Venezuela's humanitarian crisis, resurgence of vector-borne diseases, and implications for spillover in the region.

In the past 5-10 years, Venezuela has faced a severe economic crisis, precipitated by political instability and declining oil revenue. Public health provision has been affected particularly. In this Review, we assess the impact of Venezuela's health-care crisis on vector-borne diseases, and the spillover into neighbouring countries. Between 2000 and 2015, Venezuela witnessed a 359% increase in malaria cases, followed by a 71% increase in 2017 (411 586 cases) compared with 2016 (240 613). Neighbouring countries, such as Brazil, have reported an escalating trend of imported malaria cases from Venezuela, from 1538 in 2014 to 3129 in 2017. In Venezuela, active Chagas disease transmission has been reported, with seroprevalence in children (<10 years), estimated to be as high as 12·5% in one community tested (n=64). Dengue incidence increased by more than four times between 1990 and 2016. The estimated incidence of chikungunya during its epidemic peak is 6975 cases per 100 000 people and that of Zika virus is 2057 cases per 100 000 people. The re-emergence of many vector-borne diseases represents a public health crisis in Venezuela and has the possibility of severely undermining regional disease elimination efforts. National, regional, and global authorities must take action to address these worsening epidemics and prevent their expansion beyond Venezuelan borders.

Panstrongylus geniculatus and four other species of triatomine bug involved in the Trypanosoma cruzi enzootic cycle: high risk factors for Chagas' disease transmission in the Metropolitan District of Caracas, Venezuela.

BACKGROUND: Chagas' disease is caused by the protozoan Trypanosoma cruzi and is autochthonous to the Americas. Its distribution depends on triatomine bugs that are responsible for the transmission of the disease. In 2005, we reported the presence of Panstrongylus geniculatus as a risk for Chagas' disease transmission in Caracas and neighboring areas. Three massive oral outbreaks occurred in the following years. Here we report the results of a 7-year study on triatomine species found in the Metropolitan District of Caracas (MDC), Venezuela. METHODS: Triatomine species collected by inhabitants of Caracas during 7 years were analyzed for parasite infection and blood meal. Triatomines were found in 31 of the 32 parishes surveyed. Traitomines were examined for the presence of blood and parasites in the digestive tract. Molecular techniques were used for the typing of parasites. RESULTS: A total of 3551 triatomines were captured from 31 of the 32 parishes surveyed. The vast majority of these were identified as P. geniculatus (98.96%), followed by Triatoma nigromaculata (0.59%), Triatoma maculata (0.39%) and Rhodnius prolixus (0.06%). Triatomines were always most abundant between April and June, and 2010 showed the highest number. We found that 54% of the specimens were females, 42.5% males and 3.5% nymphs. Overall, 75.2% of the insects were naturally infected with T. cruzi and 48.7% had fed on blood. Analysis of the adult forms showed that 60% of the females and 31.9 % of the males had blood in their stomachs, and 77.5% of the females and 73.3% of the males were naturally infected with T. cruzi. Nearly all, 99.6% of the T. cruzi isolates analyzed belonged to the TcI genotype. CONCLUSIONS: Blood-fed triatomine bugs infected with T. cruzi were distributed throughout Caracas. Four different species of triatomines were identified of which P. geniculatus was by far the most predominant. Our previous report of Eratyrus mucronatus raises the number of triatomine species in the MDC to 5. Dramatic modifications to the surrounding natural habitats have led to the establishment of a T. cruzi urban enzootic cycle, resulting in a high risk for Chagas' disease transmission in this capital city.

Molecular epidemiologic source tracking of orally transmitted Chagas disease, Venezuela.

Oral outbreaks of Chagas disease are increasingly reported in Latin America. The transitory presence of Trypanosoma cruzi parasites within contaminated foods, and the rapid consumption of those foods, precludes precise identification of outbreak origin. We report source attribution for 2 peri-urban oral outbreaks of Chagas disease in Venezuela via high resolution microsatellite typing.

Ethnopharmacological evaluation of Trichilia hirta L. as anticancer source in traditional medicine of Santiago de Cuba / Evaluación etnofarmacológica de Trichilia hirta como una fuente anticancer en la medicina tradicional de Santiago de Cuba

