The second coming of urban yellow fever in the Americas: looking the past to see the future.

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.

A new antifungal and antiprotozoal depside from the Andean lichen Protousnea poeppigii.

Extracts from the Andean lichens Protousnea poeppigii and Usnea florida displayed antimicrobial activity against the pathogenic fungi Microsporum gypseum, Trichophyton mentagrophytes and T. rubrum with MIC values between 50 and 100 microg/mL. From the active extracts, four main metabolites were isolated and identified as the new depside, isodivaricatic acid, and the known metabolites 5-propylresorcinol, divaricatinic acid and usnic acid. Isodivaricatic acid and divaricatinic acid presented antifungal effect towards M. gypseum with a MIC of 50 microg/mL and against T. mentagrophytes and T. rubrum and with MIC values of 50 and 100 microg/mL, respectively. The new isodivaricatic acid was active towards Leishmania amazonensis, Leishmania brasiliensis and Leishmania infantum promastigotes with 100% lysis at 100 microg/mL.The activity of the new compound decreased on acetylation of the hydroxy groups as well as on methylation of the acid function. The structures were elucidated by spectroscopic means. The spectroscopic data of isodivaricatic acid are presented here for the first time.

Atividade leishmanicida in vitro de Eugenia uniflora e Momordica charantia / Antileishmanial in vitro activity of Eugenia uniflora and Momordica charantia

A Leishmaniose Tegumentar Americana no Brasil é causada por uma variedade de espécies de Leishmania e uma grande diversidade destes parasitas pode ser encontrada na Região Amazônica. Revisões recentes na quimioterapia de leishmaniose enfatizam as deficiências dos agentes terapêuticos atualmente disponíveis e mostram a necessidade urgente de novos candidatos. Uma alternativa para substituir esses medicamentos são extratos naturais de Eugenia uniflora e Momordica charantia. Foram preparados extratos etanólicos das folhas de E. uniflora e M. charantia. Para os testes in vitro de Leishmania brasiliensis foram utilizadas formas promastigotas. O ensaio de citotoxicidade foi realizado com linhagens de fibroblastos. Nossos resultados indicam que E. uniflora foi eficaz contra a cepa de parasita testada, representando uma fonte alternativa de produtos naturais com atividade contra L. brasiliensis.

Cutaneous leishmaniasis is caused in Brazil by several species of the genus Leishmania and a wide variety of these protozoan parasites can be found in Brazil, mainly in the Amazon region. Recent reviews on the chemotherapy of leishmaniasis show the low effectiveness of the usual therapeutic agents, demonstrating the need for new drugs. An interesting possible alternative to the conventional drugs is offered by natural products extracted from Eugenia uniflora and Momordica charantia. Ethanol extracts were prepared from the leaves of Eugenia uniflora and Momordica charantia and assayed in vitro against Leishmania brasiliensis promastigotes and fibroblasts to assess their antileishmanial and cytotoxic activities, respectively. Our results indicate that E. uniflora was active against the parasitic forms of L. brasiliensis

Clinical and epidemiological characterization of trypanosoma cruzi infected patients attending a referral center of chagas disease in Paraguay, preliminary results

A pesar de que la transmisión vectorial de la tripanosomiasis americana se ha interrumpido y las tasas de nuevas infecciones se han reducido en grandes áreas de América Latina, todavía existen muchos pacientes infectados crónicos. Determinamos las características clínicas y epidemiológicas de pacientes infectados con Trypanosoma cruzi que asistieron al Departamento de Medicina Tropical del Instituto de Investigaciones en Ciencias de la Salud (IICS) desde 1985 al 2007 analizando sus fichas clínicas manteniendo el anonimato y la confidencialidad. El paquete estadístico SPSS 11.5 se usó para analizar 1.024 fichas de pacientes de los cuales el 70,1 por cento (723/1024) estaba en el grupo etario de 21-60 años (38,7±10,5); 74,5 por cento (763/1024) nació en departamentos endémicos, 13,2 por cento (135/1024) en el Departamento Central, 5,9 por cento (60/1024) en Asunción y 6,4 por cento(66/1024) en otros departamentos. En el momento de la consulta, 38,2 por cento (391/1024) vivía en departamentos endémicos, 27,8 por cento (285/1024) en el Departamento Central, 22,6 por cento (231/1024) en Asunción y 11,4 por cento (117/1024) en otros. Los motivos de consulta fueron: palpitaciones (43,5 por cento; 445/1024), disnea de esfuerzo (34,1 por cento; 349/1024), decaimiento (32,8 por cento; 336/1024), cefalea (26,1 por cento; 267/1024), constipación (24,7 por cento; 253/1024) entre otros.

