were compared to a placebo lotion in a 200 sq m (10 m x 20 m) semi-field system (SFS) against laboratory-reared Anopheles arabiensis mosquitoes and in full field settings against wild malaria vectors and nuisance-biting mosquitoes. The average percentage protection against biting mosquitoes over four hours in the SFS and field setting was determined. A Poisson regression model was then used to determine relative risk of being bitten when wearing either of these repellents compared to the placebo. Average percentage protection of the lotion-based 15% DEET repellent after four hours of mosquito collection was 82.13% (95% CI 75.94-88.82) in the semi-field experiments and 85.10% (95% CI 78.97-91.70) in the field experiments. Average percentage protection of 15% DEET in ethanol after four hours was 71.29% (CI 61.77-82.28) in the semi-field system and 88.24% (84.45-92.20) in the field. Semi-field evaluation results were comparable to full-field evaluations, indicating that such systems could be satisfactorily used in measuring efficacy of topically applied mosquito repellents, thereby avoiding risks of exposure to mosquito-borne pathogens, associated with field testing

Real-world menstrual cycle characteristics of more than 600,000 menstrual cycles

The use of apps that record detailed menstrual cycle data presents a new opportunity to study the menstrual cycle. The aim of this study is to describe menstrual cycle characteristics observed from a large database of cycles collected through an app and investigate associations of menstrual cycle characteristics with cycle length, age and body mass index (BMI). Menstrual cycle parameters, including menstruation, basal body temperature (BBT) and luteinising hormone (LH) tests as well as age and BMI were collected anonymously from real-world users of the Natural Cycles app. We analysed 612,613 ovulatory cycles with a mean length of 29.3 days from 124,648 users. The mean follicular phase length was 16.9 days (95% CI: 10-30) and mean luteal phase length was 12.4 days (95% CI: 7-17). Mean cycle length decreased by 0.18 days (95% CI: 0.17-0.18, R2 = 0.99) and mean follicular phase length decreased by 0.19 days (95% CI: 0.19-0.20, R2 = 0.99) per year of age from 25 to 45 years. Mean variation of cycle length per woman was 0.4 days or 14% higher in women with a BMI of over 35 relative to women with a BMI of 18.5-25. This analysis details variations in menstrual cycle characteristics that are not widely known yet have significant implications for health and well-being. Clinically, women who wish to plan a pregnancy need to have intercourse on their fertile days. In order to identify the fertile period it is important to track physiological parameters such as basal body temperature and not just cycle length

Target-site resistance mutations (kdr and RDL), but not metabolic resistance, negatively impact male mating competiveness in the malaria vector Anopheles gambiae

The implementation of successful insecticide resistance management strategies for malaria control is currently hampered by poor understanding of the fitness cost of resistance on mosquito populations, including their mating competiveness. To fill this knowledge gap, coupled and uncoupled Anopheles gambiae s.l. males (all M form (Anopheles coluzzii)) were collected from mating swarms in Burkina Faso. This multiple insecticide resistant population exhibited high 1014F kdrR allele frequencies (460%) and RDLR (480%) in contrast to the Ace-1R allele (o6%). Kdr heterozygote males were more likely to mate than homozygote resistant (OR=2.36; Po0.001), suggesting a negative impact of kdr on An. coluzzii mating ability. Interestingly, heterozygote males were also more competitive than homozygote susceptible (OR=3.26; P=0.006), suggesting a heterozygote advantage effect. Similarly, heterozygote RDLR/RDLS were also more likely to mate than homozygote-resistant males (OR=2.58; P=0.007). Furthermore, an additive mating disadvantage was detected in male homozygotes for both kdr/RDL-resistant alleles. In contrast, no fitness difference was observed for the Ace-1 mutation. Comparative microarray-based genome-wide transcription analysis revealed that metabolic resistance did not significantly alter the mating competitiveness of male An. coluzzii mosquitoes. Indeed, no significant difference of expression levels was observed for the main metabolic resistance genes, suggesting that metabolic resistance has a limited impact on male mating competiveness. In addition, specific gene classes/GO terms associated with mating process were detected including sensory perception and peroxidase activity. The detrimental impact of insecticide resistance on mating competiveness observed here suggests that resistance management strategies such as insecticide rotation could help reverse the resistance, if implemented early

