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1.
Glob Health Promot ; 27(4): 157-163, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32794419

ABSTRACT

In 2017, the Institute of Tropical Medicine Pedro Kourí, University of Montreal Public Health Research Institute, and McGill University joined efforts to provide scenarios for scientific exchange and knowledge dissemination about the social science contribution on arboviral research. This commentary describes the scientific collaboration between Cuban and Canadian (Quebec) institutions, illustrating the need and opportunities to facilitate research and effective decision-making processes for arboviral prevention and control, going beyond traditional biomedical aspects. We organized a set of scientific activities within three international events conducted in Cuba between 2017 and 2018. Given the collaborating institutions' expertise and the knowledge gaps in arboviral research, we selected three main thematic areas: social determinants and equity, community-based interventions and use of evidence for decision-making. The partnership shows that interdisciplinary collaboration and the use and integration of quantitative and qualitative methods from the social sciences is essential to face the current challenges in arbovirus research.


Subject(s)
Arboviruses , Canada , Humans , Public Health , Quebec , Social Sciences
2.
Implement Sci ; 15(1): 32, 2020 05 14.
Article in English | MEDLINE | ID: mdl-32408903

ABSTRACT

BACKGROUND: A community-based dengue fever intervention was implemented in Burkina Faso in 2017. The results achieved vary from one area to another. The objective of this article is to analyze the implementation of this intervention, to better understand the process, and to explain the contextual elements of performance variations in implementation. METHODOLOGY: The research was conducted in the former sector 22 of the city of Ouagadougou. We adapted the Consolidated Framework for Implementation Research (CFIR) to take into account the realities of the context and the intervention. The data collected from the participants directly involved in the implementation using three techniques: document consultation, individual interview, and focus group. RESULTS: Two dimensions of CFIR emerge from the results as having had a positive influence on the implementation: (i) the characteristics of the intervention and (ii) the processes of the intervention implementation. The majority of the CFIR constructions were considered to have had a positive effect on implementation. The quality and strength of the evidence received the highest score. The dimension of the external context had a negative influence on the implementation of the intervention. CONCLUSION: The objective of the study was to analyze the influence of contextual elements on the implementation process of a community-based dengue fever intervention. We used the CFIR framework already used by many studies for implementation analysis. Although it was not possible to test this framework in its entirety, it is useful for the analysis of the implementation. Its use is simple and does not require any special skills from users. Usability is indeed an essential criterion for the relevance of using an analytical framework in implementation science.


Subject(s)
Communicable Disease Control/organization & administration , Dengue/prevention & control , Health Promotion/organization & administration , Implementation Science , Adult , Aged , Burkina Faso , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Middle Aged , Program Evaluation
3.
Trials ; 21(1): 182, 2020 Feb 14.
Article in English | MEDLINE | ID: mdl-32059693

ABSTRACT

BACKGROUND: Dengue is increasing in its global presence with an estimated 4 billion people at-risk of infection in at least 128 countries. Despite the promising results of EcoHealth and community mobilization approaches to Aedes reduction, more evidence of their efficacy on reducing dengue risk is needed. The principal research question is to determine if interventions based upon community mobilization reduce the risk of dengue virus infection among children 3 to 9 years old compared to usual dengue control practice in Fortaleza, Brazil. METHODS: The present study will follow a pragmatic cluster randomized controlled trial (cRCT) design with randomization at the census tract level with equal allocation to the two arms. In each arm, there will be 34 clusters of 86 children between 3 to 9 years old for an expected total of 5848 children enrolled in the study, assuming a risk reduction of 29.5% based upon findings from a previous multi-site cRCT. The primary outcomes are rates of anti-dengue Immunoglobulin G (IgG) seroconversion and adult female Aedes density. The intervention is based upon a participatory health research approach, Socializing Evidence for Participatory Action (SEPA), where the research evidence is used to foster community engagement and ownership of the health issue and solution. Following allocation, intervention communities will develop and implement their own solutions that will likely include a wide variety of collective events and media approaches. Data collection activities over a period of 3 years include household visits for blood collection, household surveys, and entomological surveys; and qualitative activities including focus groups, in-depth interviews, and document analysis to evaluate the process, acceptability, fidelity, and sustainability of the intervention. Study participants will be aware of their assignment and all research staff will be blinded although the intervention assignment will likely be revealed to field staff through interaction with participants. DISCUSSION: The results of our study will provide evidence on community mobilization as an intervention for dengue control. We anticipate that if community mobilization is effective in Fortaleza, the results of this study will help develop evidence-based vector control programs in Brazil, and also in other countries struggling with Aedes-transmitted diseases. TRIAL REGISTRATION: ISRCTN66131315, registration date: 1 October 2018.


