Toxicidad a dosis repetida e inmunogenicidad en Cercopithecus aethiops, del candidato vacunal SOBERANA 01 (FINLAY-FR-01) contra el coronavirus de tipo 2 causante del síndrome respiratorio agudo severo / Repeated dose toxicity and immunogenicity in Cercopithecus aethiops of SARS-CoV-2 SOBERANA 01 (FINLAY-FR-01) vaccine candidate

En el Instituto Finlay de Vacunas se desarrolló el candidato vacunal SOBERANA 01 (FINLAY-FR-01) contra el coronavirus de tipo 2 causante del síndrome respiratorio agudo severo. Este trabajo tuvo como objetivo evaluar la inmunogenicidad y posibles efectos toxicológicos del candidato vacunal SOBERANA 01 (FINLAY-FR-01 en Cercopithecus aethiops. Se utilizaron cinco primates no humanos (hembras), de 1-3 años de edad y 1-4 kg de peso corporal, distribuidos en dos grupos experimentales: Control (Solución Salina Fisiológica) y Tratado SOBERANA 01 (FINLAY-FR-01). El estudio se extendió por 84 días, en un esquema a dosis repetida de cuatro inmunizaciones los días 0, 28, 56 y 70. Se realizaron observaciones clínicas diarias, peso corporal, signos vitales (temperatura rectal, frecuencia respiratoria, y frecuencia cardíaca), exámenes electrocardiográficos, toma de la temperatura del sitio de inyección, musculometría e irritabilidad dérmica. Fueron realizados exámenes de hematología, bioquímica sanguínea, así como estudios inmunológicos. El ensayo concluyó con una supervivencia del 100por ciento, no se manifestaron signos de toxicidad, no hubo variaciones hematológicas, ni de la bioquímica sanguínea asociadas a la sustancia de ensayo. Además, no se observaron efectos locales en el sitio de administración. Por último, el candidato vacunal resultó inmunogénico, ya que se indujeron títulos altos de IgG anti-RBD, así como de la inhibición de la unión de RBD a ACE2(AU)

At Finlay Vaccine Institute has been developed the vaccine candidate SOBERANA 01 (FINLAY-FR-01) against SARS-CoV-2 virus, causing COVID-19. This work aims to evaluate the immunogenicity and possible toxicological effects of the SOBERANA 01 (FINLAY-FR-01) vaccine candidate in Cercopithecus aethiops. Five non-human primates (females) from 1-3 years old and 1-4 kg of body weight were distributed in two experimental groups: Control (Physiological Saline Solution) and Treated (SOBERANA 01 FINLAY-FR-01). The study extended through 84 days, in a repeated dose schedule of four immunizations on days 0, 28, 56, and 70. Daily clinical observations, body weight, vital signs (rectal temperature, respiratory rate, and heart rate), electrocardiographic examinations, temperature of the injection site, musculometry and dermic irritability, were performed. Hematological and blood biochemistry tests, as well as immunological studies were assessed. At the end of the assay 100percent survival was obtained, there were no signs of toxicity neither hematological or blood biochemistry variations associated with the test substance. In addition, no local effects were observed at the administration site. Finally, the vaccine candidate was immunogenic, since high titers of anti-RBD IgG, as well as inhibition of the RBD to ACE2 binding were induced(AU)

Hematological reference values for Alouatta palliata (Primates: Atelidae) and Cebus imitator (Primates: Cebidae) from the Pacific Coast of Costa Rica / Valores de referencia hematológicos para Alouatta palliata (Primates: Atelidae) y Cebus imitator (Primates: Cebidae) de la costa Pacífica de Costa Rica

Abstract Introduction: Wildlife hematological patterns are fundamental for health monitoring, and allows elucidating variations both within and between populations. Among these, hematological parameters are particularly valuable to evaluate the health status of neotropical primate species in the wild. Objective: To define hematological reference values for two species of monkeys in Costa Rica. Methods: During 2014, we collected blood samples from free-ranging mantled howler monkeys, Alouatta palliata (17 females, 18 males) and white-faced capuchin monkeys, Cebus imitator (5 females, 7 males) in seven localities of the Costa Rican Pacific coast. Results: For both species, the hematological values were higher in males, and howler monkey populations differed significantly except for platelets. Conclusions: These hematological values, which differ by sex and locality, will help evaluate the health status of these neotropical primate populations.