La mitad (512/1024) dijo no haber sido picada por vinchucas, 26,2 por cento (268/1024) no sabía o no recordaba, 23,8 por cento (244/1024) fue picado y 37,6 por cento (385/1024) tuvo vinchucas en su casa. Alrededor del 10 por cento (104/1024) recibió trasfusión de sangre y 89,8 por cento (920/1024) no; 24,8 por cento (254/1024) donó sangre mientras que el 75,2 por cento (770/1024) no. Clínicamente, el 73,2 por cento (750/1024) correspondía a pacientes indeterminados, 16,2 por cento (166/1024) tenía cardiopatía, 5,1 por cento (52/1024) megacolon y 1,5 por cento (15/1024) megaesófago. La mayoría de los pacientes estaban en el grupo etario de mayor productividad económica y aunque gran parte había nacido en regiones rurales endémicas, la mayoría vivía en áreas urbanas reflejando probablemente la migración laboral. Clínicamente, la mayoría de los pacientes eran indeterminados y las lesiones cardiacas predominaron sobre las lesiones digestivas. Esta es una población chagásica clásica y los programas de control deberían continuar desarrollando políticas de salud pública que consideren las características de las poblaciones afectadas para ofrecerles diagnóstico y tratamiento apropiados.

Although vector transmission of American trypanosomiasis has been interrupted and there are decreased rates of new infections in large areas of Latin America, there are still many chronically infected patients. We determined the clinical and epidemiological characteristics of Trypanosoma cruzi infected patients attending the Department of Tropical Medicine of the Institute of Research in Health Sciences (IICS) from 1985 to 2007 by analyzing their clinical records, maintaining anonymity and confidentiality. The SPSS 11.5 statistical package was used to analyze 1024 patient records of whom 70.1 percent (723/1024) were in the age group of 21-60 years (38.7±10.5); 74.5 percent (763/1024) were born in endemic departments, 13.2 percent (135/1024) in the Central department, 5.9 percent (60/1024) in Asunción and 6.4 percent (66/1024) in other departments. At consultation, 38.2 percent (391/1024) lived in endemic departments, 27.8 percent (285/1024) in Central Department, 22.6 percent (231/1024) in Asunción and 11.4 percent (117/1024) in others. Consultation reasons were: beatings (43.5 percent; 445/1024), effort dyspnea (34.1percent; 349/1024), enervation (32.8percent; 336/1024), headache (26.1percent; 267/1024) and constipation (24.7percent; 253/1024), among others.

Half (512/1024) said they were not bitten by kissing bugs, 26.2 percent (268/1024) did not know or remember, 23.8 percent (244/1024) were bitten and 37.6 percent (385/1024) had kissing bugs in their houses. About 10 percent (104/1024) received blood transfusion and 89.8 percent (920/1024) did not; 24.8 percent(254/1024) donated blood while 75.2 percent (770/1024) did not. Clinically, 73.2percent (750/1024) were indeterminate patients, 16.2 percent (166/1024) had cardiopathy, 5.1 percent (52/1024) megacolon and 1.5 percent (15/1024) megaesophagus. Most patients were in the age group of highest economic productivity and although the majority had been born in endemic rural regions most of them were living in urban areas, likely reflecting work migration. Clinically, most patients were indeterminate and cardiac lesions predominated over digestive lesions. This is a classical chagasic.