Pleiotropic Effects of DDT Resistance on Male Size and Behaviour

Understanding the evolution and spread of insecticide resistance requires knowing the relative fitness of resistant organisms. In the absence of insecticides, resistance is predicted to be costly. The Drosophila melanogaster DDT resistance allele (DDT-R) is associated with a male mating cost. This could be because resistant males are generally smaller, but DDT-R may also alter courtship behaviours. Here we tested for body size and courtship effects of DDT-R on mating success in competitive and non-competitive mating trials respectively. We also assessed relative aggression in resistant and susceptible males because aggression can also influence mating success. While the effect of DDT-R on male size partly contributed to reduced mating success, resistant males also had lower rates of courtship and were less aggressive than susceptible males. These differences contribute to the observed DDT-R mating costs. Additionally, these pleiotropic effects of DDT-R are consistent with the history and spread of resistance alleles in nature

Analyzing Childlessness

Childlessness has been on the rise in many European societies. In Germany, the UK, Austria, the Netherlands, and Switzerland, childlessness has increased starting with the 1950s cohorts. In these countries, about 20 % of the women born around 1965 will remain childless. In southern Europe and the former state-socialist countries of Central and Eastern Europe, the rise in levels of childlessness is a more recent phenomenon. Yet among younger cohorts in these countries, childlessness has reached levels of 15 % or higher. In this introductory chapter, we summarize the long-term trends in childlessness and discuss the differences between European countries in the prevalence of childlessness. We also outline the structure and the logic of this volume

The gut microbiota: a major player in the toxicity of environmental pollutants?

Exposure to environmental chemicals has been linked to various health disorders, including obesity, type 2 diabetes, cancer and dysregulation of the immune and reproductive systems, whereas the gastrointestinal microbiota critically contributes to a variety of host metabolic and immune functions. We aimed to evaluate the bidirectional relationship between gut bacteria and environmental pollutants and to assess the toxicological relevance of the bacteria–xenobiotic interplay for the host. We examined studies using isolated bacteria, faecal or caecal suspensions—germ-free or antibiotic-treated animals—as well as animals reassociated with a microbiota exposed to environmental chemicals. The literature indicates that gut microbes have an extensive capacity to metabolise environmental chemicals that can be classified in five core enzymatic families (azoreductases, nitroreductases, β-glucuronidases, sulfatases and β-lyases) unequivocally involved in the metabolism of >30 environmental contaminants. There is clear evidence that bacteria-dependent metabolism of pollutants modulates the toxicity for the host. Conversely, environmental contaminants from various chemical families have been shown to alter the composition and/or the metabolic activity of the gastrointestinal bacteria, which may be an important factor contributing to shape an individual’s microbiotype. The physiological consequences of these alterations have not been studied in details but pollutant-induced alterations of the gut bacteria are likely to contribute to their toxicity. In conclusion, there is a body of evidence suggesting that gut microbiota are a major, yet underestimated element that must be considered to fully evaluate the toxicity of environmental contaminants

Time to Pregnancy for Women Using a Fertility Awareness Based Mobile Application to Plan a Pregnancy

Background: Time to pregnancy (TTP) is a biomarker of fecundability and has been associated with behavioral and environmental characteristics; however, these associations have not been examined in a large population-based sample of application (app) users. Materials and Methods: This observational study followed 5,376 women with an age range of 18 to 45 years who used an app to identify their fertile window. We included women who started trying to conceive between September 30, 2017 and August 31, 2018. TTP was calculated as the number of menstrual cycles from when the user switched to "Plan" mode up to and including the cycle in which they logged a positive pregnancy test. We examined associations with several characteristics, including age, gravidity, body mass index, cycle length and cycle length variation, frequency of sexual intercourse, and temperature measuring frequency. Discrete time fecundability models were used to estimate fecundability odds ratios. Results: For the complete cohort the 6-cycle and 12-cycle cumulative pregnancy probabilities were found to be 61% (95% confidence interval [CI]: 59-62) and 74% (95% CI: 73-76), respectively. The median TTP was four cycles. The highest fecundability was associated with an age of less than 35 years, with cycle length variation <5 days and logging sexual intercourse on at least 20% of days added (the proportion of days in which intercourse was logged) (11.5% [n = 613] of entire sample). This group achieved a 6- and 12-cycle cumulative pregnancy probability of 88% (95% CI: 85-91) and 95% (95% CI: 94-97), respectively, and a TTP of 2 cycles. Conclusions: Natural Cycles was an effective method of identifying the fertile window and a noninvasive educational option for women planning a pregnancy. Women under age 35 with regular cycles showed a high pregnancy rate