Resumen Introducción: Los patrones hematológicos de la vida silvestre son fundamentales para el monitoreo de la salud y permiten dilucidar las variaciones tanto dentro como entre poblaciones. Entre estos, los parámetros hematológicos son particularmente valiosos para evaluar el estado de salud de las especies de primates neotropicales en la naturaleza. Objetivo: Definir valores de referencia hematológicos para dos especies de monos en Costa Rica. Métodos: Durante el 2014 recolectamos muestras de sangre de monos aulladores de manto, Alouatta palliata (17 hembras, 18 machos) y monos capuchinos cariblancos, Cebus imitador (5 hembras, 7 machos) en siete localidades de la costa Pacífica de Costa Rica. Resultados: Para ambas especies, los valores hematológicos fueron mayores en los machos, y las poblaciones de monos aulladores difirieron significativamente con excepción de las plaquetas. Conclusiones: Estos valores hematológicos, que difieren según el sexo y la localidad, ayudarán a evaluar el estado de salud de estas poblaciones de primates neotropicales.

Boletín epidemiológico 21 - 2022. Semana epidemiológica del 22 al 28 de mayo del 2022 / Epidemiological bulletin 21 - 2022. Epidemiological week from May 22 to 28, 2022

En los momentos actuales se viene observando con incertidumbre el aumento de casos por transmisión persona a persona de la viruela del mono, también conocida como viruela símica, viruela de los monos o monkeypox (en inglés) en países no endémicos. Del 13 de mayo al 2 de junio del 2022 se han registrado 780 casos confirmados en 27 países de cuatro regiones de la Organización Mundial de la salud (OMS), siendo Europa la región con el mayor número de casos y que representa el 88% (688 casos) en 20 países, seguido de la Región de las Américas con el 10% (80 casos), Región del Mediterráneo Oriental con el 1% (9 casos) y la Región del Pacífico Occidental con menos del 1 % (3 casos). Los casos reportados al 02 de junio representan un aumento en +203% de lo comunicado al 29 de mayo del 2022. (1) La mayoría de los casos confirmados con antecedentes de viaje informaron que estos fueron a países de Europa y América del Norte, en lugar de África occidental o central que son las áreas endémicas. Ninguno de los casos estuvo asociado a muerte a diferencia de las 66 defunciones ocurridas en países endémicos en el presente año.

TRYPANOSOMA spp. in captive primates in a brazilian zoo

Captive animals, despite the constant care provided, are susceptible to infections from different sources. We herein report the natural trypanosome infection of 11 (28.2% positive) out of 39 non-human primates from 13 different species, in a Brazilian zoological park. Immunofluorescent antibody test (IFAT) and conventional polymerase chain reaction (cPCR) ruled out Trypanosoma cruzi, the etiological agent of Chagas disease. However, sequencing performed with positive samples employing hsp70 primers revealed similarities from 86% to 88% to diverse trypanosomes, including T. cruzi, Trypanosoma grayi, Trypanosoma lewisi, Trypanosoma rangeli and Trypanosoma vivax. We believe that the low similarity values obtained by sequencing reflect the difficulties in the molecular identification of trypanosomes, which share a large portion of their genetic material; this similarity may also preclude the diagnosis of co-infection by more than one trypanosome species. Thus, our study demonstrates the presence of diverse trypanosomes in primates, which are susceptible to infection by these parasites. Mechanical devices such as windows and bed nets, etc., are required to avoid vector insects in these environments, in addition to preventive quarantining of animals recently introduced into zoos. Therefore, investigation of the parasites in both the animals already residing in the zoo and those being introduced is of paramount importance, although no easy task.

Effects of cyclosporin, nifedipine and phenytoin on gingival myofibroblast transdifferentiation in monkeys

Abstract Objective: Myofibroblasts have been associated with the development of several pathologic fibrotic conditions. This longitudinal study aims to assess the proliferative and antiapoptotic effects of cyclosporin, nifedipine and phenytoin on gingival connective tissue cells of nonhuman primate, as well as to analyze a possible role of myofibroblasts in gingival overgrowth. Materials and Methods: Gingival samples from the right superior canine area were obtained from 12 male monkeys ( Sapajus spp ) to comprise the control group. After one week, the animals were randomly assigned to three groups, which received daily oral doses of cyclosporin, nifedipine or phenytoin for 120 days. Gingival samples were collected from the left superior canine area of two animals of each group at 52 and 120 days. Histological sections were stained with hematoxylin and eosin, and immunoreacted against α-SMA, Ki- 67 and bcl-2. Results: α-SMA immunoreaction was negative in the control and experimental groups. Similarly, no difference between groups concerning immunostaining against Ki-67 and bcl-2 was observed in connective tissue cells. Conclusion: Based on this methodology, it may be concluded that gingival overgrowths induced by cyclosporin, nifedipine and phenytoin are not associated with neither myofibroblast transdifferentiation, proliferation nor apoptosis of gingival connective cells in monkeys.

