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The immune equilibrium model suggests that exposure to microbes during early life primes immune responses for pathogen exposure later in life. While recent studies using a range of gnotobiotic (germ-free) model organisms offer support for this theory, we currently lack a tractable model system for investigating the influence of the microbiome on immune system development. Here, we used an amphibian species ( Xenopus laevis ) to investigate the importance of the microbiome in larval development and susceptibility to infectious disease later in life. We found that experimental reductions of the microbiome during embryonic and larval stages effectively reduced microbial richness, diversity and altered community composition in tadpoles prior to metamorphosis. In addition, our antimicrobial treatments resulted in few negative effects on larval development, body condition, or survival to metamorphosis. However, contrary to our predictions, our antimicrobial treatments did not alter susceptibility to the lethal fungal pathogen Batrachochytrium dendrobatidis ( Bd ) in the adult life stage. While our treatments to reduce the microbiome during early development did not play a critical role in determining susceptibility to disease caused by Bd in X. laevis , they nevertheless indicate that developing a gnotobiotic amphibian model system may be highly useful for future immunological investigations. This article is part of the theme issue ‘Amphibian immunity: stress, disease and ecoimmunology’. 

To combat the loss of species due to emerging infectious diseases, scientists must incorporate ecological parameters, such as temperature and humidity, to understand how the environment affects host–pathogen interactions. The fungal disease chytridiomycosis is a compelling case study to investigate the role of both temperature and humidity on infectious disease, as both the fungal pathogen (Batrachochytrium dendrobatidis, Bd) and the host (amphibians) are heavily influenced by these abiotic factors. We performed two experiments to investigate the importance of relative humidity and temperature on frog immunity (production of antimicrobial skin secretions) and disease development in captive golden frogs (Atelopus zeteki) of Panama. We found that the quantity of skin secretions significantly decreased over time in frogs moved from low to medium and high relative humidity treatments. FollowingBdexposure, frogs in high temperature (26–27 °C) and high relative humidity (80–90%) had lower pathogen loads and survived significantly longer than frogs kept in all other treatment conditions, including high temperature and low relative humidity. These results suggest that high relative humidity may be an important, although less understood, mediator ofBdinfection and the survival of golden frogs. Because the environment can drastically alter disease dynamics, understanding how temperature and humidity influence chytridiomycosis outcomes in golden frogs may be essential for the success of the reintroduction of captive frogs.

 

The nanomachine from the ATPases associated with various cellular activities superfamily, called spastin, severs microtubules during cellular processes. To characterize the functionally important allostery in spastin, we employed methods from evolutionary information, to graph-based networks, to machine learning applied to atomistic molecular dynamics simulations of spastin in its monomeric and the functional hexameric forms, in the presence or absence of ligands. Feature selection, using machine learning approaches, for transitions between spastin states recognizes all the regions that have been proposed as allosteric or functional in the literature. The analysis of the composition of the Markov State Model macrostates in the spastin monomer, and the analysis of the direction of change in the top machine learning features for the transitions, indicate that the monomer favors the binding of ATP, which primes the regions involved in the formation of the inter-protomer interfaces for binding to other protomer(s). Allosteric path analysis of graph networks, built based on the cross-correlations between residues in simulations, shows that perturbations to a hub specific for the pre-hydrolysis hexamer propagate throughout the structure by passing through two obligatory regions: the ATP binding pocket, and pore loop 3, which connects the substrate binding site to the ATP binding site. Our findings support a model where the changes in the terminal protomers due to the binding of ligands play an active role in the force generation in spastin. The secondary structures in spastin, which are found to be highly degenerative within the network paths, are also critical for feature transitions of the classification models, which can guide the design of allosteric effectors to enhance or block allosteric signaling. 