Subject(s)
Aedes/virology , Community Participation , Dengue/prevention & control , Mosquito Control/organization & administration , Mosquito Vectors/virology , Adult , Animals , Brazil , Child , Child, Preschool , Cities , Community-Based Participatory Research/methods , Community-Based Participatory Research/organization & administration , Dengue/transmission , Dengue/virology , Female , Health Education/methods , Health Education/organization & administration , Health Knowledge, Attitudes, Practice , Humans , Mosquito Control/methods , Randomized Controlled Trials as Topic
4.
Appl Health Econ Health Policy ; 18(6): 825-840, 2020 12.
Article in English | MEDLINE | ID: mdl-31359270

ABSTRACT

We conducted a scoping review with the objective of synthesizing available literature and mapping what designs and methods have been used to evaluate health insurance reforms in sub-Saharan Africa. We systematically searched for scientific and grey literature in English and French published between 1980 and 2017 using a combination of three key concepts: "Insurance" and "Impact evaluation" and "sub-Saharan Africa". The search led to the inclusion of 66 articles with half of the studies pertaining to the evaluation of National Health Insurance schemes, especially the Ghanaian one, and one quarter pertaining to Community-Based Health Insurance and Mutual Health Organization schemes. Sixty-one out of the 66 studies (92%) included were quantitative studies, while only five (8%) were defined as mixed methods. Most studies included applied an observational design (n = 37; 56%), followed by a quasi-experimental (n = 27; 41%) design; only two studies (3%) applied an experimental design. The findings of our scoping review are in line with the observation emerging from prior reviews focused on content in pointing at the fact that evidence on the impact of health insurance is still relatively weak as it is derived primarily from studies relying on observational designs. Our review did identify an increase in the use of quasi-experimental designs in more recent studies, suggesting that we could observe a broadening and deepening of the evidence base on health insurance in Africa over the next few years.


Subject(s)
Insurance, Health , National Health Programs , Ghana , Humans
5.
Soc Sci Med ; 232: 168-180, 2019 07.
Article in English | MEDLINE | ID: mdl-31100697

ABSTRACT

System resilience has long been an area of study, and the term has become increasingly used across different sectors. Studies on resilience in health systems are more recent, multiplying particularly since the 2014 Ebola epidemic in West Africa. The World Health Organization (WHO) is calling for national governments to increase the resilience of their health systems. Concepts help define research objects and guide the analysis. Yet, to be useful, concepts need to be clear and precise. We aimed to improve the conceptual understanding of health systems resilience by conducting a scoping review to describe the state of knowledge in this area. We searched for literature in 10 databases, and analyzed data using a list of themes. We evaluated the clarity and the precision of the concept of health systems resilience using Daigneault & Jacob's three dimensions of a concept: term, sense, and referent. Of the 1091 documents initially identified, 45 met the inclusion criteria. Term: multiple terms are used, switching from one to the other to speak about the same subject. Sense: there is no consensus yet on a unique definition. Referent: the magnitude and nature of events that resilient health systems face differ with context, covering a broad range of situations from sudden crisis to everyday challenges. The lack of clarity in this conceptualization hinders the expansion of knowledge, the creation of reliable analytical tools, and the effectiveness of communication. The current conceptualization of health systems resilience is too scattered to enable the enhancement of this concept with great potential, opening a large avenue for future research.


