A SmI2-mediated reductive cyclisation reaction using the trifluoroacetamide group as the radical precursor.

A samarium(II)-mediated reductive cyclisation reaction with the aminoketyl radical from the trifluoroacetamide group for synthesising 2-trifluoromethylindolines was developed. This reaction is the first example of using an acyclic amide group, which is considered difficult to react with SmI2, in a reductive cyclisation. Additionally, the conversion of the obtained product into 2-trifluoromethylindole was achieved.

The current status of neglected tropical diseases in Japan: A scoping review.

Little attention has been paid to neglected tropical diseases (NTDs) in high-income countries and no literature provides an overview of NTDs in Japan. This scoping review aims to synthesize the latest evidence and information to understand epidemiology of and public health response to NTDs in Japan. Using three academic databases, we retrieved articles that mentioned NTDs in Japan, written in English or Japanese, and published between 2010 and 2020. Websites of key public health institutions and medical societies were also explored. From these sources of information, we extracted data that were relevant to answering our research questions. Our findings revealed the transmission of alveolar echinococcosis, Buruli ulcer, Chagas disease, dengue, foodborne trematodiases, mycetoma, scabies, and soil-transmitted helminthiasis as well as occurrence of snakebites within Japan. Other NTDs, such as chikungunya, cystic echinococcosis, cysticercosis, leishmaniasis, leprosy, lymphatic filariasis, rabies, and schistosomiasis, have been imported into the country. Government agencies tend to organize surveillance and control programs only for the NTDs targeted by the Infectious Disease Control Law, namely, echinococcosis, rabies, dengue, and chikungunya. At least one laboratory offers diagnostic testing for each NTD except for dracunculiasis, human African trypanosomiasis, onchocerciasis, and yaws. No medicine is approved for treatment of Chagas disease and fascioliasis and only off-label use drugs are available for cysticercosis, opisthorchiasis, human African trypanosomiasis, onchocerciasis, schistosomiasis, and yaws. Based on these findings, we developed disease-specific recommendations. In addition, three policy issues are discussed, such as lack of legal frameworks to organize responses to some NTDs, overreliance on researchers to procure some NTD products, and unaffordability of unapproved NTD medicines. Japan should recognize the presence of NTDs within the country and need to address them as a national effort. The implications of our findings extend beyond Japan, emphasizing the need to study, recognize, and address NTDs even in high-income countries.

Access to Chagas disease treatment in the United States after the regulatory approval of benznidazole.

Approximately 300,000 persons in the United States (US) are infected with Trypanosoma cruzi, the protozoan that causes Chagas disease, but less than 1% are estimated to have received antiparasitic treatment. Benznidazole was approved by the US Food and Drug Administration (FDA) for treatment of T. cruzi infection in 2017 and commercialized in May 2018. This paper analyzes factors that affect access to benznidazole following commercialization and suggests directions for future actions to expand access. We applied an access framework to identify barriers, facilitators, and key actors that influence the ability of people with Chagas disease to receive appropriate treatment with benznidazole. Data were collected from the published literature, key informants, and commercial databases. We found that the mean number of persons who obtained benznidazole increased from just under 5 when distributed by the CDC to 13 per month after the commercial launch (from May 2018 to February 2019). Nine key barriers to access were identified: lack of multi-sector coordination, failure of health care providers to use a specific order form, lack of an emergency delivery system, high medical costs for uninsured patients, narrow indications for use of benznidazole, lack of treatment guidelines, limited number of qualified treaters, difficulties for patients to make medical appointments, and inadequate evaluation by providers to determine eligibility for treatment. Our analysis shows that access to benznidazole is still limited after FDA approval. We suggest six areas for strategic action for the pharmaceutical company that markets benznidazole and its allied private foundation to expand access to benznidazole in the US. In addition, we recommend expanding the existing researcher-clinician network by including government agencies, companies and others. This paper's approach could be applied to access programs for benznidazole in other countries or for other health products that target neglected populations throughout the world.

The resilience of Triatoma dimidiata: An analysis of reinfestation in the Nicaraguan Chagas disease vector control program (2010-2016).

