CRISPR-mediated germline mutagenesis for genetic sterilization of Anopheles gambiae males.

Rapid spread of insecticide resistance among anopheline mosquitoes threatens malaria elimination efforts, necessitating development of alternative vector control technologies. Sterile insect technique (SIT) has been successfully implemented in multiple insect pests to suppress field populations by the release of large numbers of sterile males, yet it has proven difficult to adapt to Anopheles vectors. Here we outline adaptation of a CRISPR-based genetic sterilization system to selectively ablate male sperm cells in the malaria mosquito Anopheles gambiae. We achieve robust mosaic biallelic mutagenesis of zero population growth (zpg, a gene essential for differentiation of germ cells) in F1 individuals after intercrossing a germline-expressing Cas9 transgenic line to a line expressing zpg-targeting gRNAs. Approximately 95% of mutagenized males display complete genetic sterilization, and cause similarly high levels of infertility in their female mates. Using a fluorescence reporter that allows detection of the germline leads to a 100% accurate selection of spermless males, improving the system. These males cause a striking reduction in mosquito population size when released at field-like frequencies in competition cages against wild type males. These findings demonstrate that such a genetic system could be adopted for SIT against important malaria vectors.

CRISPR-mediated germline mutagenesis for genetic sterilization of Anopheles gambiae males.

Rapid spread of insecticide resistance among anopheline mosquitoes threatens malaria elimination efforts, necessitating development of alternative vector control technologies. Sterile Insect Technique (SIT) has been successfully implemented in multiple insect pests to suppress field populations by the release of large numbers of sterile males, yet it has proven difficult to adapt to Anopheles vectors. Here we outline adaptation of a CRISPR-based genetic sterilization system to selectively ablate male sperm cells in the malaria mosquito Anopheles gambiae. We achieve robust mosaic biallelic mutagenesis of zero population growth (zpg, a gene essential for differentiation of germ cells) in F1 individuals after intercrossing a germline-expressing Cas9 transgenic line to a line expressing zpg-targeting gRNAs. Approximately 95% of mutagenized males display complete genetic sterilization, and cause similarly high levels of infertility in their female mates. Using a fluorescence reporter that allows detection of the germline leads to a 100% accurate selection of spermless males, improving the system. These males cause a striking reduction in mosquito population size when released at field-like frequencies in competition cages against wild type males. These findings demonstrate that such a genetic system could be adopted for SIT against important malaria vectors.

Targeting malaria parasites inside mosquitoes: ecoevolutionary consequences.

Proof-of-concept studies demonstrate that antimalarial drugs designed for human treatment can also be applied to mosquitoes to interrupt malaria transmission. Deploying a new control tool is ideally undertaken within a stewardship programme that maximises a drug's lifespan by minimising the risk of resistance evolution and slowing its spread once emerged. We ask: what are the epidemiological and evolutionary consequences of targeting parasites within mosquitoes? Our synthesis argues that targeting parasites inside mosquitoes (i) can be modelled by readily expanding existing epidemiological frameworks; (ii) provides a functionally novel control method that has potential to be more robust to resistance evolution than targeting parasites in humans; and (iii) could extend the lifespan and clinical benefit of antimalarials used exclusively to treat humans.

Using an antimalarial in mosquitoes overcomes Anopheles and Plasmodium resistance to malaria control strategies.

The spread of insecticide resistance in Anopheles mosquitoes and drug resistance in Plasmodium parasites is contributing to a global resurgence of malaria, making the generation of control tools that can overcome these roadblocks an urgent public health priority. We recently showed that the transmission of Plasmodium falciparum parasites can be efficiently blocked when exposing Anopheles gambiae females to antimalarials deposited on a treated surface, with no negative consequences on major components of mosquito fitness. Here, we demonstrate this approach can overcome the hurdles of insecticide resistance in mosquitoes and drug resistant in parasites. We show that the transmission-blocking efficacy of mosquito-targeted antimalarials is maintained when field-derived, insecticide resistant Anopheles are exposed to the potent cytochrome b inhibitor atovaquone, demonstrating that this drug escapes insecticide resistance mechanisms that could potentially interfere with its function. Moreover, this approach prevents transmission of field-derived, artemisinin resistant P. falciparum parasites (Kelch13 C580Y mutant), proving that this strategy could be used to prevent the spread of parasite mutations that induce resistance to front-line antimalarials. Atovaquone is also highly effective at limiting parasite development when ingested by mosquitoes in sugar solutions, including in ongoing infections. These data support the use of mosquito-targeted antimalarials as a promising tool to complement and extend the efficacy of current malaria control interventions.

