Onchocerciasis in Ecuador: the situation in 1989

Details are given of the prevalence rates of onchocerciasis from the most recent surveys (1989) conducted in northern Ecuador. The disease has intensified and dispersed considerably due to migration of infected individuals and the presence of a highly efficient vector. Comparison of these data with those from two previous surveys carried out in 1982/83 and 1986 and correlated with entomological findings highly the danger of the formation of new foci of onchocerciasis in areas currently free of the disease. Recommendations are made for further entomological studies in areas either recently or likely to be affected by the disease where potential vectors are unknown or different to those registred in the Santiago focus. Invermectin treatment with local vector control in specific areas is advocated to reduce the disease to a low level of public health importance.

Activation of a dendritic cell-T cell axis by Ad5 immune complexes creates an improved environment for replication of HIV in T cells.

The STEP HIV vaccine trial, which evaluated a replication-defective adenovirus type 5 (Ad5) vector vaccine, was recently stopped. The reasons for this included lack of efficacy of the vaccine and a twofold increase in the incidence of HIV acquisition among vaccinated recipients with increased Ad5-neutralizing antibody titers compared with placebo recipients. To model the events that might be occurring in vivo, the effect on dendritic cells (DCs) of Ad5 vector alone or treated with neutralizing antiserum (Ad5 immune complexes [IC]) was compared. Ad5 IC induced more notable DC maturation, as indicated by increased CD86 expression, decreased endocytosis, and production of tumor necrosis factor and type I interferons. We found that DC stimulation by Ad5 IC was mediated by the Fcgamma receptor IIa and Toll-like receptor 9 interactions. DCs treated with Ad5 IC also induced significantly higher stimulation of Ad5-specific CD8 T cells equipped with cytolytic machinery. In contrast to Ad5 vectors alone, Ad5 IC caused significantly enhanced HIV infection in DC-T cell cocultures. The present results indicate that Ad5 IC activates a DC-T cell axis that, together with the possible persistence of the Ad5 vaccine in seropositive individuals, may set up a permissive environment for HIV-1 infection, which could account for the increased acquisition of HIV-1 infection among Ad5 seropositive vaccine recipients.

Expression of a functional single chain antibody on the surface of extracellular enveloped vaccinia virus as a step towards selective tumour cell targeting.

Recombinant vaccinia virus with tumour cell specificity may provide a versatile tool either for direct lysis of cancer cells or for the targeted transfer of genes encoding immunomodulatory molecules. We report the expression of a single chain antibody on the surface of extracellular enveloped vaccinia virus. The wild-type haemagglutinin, an envelope glycoprotein which is not required for viral infection and replication, was replaced by haemagglutinin fusion molecules carrying a single chain antibody directed against the tumour-associated antigen ErbB2. ErbB2 is an epidermal growth factor receptor-related tyrosine kinase overexpressed in a high percentage of human adenocarcinomas. Two fusion proteins carrying the single chain antibody at different NH2-terminal positions were expressed and exposed at the envelope of the corresponding recombinant viruses. The construct containing the antibody at the site of the immunoglobulin-like loop of the haemagglutinin was able to bind solubilized ErbB2. This is the first report of replacement of a vaccinia virus envelope protein by a specific recognition structure and represents a first step towards modifying the host cell tropism of the virus.

Epidemiology and control of malaria and other arthropod born diseases

Malaria and other arthropod born diseases remain a serious public health problem affecting the lives and health of certain social groups when the two basic strategies to control fail due to : (1) the lack of effective chemoprophylaxis/chemotherapy or the rapid development of drug resistance of the infectious agents and (2) the ineffectiveness of pesticides or the arthropod vectors develop resistance to them. These situations enhances the need for the design and implementation of other alternatives for sustainable health programmes. The application of the epidemiological methods is essential not only for analyzing the relevant data for the understanding of the biological characteristics of the infectious agents, their reservoirs and vectors and the methods for their control, but also for the assessment of the human behaviour, the environmental, social and economic factors involved in disease transmission and the capacity of the health systems to implement interventions for both changes in human behaviour and environmental management to purpose guaranteed prevention and control of malaria and other arthropod born diseases with efficiency, efficacy and equity. This paper discuss the evolution of the malaria arthropod diseases programmes in the American Region and the perspectives for their integration into health promotion programs and emphasis is made in the need to establish solid basis in the decision-making process for the selection of intervention strategies to remove the risk factors determining the probability to get sick or die from ABDs. The implications of the general planning and the polices to be adopted in an area should be analyzed in the light of programme feasibility at the local level, in the multisectoral context specific social groups and taking in consideration the principles of stratification and equity

Recombinant adeno-associated virus serotype 6 (rAAV2/6)-mediated gene transfer to nociceptive neurons through different routes of delivery.

