Malaria transmission blocking immunity and sexual stage vaccines for interrupting malaria transmission in Latin America.

Malaria is a vector-borne disease that is considered to be one of the most serious public health problems due to its high global mortality and morbidity rates. Although multiple strategies for controlling malaria have been used, many have had limited impact due to the appearance and rapid dissemination of mosquito resistance to insecticides, parasite resistance to multiple antimalarial drug, and the lack of sustainability. Individuals in endemic areas that have been permanently exposed to the parasite develop specific immune responses capable of diminishing parasite burden and the clinical manifestations of the disease, including blocking of parasite transmission to the mosquito vector. This is referred to as transmission blocking (TB) immunity (TBI) and is mediated by specific antibodies and other factors ingested during the blood meal that inhibit parasite development in the mosquito. These antibodies recognize proteins expressed on either gametocytes or parasite stages that develop in the mosquito midgut and are considered to be potential malaria vaccine candidates. Although these candidates, collectively called TB vaccines (TBV), would not directly stop malaria from infecting individuals, but would stop transmission from infected person to non-infected person. Here, we review the progress that has been achieved in TBI studies and the development of TBV and we highlight their potential usefulness in areas of low endemicity such as Latin America.

Malaria vector species in Colombia: a review.

Here we present a comprehensive review of the literature on the vectorial importance of the major Anopheles malaria vectors in Colombia. We provide basic information on the geographical distribution, altitudinal range, immature habitats, adult behaviour, feeding preferences and anthropophily, endophily and infectivity rates. We additionally review information on the life cycle, longevity and population fluctuation of Colombian Anopheles species. Emphasis was placed on the primary vectors that have been epidemiologically incriminated in malaria transmission: Anopheles darlingi, Anopheles albimanus and Anopheles nuneztovari. The role of a selection of local, regional or secondary vectors (e.g., Anopheles pseudopunctipennis and Anopheles neivai) is also discussed. We highlight the importance of combining biological, morphological and molecular data for the correct taxonomical determination of a given species, particularly for members of the species complexes. We likewise emphasise the importance of studying the bionomics of primary and secondary vectors along with an examination of the local conditions affecting the transmission of malaria. The presence and spread of the major vectors and the emergence of secondary species capable of transmitting human Plasmodia are of great interest. When selecting control measures, the anopheline diversity in the region must be considered. Variation in macroclimate conditions over a species' geographical range must be well understood and targeted to plan effective control measures based on the population dynamics of the local Anopheles species.

Effects of anticoagulants on Plasmodium vivax oocyst development in Anopheles albimanus mosquitoes.

Artificial membrane feeding (AMF) assays are used to determine malaria transmission-blocking activity in Anopheles. The purpose of this study was to determine the effect of the most widely used anticoagulants, EDTA and heparin, on development of the Plasmodium vivax sporogonic cycle. Blood samples collected from 60 patients carrying P. vivax infections were used to feed An. albimanus using AMF. Seven days after feeding, mosquitoes were dissected to assess mosquito infection. Mosquitoes fed with blood containing EDTA showed a lower mean oocyst number as compared with those fed blood with heparin. However, this effect was minimized upon reduction of EDTA concentrations in the serum. This result may be explained by the fact that microgametocytes require Ca(2+), Mn(2+), and Mg(+2) to activate enzymes important for exflagellation process and for motility of ookinetes. We therefore recommend that heparin be used as the anticoagulant of choice for blood used in AMF assays.

Aotus lemurinus griseimembra monkeys: a suitable model for Plasmodium vivax sporozoite infection.

