TABLE 2. Summary of road map for leptospirosis research and health policies in Latin America.

Report of countries’ needs	State of the art	Recommendations for decision makers and PAHO/WHO	Priorities for research, technological development, and innovation (RTDI)
Surveillance	- Availability of diagnostic tests - Capacity-building for clinical and laboratorial diagnosis - Strengthening surveillance for human and animal leptospirosis and for environmental contamination	- Many countries in Latin America with surveillance systems in place ready to recognize human and animal leptospirosis - Leptospirosis is notifiable in many countries of Latin America - Laboratory confirmation is usually based on conventional serological tests - Isolation and identification of Leptospira is rare - PCR-based techniques are usually performed in-house in a few central laboratories	- Provide guidelines for leptospirosis surveillance and information materials - Put forward training programs on clinical and laboratory diagnosis - Improve national surveillance systems to increase the geographical coverage of leptospirosis data in Latin America - Monitor outbreaks - Evaluate criteria for case definition and laboratory confirmation - Adopt prevention and control measures - Develop a collaborative data-sharing program to integrate human-animal-environment interface	- New, affordable diagnostic tests to support laboratory-based surveillance - Accurate quantification of human and animal leptospirosis cases - Geographic distribution of Leptospira species and serovars, animal carriers, and human cases
Prediction	- Software to integrate different types of databases for risk stratification, prediction, and forecasting - Training for personnel in appropriate quantitative methods - Integration of multidisciplinary research teams - Exchange of timely information among sectors	- An increasing number of scientific groups are working on leptospirosis prediction, and several studies including modeling have been published - Country surveillance data could be used for epidemiological analysis and prediction - Several countries have epidemiological information, but it is usually not open access - There are some open-access environmental and socioeconomic databases that can be integrated into surveillance case data	- Description and analysis of country case data should be done at different scales - Improve and standardize methodology to produce the needed epidemiological information for predictive modeling - Support the identification of risk areas and risk groups - Training in outbreak detection and response - Training in quantitative methods for data management and analysis - Support research that shares surveillance data for prediction	- Understand the transmission patterns at the community level - Develop prediction tools to support countries for early warning of possible outbreaks - Partnership among researchers and health authorities in information exchange and use of the prediction models - Define set of variables (possible drivers) to explain outbreaks and higher incidence, in order to support interventions - Large-scale spatial-temporal modeling for early warning system for leptospirosis outbreaks - Modeling effectiveness and impact of chemoprophylaxis as an intervention for infection risk reduction - Model to evaluate vaccine interventions based on occupational risk and geographical risk areas
Diagnosis	- Availability of tests, reagents, and reference strains for case confirmation - Establish or strengthen national laboratory networks - Training of personnel in new methods of diagnosis	- Available diagnostic tools may not be enough for timely aid in clinical management and may be of limited support for epidemiological surveillance	- Commercial tests must be validated on-site before being recommended by surveillance systems - Establish and use algorithms for proper diagnosis according to set times for detection of antigens, amplified nucleic acids, and antibodies	- New developments on nucleic acid amplification–based techniques for early diagnosis - Rapid diagnostic tests (RDTs) for point-of-care diagnostic testing - Improvement of current systems for identification of clinical isolates
Human clinical management	- Training of physicians on clinical diagnosis and treatment - Including leptospirosis in medical students’ clinical program - Updated available guidelines - Research on new treatments - Educational materials	- Misdiagnosis with acute febrile diseases and hemorrhagic febrile diseases - Severe forms of leptospirosis still represent a challenge in clinical practice, with high case-fatality rates - A major issue is the clinical management of the pulmonary hemorrhage syndrome associated with leptospirosis (PHSL)	- Provide guidelines for leptospirosis clinical management - Design and deliver training programs for leptospirosis recognition and clinical care - Support researchers to identify clinical isolates	- Tests for early diagnosis and timely aid in clinical treatment - Clinical studies to provide scientific evidence for clinical management of severe forms - New therapeutic alternatives to reduce case-fatality rates
Vaccines	Vaccine (if available) could be used in the following occupational groups: agricultural workers, animal handlers, sewage and water supply workers, veterinarians, and the military	- Only one country in the Americas uses human vaccine on a regular basis - Current vaccines for human and veterinary use are whole-cell vaccines - There are two vaccines licensed for human use - Limitations and controversies are mainly related to the formulations (immunity is serovar- specific) and the lack of robust evidence from randomized controlled trials (RCTs) - Recent efforts have been largely focused on subunit vaccine candidates	- Evaluating the recommendation of vaccines licensed for human use to prevent leptospirosis	- Studies about candidates for subunit vaccines, natural immunity, experimental models for proof of concept, and target populations to be vaccinated
Studies and interventions in animals	-Training technical health and agriculture personnel in rodent control methods - Guidelines and methodologies for rodent control - Conduct studies on rodents and other animal reservoirs	- Animal vaccines available in most of the countries but not always with official quality control - Animal vaccination for leptospirosis in dairy farms has been successful in other world regions - Many countries in Latin America (especially Brazil) have experience in rodent control, but this knowledge needs to be shared with other countries - Criteria for risk areas used for rodent control in São Paulo	- Provide guidelines for rodent control in urban and rural settings - Hold training on rodent control - Use of personal protection for workers at risk - Coordinate partnerships between public health and agriculture to meet goals of surveillance and control for human and animal leptospirosis, considering the One Health perspective	- Studies on new vaccines for livestock to prevent the disease and the carrier state - Studies about dynamics of rodent populations and human infection
RTDI	- Simple tests for diagnosis - Identification of the etiological agent, animal carriers, and risk areas - Studies about incidence, prevalence, and case-fatality rate in humans	- Knowledge gaps on leptospirosis biomedical research must be considered globally - Only new and cutting-edge technologies could bring about the required progress on diagnosis, vaccines, and therapeutic alternatives - Epidemiological and clinical studies are essential to leverage and support other fundamental research areas (molecular pathogenesis, immunology, genome, proteome, and related fields)	- Stimulate operational research to support the needs related to surveillance systems	- Biodiversity and geographic distribution of Leptospira spp. and serovars - Application of new tools for development of diagnostic tests, vaccines, and therapeutic alternatives - Experimental models to better understand the leptospirosis pathogenesis and to support new developments on vaccines and therapeutic alternatives

Source: Developed by the authors, based on information presented at the Rio de Janeiro November 2015 meeting. as well as other, relevant scientific literature.