Abstract Yellow fever (YF) epizootics in South America during the 21st century have an unprecedented recorded magnitude and geographical dispersion. The YF spread progressively involved areas considered previously free of risk reaching the edge of cities with large unvaccinated populations, and urban outbreaks were frequently forecasted. We critically reviewed the initial stages and enhancing contexts of YF urban epidemics since the 17th century in the Americas, and the modeling attempts of YF epidemic risk by of Aedes-Human transmission, to find common factors that increase the probability of these events in the current scenarios. The YF urban outbreaks of the past showed as necessary conditions the multiple introduction by viremic carriers clustered in time and space, coincident with population peaks of Aedes. These conditions are not met in the current outbreaks in the Americas by sylvatic YF cycles, besides the protective impact of vector control campaigns, vaccination coverage, improved surveillance, and case management. Therefore, urban Aedes-Human YF outbreaks in the Americas are still possible but with low probability or very focal transmission, while the conditions reported in the past were avoided, and the surveillance and control measures sustained, including the vaccination of the population at risk.

Chagas disease (CD) still imposes a heavy burden on most Latin American countries. Vector-borne and mother-to-child transmission cause several thousand new infections per year, and at least 5 million people carry Trypanosoma cruzi. Access to diagnosis and medical care, however, is far from universal. Starting in the 1990s, CD-endemic countries and the Pan American Health Organization-World Health Organization (PAHO-WHO) launched a series of multinational initiatives for CD control-surveillance. An overview of the initiatives’ aims, achievements, and challenges reveals some key common themes that we discuss here in the context of the WHO 2030 goals for CD. Transmission of T. cruzi via blood transfusion and organ transplantation is effectively under control. T. cruzi, however, is a zoonotic pathogen with 100+ vector species widely spread across the Americas; interrupting vector-borne transmission seems therefore unfeasible. Stronger surveillance systems are, and will continue to be, needed to monitor and control CD. Prevention of vertical transmission demands boosting current efforts to screen pregnant and childbearing-aged women. Finally, integral patient care is a critical unmet need in most countries. The decades-long experience of the initiatives, in sum, hints at the practical impossibility of interrupting vector-borne T. cruzi transmission in the Americas. The concept of disease control seems to provide a more realistic description of what can in effect be achieved by 2030. (CD Vectorborne Vector borne mothertochild mother child year however universal 1990s s CDendemic endemic OrganizationWorld World PAHOWHO PAHO (PAHO-WHO controlsurveillance. controlsurveillance surveillance. control-surveillance aims achievements 203 T 100 Americas vectorborne unfeasible are childbearingaged childbearing aged women Finally decadeslong decades long sum 20 10 2 1

ABSTRACT Scorpionism is the accident resulting from the envenomation of humans by toxic scorpions. It is considered a health public problem in several tropical and subtropical regions of the world, including the Americas. The extreme venom toxicity of some species belonging to the genus Tityus has prompted the preparation of specific antivenoms in Latin America, which use is considered the only efficacious therapeutic strategy for treating scorpionism. Paraguay is inhabited by three Tityus species of reknown toxicity in neighbouring Brazil and Argentina (T. trivittatus, T. confluens, and T. bahiensis) but their sanitary importance in the country remains unknown. This review updates the list of known scorpion species in Paraguay and their distribution, and also presents data on their toxicity, with the intent to arise interest in the subject considering the recording of severe accidents in children, the possible increase in the number of scorpionism cases in the country as a result of global warming, and the need to identify effective scorpion antivenoms in the country.

RESUMEN El escorpionismo, como se conoce al accidente producido por escorpiones tóxicos en humanos, es un problema de salud pública en varias regiones del mundo, incluyendo centros urbanos de la América Tropical. La elevada toxicidad de algunas de las especies del género Tityus ha demandado la preparación de antivenenos específicos en América Latina, única estrategia terapéutica eficaz para el tratamiento de estos accidentes. En Paraguay habitan tres especies del género (T. trivittatus, T. confluens y T. bahiensis) de reconocida peligrosidad en Argentina y Brasil, pero cuya real importancia sanitaria en el país es desconocida. Ante el registro de accidentes severos y el posible escenario de un incremento epidemiológico del escorpionismo en Paraguay producto del calentamiento global, esta revisión presenta las especies conocidas del país, su distribución y datos sobre su toxicidad, a fin de sentar las bases para un necesario estudio que aclare la real magnitud del problema en el país e identifique los antivenenos antiescorpiónicos efectivos en Paraguay.

ABSTRACT Cutaneous and mucocutaneous leishmaniases are endemic in the department of Alto Paraná. In recent years, the number of cases has decreased and the first patients and positive dogs with visceral leishmaniasis have been diagnosed. In order to describe the current situation of leishmaniasis in this department and to identify the perception of political actors, agents of the health system and key community informants in relation to different forms of the disease, a documentary review about the control, diagnosis and treatment was performed. An exploratory, observational, descriptive and qualitative study with the interviewees was also carried out. In urban areas they knew the disease in all its forms, but not in rural areas, where young health officials did not identify signs or symptoms due to their high turnover while training in veterinary medicine at the rural level is limited. SENEPA works in coordination with the municipalities and the Family Health Units. The diagnosis is centralized in the Health Centers and in the Regional Hospital of Ciudad del Este, where medicines are received from the Treatment Program. The Family Health Units do not have laboratories and do not have supplies for diagnosis and treatment. The main complication for treatment is the discontinuity and the economic problems of the population to move to the city, making difficult the access to laboratory tests or other diagnostic studies that are only available there.