Trichilia hirta L. (Meliaceae) is traditionally used as antitumor source in Santiago de Cuba. Therefore, the aim of this study was to document and analyze the traditional medicinal use of this plant by cancer patients in Santiago de Cuba and to evaluate its antiproliferative activity on human normal and cancer cells. Cancer patients consuming Trichilia hirta extracts (Jubabán) were randomly selected and interviewed. The antiproliferative activity of a polysaccharide-rich fraction from leaves was evaluated against normal (MRC-5) and cancer cells (A-549, HeLa and Hep-2) by MTT assay. The study revealed that Trichilia hirta extracts are mainly used as anticancer source (46 percent. Moreover, the majority of cancer patients consuming Trichilia hirta extracts had carcinoma (86 percent). In particular, the most frequent were lung (26 percent) and prostate (18 percent) carcinoma. The majority (90 percent) of patients were consuming the extracts simultaneously, or after the chemotherapy and radiotherapy treatment. The polysaccharide-rich fraction showed antiproliferative activity against human lung cancer cells (A-549) and human cervix carcinoma (HeLa) cancer cells. However, no toxicity was observed in human normal fibroblasts (MRC-5). These results suggest that polysaccharide-rich fraction from Trichilia hirta contribute to the antitumor properties of this specie.

Trichilia hirta L. (Meliaceae) es tradicionalmente usada como recurso antitumoral en Santiago de Cuba. Por lo que, el objetivo de este estudio fue documentar y analizar el uso tradicional de esta planta por pacientes con cáncer en Santiago de Cuba y evaluar su actividad antiproliferativa sobre células humanas normales y tumorales. Pacientes con cáncer consumiendo los extractos de Trichilia hirta (jubabán) fueron aleatoriamente seleccionados y entrevistados. La actividad antiproliferativa de la fracción rica en polisacáridos de hojas fue evaluada en células normales (MRC-5) y en células tumorales (A-549, HeLa y Hep-2) a través del ensayo con MTT. El estudio reveló que los extractos de Trichilia hirta eran usados mayoritariamente como recurso antitumoral (46 por ciento). Además, la mayoría de los pacientes consumiendo extractos de Trichilia hirta presentaron carcinoma (86 por ciento). En particular, los más frecuentes fueron carcinomas de pulmón (26 por ciento) y próstata (18 por ciento). También la mayoría de los pacientes (90 por ciento) consumieron los extractos simultáneamente o después de tratamientos con quimioterapia y radioterapia. La fracción rica en polisacáridos mostró actividad antiproliferativa contra las células de cáncer de pulmón humano (A-549) y carcinoma de cerviz humano (HeLa). Sin embargo, no se observó toxicidad en fibroblastos humanos normales (MRC-5). Estos resultados sugieren que la fracción rica en polisacáridos de hojas de Trichilia hirta contribuye a la actividad antitumoral de esta especie.

Ethnopharmacological evaluation of Trichilia hirta L. as anticancer source in traditional medicine of Santiago de Cuba

Trichilia hirta L. (Meliaceae) is traditionally used as antitumor source in Santiago de Cuba. Therefore, the aim of this study was to document and analyze the traditional medicinal use of this plant by cancer patients in Santiago de Cuba and to evaluate its antiproliferative activity on human normal and cancer cells. Cancer patients consuming Trichilia hirta extracts (Jubabán) were randomly selected and interviewed. The antiproliferative activity of a polysaccharide-rich fraction from leaves was evaluated against normal (MRC-5) and cancer cells (A-549, HeLa and Hep-2) by MTT assay. The study revealed that Trichilia hirta extracts are mainly used as anticancer source (46 percent). Moreover, the majority of cancer patients consuming Trichilia hirta extracts had carcinoma (86 percent). In particular, the most frequent were lung (26 percent) and prostate (18 percent) carcinoma. The majority (90 percent) of patients were consuming the extracts simultaneously, or after the chemotherapy and radiotherapy treatment. The polysaccharide-rich fraction showed antiproliferative activity against human lung cancer cells (A-549) and human cervix carcinoma (HeLa) cancer cells. However, no toxicity was observed in human normal fibroblasts (MRC-5). These results suggest that polysaccharide-rich fraction from Trichilia hirta contribute to the antitumor properties of this specie(AU)

Trichilia hirta L. (Meliaceae) es tradicionalmente usada como recurso antitumoral en Santiago de Cuba. Por lo que, el objetivo de este estudio fue documentar y analizar el uso tradicional de esta planta por pacientes con cáncer en Santiago de Cuba y evaluar su actividad antiproliferativa sobre células humanas normales y tumorales. Pacientes con cáncer consumiendo los extractos de Trichilia hirta (jubabán) fueron aleatoriamente seleccionados y entrevistados. La actividad antiproliferativa de la fracción rica en polisacáridos de hojas fue evaluada en células normales (MRC-5) y en células tumorales (A-549, HeLa y Hep-2) a través del ensayo con MTT. El estudio reveló que los extractos de Trichilia hirta eran usados mayoritariamente como recurso antitumoral (46 por ciento). Además, la mayoría de los pacientes consumiendo extractos de Trichilia hirta presentaron carcinoma (86 por ciento). En particular, los más frecuentes fueron carcinomas de pulmón (26 por ciento) y próstata (18 por ciento). También la mayoría de los pacientes (90 por ciento) consumieron los extractos simultáneamente o después de tratamientos con quimioterapia y radioterapia. La fracción rica en polisacáridos mostró actividad antiproliferativa contra las células de cáncer de pulmón humano (A-549) y carcinoma de cerviz humano (HeLa). Sin embargo, no se observó toxicidad en fibroblastos humanos normales (MRC-5). Estos resultados sugieren que la fracción rica en polisacáridos de hojas de Trichilia hirta contribuye a la actividad antitumoral de esta especie