Abstract Introduction In Rwanda, only 20% of sexually active unmarried young women use family planning as compared to 64% of married women. Adolescence is an important time of growth and development that often includes the initiation of sexual activity. Sexually active adolescents need support in accessing contraceptive services to prevent negative health outcomes. In sub-Saharan Africa, the adolescent population represents a large share of the total population and that proportion is predicted to expand over time. Adolescent contraceptive needs have largely been unmet, and with growing numbers, there is increased potential for negative health sequelae. Due to the low use of contraception by adolescents in Rwanda, and the growing population of adolescents, this study aims to explore the perspectives of family planning providers and adult modern contraceptive users on adolescent contraceptive use. Inclusion of adult community members in the study is a unique contribution, as research on adolescent contraceptive use in sub-Saharan Africa relies primarily on perspectives from adolescents and family planning providers. Methods This qualitative study in 2018 utilized 32 in-depth interviews with modern contraceptive users and eight focus group discussions with family planning providers. Respondents were from Musanze and Nyamasheke districts in Rwanda, the districts with the highest and lowest modern contraceptive use among married women, respectively. Coding was conducted in Atlas.ti. Results Stigma regarding premarital sex results in barriers to adolescent access to contraceptive services. Family planning providers do provide services to adolescents; however, they often recommend secondary abstinence, offer a limited method selection, and accentuate risks associated with sexual activity and contraceptive use. Providers support adolescent clients by emphasizing the need for privacy, confidentiality, and expedient services, particularly through youth corners, which are spaces within health facilities designed to meet youth needs specifically. Modern contraceptive-using adult female community members advocate for youth access to contraception, however mothers have mixed comfort discussing sexual health with their own youth. Conclusion To destigmatize premarital sexual activity, government efforts to initiate communication about this topic must occur at national and community levels with the goal of continued conversation within the family. The government should also train family planning providers and all health personnel interacting with youth on adolescent-friendly health services. Dialogue between community members and family planning providers about adolescent access to contraceptive services could also reduce barriers for adolescents due to community members’ generally supportive views on adolescent contraceptive use. Efforts to engage adolescent caregivers in how to talk to youth about sex could also contribute to expanded use. 

Abstract Background Contraceptive use in Rwanda tripled since 2005. This study aims to understand the role of coordinated and integrated public family planning service delivery in achieving this increase in contraceptive use in Rwanda. Methods This qualitative study in 2018 included eight focus group discussions with family planning providers and 32 in-depth interviews with experienced family planning users. Results Results indicate a well-coordinated public family planning service delivery system with community health workers and nurses filling different and complementary roles in meeting family planning client needs at the local level. In addition, integration of family planning into other maternal and child health services is the norm. Conclusions The coordination and integration of family planning across both providers and services may help explain the rapid increase in Rwanda’s contraceptive use and has potential applications for enhancing family planning service delivery in other settings. 

In Rwanda, nearly a third of contraceptive users discontinue within the first year of use. Family planning programs often focus more on recruitment of new users as opposed to maintaining use among current users. A focus on sustaining users and minimizing discontinuation is imperative for long-term family planning program success. This study explores the efforts providers and contraceptive users in Rwanda employ to prevent one of the greatest challenges to family planning programs: contraceptive discontinuation.

This was a qualitative study conducted in Rwanda between February and July 2018. It included eight focus group discussions with 88 family planning providers and 32 in-depth interviews with experienced modern contraceptive users. Data were collected in two districts with the highest (Musanze) and lowest (Nyamasheke) rates of contraceptive use. Data were analyzed using thematic content approach.

Family planning providers in this study used the following strategies to prevent discontinuation: counseling new users on the potential for side effects and switching, reminding clients about appointments for resupply, as well as supporting dissatisfied users by providing counseling, medicine for side effects, and discussing options for switching methods. Users, on the other hand, employed the following strategies to prevent discontinuation: having an understanding that experiences of side effects vary by individuals, supporting peers to sustain use, persisting with use despite experiences of side effects, and switching methods.

The strategies used by family planning providers and users in Rwanda to prevent discontinuation suggest the possibility of long-term sustained use of contraception in the country. Harnessing and supporting such strategies could contribute to sustaining or improving further contraceptive use in the country.