Modelos animais na síndrome metabólica / Animal models in metabolic syndrome

RESUMO O conhecimento sobre modelos animais para estudo metabólico representa a base da pesquisa nessa área. Este trabalho tem por objetivo revisar os principais modelos animais a serem utilizados no estudo da obesidade e da síndrome metabólica. Para isso, pesquisa no banco de dados Pubmed foi realizada usando as palavras-chave "animal models", "obesity", "metabolic syndrome", e "bariatric surgery". Várias espécies de animais podem ser usadas para o estudo de distúrbios metabólicos, no entanto, os roedores, tanto modelos monogênicos quanto modelos de obesidade induzida por dieta (DIO), são os animais mais utilizados nessa área. Animais monogênicos são a melhor escolha se apenas um aspecto estiver sendo avaliado. Animais DIO tendem a demonstrar melhor a interação entre doença, ambiente e gene. No entanto, eles ainda não são totalmente eficazes para a compreensão de todos os mecanismos dessa doença.

ABSTRACT Knowledge about animal models for metabolic study is the basis of research in this area. This work aims to review the main animal models used in the study of obesity and metabolic syndrome. For this, we performed a search in the Pubmed database using the terms "animal models", "obesity", "metabolic syndrome" and "bariatric surgery". Several species of animals can be used for the study of metabolic disorders. However, rodents are the most commonly used, both as monogenic models and as diet-induced obesity (DIO) ones. Monogenic animals are the best choice if only one aspect is being evaluated. DIO animals tend to better demonstrate the interaction between disease, environment and genetics. However, they are still not fully effective in providing understanding of all disease mechanisms.

Antiplasmodial activity of iron(II) and ruthenium(II) organometallic complexes against Plasmodium falciparum blood parasites

This work reports the in vitro activity against Plasmodium falciparumblood forms (W2 clone, chloroquine-resistant) of tamoxifen-based compounds and their ferrocenyl (ferrocifens) and ruthenocenyl (ruthenocifens) derivatives, as well as their cytotoxicity against HepG2 human hepatoma cells. Surprisingly with these series, results indicate that the biological activity of ruthenocifens is better than that of ferrocifens and other tamoxifen-like compounds. The synthesis of a new metal-based compound is also described. It was shown, for the first time, that ruthenocifens are good antiplasmodial prototypes. Further studies will be conducted aiming at a better understanding of their mechanism of action and at obtaining new compounds with better therapeutic profile.

Insight em macacos-prego (Sapajus spp) com diferentes contextos de treino das habilidades pré-requisitos / Insight in Capuchin-monkeys (Sapajus spp) with different contexts of training of prerequisite abilities

Insight, na Psicologia Experimental, indica, tradicionalmente, a resolução súbita e espontânea de um determinado problema. O presente estudo verificou a ocorrência de resolução súbita em macacos-prego (Sapajus spp.) a partir do treino de habilidades pré-requisitos de uma tarefa. Adicionalmente o estudo avaliou se a manipulação do local de treino altera a topografia de solução do problema. Dois sujeitos foram treinados a: a) encaixar objetos e b) pescar objetos fora do alcance utilizando uma ferramenta. O treino das duas habilidades se deu de forma independente e em diferentes contextos. A tarefa final consistiiu em pescar um alimento fora do alcance encaixando um par de ferramentas nunca antes manuseado. Os dois sujeitos resolveram a tarefa, entretanto, nenhum apresentou um desempenho tipicamente de insight, na medida em que as resoluções foram pouco fluidas, com pausas entre suas etapas, e aparentemente sem direcionamento. Discute-se o papel do treino das habilidades pré-requisitos em ambientes diferenciados como um fator que dificulta a resolução da tarefa