Subject(s)
Concept Formation , Delivery of Health Care/standards , Delivery of Health Care/methods , Delivery of Health Care/trends , Global Health/standards , Global Health/trends , Government Programs/standards , Humans
6.
Infect Dis Poverty ; 7(1): 99, 2018 Sep 03.
Article in English | MEDLINE | ID: mdl-30217142

ABSTRACT

BACKGROUND: Vector-borne diseases (VBDs) continue to represent a global threat, with "old" diseases like malaria, and "emergent" or "re-emergent" ones like Zika, because of an increase in international trade, demographic growth, and rapid urbanization. In this era of globalization, surveillance is a key element in controlling VBDs in urban settings, but surveillance alone cannot solve the problem. A review of experiences is of interest to examine other solution elements. The objectives were to assess the different means of VBD surveillance in urban environments, to evaluate their potential for supporting public health actions, and to describe the tools used for public health actions, the constraints they face, and the research and health action gaps to be filled. MAIN BODY: For this scoping review we searched peer-reviewed articles and grey literature published between 2000 and 2016. Various tools were used for data coding and extraction. A quality assessment was done for each study reviewed, and descriptive characteristics and data on implementation process and transferability were analyzed in all studies. After screening 414 full-text articles, we retained a total of 79 articles for review. The main targets of the articles were arboviral diseases (65.8%) and malaria (16.5%). The positive aspects of many studies fit within the framework of integrated vector management. Public awareness is considered a key to successful vector control programs. Advocacy and legislation can reinforce both empowerment and capacity building. These can be achieved by collaboration within the health sector and with other sectors. Research is needed to develop well designed studies and new tools for surveillance and control. CONCLUSIONS: The need for surveillance systems in urban settings in both developing and developed countries was highlighted. Countries face the same challenges relating to human, financial, and structural resources. These findings also constitute a wake-up call for governments, academia, funders, and World Health Organization to strengthen control programs and enhance VBD research in urban environments.


Subject(s)
Infections/transmission , Sentinel Surveillance , Urban Health , Animals , Disease Vectors , Humans , Infection Control , Public Health , Urban Health/statistics & numerical data
7.
Infect Dis Poverty ; 7(1): 90, 2018 Sep 03.
Article in English | MEDLINE | ID: mdl-30173661

ABSTRACT

BACKGROUND: Transmission dynamics, vectorial capacity, and co-infections have substantial impacts on vector-borne diseases (VBDs) affecting urban and suburban populations. Reviewing key factors can provide insight into priority research areas and offer suggestions for potential interventions. MAIN BODY: Through a scoping review, we identify knowledge gaps on transmission dynamics, vectorial capacity, and co-infections regarding VBDs in urban areas. Peer-reviewed and grey literature published between 2000 and 2016 was searched. We screened abstracts and full texts to select studies. Using an extraction grid, we retrieved general data, results, lessons learned and recommendations, future research avenues, and practice implications. We classified studies by VBD and country/continent and identified relevant knowledge gaps. Of 773 articles selected for full-text screening, 50 were included in the review: 23 based on research in the Americas, 15 in Asia, 10 in Africa, and one each in Europe and Australia. The largest body of evidence concerning VBD epidemiology in urban areas concerned dengue and malaria. Other arboviruses covered included chikungunya and West Nile virus, other parasitic diseases such as leishmaniasis and trypanosomiasis, and bacterial rickettsiosis and plague. Most articles retrieved in our review combined transmission dynamics and vectorial capacity; only two combined transmission dynamics and co-infection. The review identified significant knowledge gaps on the role of asymptomatic individuals, the effects of co-infection and other host factors, and the impacts of climatic, environmental, and socioeconomic factors on VBD transmission in urban areas. Limitations included the trade-off from narrowing the search strategy (missing out on classical modelling studies), a lack of studies on co-infections, most studies being only descriptive, and few offering concrete public health recommendations. More research is needed on transmission risk in homes and workplaces, given increasingly dynamic and mobile populations. The lack of studies on co-infection hampers monitoring of infections transmitted by the same vector. CONCLUSIONS: Strengthening VBD surveillance and control, particularly in asymptomatic cases and mobile populations, as well as using early warning tools to predict increasing transmission, were key strategies identified for public health policy and practice.