This study describes a successful Plasmodium vivax sporozoite infection in Aotus lemurinus griseimembra. Twenty-eight naive or previously infected monkeys, either splenectomized or spleen intact, were inoculated intravenously or subcutaneously with Plasmodium vivax sporozoites of the Salvador I strain or with two wild isolates (VCC-4 and VCC-5; Vivax-Cali-Colombia). The monkeys were successfully infected regardless of the parasite strain, spleen presence, or inoculation route and showed prepatent periods that ranged from 16 to 89 days. Only one monkey inoculated intravenously failed to develop parasitemia. Since immune protection against malaria pre-erythrocytic forms is mediated by both helper and cytolytic T cells that may home in the spleen and P. vivax cultures are not yet available; the use of spleen-intact A. lemurinus griseimembra, susceptible to both adapted and non-adapted strains of P. vivax sporozoites, is a valuable model for evaluation of pre-erythrocytic vaccine candidates.

Induction of transmission-blocking immunity in Aotus monkeys by vaccination with a Plasmodium vivax clinical grade PVS25 recombinant protein.

Aotus monkeys were used to determine the immunogenicity of Pvs25 protein expressed in the zygote/ookinete surface. Animals were immunized in three times with 100 microg of Pvs25 formulated in Montanide ISA-720. Antibodies to Pvs25 detected by an enzyme-linked immunosorbent assay appeared by day 30 after the first immunization, with a peak of antibodies levels on day 150. These antibodies were still detectable on day 300. Plasma samples on day 150 from experimental group were able to completely block the development of the parasite in Anopheles albimanus mosquitoes artificially fed with human isolates of Plasmodium vivax. Immunized Aotus monkeys were infected with blood forms of the P. vivax Salvador I strain and no boosting effect of blood infection on titers of antibodies to Pvs25 was observed despite the presence of infective gametocytes. In conclusion, Pvs25 protein formulated in Montanide ISA-720 induces efficient and long-lasting transmission-blocking antibodies that cannot be boosted by parasite infection.

Plasmodium vivax: transmission-blocking immunity in a malaria-endemic area of Colombia.

Plasmodium vivax transmission-blocking activity was assessed in sera from acutely infected patients from a malaria-endemic area in Colombia. We measured reduction in the number of oocysts that developed in the midguts of Anopheles albimanus mosquitoes artificially fed with blood from these patients. Of 88 mosquito batches that developed infections when parasites were mixed with normal AB human serum, one-third (36.4%) showed full transmission-blocking activity (>or= 90% inhibition) when mixed with autologous sera, 29.6% showed partial activity (50-89%), 17.0% did not block transmission (0-50%), and 17% did not enhance transmission. Transmission-blocking activity correlated with antibody titer by an immunofluorescent antibody test and decreased with the serial dilution of the sera. This activity disappeared at a 1:4 dilution in most sera tested. Afro-Colombian individuals showed lower activity than other ethnic groups and febrile patients produced stronger inhibition than those without fever.

Recombinant Pvs48/45 antigen expressed in E. coli generates antibodies that block malaria transmission in Anopheles albimanus mosquitoes.

Transmission of malaria parasites from humans to Anopheles mosquitoes can be inhibited by specific antibodies elicited during malaria infection, which target surface Plasmodium gametocyte/gamete proteins. Some of these proteins may have potential for vaccine development. Pvs48/45 is a P. vivax gametocyte surface antigen orthologous to Pfs48/45, which may play a role during parasite fertilization and thus has potential for transmission blocking (TB) activity. Here we describe the expression of a recombinant Pvs48/45 protein expressed in Escherichia coli as a ∼60kDa construct which we tested for antigenicity using human sera and for its immunogenicity and transmission blocking activity of specific anti-mouse and anti-monkey Pvs48/45 antibodies. The protein reacted with sera of individuals from malaria-endemic areas and in addition induced specific IgG antibody responses in BALB/c mice and Aotus l. griseimembra monkeys. Sera from both immunized animal species recognized native P. vivax protein in Western blot (WB) and immunofluorescence assays. Moreover, sera from immunized mice and monkeys produced significant inhibition of parasite transmission to An. Albimanus mosquitoes as shown by membrane feeding assays. Results indicate the presence of reactive epitopes in the Pvs48/45 recombinant product that induce antibodies with TB activity. Further testing of this protein is ongoing to determine its vaccine potential.