Insight, in Experimental Psychology, traditionally refers a sudden and spontaneous solution of a specific problem. The present study aims to verify the occurrence of sudden problem resolution in capuchin monkeys (Sapajus spp.) based on explicit training of two pre-requisite repertoires. Additionally, we examined if the manipulation of the context of training alters the topography of the problem solution response. Two subjects were trained to: a) join objects, and b) to rake objects with a tool. The training of the two repertoires was independent and was carried out in different contexts. The final task consists in raking a piece of food with a joinable tool that was never seen before. The two subjects solved the task, but the topography of solution was not clearly compatible with insight interpretation. The solutions had pauses between steps, and the behavior was not goal directed. The negative effects of different contexts for the training of the pre-requisite repertoires are discussed

Chikungunya en la República Dominicana: lecciones aprendidas en los primeros seis meses / Chikungunya in the Dominican Republic: lessons learned in the first six months

La epidemia de chikungunya en la República Dominicana se inició en febrero de 2014. En los primeros seis meses se registraron 429 421 casos, que representaron 65% de todos los notificados a la Organización Panamericana de la Salud por 33 países y territorios de la Región de las Américas. Esta epidemia se ha transmitido con rapidez en dicho país y ha demandado una intensa respuesta intersectorial, que ha liderado el Ministerio de Salud Pública y, especialmente, el Sistema Nacional de Vigilancia Epidemiológica y la red de los servicios de salud. Considerando que afectará a miles de personas, el objetivo de este artículo es describir las actuaciones realizadas y compartir los resultados y las lecciones aprendidas durante estos primeros meses con los ministerios de salud y los profesionales de los países de la Región para ayudarles a preparar una respuesta adecuada para afrontarla de forma efectiva y eficiente.

The chikungunya epidemic in the Dominican Republic began in February 2014. During the first six months 429 421 cases were recorded, representing 65% of all those notified to the Pan American Health Organization by 33 countries and territories of the Region of the Americas. This epidemic has spread quickly in the Dominican Republic, requiring a focused intersectoral response, led by the Ministry of Public Health and involving major efforts by the National Epidemiological System and the health services network. Given that the virus will affect thousands of people, this article seeks to describe the actions that have already been carried out, and to share the results and lessons learned during these first months with health ministries and professionals in the countries of the Region, in order to assist them to prepare an appropriate response to confront the epidemic effectively and efficiently.

Animal models frr the study of leishmaniasis immunolggy / Modelos animales para el estudio de la inmunologia de la leishmaniosis

Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail) are being infected, and different numbers (“low” 1×102 and “high” 1×106) of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease.

Las leishmaniosis siguen siendo un importante problema de salud pública a nivel mundial y se clasifican como categoría I por el programa TDR/WHO, debido principalmente a la ausencia de control. Muchos modelos experimentales tales como roedores, perros y monos han sido desarrollados, cada uno con características específicas, para caracterizar la respuesta inmune a las diferentes especies de Leishmania, sin embargo ninguno reproduce la patología observada en la enfermedad humana. La diversidad en los resultados obtenidos podría deberse en parte a que diferentes cepas de parásitos o especies están siendo examinadas, diferentes tejidos (cojinete plantar, oreja o base de la cola) han sido infectados y diferente número (“bajo” 1×102 y “alto” 1×106) de promastigotes metacíclicos han sido inoculados. Recientemente, nuevos enfoques han sido propuestos con el fin de obtener datos más significativos en cuanto a la respuesta inmune del huésped y a la patogénesis, de tal forma que reproduzcan lo que ocurre en la enfermedad humana. El uso de la saliva del insecto y de un número de parásitos menor en las infecciones experimentales ha permitido reproducir la transmisión natural, identificar nuevas moléculas, así como mecanismos inmunes que deberían ser considerados en el diseño de vacunas y estrategias de control. Adicionalmente, se ha propuesto como una buena alternativa el uso de roedores silvestres como modelos experimentales tanto para el estudio de las relaciones huésped-patógeno como para probar nuevas vacunas. A la fecha, el uso de reservorios naturales para estudiar la infección por Leishmania ha sido un reto, debido a la carencia de reactivos inmunológicos para uso en roedores silvestres. Esta revisión describe los principales hallazgos inmunológicos ante la infección por Leishmania, en los diferentes modelos animales, destacando la importancia del uso de condiciones experimentales similares a la transmisión natural y de reservorios como modelos experimentales para el estudio de la inmunopatología de la enfermedad.