Subject(s)
Coinfection/transmission , Dengue/transmission , Insect Vectors/physiology , Malaria/transmission , Parasitic Diseases/transmission , Animals , Humans , Urban Health
8.
Infect Dis Poverty ; 7(1): 87, 2018 Sep 03.
Article in English | MEDLINE | ID: mdl-30173662

ABSTRACT

BACKGROUND: Health personnel face challenges in diagnosing vector-borne and other diseases of poverty in urban settings. There is a need to know what rapid diagnostic technologies are available, have been properly assessed, and are being implemented to improve control of these diseases in the urban context. This paper characterizes evidence on the field validation and implementation in urban areas of rapid diagnostics for vector-borne diseases and other diseases of poverty. MAIN BODY: A scoping review was conducted. Peer-reviewed and grey literature were searched using terms describing the targeted infectious diseases, diagnostics evaluations, rapid tests, and urban setting. The review was limited to studies published between 2000 and 2016 in English, Spanish, French, and Portuguese. Inclusion and exclusion criteria were refined post hoc to identify relevant literature regardless of study design and geography. A total of 179 documents of the 7806 initially screened were included in the analysis. Malaria (n = 100) and tuberculosis (n = 47) accounted for the majority of studies that reported diagnostics performance, impact, and implementation outcomes. Fewer studies, assessing mainly performance, were identified for visceral leishmaniasis (n = 9), filariasis and leptospirosis (each n = 5), enteric fever and schistosomiasis (each n = 3), dengue and leprosy (each n = 2), and Chagas disease, human African trypanosomiasis, and cholera (each n = 1). Reported sensitivity of rapid tests was variable depending on several factors. Overall, specificities were high (> 80%), except for schistosomiasis and cholera. Impact and implementation outcomes, mainly acceptability and cost, followed by adoption, feasibility, and sustainability of rapid tests are being evaluated in the field. Challenges to implementing rapid tests range from cultural to technical and administrative issues. CONCLUSIONS: Rapid diagnostic tests for vector-borne and other diseases of poverty are being used in the urban context with demonstrated impact on case detection. However, most evidence comes from malaria rapid diagnostics, with variable results. While rapid tests for tuberculosis and visceral leishmaniasis require further implementation studies, more evidence on performance of current tests or development of new alternatives is needed for dengue, Chagas disease, filariasis, leptospirosis, enteric fever, human African trypanosomiasis, schistosomiasis and cholera.


Subject(s)
Communicable Diseases/diagnosis , Diagnostic Tests, Routine/methods , Urban Health/economics , Animals , Communicable Diseases/economics , Communicable Diseases/transmission , Diagnostic Tests, Routine/economics , Disease Vectors , Humans , Poverty
9.
Infect Dis Poverty ; 7(1): 85, 2018 Sep 03.
Article in English | MEDLINE | ID: mdl-30173663