Public Intention to Prepare for Earthquakes: Psychometric Properties of Persian Version.

BACKGROUND: People are still not prepared for earthquakes in vulnerable areas although preparedness considered an effective way of reducing the disastrous consequences. A proper tool was needed to assess the predicting factors of mitigation behaviors in a large vulnerable community who speak Persian. This study aimed to introduce the valid and reliable Persian version of public intention to prepare against earthquakes. METHODS: Translation, validation and reliability checking articulated according to the standard methodology for Forward-Backward translation and psychometric evaluation. Totally, 369 Tehran households were selected through stratified random sampling from Oct 2016 to Jun 2017. Exploratory Factor Analysis used to check the construct validity of all scales. RESULTS: Face, content and construct validity of all scales confirmed (S-CVR: .65) and (S-CVI/Universal: .98). The finalized Persian version (69 items in 8 scales) showed good reliability over time in test-retest (ICC: .92) and high internal consistency both in the pilot (α: .94) and main studies (α: .94). No significant floor and ceiling effects were found in any of scales. CONCLUSION: Persian version of Earthquake Public Intention to Prepare is applicable as a valid and reliable instrument for research regarding disaster preparedness in Persian speaking communities.

Individuals of refugee background resettled in regional and rural Australia: A systematic review of mental health research.

INTRODUCTION: The Australian Government aims to increase the number of individuals on humanitarian resettlement visas allocated to regional locations to 50% by the year 2022. A significant issue with this, given the substantive body of research identifying that refugee populations face chronic mental health concerns during resettlement, is the lack of health-related research focusing on the resettlement of individuals of refugee background to rural and regional locations in Australia, especially in the area of mental health. OBJECTIVE: To provide a foundation for rectifying this omission, this review is the first to synthesise mental health research focusing on individuals of refugee background specifically resettled to rural and regional locations in Australia. DESIGN: The review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Findings were synthesised using thematic analytic techniques. FINDINGS: 14 relevant studies (3 quantitative, one mixed-method, 10 qualitative) were identified. Findings indicated that individuals of refugee background resettled in rural and regional Australia not only experienced higher levels of psychological distress than the general population but also had significant difficulty and limited options when accessing mental health services. Furthermore, resettlement in rural and regional locations increased the risk of experiencing many interrelated factors associated with adverse mental health outcomes and distress, including very limited access to support services, with the latter being identified as vital for well-being. CONCLUSION: This review highlights the disparity between the Australian Government's policies and plans regarding regional resettlement, what is happening on the ground, and identifies key gaps in research and practice which must be addressed.

A qualitative investigation of mental health in women of refugee background resettled in Tasmania, Australia.

BACKGROUND: Women of Refugee Background (WoRB) are a highly vulnerable population with complex going mental health needs following resettlement. In Australia, there has been a substantial increase in WoRB being resettled in rural and regional locations. Despite this, no research to date has specifically focused on factors contributing to mental distress in WoRB in regional resettlement locations. The current study aimed to address this gap in literature. METHODS: 21 semi-structured qualitative interviews were conducted with WoRB and service providers in regional locations of Tasmania, Australia. Interviews were audio recorded and transcribed verbatim. Transcripts were analysed utilising Braun and Clarke (Qual Res Psychol 3(2):77-101, 2006) framework for conducting thematic analysis. RESULTS: Thematic analysis revealed that WoRB conceptualised mental health as a pathogenic entity, which significantly influenced their mental health help-seeking behaviours. The findings also highlighted how resettlement to a rural and regional location of Australia may exacerbate many of the factors which contribute to ongoing mental distress in WoRB. CONCLUSIONS: The findings of the current study build upon existing research which indicates the adverse impacts post-migrations stressors can have on the mental health of individuals of refugee background. Furthermore, this study suggests that the current services and supports available to WoRB resettled in regional locations of Australia are inadequate, and under-resources. These findings are discussed in regard to practical and policy implications which should be addressed to better support the mental health of WoRB resettled in rural and regional locations of Australia.