BACKGROUND: Gene transfer to nociceptive neurons of the dorsal root ganglia (DRG) is a promising approach to dissect mechanisms of pain in rodents and is a potential therapeutic strategy for the treatment of persistent pain disorders such as neuropathic pain. A number of studies have demonstrated transduction of DRG neurons using herpes simplex virus, adenovirus and more recently, adeno-associated virus (AAV). Recombinant AAV are currently the gene transfer vehicles of choice for the nervous system and have several advantages over other vectors, including stable and safe gene expression. We have explored the capacity of recombinant AAV serotype 6 (rAAV2/6) to deliver genes to DRG neurons and characterized the transduction of nociceptors through five different routes of administration in mice. RESULTS: Direct injection of rAAV2/6 expressing green fluorescent protein (eGFP) into the sciatic nerve resulted in transduction of up to 30% eGFP-positive cells of L4 DRG neurons in a dose dependent manner. More than 90% of transduced cells were small and medium sized neurons (< 700 microm 2), predominantly colocalized with markers of nociceptive neurons, and had eGFP-positive central terminal fibers in the superficial lamina of the spinal cord dorsal horn. The efficiency and profile of transduction was independent of mouse genetic background. Intrathecal administration of rAAV2/6 gave the highest level of transduction (approximately 60%) and had a similar size profile and colocalization with nociceptive neurons. Intrathecal administration also transduced DRG neurons at cervical and thoracic levels and resulted in comparable levels of transduction in a mouse model for neuropathic pain. Subcutaneous and intramuscular delivery resulted in low levels of transduction in the L4 DRG. Likewise, delivery via tail vein injection resulted in relatively few eGFP-positive cells within the DRG, however, this transduction was observed at all vertebral levels and corresponded to large non-nociceptive cell types. CONCLUSION: We have found that rAAV2/6 is an efficient vector to deliver transgenes to nociceptive neurons in mice. Furthermore, the characterization of the transduction profile may facilitate gene transfer studies to dissect mechanisms behind neuropathic pain.

Generation of a recombinant mouse-human chimaeric monoclonal antibody directed against human carcinoembryonic antigen.

A procedure was devised for the identification and specific cloning of functionally rearranged variable region immunoglobulin (Ig) gene segments from genomic DNA of a murine hybridoma cell line which produces a high-affinity monoclonal antibody (MAb) directed against human carcinoembryonic antigen (CEA). The cloned, functionally-rearranged murine Ig H-chain and L-chain variable region gene segments were incorporated into plasmid vectors capable of directing the expression of a chimaeric mouse-human antibody molecule with human (gamma 4, kappa) constant region sequences. Expression plasmids were transfected into a mouse myeloma cell line by electroporation and transfectomas secreting functional chimaeric antibody selected. Chimaeric antibody generated by transfectomas was analysed and shown to compete effectively with its murine counterpart for binding to the CEA epitope, and to have an equivalent antigen-binding affinity. This anti-CEA recombinant antibody should find application in in vivo diagnosis by immunoscintigraphy of human colonic carcinoma, and possibly also in therapy of the disease, overcoming some of the difficulties associated with the repeated use of non-human immunoglobulins in human patients.

Transmission factors in malaria epidemiology and control in Africa

Genetic and environmental components of factors contributing in malaria transmission are reviewed. Particular attention is given to density dependent regulation of vector populations in relation to the survival rate anophelines. The expectation of vector activities are different according to the epidemiological characteristics of malaria, mainly its stability. In areas with perennial and high transmission (stable malaria) vector control could reduce malaria related morbidity and mortality, whithout any effect on the endemicity. However this need further investigations. In areas where the transmission period is very short (unstable malaria), vector control will have an important impact on the disease and the endemicity. Control projects using indoor spraying with insecticide and impregnated bed nets are discussed.