RESUMEN Las leishmaniosis cutánea y mucocutánea son endémicas en el departamento de Alto Paraná. En los últimos años ha disminuido el número de casos y se han diagnosticado los primeros pacientes y perros positivos con leishmaniosis visceral. Con el objetivo de describir la situación actual de las leishmaniosis en este departamento e identificar la percepción de actores políticos, agentes del sistema de salud e informantes claves de la comunidad en relación a diferentes formas de la enfermedad, se realizó una revisión documental sobre el control, diagnóstico y tratamiento, además de un estudio exploratorio observacional, descriptivo y cualitativo con los entrevistados. En zonas urbanas conocían la enfermedad en todas sus formas, no así en zonas rurales, donde los funcionarios jóvenes de salud, no identificaron signos ni síntomas debido a la alta rotación, mientras que la capacitación en las veterinarias a nivel rural es limitada. El SENEPA trabaja en coordinación con las municipalidades y las Unidades de Salud Familiar. El diagnóstico está centralizado en los Centros de Salud y en el Hospital Regional de Ciudad del Este, donde se reciben los medicamentos por parte del Programa para el tratamiento. Las Unidades de Salud Familiar no poseen laboratorios y no disponen de fichas ni de insumos para el diagnóstico y tratamiento. La principal dificultad para el tratamiento es su discontinuidad y las dificultades económicas de la población para trasladarse a la ciudad, lo que dificulta el acceso a exámenes de laboratorio u otros estudios diagnósticos que sólo ahí se brindan.

It is in our interest, in this brief manuscript, to report the creation of the first program of regional integration of a network of research institutes in Biomedicine belonging to members of the MERCOSUR countries. We discuss some of the foundations that gave sustenance to its creation and its objectives in the medium and long term. In addition, we consider the potential of the results of this program in the fields of applied medical research, education and biotechnology.

Se da a conocer la creación del primer programa de integración regional de una red de Institutos de Investigación en Biomedicina pertenecientes a países miembros del MERCOSUR. Se analizan las bases que dieron sustento a su creación y sus objetivos en el mediano y largo plazo. Además, se estima el potencial de los resultados de este programa en los campos de la investigación médica aplicada, educación y biotecnología.

Zanthoxylum chiloperone var. angustifolium Engl., Rutaceae, is used in traditional medicine to treat fungal and protozoal infections in the central area of South America. Considering the increasing resistance of Plasmodium falciparum in malarial ridden areas, we explored the anti-plasmodial effects of three compounds isolated from Z. chiloperone. The pyranocoumarin transavicennol and the canthinone alkaloids, canthin-6-one and 5-methoxycanthin-6-one, were found to have IC50 on chloroquine/mefloquine resistant and sensitive strains of P. falciparum of 0.5-2.7, 2.0-5.3 and 5.1-10.4 ƒÊg/mL, respectively. Moreover, the formation of heme adducts by these compounds is described by a novel alternative method based on MS-CID methods. The alkylamide sanshool was also identified, for first time in this plant, in the dichloromethanic and ethanolic extracts and the extracts were found to be notably non-toxic and displayed good anti-plasmodial effects.

Extracts from the Argentinean herb Tagetes mendocina Phil. (Asteraceae) were tested for antimicrobial activity against fungi, bacteria and protozoa. The different extracts (PE, DCM, MeOH and EtOAc) and the essential oil displayed activity mainly against dermatophytes, a group of fungi that produces skin infections. The bioassay-guided fractionation of PE, DCM and EtOAc extracts led to the isolation of eight compounds including two thiophenes, two acetophenone derivatives, dihydrorosefuran and three flavonoids. ITie thiophenes 5-(4-hydroxy- l-butynyl)-2,2'-bithienyl (BBTOH) (1) and its acetate (BBTOAc) (2) proved to be highly active against the dermatophytes Microsporum gypseum, Trichophyton rubrum and T. mentagrophytes with MIC values of 3.12, 3.12 and 6.25 µg/mL for compound 1 and 25, 3.12 and 6.25 µg/mLfor compound 2, respectively. In turn, the essential oil displayed a weak to modérate antifungal effect against M. gypseum with MIC = 250 µg/mL. ITie essential oil was examined by GC and GC-MS and 21 constituents (97.3%) were identified. (E) p-ocimene, (Z)-tagetone, (ii)-tagetone, (Z)-ocimenone, á-pinene and (E)-ocimenone were the major components. In addition, thiophenes 1 and 2 and 2-hydroxyacetophenone 3 showed antiprotozoal activity against Leishmania amazonensis, L. brasiliensis andi. infantum promastigotes with 100% lysis at 100 µg/mL.