Reemergence of yellow fever: detection of transmission in the State of São Paulo, Brazil, 2008 / Reemergência de febre amarela: detecção de transmissão no Estado de São Paulo, Brasil, 2008

INTRODUCTION: Following yellow fever virus (YFV) isolation in monkeys from the São José do Rio Preto region and two fatal human autochthonous cases from the Ribeirão Preto region, State of São Paulo, Brazil, two expeditions for entomological research and eco-epidemiological evaluation were conducted. METHODS: A total of 577 samples from humans, 108 from monkeys and 3,049 mosquitoes were analyzed by one or more methods: virus isolation, ELISA-IgM, RT-PCR, histopathology and immunohistochemical. RESULTS: Of the 577 human samples, 531 were tested by ELISA-IgM, with 3 positives, and 235 were inoculated into mice and 199 in cell culture, resulting in one virus isolation. One sample was positive by histopathology and immunohistochemical. Using RT-PCR, 25 samples were processed with 4 positive reactions. A total of 108 specimens of monkeys were examined, 108 were inoculated into mice and 45 in cell culture. Four virus strains were isolated from Alouattacaraya. A total of 931 mosquitoes were captured in Sao Jose do Rio Preto and 2,118 in Ribeirão Preto and separated into batches. A single isolation of YFV was derived from a batch of 9 mosquitoes Psorophoraferox, collected in Urupês, Ribeirão Preto region. A serological survey was conducted with 128 samples from the municipalities of São Carlos, Rincão and Ribeirão Preto and 10 samples from contacts of patients from Ribeirão Preto. All samples were negative by ELISA-IgM for YFV. CONCLUSIONS: The results confirm the circulation of yellow fever, even though sporadic, in the Sao Paulo State and reinforce the importance of vaccination against yellow fever in areas considered at risk.

INTRODUÇÃO: A partir do isolamento do vírus febre amarela (VFA), de macacos, da região de São José do Rio Preto e de dois casos humanos autóctones fatais, da região de Ribeirão Preto, Estado de São Paulo, foram realizadas duas expedições para pesquisa entomológica e avaliação ecoepidemiológica. MÉTODOS: Um total de 577 amostras de humanos, 108 de macacos e 3.049 mosquitos foram analisados por um ou mais métodos: isolamento viral, ELISA-IgM, RT-PCR, histopatologia e imunohistoquímica. RESULTADOS: De 577 amostras humanas, 531 foram testadas por ELISA-IgM, sendo 3 positivas, 235 foram inoculadas em camundongos, 199 em cultura de células, obtendo-se 1 isolamento viral. Uma amostra foi positiva por histopatologia e imunohistoquímica. Por RT-PCR foram processadas 25 amostras com 4 reações positivas. Os 108 espécimes de macacos foram inoculados em camundongos, 45 em cultura de células, obtendo-se 4 isolamentos de VFA, de Alouatta caraya. Um total de 931 mosquitos foram capturados em São José do Rio Preto e 2.118 em Ribeirão Preto e separados em lotes. Um único isolamento de VFA foi derivado de um lote de 9 mosquitos Psorophora ferox, coletados em Urupês, região de Ribeirão Preto. Um inquérito sorológico foi realizado com 128 amostras dos municípios de São Carlos, Rincão e Ribeirão Preto e mais 10 amostras de contactantes de pacientes de Ribeirão Preto. Todas as amostras foram negativas por ELISA-IgM para VFA. CONCLUSÕES: Os resultados confirmam a circulação, mesmo que esporádica, do VFA no Estado de São Paulo e reforça a importância da vacinação antiamarílica nas áreas consideradas de risco.

De monos y humanos: la búsqueda de una estrategia de vacunación antipalúdica basada en péptidos sintéticos: [Editorial] / From Apes to Humans: search for an antipaludian inoculation strategy based on synthetic peptides: [Editorial]

El trabajo del grupo de investigación de la Fundación Instituto de Inmunología de Colombia (FIDIC), liderado por el doctor Manuel Elkin Patarroyo, se ha centrado principalmente en el estudio de la interacción microbio-huésped a nivel molecular. Sus resultados se pueden consultar en detalle en más de 250 publicaciones científicas disponibles en PubMed (2). Entre éstas, se destaca el reporte publicado en 1987 en la revista Nature, sobre la molécula sintética SPf66 que fue postulada como precursora de una eventual vacuna antipalúdica, en la medida en que generó protección total en 40 % del modelo animal experimental, Aotus trivirgatus.