Vector incrimination and effects of antimalarial drugs on malaria transmission and control in the Amazon Basin of Brazil

World ecosystems differ significantly and a multidisciplinary malaria control approach must be adjusted to meet these requirements. These include a comprehensive understanding of the malaria vectors, their behavior, seasonal distribution and abundance, susceptibility to insecticides (physiological and behavioral), methods to reduce the numbers of human gametocyte carriers through effective health care systems and antimalarial drug treatment, urban malaria transmission versus rural or forest malaria transmission, and the impact of vaccine development. Many malaria vectors are members of species complexes and individual relationship to malaria transmission, seasonal distribution, bitting behavior, etc. is poorly understood. Additionaly, malaria patients are not examined for circulating gametocytes and both falciparum and vivax malaria patients may be highly infective to mosquitoes after treatment with currently used antimalarial drugs. Studies on the physiological and behavioral effects of DDT and other insecticides are inconclusive and need to be evalusted.

Métodos de diagnóstico malacológico

Specific identification of the snail vectors: (a) shell features; (b) animal features (genital organs); (c) biochemical techniques (electrophoresis). The snail infection rates: (a) exposure to light and cercarial identification; (b) snail crushing and identification or the larval forms in the tissues.

Modern immunological approaches to assess malaria transmission and immunity and to diagnose plasmodial infection

The present paper reviews our recent data concerning the use of immunological methods employing monoclonal antibodies and synthetic peptides to study malaria transmission and immunity and to diagnose plasmodial infection. As concerns malaria transmission, we studied the main vectors of human malaria and the plasmodial species transmitted in endemic areas of Rondônia state, Brazil. The natural infection on anopheline was evaluated by immunoradiometric assay (IRMA) using monoclonal antibodies to an immunodominant sporozoite surface antigen (CS protein) demonstrated to be species specific. Our results showed that among six species of Anopheles found infected, An. darlingi was the main vector transmitting Plasmodium falciparum and P. vivax malaria in the immediate vicinity of houses. In order to assess the level of anti-CS antibodies we studied, by IRMA using the synthetic peptide corresponding to the repetitive epitope of the sporozoite CS protein, sera of individuals living in the same areas where the entomological survey has been performed. In this assay the prevalence of anti-CS antibodies was very low and did not reflect the malaria transmission rate in the studied areas. In relation to malaria diagnosis, a monoclonal antibody specific to an epitope of a 50 kDa exoantigen, the major component of supernatant collected at the time of schizont rupture, was used as a probe for the detection of P. falciparum antigens. This assay seemed to be more sensitive than parasitological examination for malaria diagnosis since it was able to detect plasmodial antigens in both symptomatic and asymtomatic individuals with negative thick blood smear at different intervals after a last parasitologically confirmed confirmed attack of malaria.

Auditoria ambiental de l'edifici de l'Àrea de Territori, Medi Ambient, Paisatge i Espai Urbà de l'Ajuntament de Sitges

Aquest projecte realitza una auditoria ambiental de l’edifici de l’Àrea de Territori, Medi Ambient, Paisatge i Espai Urbà de l’Ajuntament de Sitges, com a primer pas per a la implantació d’un sistema de gestió ambiental (SGA), en acord amb el Reglament (CE) nº 761/2001, i la posterior obtenció d’un certificat de gestió i auditories ambientals (EMAS). L’auditoria s’inicia amb la identificació dels aspectes ambientals de l’edifici, mitjançant la recopilació de dades sobre consums energètics i hídrics, la estimació de la generació de residus i enquestes de mobilitat als treballadors. Aquestes dades són utilitzades per determinar els aspectes ambientals significatius i posteriorment, exposar una sèrie de propostes de millora per tal de corregir-los o minimitzar-los, com ara sistemes d’estalvi d’aigua, d’enllumenat, de producció d’electricitat i l’educació ambiental dels treballadors. Per a la implantació d’un SGA en la situació actual de l’edifici, es necessària, entre altres coses, la implantació d’un sistema de registre que arxivi els consums d’aigua, energia i generació de residus, per tal de dur un control de les despeses de cadascun dels vectors. A més, caldrà implementar un Programa de bones pràctiques ambientals en l’oficina per tal de reduir el consum elèctric, d’aigua i generació de residus, i la seva classificació per part dels treballadors.