Exploring Resilience, Coping and Wellbeing in Women of Refugee Background Resettled in Regional Australia.

This study aimed to address a significant gap in the literature by investigating how Women of Refugee Background (WoRB) conceptualise resilience and identify factors that WoRB endorse as contributing to their wellbeing and coping during resettlement. Qualitative interviews were conducted with a group of 21 individuals (nine WoRB and 12 service providers). Thematic analysis identified that WoRB struggled to define resilience, with endorsed factors not fitting with current hegemonic Western understandings and theoretical understandings of resilience. The findings also highlighted how religious practice, finding a community and having a sense of meaning and contribution in their daily life were significant coping and wellbeing factors during resettlement, however, were difficult to access in regional resettlement locations. Results of the current study are discussed regarding theoretical and practical implications, taking into consideration the unique vulnerabilities experienced by WoRB resettled in regional locations of Australia.

Cuticular hydrocarbons are associated with mating success and insecticide resistance in malaria vectors.

Anopheles coluzzii females, important malaria vectors in Africa, mate only once in their lifetime. Mating occurs in aerial swarms with a high male-to-female ratio, where traits underlying male mating success are largely unknown. Here, we investigated whether cuticular hydrocarbons (CHCs) influence mating success in natural mating swarms in Burkina Faso. As insecticides are widely used in this area for malaria control, we also determined whether CHCs affect insecticide resistance levels. We find that mated males have higher CHC abundance than unmated controls, suggesting CHCs could be determinants of mating success. Additionally, mated males have higher insecticide resistance under pyrethroid challenge, and we show a link between resistance intensity and CHC abundance. Taken together, our results suggest that CHC abundance may be subject to sexual selection in addition to selection by insecticide pressure. This has implications for insecticide resistance management, as these traits may be sustained in the population due to their benefits in mating even in the absence of insecticides.

Resettlement Stressors for Women of Refugee Background Resettled in Regional Australia.

Women of Refugee Background (WoRB) have been repeatedly identified as an extremely vulnerable population. Within an Australian context, WoRB are increasingly resettled to non-metropolitan locations, otherwise known as regional locations. Despite this, to date, no research has focused on the lived experience and challenges associated with the resettlement of WoRB to regional contexts. This study aimed to address this gap in the literature by investigating the resettlement experience of WoRB resettled in Tasmania-a state in Australia classified as a rural and regional location. Qualitative interviews were conducted with a group of 21 individuals (nine WoRB and 12 service providers). Thematic analysis identified four overarching themes-Communication Barriers and Lack of Fluency in English, Challenges Accessing Everyday Basic Needs, Loss of Connection to Culture of Origin and Inability to Access Mainstream Mental Health Services for Help. Participants also highlighted a number of unique gender-related vulnerabilities experienced during resettlement, which were exacerbated in regional locations due to health services being overstretched and under-resourced. Results of the current study are discussed in regard to policy and practical implications, taking into consideration the unique vulnerabilities experienced by WoRB, which, to date, are often overlooked.

Professional mental health support seeking in Women of Refugee Background resettled in Australia: An exploratory study of facilitators and barriers.