Propuesta para la formación en Medicina Familiar y Comunitaria, desde la percepción, conceptualización y experiencia práctica de los enfoques de Salud Familiar / Proposal for training in Family and Community Medicine, from the perception, conceptualization and practical experience of Family Health approaches / Proposta de formação em Medicina Familiar e Comunitária, a partir da percepção, conceituação e experiência prática de abordagens de Saúde Familiar

Resumen La existencia de un Plan Decenal de Salud Pública para Colombia y la definición de una Política de Atención Integral en Salud concretaron un nuevo Modelo de Atención basado en la Atención Primaria de la Salud. Esto ubicó a la Salud Familiar y Comunitaria como núcleo fundamental y definió un rol al Médico y al Profesional Familiar y Comunitario, que dimensiona los procesos transdisciplinarios y la articulación de acciones individuales y colectivas, con esquemas pedagógicos holísticos transformadores. Este planteamiento generó un análisis y reflexión de la opinión de una muestra del 14,6% de los clasificados como Salubristas por el Observatorio Laboral del Ministerio de Educación quienes, con la respuesta a 13 preguntas enviadas por vía electrónica, libremente plantearon su percepción, conceptualización y experiencia práctica de los enfoques de Salud Familiar y Comunitaria. Con esta medición se definieron los contenidos básicos que se presentan en este documento con un nuevo enfoque transversal en el Pregrado y los Posgrados, de acuerdo con una propuesta pedagógica transformadora y con visión práctica, encontrándose aquí como destacable, la importante relación entre la educación y la salud integral; el concepto que en el 80% de las observaciones se expresó al denominar el poco compromiso de la comunidad y los profesionales de la salud con una "Cultura de la Salud Integralmente Concebida".

Abstract The existence of a Decennial Public Health Plan for Colombia and the definition of a Comprehensive Health Care Policy concretized a new Model of Care based on Primary Health Care. This placed Family and Community Health as a fundamental nucleus and defined a role for the Family and Community Physician and Practitioner, who dimension the transdisciplinary processes and the articulation of individual and collective actions, with transformational holistic pedagogical schemes. This approach generated an analysis and reflection of the opinion of a sample of 14.6% of those classified as Salubristas by the Labor Observatory of the Ministry of Education who, with the answer to 13 questions sent electronically, freely raised their perception, conceptualization and practical experience of Family and Community Health approaches. With this measurement the basic contents that are presented in this document with a new transversal approach in the Undergraduate and Postgraduates were defined, according to a pedagogical proposal transforming and with practical vision, being here like remarkable, the important relation between the education and integral health; the concept that in 80% of the observations was expressed when denominating the little commitment of the community and the professionals of the health with an "Culture of the Health Integrally Conceived".

Resumo A existência de um Plano de Saúde Pública de dez anos para a Colômbia ea definição de uma Política Integral de Saúde resultou em um novo Modelo de Cuidados Baseado em Atenção Primária à Saúde. Isso colocou a Familia e a Saúde Comunitária como um núcleo fundamental e definiu um papel para o Médico e o Profissional Familiar e Comunitário, que dimensiona os processos transdisciplinares e a articulação de ações individuais e coletivas, com esquemas pedagógicos transformadores holísticos. Esta abordagem gerou uma análise e reflexão da opinião de uma amostra de 14,6% das classificadas como Salubristas pelo Observatório do Trabalho do Ministério da Educação que, com a resposta a 13 questões enviadas eletronicamente, aumentou livremente sua percepção, conceituação e experiência prática de abordagens de saúde familiar e comunitária. Com esta medida, os conteúdos básicos apresentados neste documento foram definidos com um novo foco transversal em Estudos de Graduação e Pós-Graduação, de acordo com uma proposta pedagógica transformadora e com uma visão prática, sendo aqui a relação notável entre educação e saúde abrangente; o conceito de que em 80% das observações foi expressado chamando o pequeno compromisso da comunidade e os profissionais de saúde com uma "Cultura de Saúde Integralmente Concebida".