Geographical distribution of Trypanosoma cruzi genotypes in Venezuela.

Chagas disease is an endemic zoonosis native to the Americas and is caused by the kinetoplastid protozoan parasite Trypanosoma cruzi. The parasite is also highly genetically diverse, with six discrete typing units (DTUs) reported TcI - TcVI. These DTUs broadly correlate with several epidemiogical, ecological and pathological features of Chagas disease. In this manuscript we report the most comprehensive evaluation to date of the genetic diversity of T. cruzi in Venezuela. The dataset includes 778 samples collected and genotyped over the last twelve years from multiple hosts and vectors, including nine wild and domestic mammalian host species, and seven species of triatomine bug, as well as from human sources. Most isolates (732) can be assigned to the TcI clade (94.1%); 24 to the TcIV group (3.1%) and 22 to TcIII (2.8%). Importantly, among the 95 isolates genotyped from human disease cases, 79% belonged to TcI - a DTU common in the Americas, however, 21% belonged to TcIV- a little known genotype previously thought to be rare in humans. Furthermore, were able to assign multiple oral Chagas diseases cases to TcI in the area around the capital, Caracas. We discuss our findings in the context of T. cruzi DTU distributions elsewhere in the Americas, and evaluate the impact they have on the future of Chagas disease control in Venezuela.

Toxicidad por dosis repetidas de la solución CM-95 tratada magnéticamente en ratas Sprague Dawley / Toxicity by repeated dose of magnetically treated CM-95 Solution in Sprague Dawley rats

En este trabajo se realizó la evaluación toxicológica a dosis repetidas por el método de test límite del candidato ainmunopotenciador, la solución CM-95 tratada magnéticamente, acorde con las regulaciones de la Organización para la Colaboración Económica y el Desarrollo, incluida en la Guía 407. El objetivo fue establecer las posibles lesiones orgánicas y funcionales ocasionadas por la solución CM-95, tratada magnéticamente con la máxima inducción magnética permisible (0,16 T), para la obtención del candidato a inmunopotenciador. Se emplearon tres grupos: Experimental, Control y Satélite. Como Biomodelo experimental se utilizaron ratas Sprague Dawley machos y hembras con pesos de 150 a 200 g. Durante el estudio no se registraron signos clínicos de toxicidad ni muertes en ninguno de los animales de los grupos tratados, ni en los controles. No hubo afectación del peso corporal durante elensayo. Aunque hubo variaciones en los valores de algunos parámetros hematológicos y bioquímicos, estos no tuvieron significación biológica. No se encontraron lesiones macroscópicas, ni microscópicas; solo se observaron efectos proliferativos en el tejido linfoide de timo y bazo, relacionados con la respuesta del sistema inmune. Lasolución CM-95 tratada magnéticamente, no mostró toxicidad en el modelo animal y nivel de dosis utilizado, y bajo las condiciones experimentales ensayadas(AU)

In this study the toxicological evaluation at repeated dose by the method of limit test of the candidate to magnetically treated immunopotentiator CM-95 Solution was carried out; according with regulations of the Organization for Economic Cooperation and Development included in guide 407. The objective was to establish the possible organic and functional lesions caused bythe magnetically treated CM-95 Solution with maximum permissible magnetic induction (0,16 T), for obtaining the candidate to immunopotentiator. Three groups were used: Experimental, Control and Satellite. As experimental Biomodels, male and female Sprague Dawley rats were used, with 150 to 200 g weights. During the study neither clinical signs of toxicity nor deathsin any of the animals of the treated groups were registered. There was not affectation of the corporal weight during the test. There was not change of the corporal weight during the trial. Although there were variations of some haematology and biochemical parameters, they had no biological significance. Macroscopic or microscopic lesions were not found; justproliferation effects were observed, in the lymphoid tissues of the thymus and spleen, related to the response of immune system. Magnetically treated CM-95 Solution, showed no toxicity in the animal model and dose level used, and under the observed experimental conditions(AU)