Clinical and epidemiological characterization of trypanosoma cruzi infected patients attending a referral center of chagas disease in Paraguay, preliminary results

A pesar de que la transmisión vectorial de la tripanosomiasis americana se ha interrumpido y las tasas de nuevas infecciones se han reducido en grandes áreas de América Latina, todavía existen muchos pacientes infectados crónicos. Determinamos las características clínicas y epidemiológicas de pacientes infectados con Trypanosoma cruzi que asistieron al Departamento de Medicina Tropical del Instituto de Investigaciones en Ciencias de la Salud (IICS) desde 1985 al 2007 analizando sus fichas clínicas manteniendo el anonimato y la confidencialidad. El paquete estadístico SPSS 11.5 se usó para analizar 1.024 fichas de pacientes de los cuales el 70,1 por cento (723/1024) estaba en el grupo etario de 21-60 años (38,7±10,5); 74,5 por cento (763/1024) nació en departamentos endémicos, 13,2 por cento (135/1024) en el Departamento Central, 5,9 por cento (60/1024) en Asunción y 6,4 por cento(66/1024) en otros departamentos. En el momento de la consulta, 38,2 por cento (391/1024) vivía en departamentos endémicos, 27,8 por cento (285/1024) en el Departamento Central, 22,6 por cento (231/1024) en Asunción y 11,4 por cento (117/1024) en otros. Los motivos de consulta fueron: palpitaciones (43,5 por cento; 445/1024), disnea de esfuerzo (34,1 por cento; 349/1024), decaimiento (32,8 por cento; 336/1024), cefalea (26,1 por cento; 267/1024), constipación (24,7 por cento; 253/1024) entre otros...

Although vector transmission of American trypanosomiasis has been interrupted and there are decreased rates of new infections in large areas of Latin America, there are still many chronically infected patients. We determined the clinical and epidemiological characteristics of Trypanosoma cruzi infected patients attending the Department of Tropical Medicine of the Institute of Research in Health Sciences (IICS) from 1985 to 2007 by analyzing their clinical records, maintaining anonymity and confidentiality. The SPSS 11.5 statistical package was used to analyze 1024 patient records of whom 70.1 percent (723/1024) were in the age group of 21-60 years (38.7±10.5); 74.5 percent (763/1024) were born in endemic departments, 13.2 percent (135/1024) in the Central department, 5.9 percent (60/1024) in Asunción and 6.4 percent (66/1024) in other departments. At consultation, 38.2 percent (391/1024) lived in endemic departments, 27.8 percent (285/1024) in Central Department, 22.6 percent (231/1024) in Asunción and 11.4 percent (117/1024) in others. Consultation reasons were: beatings (43.5 percent; 445/1024), effort dyspnea (34.1percent; 349/1024), enervation (32.8percent; 336/1024), headache (26.1percent; 267/1024) and constipation (24.7percent; 253/1024), among others...

Avaliação da atividade anti-Trypanosoma e anti-Leishmania de Mentha arvensis e Turnera ulmifolia / Evaluation of the anti-Trypanosoma and anti-Leishmania activity of Mentha arvensis and Turnera ulmifolia

Tripanosomiasis or “Chagas disease”, caused by Trypanosoma cruzi, affect 10 million people in Latin America. Today, the chemotherapy is the only specific treatment against this disease, being the most used drugs the nifurtimox and benznidazole. Leishmaniasis is a disease caused by parasites of the genus Leishmania, mainly founded in regions with forests, as the Amazonia. Recent reports about the Leishmaniasis indicate a deficit of therapeutical drugs available against this disease and reinforce the necessity of the discovering of new drugs. An interesting approach against these diseases is the use of natural products, as the extracts of plants as Mentha arvensis and Turnera ulmifolia. For the in vitro assays against T. cruzi and Leishmania, was used the clone CL-B5 and promastigote forms, respectively. The cytotoxic assay was performed using fibroblasts. Our results indicated that M. arvensis was active against all strains assayed, inhibiting 65 e 47 percent of the assayed strains (IC50 = 192.3 and 531.9 ug/mL respectively), representing an interesting and alternative source of natural products with anti-kinetoplastida activity.