ABSTRACT

BACKGROUND: In 2015, following a call for proposals from the Special Programme for Research and Training in Tropical Diseases (TDR), six scoping reviews on the prevention and control of vector-borne diseases in urban areas were conducted. Those reviews provided a clear picture of the available knowledge and highlighted knowledge gaps, as well as needs and opportunities for future research. Based on the research findings of the scoping reviews, a concept mapping exercise was undertaken to produce a list of priority research needs to be addressed. METHODS: Members of the six research teams responsible for the "VEctor boRne DiseAses Scoping reviews" (VERDAS) consortium's scoping reviews met for 2 days with decision-makers from Colombia, Brazil, Peru, Pan-American Health Organization, and World Health Organization. A total of 11 researchers and seven decision-makers (from ministries of health, city and regional vector control departments, and vector control programs) completed the concept mapping, answering the question: "In view of the knowledge synthesis and your own expertise, what do we still need to know about vector-borne diseases and other infectious diseases of poverty in urban areas?" Participants rated each statement on two scales from 1 to 5, one relative to 'priority' and the other to 'policy relevance', and grouped statements into clusters based on their own individual criteria and expertise. RESULTS: The final map consisted of 12 clusters. Participants considered those entitled "Equity", "Technology", and "Surveillance" to have the highest priority. The cluster considered the most important concerns equity issues, confirming that these issues are rarely addressed in research on vector-borne diseases. On the other hand, the "Population mobility" and "Collaboration" clusters were considered to be the lowest priority but remained identified by participants as research priorities. The average policy relevance scores for each of the 12 clusters were roughly the same as the priority scores for all clusters. Some issues were not addressed during the brain-storming. This is the case for governance and for access and quality of care. CONCLUSIONS: Based on this work, and adopting a participatory approach, the concept mapping exercise conducted collaboratively with researchers from these teams and high-level decision-makers identified research themes for which studies should be carried out as a priority.


Subject(s)
Health Services Research , Urban Health , Brazil , Colombia , Female , Health Policy , Health Priorities , Health Services Research/legislation & jurisprudence , Health Services Research/organization & administration , Humans , Intersectoral Collaboration , Male , Peru , Urban Health/legislation & jurisprudence
10.
Infect Dis Poverty ; 7(1): 96, 2018 Sep 03.
Article in English | MEDLINE | ID: mdl-30173670

ABSTRACT

BACKGROUND: Over half the world's human populations are currently at risk from vector-borne diseases (VBDs), and the heaviest burden is borne by the world's poorest people, communities, and countries. The aim of this study was to conduct a review on VBD interventions relevant to housing and hygiene (including sanitation and waste management) in urban areas. MAIN BODY: We conducted a scoping review, which involved systematically searching peer-reviewed and grey literature published between 2000 and 2016 using five scientific databases and one database for grey literature. Different data extraction tools were used for data coding and extraction. We assessed the quality of each study using the Mixed Methods Appraisal Tool and extracted descriptive characteristics and data about implementation process and transferability from all studies using the Template for Intervention Description and Replication and ASTAIRE (a tool for analyzing the transferability of health promotion interventions) tools. We reviewed 44 studies. Overall, the studies were judged to be of high risk for bias. Our results suggest multifaceted interventions, particularly community-based interventions, have the potential to achieve wider and more sustained effects than do standard vertical single-component programs. The evaluations of multifaceted interventions tend to include integrated evaluations, using not only entomological indicators but also acceptability and sustainability indicators. CONCLUSIONS: This review highlighted the important need for higher quality research in VBDs and improved and standardized reporting of interventions. Significant research gaps were found regarding qualitative research and implementation research, and results highlighted the need for more interventions focus on sanitation and hygiene practices.


Subject(s)
Housing/standards , Hygiene/standards , Infection Control , Urban Health , Animals , Disease Vectors , Health Promotion , Humans , Infection Control/standards , Infections/transmission
11.
Infect Dis Poverty ; 7(1): 95, 2018 Sep 03.
Article in English | MEDLINE | ID: mdl-30173673