The work of the research group of the Colombian Immunology Institute Foundation (FIDIC), led by Dr. Manuel Elkin Patarroyo, has focused mainly on the study of the microbe-host interaction at the molecular level. Its results can be consulted in detail in more than 250 scientific publications available in PubMed (2). Among these, the report published in 1987 in the journal Nature stands out, on the synthetic molecule SPf66, which was postulated as a precursor of an eventual antimalarial vaccine, insofar as it generated total protection in 40% of the experimental animal model, Aotus trivirgatus.

The emerging of the fifth malaria parasite (Plasmodium knowlesi): a public health concern?

After examining the most recent scientific evidences, which assessed the role of some malaria plasmodia that have monkeys as natural reservoirs, the authors focus their attention on Plasmodium knowlesi. The infective foci attributable to this last Plasmodium species have been identified during the last decade in Malaysia, in particular in the states of Sarawak and Sabah (Malaysian Borneo), and in the Pahang region (peninsular Malaysia). The significant relevance of molecular biology assays (polymerase chain reaction, or PCR, performed with specific primers for P. knowlesi), is underlined, since the traditional microscopic examination does not offer distinguishing features, especially when the differential diagnosis with Plasmodium malariae is of concern. Furthermore, Plasmodium knowlesi disease may be responsible of fatal cases, since its clinical presentation and course is more severe compared with those caused by P. malariae, paralleling a more elevated parasitemia. The most effective mosquito vector is represented by Anopheles latens; this mosquito is a parasite of both humans and monkeys. Among primates, the natural hosts are Macaca fascicularis, M. nemestina, M. inus, and Saimiri scirea. When remarking the possible severe evolution of P. knowlesi malaria, we underline the importance of an early recognition and a timely management, especially in patients who have their first onset in Western Hospitals, after journeys in Southeast Asian countries, and eventually participated in trekking excursions in the tropical forest. When malaria-like signs and symptoms are present, a timely diagnosis and treatment become crucial. In the light of its emerging epidemiological features, P. knowlesi may be added to the reknown human malaria parasites, whith includes P. vivax, P. ovale, P. malariae, and P. falciparum, as the fifth potential ethiologic agent of human malaria. Over the next few years, it will be mandatory to support an adequate surveillance and epidemiological network. In parallel with epidemiological and health care policy studies, also an accurate appraisal of the clinical features of P. knowlesi-affected patients will be strongly needed, since some preliminary experiences seem to show an increased disease severity, associated with increased parasitemia, in parallel with the progressive increase of inter-human infectious passages of this emerging Plasmodium.

The utility of rhesus monkey (Macaca mulatta) and other non-human primate models for preclinical testing of Leishmania candidate vaccines

Leishmaniasis causes significant morbidity and mortality, constituting an important global health problem for which there are few effective drugs. Given the urgent need to identify a safe and effective Leishmania vaccine to help prevent the two million new cases of human leishmaniasis worldwide each year, all reasonable efforts to achieve this goal should be made. This includes the use of animal models that are as close to leishmanial infection in humans as is practical and feasible. Old world monkey species (macaques, baboons, mandrills etc.) have the closest evolutionary relatedness to humans among the approachable animal models. The Asian rhesus macaques (Macaca mulatta) are quite susceptible to leishmanial infection, develop a human-like disease, exhibit antibodies to Leishmania and parasite-specific T-cell mediated immune responses both in vivo and in vitro, and can be protected effectively by vaccination. Results from macaque vaccine studies could also prove useful in guiding the design of human vaccine trials. This review summarizes our current knowledge on this topic and proposes potential approaches that may result in the more effective use of the macaque model to maximize its potential to help the development of an effective vaccine for human leishmaniasis.

Niveles de óxido nítrico en monos Macacus irus inoculados con virus dengue / Serum nitric oxide in Macacus irus monkeys inoculated with dengue virus

Objetivo: partiendo de que los anticuerpos preexistentes en la infección secundaria por dengue suprimen la acción de moléculas con acciones antivirales como el óxido nítrico, se determinó el comportamiento de esa molécula en suero de monos Macacus irus inoculados con virus dengue 2 como infección primaria y en monos con una infección secuencial dengue 4-dengue2. Métodos: los niveles de óxido nítrico referidos como niveles de nitritos fueron detectados mediante la reacción de Griess. Resultados: los niveles máximos de óxido nítrico se detectaron en los animales que sufrieron una infección primaria a partir del séptimo día posinoculación, a diferencia de los monos con infección secundaria en que no se obtuvieron niveles mayores de 100 µM. Conclusiones: al parecer existe una asociación entre la infección secundaria y la inhibición de la producción del óxido nítrico.