El laboratorio clínico en colombia: orígenes, historia, nacimiento y desarrollo / The clinical laboratory in Colombia: origins, history, birth and development

El laboratorio clínico, tal como se conoce en la actualidad, ha vivido un proceso de transformación histórica que contempla desde lo empírico, lo sistemático y lo organizacional.Teniendo sus orígenes en los saberes, conocimientos y técnicas aplicadas, de las ciencias exactas y sus disciplinas, impulsados por la necesidad de implementar un recurso diagnóstico en el manejo y tratamiento de las enfermedades.En Colombia el laboratorio clínico, tiene sus inicios a principios del s XX, acorde con las necesidades económicas y sanitarias de la época. El mayor impulso a la consolidación del laboratorio se realizó a través del surgimiento del Instituto Nacional de Salud como organismo nacional de referencia, adoptando modelos estructurales y organizativos de Europa y Estados Unidos.La intención de este documento es dar un vistazo a través de los orígenes, la historia, el nacimiento y desarrollo del laboratorio clínico en Colombia...(AU)

The clinical laboratory as it is known today has undergone a process of historical transformation that viewed from the empirical, the systematic and organizational. Given its origins in knowledge, skills and applied techniques of exact sciences and disciplines, driven by the need to implement a diagnostic tool in the management and treatment of diseases.In Colombia the clinical laboratory, has its beginnings in the early twentieth s, according to the economic and health needs of the time. The greatest impetus to laboratory consolidation was conducted through the emergence of the National Institute of Health as the national reference, adopting structural and organizational models in Europe and the United States.The intent of this document is to look through the origins, history, the birth and development of the clinical laboratory in Colombia...(AU)

Plasmodium vivax sporozoite production in Anopheles albimanus mosquitoes for vaccine clinical trials.

Vaccine development for Plasmodium vivax malaria is underway. A model to assess the protective efficacy of vaccine candidates in humans is urgently needed. Given the lack of continuous P. vivax cultures, we developed a system to infect Anopheles albimanus mosquitoes using blood from P. vivax-infected patients and determined parameters for challenge of malaria-naive volunteers by mosquito bite. Absence of co-infections in parasitized blood was confirmed by tests consistent with blood bank screening. A total of 119 experiments were conducted using batches of 900-4,500 mosquitoes fed by an artificial membrane feeding method. Optimal conditions for mosquito probing and infection were determined. Presence of oocyst and sporozoites were assessed on Days 7-8 and 14-15, respectively, and conditions to choose batches of infected mosquitoes for sporozoite challenge were established. Procedures to infect volunteers took a 2-hour period including verification of inoculum dose. Anopheles albimanus mosquitoes represent a valuable resource for P. vivax sporozoite challenge of volunteers.

Characterization of Plasmodium vivax transmission-blocking activity in low to moderate malaria transmission settings of the Colombian Pacific coast.

Malaria infection induces antibodies capable of suppressing the infectivity of gametocytes and gametes, however, little is known about the duration of the antibody response, the parasite specificity, and the role of complement. We report the analyses of the transmission-blocking (TB) activity of sera collected from 105 Plasmodium vivax-infected and 44 non-infected individuals from a malaria endemic region of Colombia, using a membrane feeding assay in Anopheles albimanus mosquitoes. In infected donors we found that TB activity was antibody dose dependent (35%), lasted for 2-4 months after infection, and in 70% of the cases different P. vivax wild isolates displayed differential susceptibility to blocking antibodies. Additionally, in a number of assays TB was complement-dependent. Twenty-seven percent of non-infected individuals presented TB activity that correlated with antibody titers. Studies here provide preliminary data on factors of great importance for further work on the development of TB vaccines.

Consistent safety and infectivity in sporozoite challenge model of Plasmodium vivax in malaria-naive human volunteers.