ABSTRACT

BACKGROUND: The emergence and re-emergence of vector-borne and other infectious diseases of poverty pose a threat to the health of populations living in urban and low-income settings. A detailed understanding of intervention strategies, including effectiveness of past outbreak containment, is necessary to improve future practices. The objective was to determine what is known about the effectiveness of containment measures for emerging and re-emerging vector-borne and other infectious diseases of poverty in urban settings and identify research gaps and implications for public health practice. MAIN BODY: We conducted a scoping review and systematically searched peer-reviewed and grey literature published between 2000 and 2016. Different data extraction tools were used for data coding and extraction, and data on implementation process and transferability were extracted from all studies. A quality assessment was conducted for each included study. We screened 205 full-text articles and reports for a total of 31 articles included in the review. The quality of the studies was generally low to moderate. The largest body of evidence concerned control activities for Ebola virus and dengue fever. The majority of interventions (87%) relied on multiple types of measures, which were grouped into four categories: 1) healthcare provision; 2) epidemiological investigation and/or surveillance; 3) environmental or sanitary interventions; and 4) community-based interventions. The quality of the majority of studies (90%) was poor or moderate, and one-third of the studies did not provide a clear description of the outcomes and of the procedures and/or tools used for the intervention. CONCLUSIONS: Our results highlight the difficulty of establishing causation when assessing the effect of containment measures. Studies that extend beyond solely reporting on effectiveness and take into account the complexity of real-world settings are urgently needed. We recommend the allocation of research efforts to the evaluation of the implementation processes of interventions as well as their comprehensive and systematic description using validated checklists.


Subject(s)
Communicable Diseases, Emerging/economics , Communicable Diseases/economics , Urban Health/economics , Animals , Communicable Diseases, Emerging/prevention & control , Disease Vectors , Humans , Poverty
12.
Infect Dis Poverty ; 7(1): 98, 2018 Sep 03.
Article in English | MEDLINE | ID: mdl-30173674

ABSTRACT

BACKGROUND: This paper presents the overall approach undertaken by the "VEctor boRne DiseAses Scoping reviews" (VERDAS) consortium in response to a call issued by the Vectors, Environment and Society unit of the Special Programme for Research and Training in Tropical Diseases hosted by the World Health Organization. The aim of the project was to undertake a broad knowledge synthesis and identify knowledge gaps regarding the control and prevention of vector-borne diseases in urban settings. METHODS: The consortium consists of 14 researchers, 13 research assistants, and one research coordinator from seven different institutions in Canada, Colombia, Brazil, France, Spain, and Burkina Faso. A six-step protocol was developed for the scoping reviews undertaken by the consortium, based on the framework developed by Arksey and O'Malley and improved by Levac et al. In the first step, six topics were identified through an international eDelphi consultation. In the next four steps, the scoping reviews were conducted. The sixth step was the VERDAS workshop held in Colombia in March 2017. DISCUSSION: In this article, we discuss several methodological issues encountered and share our reflections on this work. We believe this protocol provides a strong example of an exhaustive and rigorous process for performing broad knowledge synthesis for any given topic and should be considered for future research initiatives and donor agendas in multiple fields to highlight research needs scientifically.


Subject(s)
Biomedical Research , Communicable Diseases/economics , Urban Health , Animals , Biomedical Research/economics , Disease Vectors , Humans , Poverty , Systematic Reviews as Topic , Urban Health/economics
13.
Infect Dis Poverty ; 7(1): 83, 2018 Sep 03.
Article in English | MEDLINE | ID: mdl-30173675

ABSTRACT

BACKGROUND: The control of vector-borne diseases (VBD) is one of the greatest challenges on the global health agenda. Rapid and uncontrolled urbanization has heightened the interest in addressing these challenges through an integrated vector management (IVM) approach. The aim was to identify components related to impacts, economic evaluation, and sustainability that might contribute to this integrated approach to VBD prevention. MAIN BODY: We conducted a scoping review of available literature (2000-2016) using PubMed, Web of Science, Cochrane, CINAHL, Econlit, LILACS, Global Health Database, Scopus, and Embase, as well as Tropical Diseases Bulletin, WHOLIS, WHO Pesticide Evaluation Scheme, and Google Scholar. MeSH terms and free-text terms were used. A data extraction form was used, including TIDieR and ASTAIRE. MMAT and CHEERS were used to evaluate quality. Of the 42 documents reviewed, 30 were focused on dengue, eight on malaria, and two on leishmaniasis. More than a half of the studies were conducted in the Americas. Half used a quantitative descriptive approach (n = 21), followed by cluster randomized controlled trials (n = 11). Regarding impacts, outcomes were: a) use of measures for vector control; b) vector control; c) health measures; and d) social measures. IVM reduced breeding sites, the entomology index, and parasite rates. Results were heterogeneous, with variable magnitudes, but in all cases were favourable to the intervention. Evidence of IVM impacts on health outcomes was very limited but showed reduced incidence. Social outcomes were improved abilities and capacities, empowerment, and community knowledge. Regarding economic evaluation, only four studies performed an economic analysis, and intervention benefits outweighed costs. Cost-effectiveness was dependent on illness incidence. The results provided key elements to analyze sustainability in terms of three dimensions (social, economic, and environmental), emphasizing the implementation of a community-focused eco-bio-social approach. CONCLUSIONS: IVM has an impact on reducing vector breeding sites and the entomology index, but evidence of impacts on health outcomes is limited. Social outcomes are improved abilities and capacities, empowerment, and community knowledge. Economic evaluations are scarce, and cost-effectiveness is dependent on illness incidence. Community capacity building is the main component of sustainability, together with collaboration, institutionalization, and routinization of activities. Findings indicate a great heterogeneity in the interventions and highlight the need for characterizing interventions rigorously to facilitate transferability.