The present study is the first to investigate factors influencing professional mental health support seeking in Women of Refugee Background (WoRB) in Australia. WoRB are a vulnerable population with a range of complex mental health needs. Despite this, research has indicated that WoRB are an underrepresented population in the utilisation of mental health support services. This is a particular concern in Australia, due to an increasing number of WoRB being resettled. A multivariate logistical regression was conducted on a sample of 450 WoRB resettled in Australia from the Building a New Life in Australia (BNLA) data set to investigate factors associated with seeking professional mental health support. Several factors were identified as being significantly associated with professional mental health support seeking in WoRB resettled in Australia, including age, resettlement location, marital status, prearrival trauma involving violence against women, language barriers and health-related variables, including mental distress and long-term disability. The current study provides a unique insight into professional mental health support seeking from a gendered perspective in WoRB resettled in Australia. Insights into factors that influence seeking professional mental health support in this highly vulnerable population must inform mental health practice, service delivery and policies.

Facilitating Sustainable Disaster Risk Reduction in Indigenous Communities: Reviving Indigenous Worldviews, Knowledge, and Practices through Two-Way Partnering.

The Sendai Framework of Action 2015-2030 calls for holistic Indigenous disaster risk reduction (DRR) research. Responding to this call, we synergized a holistic philosophical framework (comprising ecological systems theory, symbolic interactionism, and intersectionality) and social constructionist grounded theory and ethnography within a critical Indigenous research paradigm as a methodology for exploring how diverse individual and contextual factors influence DRR in a remote Indigenous community called Galiwinku, in the Northern Territory of Australia. Working together, Indigenous and non-Indigenous researchers collected stories in local languages using conversations and yarning circles with 20 community members, as well as participant observations. The stories were interpreted and analysed using social constructivist grounded theory analysis techniques. The findings were dialogued with over 50 community members. The findings deeply resonated with the community members, validating the trustworthiness and relevance of the findings. The grounded theory that emerged identified two themes. First, local Indigenous knowledge and practices strengthen Indigenous people and reduce the risks posed by natural hazards. More specifically, deep reciprocal relationships with country and ecological knowledge, strong kinship relations, Elder's wisdom and authority, women and men sharing power, and faith in a supreme power/God and Indigenous-led community organizations enable DRR. Second, colonizing practices weaken Indigenous people and increase the risks from natural hazards. Therefore, colonization, the imposition of Western culture, the government application of top-down approaches, infiltration in Indigenous governance systems, the use of fly-in/fly-out workers, scarcity of employment, restrictions on technical and higher education opportunities, and overcrowded housing that is culturally and climatically unsuitable undermine the DRR capability. Based on the findings, we propose a Community-Based DRR theory which proposes that facilitating sustainable Indigenous DRR in Australian Indigenous communities requires Indigenous and non-Indigenous partners to genuinely work together in two-directional and complementary ways.

Multiple blood feeding in mosquitoes shortens the Plasmodium falciparum incubation period and increases malaria transmission potential.

Many mosquito species, including the major malaria vector Anopheles gambiae, naturally undergo multiple reproductive cycles of blood feeding, egg development and egg laying in their lifespan. Such complex mosquito behavior is regularly overlooked when mosquitoes are experimentally infected with malaria parasites, limiting our ability to accurately describe potential effects on transmission. Here, we examine how Plasmodium falciparum development and transmission potential is impacted when infected mosquitoes feed an additional time. We measured P. falciparum oocyst size and performed sporozoite time course analyses to determine the parasite's extrinsic incubation period (EIP), i.e. the time required by parasites to reach infectious sporozoite stages, in An. gambiae females blood fed either once or twice. An additional blood feed at 3 days post infection drastically accelerates oocyst growth rates, causing earlier sporozoite accumulation in the salivary glands, thereby shortening the EIP (reduction of 2.3 ± 0.4 days). Moreover, parasite growth is further accelerated in transgenic mosquitoes with reduced reproductive capacity, which mimic genetic modifications currently proposed in population suppression gene drives. We incorporate our shortened EIP values into a measure of transmission potential, the basic reproduction number R0, and find the average R0 is higher (range: 10.1%-12.1% increase) across sub-Saharan Africa than when using traditional EIP measurements. These data suggest that malaria elimination may be substantially more challenging and that younger mosquitoes or those with reduced reproductive ability may provide a larger contribution to infection than currently believed. Our findings have profound implications for current and future mosquito control interventions.