BACKGROUND: The control of Triatoma dimidiata, a major vector of Chagas disease, was believed to eliminate Trypanosoma cruzi transmission in Central America. This vector was known for its ability to repeatedly reinfest human dwellings even after initial insecticide spraying. Current vector control programs assume that community-based surveillance can maintain low levels of infestation over many years, despite a lack of evidence in the literature to corroborate this assumption. This study aims to evaluate long-term reinfestation risk in the Nicaraguan vector control program from 2010 to 2016. METHODS: We collected data from a cohort of 395 houses in Pueblo Nuevo, Nicaragua. Primary data were collected through a field survey to assess post-intervention levels of T. dimidiata house infestation in 2016, two years after the large-scale insecticide spraying. We obtained secondary data from the records about past infestation levels and control activities between 2010 and 2015. Multilevel mixed-effects logistic regression analyses were used to identify factors associated with post-intervention house infestation. RESULTS: The control program effectively reduced the infestation level from 2010 to 2014. Community-based surveillance was introduced in 2013; however, post-intervention infestation in 2016 had nearly reached pre-intervention levels in rural villages. Post-intervention house infestation was positively associated with poor wall construction, roofing tiles piled in the peri-domestic areas or the presence of dogs. Interestingly, the odds of post-intervention house infestation were one-fifth less when villagers sprayed their own houses regularly. Past infestation levels and the intensity of government-led insecticide spraying did not explain post-intervention house infestation. CONCLUSIONS: The vector control program failed to offer sustained reductions in T. dimidiata house infestation. This experience would suggest that community-based surveillance is an insufficient approach to suppressing T. dimidiata house infestation over many years. This study provides evidence to suggest that control policies for T. dimidiata should be reconsidered throughout Central America.

Implementing a vector surveillance-response system for chagas disease control: a 4-year field trial in Nicaragua.

BACKGROUND: Chagas disease is one of the neglected tropical diseases (NTDs). International goals for its control involve elimination of vector-borne transmission. Central American countries face challenges in establishing sustainable vector control programmes, since the main vector, Triatoma dimidiata, cannot be eliminated. In 2012, the Ministry of Health in Nicaragua started a field test of a vector surveillance-response system to control domestic vector infestation. This paper reports the main findings from this pilot study. METHODS: This study was carried out from 2012 to 2015 in the Municipality of Totogalpa. The Japan International Cooperation Agency provided technical cooperation in designing and monitoring the surveillance-response system until 2014. This system involved 1) vector reports by householders to health facilities, 2) data analysis and planning of responses at the municipal health centre and 3) house visits or insecticide spraying by health personnel as a response. We registered all vector reports and responses in a digital database. The collected data were used to describe and analyse the system performance in terms of amount of vector reports as well as rates and timeliness of responses. RESULTS: During the study period, T. dimidiata was reported 396 times. Spatiotemporal analysis identified some high-risk clusters. All houses reported to be infested were visited by health personnel in 2013 and this response rate dropped to 39% in 2015. Rates of insecticide spraying rose above 80% in 2013 but no spraying was carried out in the following 2 years. The timeliness of house visits improved significantly after the responsibility was transferred from a vector control technician to primary health care staff. CONCLUSIONS: We argue that the proposed vector surveillance-response system is workable within the resource-constrained health system in Nicaragua. Integration to the primary health care services was a key to improve the system performance. Continual efforts are necessary to keep adapting the surveillance-response system to the dynamic health systems. We also discuss that the goal of eliminating vector-borne transmission remains unachievable. This paper provides lessons not only for Chagas disease control in Central America, but also for control efforts for other NTDs that need a sustainable surveillance-response system to support elimination.

Effectiveness of Large-Scale Chagas Disease Vector Control Program in Nicaragua by Residual Insecticide Spraying Against Triatoma dimidiata.