Subject(s)
Dengue/economics , Leishmaniasis/economics , Malaria/economics , Urban Health/economics , Animals , Dengue/prevention & control , Dengue/transmission , Disease Vectors , Humans , Leishmaniasis/prevention & control , Leishmaniasis/transmission , Malaria/prevention & control , Malaria/transmission
14.
Neurotoxicol Teratol ; 66: 132-138, 2018.
Article in English | MEDLINE | ID: mdl-29305196

ABSTRACT

BACKGROUND: Folates in their role as key one carbon donors, are essential for two major pathways: the synthesis of DNA and RNA precursors and DNA methylation. A growing body of evidence from epidemiological studies indicates a possible association between nutritional and functional deficiency in folates and Autism Spectrum Disorders (ASD). However, there are no available behavioral animal studies on periconceptional one­carbon donor deficiency during gestation and the autistic phenotype. OBJECTIVE: The objective of this study was to determine if the periconceptional alteration of one­carbon metabolism induced with a folate deficient diet would affect the behaviour of rat offspring. METHODS: Female Wistar rats were divided in two groups: control (basal diet, in compliance with standards of regular laboratory diets), or exposed during one month before breeding until Gestational Day 15 to a modified diet with no added folic acid (0.2mg/kg of food), reduced choline (750mg/kg of food), and added 1% SST (a non-absorbable antibiotic used to inhibit folate synthesis by gut bacteria). We administered behavioral tests to offspring, i.e., open field (P20), social interactions (P25), marble burying (P30), elevated plus maze (P35), and prepulse inhibition of the acoustic startle reflex (sensorimotor gating) (P45). Blood homocysteine levels were used to confirm the deficit in one­carbon donors. RESULTS: Compared to controls, offspring with the periconceptional deficit in folate showed: (i) congenital body malformations; (ii) reduced social interactions, with a ~30% decrease in social sniffing behavior; (iii) reduced exploration of the open arm by 50% in the elevated plus maze test, indicating increased anxiety; (iv) a ~160% increased number of marbles buried, indicating repetitive behaviors; and (v) altered sensorimotor gating, with a global 50% decrease in startle inhibition. CONCLUSION: Maternal periconceptional deficit in folate provokes alterations in the behavior of offspring relevant to the autistic-like phenotype.


Subject(s)
Autistic Disorder/psychology , Behavior, Animal , Folic Acid Deficiency/complications , Prenatal Exposure Delayed Effects/psychology , Animals , Female , Folic Acid Deficiency/blood , Homocysteine/blood , Male , Pregnancy , Prenatal Exposure Delayed Effects/blood , Prenatal Exposure Delayed Effects/etiology , Rats, Wistar
15.
J Neurosci Methods ; 276: 13-22, 2017 01 30.
Article in English | MEDLINE | ID: mdl-27856274