Objective: To determine the action of nitric Oxide (NO) in serum samples of dengue 2 inoculated Macacus irus monkeys as primary infection and in dengue 4 -dengue 2 inoculated monkeys as secondary infection, taking into account that preexisting antibodies in secondary dengue infection elicit the action of antiviral molecules such as nitric oxide. Methods: NO levels referred as nitrite levels were detected by Griess colorimetric reaction. Results: The highest nitric oxide levels were detected in those animals with primary infection seven days after inoculation monkeys whereas those monkeys with secondary infection did not show NO levels over 100 µM. Conclusions: Our results suggest that there seems to be a relationship between secondary infection and NO production inhibition.

Cryptosporidium parvum en animales domésticos y en monos de un zoológico / Cryptosporidium parvum in domestic animals and in monkeys from a zoo

El objetivo del trabajo fue detectar infecciones por Cryptosporidium sp en animales domésticos y en monos de un zoológico, en la provincia de Buenos Aires, Argentina. Se procesaron 375 muestras de materia fecal de distintas especies mediante la técnica de sedimentación de Ritchie modificada (formol -éter) para concentrar los ooquistes. El sedimento se tiñó mediante la técnica de Ziehl-Neelsen modificada. Se detectaron ooquistes de Cryptosporidium sp en 7 de 175 muestras de materia fecal de perro, en 2 de 17 de gato, en 4 de 22 de ovinos, en 21 de 131 cabras, en 29 de 109 de terneros, en 2 de 2 de equinos y en 2 de 5 de cobayos (Cavia porcellus). Se examinaron 14 muestras de heces de monos, entre ellas, se detectaron ooquistes en la muestra de 1 hembra carayá (Alouatta caraya) adulta, en la de 1 mono araña (Ateles paniscus) macho adulto, en la muestra colectiva de 7 monos saimiri (Saimiri boliviensis) adultos, en la muestra de 2 hembras y 1 macho caí (Cebus apella), en la muestra colectiva de hamadríades (Papio hamadryas) y en la de 1 chimpancé joven (Pan troglodytes).

Osseointegração de implantes usinados e oxidados em seio maxilar preenchido por coágulo com ou sem osso autógeno: estudo histológico, histométrico e de RFA em macacos / Osseointegration of machined and oxidized titanium implants placed with maxillary sinus floor augmentation using coagulum with or without autogenous bone: a histologic, histometric and RFA study in monkeys

O objetivo deste estudo experimental foi comparar histologicamente o preenchimento do assoalho do seio maxilar por coágulo local com ou sem a associação de osso autógeno (controle), bem como investigar a osseointegração em duas diferentes superfícies de implante sob essas condições, através de medidas histométricas, análises histológicas e em freqüência de ressonância (RFA). Quatro macacos prego (tufted capuchin) tiveram todos os pré-molares e os primeiros molares superiores extraídos. Após quatro meses de reparo, os animais foram submetidos a cirurgia para acessar o assoalho do seio maxilar, através de uma janela óssea, para elevação da membrana do seio. O seio direito foi deixado para que se reparasse espontaneamente (somente coágulo), enquanto o esquerdo foi preenchido com enxerto ósseo autógeno. A membrana dos seios foram mantidas elevadas pela inserção simultânea de dois implantes (um usinado e outro oxidado eletroliticamente, Sistema Branemark®, Nobel Biocare) em cada lado da maxila. A estabilidade dos implantes foi acessada através da freqüência de ressonância (RFA, Ostell®) no momento da fixação dos implantes e no dia do sacrifício. Com a injeção de fluorocromos foi possível investigar o processo de neoformação óssea nos animais bem como relacioná-lo às diferentes superfícies dos implantes. Os animais foram sacrificados 6 meses após a cirurgia para análise histológica e de histomorfometria (contato-osso-implante - BIC, área de osso nas roscas - BA, e área de osso em um retângulo desenhado - BAR). Concluímos que não houve diferença entre o seio preenchido somente com coágulo local e o seio preenchido com osso autógeno, em relação à RFA, BIC, BA e BAR. O BIC nos implantes oxidados exibiu melhor integração óssea comparado com os implantes usinados. Os implantes oxidados mostraram maior BA nos seios com enxertos ósseos quando comparados com os implantes usinados. A quantidade de osso neoformado não foi diferente do seio preenchido somente com o coágulo...