Doença de Chagas, causada por Trypanosoma cruzi, afeta cerca de 10 milhões de pessoas nas Américas. Atualmente, a quimioterapia é o único tratamento específico disponível para esta doença, onde os medicamentos utilizados são nifurtimox e benzonidazol. Leishmaniose tegumentar Americana no Brasil é causada por uma variedade de espécies de Leishmania e uma grande diversidade destes parasitos pode ser encontrada na Região Amazônica. Revisões recentes na quimioterapia de leishmaniose enfatizam as deficiências dos agentes terapêuticos atualmente disponíveis e mostram a necessidade urgente de novos candidatos. Uma alternativa para substituir esses medicamentos são extratos naturais de Mentha arvensis e Turnera ulmifolia. Foram preparados extratos etanólicos das folhas de M. arvensis e T. ulmifolia. Para os testes in vitro de T. cruzi, foi utilizado o clone CL-B5 e para Leishmania brasiliensis foram utilizadas formas promastigotas. O ensaio de citotoxicidade foi realizado com linhagens de fibroblastos. Nossos resultados indicam que M. arvensis foi eficaz contra as cepas de parasitos testadas apresentando 65 e 47 por cento de inibição em uma concentração de 500 ug/mL (respectivamente, CE50 = 192.3 e 531.9 ug/mL), sendo considerada uma fonte alternativa de produtos naturais com atividade contra T. cruzi e L. brasiliensis.

Community participation in Chagas disease vector surveillance: systematic review

Background: Vector control has substantially reduced Chagas disease (ChD) incidence. However, transmission by household-reinfesting triatomines persists, suggesting that entomological surveillance should play a crucial role in the long-term interruption of transmission. Yet, infestation foci become smaller and harder to detect as vector control proceeds, and highly sensitive surveillance methods are needed. Community participation (CP) and vector-detection devices (VDDs) are both thought to enhance surveillance, but this remains to be thoroughly assessed.Methodology/principal findings: We searched Medline, Web of Knowledge, Scopus, LILACS, SciELO, the bibliographies of retrieved studies, and our own records. Data from studies describing vector control and/or surveillance interventions were extracted by two reviewers. Outcomes of primary interest included changes in infestation rates and the detection of infestation/reinfestation foci. Most results likely depended on study- and site-specific conditions, precluding meta-analysis, but we re-analysed data from studies comparing vector control and detection methods whenever possible. Results confirm that professional, insecticide-based vector control is highly effective, but also show that reinfestation by native triatomines is common and widespread across Latin America. Bug notification by householders (the simplest CP-based strategy) significantly boosts vector detection probabilities; in comparison, both active searches and VDDs perform poorly, although they might in some cases complement each other.Conclusions/significance: CP should become a strategic component of ChD surveillance, but only professional insecticide spraying seems consistently effective at eliminating infestation foci. Involvement of stakeholders at all process stages, from planning to evaluation, would probably enhance such CP-based strategies.

The antiplasmodium effects of a traditional South American remedy: Zanthoxylum chiloperone var. angustifolium against chloroquine resistant and chloroquine sensitive strains of Plasmodium falciparum

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.

Resolution of multiclonal infections of Trypanosoma cruzi from naturally infected triatomine bugs and from experimentally infected mice by direct plating on a sensitive solid medium

The isolation of biological clones of Trypanosoma cruzi by microscopically dispensing individual organisms or by serial dilution is laborious and time consuming. The inability to resolve mixed T. cruzi infections, from vectors and hosts, and to isolate clones of slow growing genotypes by efficient plating on solid media, has hindered characterization studies and downstream applications. We have devised and validated a sensitive, solid medium plating technique for rapid in vitro isolation of clones representative of all the recognized T. cruzi lineages (TCI, TCIIa–e), including the slow growing strain CANIII (TCIIa) and Trypanosoma rangeli, with high plating efficiencies. Furthermore, the method is effective for the isolation of clones directly from silvatic triatomine bugs and from experimentally infected mice harbouring mixed infections, allowing resolution of multiclonal infections from varied sources. (AU)

Fipronil Insecticide: Novel Application against Triatomine Insect Vectors of Chagas Disease

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 per cent) 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.