Sustaining a Transformative Disaster Risk Reduction Strategy: Grandmothers' Telling and Singing Tsunami Stories for over 100 Years Saving Lives on Simeulue Island.

As projections about the number and scale of natural hazard events and their impact on human populations grow, increasing attention is being paid to developing effective means for preparing for and mitigating those impacts. At the same time there is an emerging understanding that gradual and incremental changes in disaster risk reduction (DRR) will not adequately meet the future needs of vulnerable populations. Transformational changes have been identified as a necessary requirement to avoid ongoing large-scale losses of life and property and models have been proposed to recalibrate DRR strategies to achieve transformative changes. One cited example of a transformative change in DRR is that of Simeulue Island. Simeulue Island suffered two tsunamis approximately 100 years apart (1907, 2004) with markedly different impacts. This paper looks in detail at the cognitive and developmental mechanisms Simeulue co-opted to sustain the transformational change throughout the 20th century. Information from interviews and observation identified the role of grandmothers have in the effective communication of risk as well as motivating appropriate action to save lives. The possibility of similarly overlooked, local, and pre-existing community capacities for transformative change in DRR is then discussed.

A steroid hormone agonist reduces female fitness in insecticide-resistant Anopheles populations.

Insecticide based vector control tools such as insecticide treated bednets and indoor residual spraying represent the cornerstones of malaria control programs. Resistance to chemistries used in these programs is now widespread and represents a significant threat to the gains seen in reducing malaria-related morbidity and mortality. Recently, disruption of the 20-hydroxyecdysone steroid hormone pathway was shown to reduce Plasmodium development and significantly reduce both longevity and egg production in a laboratory susceptible Anopheles gambiae population. Here, we demonstrate that disruption of this pathway by application of the dibenzoylhydrazine, methoxyfenozide (DBH-M), to insecticide resistant An. coluzzii, An. gambiae sl and An. funestus populations significantly reduces egg production in both topical and tarsal application. Moreover, DBH-M reduces adult longevity when applied topically, and tarsally after blood feeding. As the cytochrome p450s elevated in pyrethroid resistant Anopheles only bind DBH-M very weakly, this compound is unlikely to be subject to cross-resistance in a field-based setting. Manipulation of this hormonal signalling pathway therefore represents a potential complementary approach to current malaria control strategies, particularly in areas where high levels of insecticide resistance are compromising existing tools.

Enhancing Social and Emotional Wellbeing of Aboriginal Boarding Students: Evaluation of a Social and Emotional Learning Pilot Program.

Boarding schools can provide quality secondary education for Aboriginal students from remote Aboriginal Australian communities. However, transition into boarding school is commonly challenging for Aboriginal students as they need to negotiate unfamiliar cultural, social and learning environments whilst being separated from family and community support. Accordingly, it is critical for boarding schools to provide programs that enhance the social and emotional skills needed to meet the challenges. This study evaluated a 10-session social and emotional learning (SEL) program for Aboriginal boarders and identified contextual factors influencing its effectiveness. The study combined a pre-post quantitative evaluation using diverse social and emotional wellbeing measures with 28 students between 13-15 years (10 female, 11 male, 7 unidentified) and qualitative post focus groups with 10 students and episodic interviews with four staff delivering the program. Students' social and emotional skills significantly improved. The qualitative findings revealed improvements in students seeking and giving help, working in groups, managing conflict, being assertive and discussing cultural issues. The focus groups and interviews also identified program elements that worked best and that need improvement. Secure relationships with staff delivering the program and participation in single sex groups stood out as critical enablers. The findings lend evidence to the critical importance of collaborative design, provision and evaluation of SEL programs with Aboriginal peoples.

Risk, Transformation and Adaptation: Ideas for Reframing Approaches to Disaster Risk Reduction.