Chagas disease is one of the most serious health problems in Latin America. Because the disease is transmitted mainly by triatomine vectors, a three-phase vector control strategy was used to reduce its vector-borne transmission. In Nicaragua, we implemented an indoor insecticide spraying program in five northern departments to reduce house infestation by Triatoma dimidiata. The spraying program was performed in two rounds. After each round, we conducted entomological evaluation to compare the vector infestation level before and after spraying. A total of 66,200 and 44,683 houses were sprayed in the first and second spraying rounds, respectively. The entomological evaluation showed that the proportion of houses infested by T. dimidiata was reduced from 17.0% to 3.0% after the first spraying, which was statistically significant (P < 0.0001). However, the second spraying round did not demonstrate clear effectiveness. Space-time analysis revealed that reinfestation of T. dimidiata is more likely to occur in clusters where the pre-spray infestation level is high. Here we discuss how large-scale insecticide spraying is neither effective nor affordable when T. dimidiata is widely distributed at low infestation levels. Further challenges involve research on T. dimidiata reinfestation, diversification of vector control strategies, and implementation of sustainable vector surveillance.

Certifying achievement in the control of Chagas disease native vectors: what is a viable scenario?

As an evaluation scheme, we propose certifying for "control", as alternative to "interruption", of Chagas disease transmission by native vectors, to project a more achievable and measurable goal and sharing good practices through an "open online platform" rather than "formal certification" to make the key knowledge more accumulable and accessible.

Certifying achievement in the control of Chagas disease native vectors: what is a viable scenario?

As an evaluation scheme, we propose certifying for “control”, as alternative to “interruption”, of Chagas disease transmission by native vectors, to project a more achievable and measurable goal and sharing good practices through an “open online platform” rather than “formal certification” to make the key knowledge more accumulable and accessible.

Impact of a community-based bug-hunting campaign on Chagas disease control: a case study in the department of Jalapa, Guatemala.

Chagas disease control requires an innovative approach to strengthen community participation in vector surveillance. This paper presents a case study of a community-based bug-hunting campaign in Guatemala. The campaign was implemented in 2007 in the following three stages: (i) a four week preparation stage to promote bug-hunting, (ii) a one week bug-hunting stage to capture and collect bugs and (iii) a 10 week follow-up stage to analyse the bugs and spray insecticide. A total of 2,845 bugs were reported, of which 7% were Triatominae vectors, such as Rhodnius prolixus and Triatoma dimidiata. The bug-hunting campaign detected a five-six-fold higher amount of vectors in one week than traditional community-based surveillance detects in one year. The bug-hunting campaign effectively detected vectors during a short period, provided information to update the vector infestation map and increased community and political awareness regarding Chagas disease. This approach could be recommended as an effective and feasible strategy to strengthen vector surveillance on a larger scale.

Impact of a community-based bug-hunting campaign on Chagas disease control: a case study in the department of Jalapa, Guatemala

Chagas disease control requires an innovative approach to strengthen community participation in vector surveillance. This paper presents a case study of a community-based bug-hunting campaign in Guatemala. The campaign was implemented in 2007 in the following three stages: (i) a four week preparation stage to promote bug-hunting, (ii) a one week bug-hunting stage to capture and collect bugs and (iii) a 10 week follow-up stage to analyse the bugs and spray insecticide. A total of 2,845 bugs were reported, of which 7% were Triatominae vectors, such as Rhodnius prolixus and Triatoma dimidiata. The bug-hunting campaign detected a five-six-fold higher amount of vectors in one week than traditional community-based surveillance detects in one year. The bug-hunting campaign effectively detected vectors during a short period, provided information to update the vector infestation map and increased community and political awareness regarding Chagas disease. This approach could be recommended as an effective and feasible strategy to strengthen vector surveillance on a larger scale.

Review: surveillance of Chagas disease.

After remarkable reduction in prevalence through regional elimination of domestic vectors, the central challenge of Chagas disease control is shifting towards interruption of the disease transmission by non-eliminable vectors in Latin America. Vector surveillance with community participation was cost-effective against the eliminable vectors. But the efforts often failed against the non-eliminable vectors due to lack of surveillance coverage or sustainability. For instance, in El Salvador and Honduras, the operational vector control personnel lost access to many communities under decentralized health systems. To cover wider areas lastingly, the countries implemented the surveillance systems involving non-specialists from locally embedded resources, such as local health services, schools and community leaders. From these experiences, this paper outlines a common structure of the current community-based surveillance systems, consisting of five fundamental sequential functions. To increase scalability and sustainability, four of the five functions could be delegated to the locally available human resources, and the surveillance systems can be integrated into the general health systems. Challenges at national and regional levels are discussed for further evolution of the surveillance systems.