Comparative Evaluation of Pyrethroid Insecticide Formulationsagainst Triatoma infestans (Klug): Residual Efficacy on FourSubstrates

We investigated the residual efficacy of four insecticide formulations used in Chagas disease vector control campaigns: cyfluthrin 12.5 per cent suspension concentrace (SC), lambda-cyhalothrin 10 per cent wettable powder (WP), deltamethrin 2.5 per cent SC, and 2.5 per cent WP on four types of circular blocks of wood, straw with mud, straw with mud painted with lime, and mud containing 5 per cent 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 per cent) were observed for deltamethrin 2.5 per cent SC and lambda-cyhalothrin 10 per cent 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

Residual effect of lambdacyhalothrin on Triatoma infestans

Insecticidal residual effect and triatomine infestation rates in houses of a community fumigated with lambdcyhalothrin (Icon) are reported. No mortality was observed in 5th-instar Triatoma infestans nymphs in 72-hr exposure test on three different surfaces, one month after fumigation for a dose of 31.5 mg am/m2. However, during post-exposure observation a mortality of 60 per cent was recorded for those insect exposed on sprayed woodboard. The results observed with mud-containing treated walls, were markedly poorer (0per cent of mortality). Twelve month after spraying 40 per cent of mortality was observed on first-instar T. infestans nymphs in 72-hr exposure test on woodboard, but lower mortality rates were observed in mud-containing materials. When the effect of deltamethrin (109 mg ai/m2) and lambdcyhalothrin (94 mg ai/m2) was compared, the former did not appear to be superior at similar loads. Both have showed a mortality rate of 30 per cent on 5th-instar T. infestans nymphs three months post-fumigation. The dose utilized in the field fumigation was enough to get a significant (p < 0.0001) control of triatomine domestic infestation, since it was sufficient to keep 95 per cent of the houses uninfested throughout 21 months following treatment, when compared with baseline situation. A remarkable knock-down effect on adult and nymphs forms of the insect and a high in situ mortality were observed as a result of its application, even at very low doses.

Residual effect of lambdacyhalothrin on Triatoma infestans

Insecticidal residual effect and triatomine infestation rates in houses of a community fumigated with lambdcyhalothrin (Icon) are reported. No mortality was observed in 5th-instar Triatoma infestans nymphs in 72-hr exposure test on three different surfaces, one month after fumigation for a dose of 31.5 mg am/m2. However, during post-exposure observation a mortality of 60 was recorded for those insect exposed on sprayed woodboard. The results observed with mud-containing treated walls, were markedly poorer (0 of mortality). Twelve month after spraying 40 of mortality was observed on first-instar T. infestans nymphs in 72-hr exposure test on woodboard, but lower mortality rates were observed in mud-containing materials. When the effect of deltamethrin (109 mg ai/m2) and lambdcyhalothrin (94 mg ai/m2) was compared, the former did not appear to be superior at similar loads. Both have showed a mortality rate of 30 on 5th-instar T. infestans nymphs three months post-fumigation. The dose utilized in the field fumigation was enough to get a significant (p < 0.0001) control of triatomine domestic infestation, since it was sufficient to keep 95 of the houses uninfested throughout 21 months following treatment, when compared with baseline situation. A remarkable knock-down effect on adult and nymphs forms of the insect and a high in situ mortality were observed as a result of its application, even at very low doses.

A Screening Method for Natural Products on Triatomine-Bugs

A simple method for screening natural products on triatomine bugs, vectors of Chagas disease, was developed using fourth instar Rhodnius neglectus nymphs as an insect model. The statistical method of randomized blocks and randomized blocks with a dichotomous variable were compared and the minimum sample size for screening purposes was established. Tests were made on 94 plant extracts from 49 species, 28 of which are traditionally regarded as having some effect on arthropods or parasitic helminths. 50 miligrama of crude hexane or ethanol extract was topically applied to each insect. The effect on mortality and moulting was assessed. Ten plant species caused an increased mortality, 16.0 per cent to 52.3 per cent, compared with untreated controls. Moulting inhibition ranged from 22.2 per cent to 33.3 per cent and was related to insecticidal effect in most cases. Extracts from two Meliaceae plants belonging to the genera Melia and Cabralea were among the most active tested, causing 32.5 per cent and 45 per cent mortality, respectively. Extracts from a Salvia species killed 52.3 per cent of the bugs. Ten of the 13 plants showing activity are used by the rural population in various parts of Latin America for arthropod control or as vermifuges.