Recognition of projected increases in exposure to large-scale hazard events over the coming decades has identified a need to develop how disaster risk reduction and recovery are conceptualized and enacted. This paper discusses some strategies for pursing this goal in both disaster recovery and preparedness settings. The approaches discussed include understanding how communities learn from their hazardous experiences and transform these lessons into beliefs, relationships and capabilities that build future adaptive capacity. The paper draws on examples of transformative learning that illustrate how people can make fundamental shifts in how they think about, prepare for and respond to environmental challenge and change. Regarding transformation in pre-event settings, the paper first discusses why the addition of transformative strategies to disaster risk reduction programs is required. These include a need for rethinking socio-environmental relationships, increasing risk acceptance in the context of evolving hazardscapes, and countering beliefs regarding not preparing. The paper then offers strategies for motivating transformation and consolidating the outcomes of transformation in pre-event disaster risk reduction (DRR) strategies. A preliminary model that could inform the development of research questions on the development of transformative outcomes and their consolidation in enduring adaptive processes is presented.

Steroid Hormone Function Controls Non-competitive Plasmodium Development in Anopheles.

Transmission of malaria parasites occurs when a female Anopheles mosquito feeds on an infected host to acquire nutrients for egg development. How parasites are affected by oogenetic processes, principally orchestrated by the steroid hormone 20-hydroxyecdysone (20E), remains largely unknown. Here we show that Plasmodium falciparum development is intimately but not competitively linked to processes shaping Anopheles gambiae reproduction. We unveil a 20E-mediated positive correlation between egg and oocyst numbers; impairing oogenesis by multiple 20E manipulations decreases parasite intensities. These manipulations, however, accelerate Plasmodium growth rates, allowing sporozoites to become infectious sooner. Parasites exploit mosquito lipids for faster growth, but they do so without further affecting egg development. These results suggest that P. falciparum has adopted a non-competitive evolutionary strategy of resource exploitation to optimize transmission while minimizing fitness costs to its mosquito vector. Our findings have profound implications for currently proposed control strategies aimed at suppressing mosquito populations.

Exposing Anopheles mosquitoes to antimalarials blocks Plasmodium parasite transmission.

Bites of Anopheles mosquitoes transmit Plasmodium falciparum parasites that cause malaria, which kills hundreds of thousands of people every year. Since the turn of this century, efforts to prevent the transmission of these parasites via the mass distribution of insecticide-treated bed nets have been extremely successful, and have led to an unprecedented reduction in deaths from malaria1. However, resistance to insecticides has become widespread in Anopheles populations2-4, which has led to the threat of a global resurgence of malaria and makes the generation of effective tools for controlling this disease an urgent public health priority. Here we show that the development of P. falciparum can be rapidly and completely blocked when female Anopheles gambiae mosquitoes take up low concentrations of specific antimalarials from treated surfaces-conditions that simulate contact with a bed net. Mosquito exposure to atovaquone before, or shortly after, P. falciparum infection causes full parasite arrest in the midgut, and prevents transmission of infection. Similar transmission-blocking effects are achieved using other cytochrome b inhibitors, which demonstrates that parasite mitochondrial function is a suitable target for killing parasites. Incorporating these effects into a model of malaria transmission dynamics predicts that impregnating mosquito nets with Plasmodium inhibitors would substantially mitigate the global health effects of insecticide resistance. This study identifies a powerful strategy for blocking Plasmodium transmission by female Anopheles mosquitoes, which has promising implications for efforts to eradicate malaria.

Communication With Children and Families About Disaster: Reviewing Multi-disciplinary Literature 2015-2017.

PURPOSE OF REVIEW: To identify strategies for communicating with youth and children pre- and post-disaster in the context of a broader survey of child participation in disaster risk reduction as well as methods for communication with children. RECENT FINDINGS: Youth and children are capable of peer and community education and activism concerning disaster issues and such participation benefits the young actors. Family and sibling support are important in easing the impact of trauma on children. Contemporary forms of psychological first aid appear to do no harm and in line with current evidence. Generally, more evidence from evaluations is necessary to guide the development of communication strategies. Children are growing up in increasingly urban environments with less contact with nature and greater reliance on techno-social systems. Thus, young people may misunderstand natural hazards. Schools and conscious parenting can play important roles in building understanding and psychological resilience.