A safe and reproducible Plasmodium vivax infectious challenge method is required to evaluate the efficacy of malaria vaccine candidates. Seventeen healthy Duffy (+) and five Duffy (-) subjects were randomly allocated into three (A-C) groups and were exposed to the bites of 2-4 Anopheles albimanus mosquitoes infected with Plasmodium vivax derived from three donors. Duffy (-) subjects were included as controls for each group. Clinical manifestations of malaria and parasitemia were monitored beginning 7 days post-challenge. All Duffy (+) volunteers developed patent malaria infection within 16 days after challenge. Prepatent period determined by thick smear, was longer for Group A (median 14.5 d) than for Groups B and C (median 10 d/each). Infected volunteers recovered rapidly after treatment with no serious adverse events. The bite of as low as two P. vivax-infected mosquitoes provides safe and reliable infections in malaria-naive volunteers, suitable for assessing antimalarial and vaccine efficacy trials.

Prevention of sporogony of Plasmodium vivax in Anopheles albimanus by steroids of Solanum nudum Dunal (Solanaceae).

The sporontocidal activity of three steroids (SN-1, SN-2 and SN-4) from Solanum nudum Dunal (Solanaceae) was determined against naturally circulating isolates of Plasmodium vivax in Anopheles albimanus. Laboratory-reared Anopheles albimanus mosquitoes were infected with P. vivax from gametocytemic blood of volunteers resident in Buenaventura, Valle del Cauca (Colombian Pacific Coast) by using an artificial membrane feeder. Prior to mosquito feeding, gametocytemic blood was centrifuged, plasma was separated, packed blood red cells were washed with RPMI 1640 and then resuspended in non-immune AB serum, then the steroids were added at different doses. On day 7 after infection, the presence and number of oocysts in mosquitoes was determined. The steroid SN-2 reduced the infection of mosquitoes by 90% and the mean number of oocysts by 60%. These data confirmed that the experimental steroid is capable of interrupting the sporogonic development of P. vivax in Anopheles albimanus. This experimental steroid has potential for transmission blocking in vivax malaria.

Malaria transmission blocking immunity and sexual stage vaccines for interrupting malaria transmission in Latin America

Malaria is a vector-borne disease that is considered to be one of the most serious public health problems due to its high global mortality and morbidity rates. Although multiple strategies for controlling malaria have been used, many have had limited impact due to the appearance and rapid dissemination of mosquito resistance to insecticides, parasite resistance to multiple antimalarial drug, and the lack of sustainability. Individuals in endemic areas that have been permanently exposed to the parasite develop specific immune responses capable of diminishing parasite burden and the clinical manifestations of the disease, including blocking of parasite transmission to the mosquito vector. This is referred to as transmission blocking (TB) immunity (TBI) and is mediated by specific antibodies and other factors ingested during the blood meal that inhibit parasite development in the mosquito. These antibodies recognize proteins expressed on either gametocytes or parasite stages that develop in the mosquito midgut and are considered to be potential malaria vaccine candidates. Although these candidates, collectively called TB vaccines (TBV), would not directly stop malaria from infecting individuals, but would stop transmission from infected person to non-infected person. Here, we review the progress that has been achieved in TBI studies and the development of TBV and we highlight their potential usefulness in areas of low endemicity such as Latin America.

Malaria vector species in Colombia: a review

Here we present a comprehensive review of the literature on the vectorial importance of the major Anopheles malaria vectors in Colombia. We provide basic information on the geographical distribution, altitudinal range, immature habitats, adult behaviour, feeding preferences and anthropophily, endophily and infectivity rates. We additionally review information on the life cycle, longevity and population fluctuation of Colombian Anopheles species. Emphasis was placed on the primary vectors that have been epidemiologically incriminated in malaria transmission: Anopheles darlingi, Anopheles albimanus and Anopheles nuneztovari. The role of a selection of local, regional or secondary vectors (e.g., Anopheles pseudopunctipennis and Anopheles neivai) is also discussed. We highlight the importance of combining biological, morphological and molecular data for the correct taxonomical determination of a given species, particularly for members of the species complexes. We likewise emphasise the importance of studying the bionomics of primary and secondary vectors along with an examination of the local conditions affecting the transmission of malaria. The presence and spread of the major vectors and the emergence of secondary species capable of transmitting human Plasmodia are of great interest. When selecting control measures, the anopheline diversity in the region must be considered. Variation in macroclimate conditions over a species' geographical range must be well understood and targeted to plan effective control measures based on the population dynamics of the local Anopheles species.