Rhodnius prolixus en Nicaragua: distribución geogrßfica, control y vigilancia entre 1998 y 2009 / Rhodnius prolixus in Nicaragua: geographical distribution, control, and surveillance, 1998-2009

OBJETIVO: Presentar la perspectiva general del control de Rhodnius prolixus, el principal vector en la transmisión de la enfermedad de Chagas en Centroamérica, durante el período 1998-2009 en Nicaragua. Describir el control vectorial realizado y presentar la distribución geogrßfica de las localidades infestadas. MÉTODOS: Se estudió y analizó la información disponible en el Ministerio de Salud de Nica ragua. Se visualizó la distribución geogrßfica de R. prolixus mediante el programa visualiza dor de mapas Quantum GIS 1.5.0. RESULTADOS: Se determinó que 59 localidades en 14 municipios de 8 departamentos presen taron antecedentes de infestación con R. prolixus entre 1998 y 2009. La altitud de las locali dades infestadas oscila entre 160 y 1 414 metros sobre el nivel del mar. Se han tratado con mßs de dos ciclos de control químico 56 localidades. En el segundo ciclo de rociamiento se detectó la presencia del vector, pero durante el tercer ciclo no se lo encontró en ninguna localidad. CONCLUSIONES: La mayor concentración geogrßfica de R. prolixus se observó en dos depar tamentos de la región norte: Madriz y Nueva Segovia. La cantidad de localidades infestadas es menor en Nicaragua que en otros países centroamericanos. El control químico ha sido exitoso en las localidades intervenidas, pero es necesario fortalecer el sistema de vigilancia institucio nal y comunitaria tanto para vigilar la reinfestación con R. prolixus como para ampliar la cobertura del control vectorial.

OBJECTIVE: Present an overview of the control of Rhodnius prolixus, the principal vector in the transmission of Chagas' disease in Central America, during the period 1998-2009 in Nicaragua. Describe the vector control carried out and the geographical distribution of the infested localities. METHODS: The available information in Nicaragua's Ministry of Health was studied and analyzed. The geographical distribution of R. prolixus was visualized using the Quantum GIS 1.5.0 map visualization program. RESULTS: It was determined that 59 localities in 14 municipalities of 8 departments had a history of R. prolixus infestation between 1998 and 2009. The altitude of the infested localities ranges between 160 and 1 414 meters above sea level. A total of 56 localities have been treated with more than two cycles of chemical control. The presence of the vector was detected in the second spraying cycle, but it was not found in any locality during the third cycle. CONCLUSIONS: The greatest geographical concentration of R. prolixus was found in two departments in the northern region: Madriz and Nueva Segovia. There were fewer infested localities in Nicaragua than in other Central American countries. Chemical control has been successful in the localities treated, but the institutional and community surveillance system needs to be strengthened to monitor R. prolixusreinfestation and expand vector control coverage.

[Rhodnius prolixus in Nicaragua: geographical distribution, control, and surveillance, 1998-2009]. / Rhodnius prolixus en Nicaragua: distribución geográfica, control y vigilancia entre 1998 y 2009.

OBJECTIVE: Present an overview of the control of Rhodnius prolixus, the principal vector in the transmission of Chagas' disease in Central America, during the period 1998-2009 in Nicaragua. Describe the vector control carried out and the geographical distribution of the infested localities. METHODS: The available information in Nicaragua's Ministry of Health was studied and analyzed. The geographical distribution of R. prolixus was visualized using the Quantum GIS 1.5.0 map visualization program. RESULTS: It was determined that 59 localities in 14 municipalities of 8 departments had a history of R. prolixus infestation between 1998 and 2009. The altitude of the infested localities ranges between 160 and 1 414 meters above sea level. A total of 56 localities have been treated with more than two cycles of chemical control. The presence of the vector was detected in the second spraying cycle, but it was not found in any locality during the third cycle. CONCLUSIONS: The greatest geographical concentration of R. prolixus was found in two departments in the northern region: Madriz and Nueva Segovia. There were fewer infested localities in Nicaragua than in other Central American countries. Chemical control has been successful in the localities treated, but the institutional and community surveillance system needs to be strengthened to monitor R. prolixus reinfestation and expand vector control coverage.