The Multiple-partners assignment game with heterogeneous sales and multi-unit demands: competitive equilibria

A multiple-partners assignment game with heterogeneous sales and multiunit demands consists of a set of sellers that own a given number of indivisible units of (potentially many different) goods and a set of buyers who value those units and want to buy at most an exogenously fixed number of units. We define a competitive equilibrium for this generalized assignment game and prove its existence by using only linear programming. In particular, we show how to compute equilibrium price vectors from the solutions of the dual linear program associated to the primal linear program defined to find optimal assignments. Using only linear programming tools, we also show (i) that the set of competitive equilibria (pairs of price vectors and assignments) has a Cartesian product structure: each equilibrium price vector is part of a competitive equilibrium with all optimal assignments, and vice versa; (ii) that the set of (restricted) equilibrium price vectors has a natural lattice structure; and (iii) how this structure is translated into the set of agents' utilities that are attainable at equilibrium.

Annotated list of the Phlebotominae (Diptera) of Suriname

Phlebotomine sandflies were collected between 1952 and 1984 at 30 localities in the tropical rainforest and savanna regions of Suriname. Thirty-nine species were identified in the collections (2 Brumptomyia, 37 lutzomyia), including two known vectors of cutaneous leishmaniasis, Lutzomyia flaviscutellata and L. umbratilis. Nineteen of the species are new records for Suriname. In the rainforest region, the commonest phlebotomines were L. squatniventris maripaensis (79.8%), L. umbratilis (8.4%) and L. flaviscutellata (6.3%) in human bait catches, L. umbratilis (26.2%), L. infraspinosa (23.9%) and L. trichopyga (8.3%) in CDC light traps and L. umbratilis (84.3%), L. whitmani (6.8%) and L. shannoni (4.3%) in collections from tree trunks. The mean incidence of cutaneous leishmaniasis from 1979-1985 was 4.9 per 1000 inhabitants for the rainforest region and 0.66 per 1000 for Surinameas a whole.

The dermal leishmaniases of Brazil, with special reference to the eco-epidemiology of the disease in Amazonia

Six species of Leishmania are at present known to cause cutaneous and/or mucocutaneous leishamniasis in Brazil, and they are all to be found in the Amazon region of this country. The eco-epidemiology of each is discussed, with the observation that the Amazonian leishmaniases are all zoonoses, with their source in silvatic mammals and phlebotomine sandfly vectors. With man's destruction of the natural forest in southern Brazil, some sandfly species have survived by adapting to a peridomestic or domiciliary habitat in rural areas. Some domestic animals, such as dogs and equines are seemingly now involved in the epidemiology of the disease. No such process has yet been reported in the Amazon region, but may well take place with the continuing devastation of its forest.

Canvi climàtic i malalties infeccioses

El canvi climàtic és una realitat i té efectes, tant directes com indirectes, sobre la salut. Són necessàries actuacions concertades per abordar aquestes qüestions de salut pública plantejades pel canvi climàtic, així com també disposar de mecanismes per predir quina serà la seva evolució. En aquest projecte es discuteixen les malalties infeccioses adquirides a través de diferents vies (artròpodes vectors, rosegadors, aigua, aliments i aire) en referència al canvi climàtic al món i també a Catalunya. Basat en una extensa revisió dels treballs i articles publicats, i de comentaris d’experts, es presenta una avaluació dels canvis de les malalties infeccioses: incidència, prevalença i distribució dels patògens i vehicles transmissors en un entorn canviant. En el present estudi es detallen alguns dels casos més estudiats i demostrats d’emergència i reemergència de brots infecciosos a diferents zones del planeta associats a certes variacions en les variables climàtiques. Degut a l’alt nivell d’incertesa sobre el ritme del canvi climàtic i el seu impacte sobre les malalties infeccioses, es proposa un seguit de línies de futur. Una de les propostes és crear una xarxa integrada de dades ambientals i epidemiològiques, amb capacitat de connectar aquestes dades amb la vigilància dels patògens, vectors i de la qualitat de l’aigua, entre d’altres factors. Aquestes anàlisis podrien orientar les estratègies d’actuació en un futur per la protecció de la salut de la població.