Man-biting activity of Anopheles (Nyssorhynchus) albimanus and An. (Kerteszia) neivai (Diptera: Culicidae) in the Pacific lowlands of Colombia

The daily man-biting activity of Anopheles (Nyssorhynchus) albimanus and An. (Kerteszia) neivai was determined in four ecologically distinct settlements of the Naya River, Department of Valle, Colombia. Differences were found among the settlements with respect to the mosquito species present, intradomiciliary and extradomiciliary biting activity and population densities.

Transmisión de protozoarios patógenos a través del agua para consumo humano: [revisión] / Parasitic protozoa transmission by drinking water: [review]

Los protozoarios patógenos Cryptosporidium parvum y Giardia sp. han demostrado su infectividad e impacto negativo en la salud de miles de personas tanto en naciones industrializadas como en los países en desarrollo. La mayoría de los protozoarios por presentar una forma resistente a las condiciones ambientales, les permite la supervivencia a los tratamientos físico-químicos del agua para consumo humano. De igual forma, la aparición de nuevos patógenos demuestra la necesidad de desarrollar nuevos indicadores de calidad microbiológica que permitan ofrecer productos verdaderamente seguros en el agua para uso humano. El presente artículo es una revisión de literatura que señala el impacto de este riesgo microbiológico, asociado fundamentalmente con el consumo de aguas cuyos indicadores clásicos de contaminación microbiológica (coliformes fecales y Escherichia coli) en casi todos los casos cumplen con las normas vigentes.

The pathogenic protozoa Cryptosporidium sp. and Giardia sp. showed their infectivity and negative effects on the health of thousands of people in both developed and developing countries. Protozoa have ambient resistant stages that permit survived to physical and chemical treatment of drinking water. This risk is mainly related to the consumption of water whose microbiological quality indicators typically fulfill with current standards (fecal coliforms and Escherichia coli). Likewise, the discovery of new pathogens is calling for the development of new microbiological quality indicators that allow the production of really safe goods and services such as water for human consumption. Herein the authors present a literature review showing the impact of this microbiological risk in different populations.

Amibas con parasitismo facultativo en aguas termales de Trujillo, Venezuela / Amoebae with parasitic in termals water Trujillo, Venezuela

Experimentalmente se demuestra la presencia de amibas de vida libre potencialmente patógenas, en aguas termales de uso público en tres localidades de los didtritos Valera y Betijoque del Estado Trujillo, Venezuela

Incapacidad de una cepa de Toxoplasma gondii para producir quistes y ooquistes / Unability of a strain of Toxoplasma gondii to produce cysts and oocysts

Se investiga la producción de quistes en una cepa de Toxoplasma gondii mantenida por pasajes en ratones albinos observandose que solamente produce taquizoitos

Variacion fenotipica de la poblacion de anopheles (K.) neivai (Dipteria Culicidae) en la Costa Pacifica de Colombia / Phenotypical variation of the anopheles population (K.) neivai (Diphteria Culicidae) in Colombian Pacific Coast

Entre los anos 1984 y 1985 se colectaron larvas y mosquitos de Anopheles (Kerteszia) en diferentes localidades de la costa del pacifico colombiano: El Trueno, Concherito y Santa Cruz, en el Rio Naya; Juanchaco y Ladrilleros, en el departamento del Valle del Cauca; y Charambira, en el Departamento del Choco. Los muestreos iniciales parecian indicar el hallazgo de dos especies: A.neivai y A.homunculus. Debido a ciertas dudas que se originaron en algunas diferencias morfologicas en los especimenes estudiados, se realizaron observaciones mas detalladas, y se llego a la conclusion de la presencia de una sola especie, A. neivai, con variaciones fenotipicas, que plantean algunos problemas de tipo taxonomico y posiblemente epidemiologico