Insecticide effects of deltamethrin 2.5% SC (flowable solution) on different substrates and triatomine infestation rates in two indigenous villages (Estancia Salzar and Nueva Promesa) of the Paraguayan Chaco are reported. This field study was carried out to determine the extent to which variability in spray penetration may affect residual action of the insecticide. A total of 117 houses in the two villages were sprayed. Filter papers discs were placed on aluminium foil pinned to walls and roofs in selected houses and the applied insecticide concentration was determined by high pressure liquid chromatography (HPLC). The target dose rate was 25 mg a.i./m². The mean actual applied dose in Estancia Salazar was 11.2 ± 3.1 mg a.i./m² in walls and 11.9 ± 5.6 mg a.i./m² in roofs while in Nueva Promesa, where duplicates were carried out, the mean values were 19.9 ± 6.9 mg a.i./m² and 34.7 ± 10.4 mg a.i./m² in walls and 28.8 ± 19.2 mg a.i./m² and 24.9 ± 21.8 mg a.i./m² in roofs. This shows the unevenness and variability of applied doses during spraying campaigns, and also the reduced coverage over roof surfaces. However, wall bioassays with Triatoma infestans nymphs in a 72 h exposure test showed that deposits of deltamethrin persisted in quantities sufficient to kill triatomines until three months post spraying. Knockdown by deltamethrin on both types of surfaces resulted in 100% final mortality. A lower insecticidal effect was observed on mud walls. However, three months after treatment, sprayed lime-coated mud surfaces displayed a twofold greater capacity (57.5%) to kill triatomines than mud sprayed surfaces (25%). Re-infestation was detected by manual capture only in one locality, six months after spraying,

We investigated the residual efficacy of four insecticide formulations used in Chagas disease vector control campaigns: cyfluthrin 12.5% suspension concentrace (SC), lambda-cyhalothrin 10% wettable powder (WP), deltamethrin 2.5% SC, and 2.5% WP on four types of circular blocks of wood, straw with mud, straw with mud painted with lime, and mud containing 5% of cement. Three concentrations of these insecticides were tested: the LC90 (previously determined on filter paper), the double of the LC90, and the recommended operational dose. For each bioassay test, 15 third-stage nymphs of Triatoma infestans (Klug) (Hemiptera: Reduviidae) were exposed for 120 h to each treatment at 24 h, 30, 60, 90, and 180 days post-spraying. Mortality rates, moulting history and behaviour were recorded at 24, 48, 72, and 120 h of exposure. Mortality rates were highest during the first 30 days post-spraying. Highest mortality rates (above 50%) were observed for deltamethrin 2.5% SC and lambda-cyhalothrin 10% WP on wood blocks up to three months post-spraying. Mud was the substrate on which treatments showed lowest persistence, with the other two substrates showing intermediate residual efficacy of all treatments. During the first 30 days WP formulations were not as effective as SC flowable formulations but, overall in the longer term, WP gave grater mortality rates of T. infestans nymphs exposed at up to six months post-spraying. Porous surfaces, especially mud, showed most variability presumably due to absorption of the insecticide. In contrast the less porous surfaces (i.e. wood and lime-coated mud) kept mortality rates high for longer post-treatment, irrespective of the insecticide concentration used.

From September 1993 to August 2001, 7,190 phlebotomine were collected with CDC light trap in an endemic area for human leishmaniasis, in the departments of Misiones and Itapúa, Paraguay. Eleven species were identified: Lutzomyia neivai (93.7%), L. whitmani (4.1%), and L. fischeri, L. shannoni, L. migonei, L. misionensis, L. cortelezzii, L. pessoai, L. alphabetica, Brumptomyia avellari and B. guimaraesi (less than 1%). The last three species are new records for the country. The biodiversity and phlebotomine abundance were associated with the proximity to primary forest or gallery forest, but L. neivai was also found in peridomestic periurban environment. L. neivai was found throughout the year, and showed a period of higher activity from September to April (spring to fall) with a unimodal or bimodal pattern in relation to the annual rainy peaks during the summer. Background literature about phlebotomine from Paraguay has been reviewed.

We investigated the efficacy and the residual effect of fipronil® against two species of triatomine bugs, Triatoma infestans and Rhodnius neglectus, in laboratory conditions measuring concentration-response and residual activity on different surfaces (dried mud and lime coated mud). Lethal concentrations (LC50,90) were determined on filter paper. The higher insecticide efficacy against R. neglectus when compared to T. infestans may be partially attributed to the differences in their biological cycles and genetic structures. Comparison with lambdacyhalothrin wettable powder showed that fipronil mortality rates (above 50%) were observed on mud blocks and lime-coated mud blocks up to 3 months when fipronil was sprayed at 100 and 200 mg a.i./m². Residual effect deeply decayed after 3 months; and at 6 months post treatment mortality was not observed. In contrast, lambdacyhalothrin showed a long lasting residual effect on both surfaces up to 6 months. Also, it should be mentioned that fipronil had a slow, but lethal activity on the triatomine bugs when wettable formulations were used on porous surfaces.