ABSTRACT

BACKGROUND: The PrePulse Inhibition (PPI) of the acoustic startle reflex is a neurobehavioral test frequently used in neurodevelopmental studies. Most PPI studies have used rodent models of schizophrenia; however, the currently used data analysis method does not take into account the variability present in autistic preclinical models. NEW METHOD: We propose a new data modelling approach for PPI data obtained from animals exposed to valproic acid or endocrine disruptors, using mixed modeling; and a new calculation of inhibition of the acoustic startle, which takes into account the habituation phenomenon. RESULTS: Habituation, or possibly exhaustion, occurred in all groups. The classic method of calculation of inhibition analysed with ANOVA indicated no group or sex effect for the overall inhibition of startle. In contrast, when analysed using mixed models, group and sex effects were observed. In addition, using the new method of calculation, both statistical analyses showed a sex effect, with females having decreased global inhibition but no group effect. ANOVA generated more false positive results for PPI in relation to prepulse intensities. COMPARISON WITH EXISTING METHOD: The current classic method of analysis of PPI test is a calculation of inhibition based on average startle amplitude throughout the test session and a statistical ANOVA analysis. This method does not take into account habituation/exhaustion and within-subject and -group variability. CONCLUSIONS: The results of this study demonstrate that use of ANOVA analysis leads to misinterpretation of PPI data in autistic preclinical models and we propose a new data analysis adapted to these models.


Subject(s)
Autism Spectrum Disorder , Data Interpretation, Statistical , Disease Models, Animal , Neuropsychological Tests , Prepulse Inhibition , Reflex, Startle , Acoustic Stimulation/methods , Analysis of Variance , Animals , Auditory Perception , Autism Spectrum Disorder/diagnosis , Autism Spectrum Disorder/physiopathology , False Positive Reactions , Female , Habituation, Psychophysiologic , Inhibition, Psychological , Male , Random Allocation , Rats, Inbred Lew , Sex Characteristics
16.
Article in English | MEDLINE | ID: mdl-27346743

ABSTRACT

BACKGROUND: A growing body of evidence indicates that gut microbiota characteristics may be closely related to mental dysfunctions. However, no studies have investigated fetal brain development in relation to the maternal gut microbiota, despite the extensive use of antibiotics in obstetric practice. OBJECTIVE: To determine how periconceptional exposure to SuccinylSulfaThiazole (SST), a non-absorbable antibiotic, can affect behavior in rat offspring. This antibiotic drug has previously been shown to substantially perturb the gut microbiota in rats following a 28-day exposure. METHODS: Female Wistar rats were divided in two groups: control, or exposed during one month before breeding until gestational day 15 to a diet containing 1% SST. We administered behavioral tests to offspring, i.e., open field (post-natal day 20), social interactions (P25), marble burying (P30), elevated plus maze (P35), and prepulse inhibition of the acoustic startle reflex (sensory gating) (P45). RESULTS: Both male and female offspring exposed peri-conceptionally to SST showed reduced social interactions, with a decrease of about half in time spent in social interactions compared to controls, reduced exploration of the open arm by 20% in the elevated plus maze test indicating increased anxiety and altered sensorimotor gating, with a 1.5-2-fold decrease in startle inhibition. CONCLUSION: Maternal periconceptional exposure to SST provokes alterations in offspring behavior in the absence of maternal infection. Because we administered SST, a non-absorbable antibiotic, only to the dam, we conclude that these neurobehavioral alterations in the offspring are related to maternal gut microbiota alterations.


Subject(s)
Anti-Infective Agents/adverse effects , Anxiety/etiology , Interpersonal Relations , Prenatal Exposure Delayed Effects , Sulfathiazoles/adverse effects , Acoustic Stimulation , Animals , Animals, Newborn , Eating/drug effects , Exploratory Behavior/drug effects , Female , Homocysteine/metabolism , Male , Maze Learning/drug effects , Pregnancy , Prenatal Exposure Delayed Effects/physiopathology , Prenatal Exposure Delayed Effects/psychology , Prepulse Inhibition/drug effects , Rats , Rats, Wistar , Tryptophan/metabolism
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