Prevalence of antibodies to dengue virus, hepadnavirus and rotavirus in non-human primates

The aim of this study was to determine the prevalence of several viral antibodies in non-human primates from two zoological gardens from Venezuela. Only two out of 66 sera were positive for antibodies to dengue virus by hemagglutination inhibition. Six out of 62 sera exhibited antibodies against Hepatitis B virus (HBV) core antigen. Viral DNA was detected by nested PCR in one positive serum and in three negative without serological evidence of HBV infection. Sequence analysis showed the circulation of HBV genotype F, predominant in Venezuela. Antibodies against rotavirus antigens were found in 87 percent (20/23) of Old World primates and in 50 percent (13/26) of New World primates. Both the prevalence of antibodies and the mean O.D. value by ELISA were significantly lower in New World primate sera. These results suggest that non-human primates do not seem to represent an important reservoir for dengue virus infection, highly endemic in Venezuela. Anthropozoonotic infection of HBV seems to occur among primates not only from the Old but also from the New World, reinforcing the importance of vaccination of species at risk. This study also suggests a lower frequency of infection by rotavirus of non-human primates from the New World, compared to primates from the Old World.

En este estudio se determinó la prevalencia de anticuerpos contra varios virus en primates no humanos de dos parques zoológicos de Venezuela. Sólo dos de 66 sueros fueron positivos, por inhibición de la hemaglutinación, para anticuerpos contra virus dengue. Seis de 62 sueros presentaron anticuerpos contra la cápside del virus de la hepatitis B virus (VHB). Se detectó el ADN viral, mediante PCR en dos rondas, en uno de éstos y en tres sueros sin evidencia serológica de infección por VHB. El análisis de la secuencia mostró la circulación del VHB genotipo F, predominante en Venezuela. Un 87 por ciento (20/23) de los sueros de primates del Viejo Mundo y un 50 (13/26) de los del Nuevo Mundo mostraron anticuerpos contra antígenos de rotavirus. Tanto la prevalencia de anticuerpos como los valores promedio de D.O. por ELISA fueron significativamente menores en sueros de primates del Nuevo Mundo. Los primates no humanos no parecen jugar un papel importante como reservorio de la infección por virus dengue, altamente prevalente en el país. La infección por cepas humanas del VHB en primates sugiere infección antroponótica y la importancia de vacunar las especies a riesgo. Los resultados sugieren igualmente una menor frecuencia de infección por rotavirus en primates del Nuevo Mundo.

Humoral immune response in capuchin monkeys (Cebus apella) after vaccination with inactivated suckling mouse brain rabies vaccine: comparison of two schedules of immunization

Foram vacinados contra a raiva, dois grupos de macacos-pregos adultos, com a vacina inativada preparada em cérebros de camundongos lactentes, administrada pela via intramuscular, na Fundação Parque Zoológico de São Paulo. Os animais em momento algum haviam sido imunizados contra a raiva. O grupo I consistia de nove animais, que receberam três doses de 1,0 mL nos dias 0, 30 e uma dose de reforço aos 210 dias, e o grupo II continha 10 animais que receberam duas doses de 1,0 mL no dia 0 e uma dose de reforço aos 210 dias. As amostras de sangue foram colhidas aos 0,30°,60°,90°, 150°, 210°, 240°, 300° e 365° dias, e os anticorpos neutralizantes titulados pela técnica simplificada da inibição de focos fluorescentes. A vacina induziu uma resposta imune de curta duração com títulos de anticorpos neutralizantes acima de 0.5 UI/ mL em ambos os grupos; entretanto a resposta imune persistiu por apenas 54,9 mais ou menos 57,0 e 36,1 mais ou menos 60,2 dias nos Grupos I e II respectivamente após a primo vacinação, e, por apenas 62,6 mais ou menos 74,0 e 86,4 mais ou menos 61,5 dias nos Grupos I e II respectivamente após o reforço. Não houve diferença estatística significante entre os grupos estudados (p > 0,05).