Consecuencias de la infección malárica gestacional en la función inmune y en la inmunomodulación de la madre y el neonato / Consequences of gestational malaria infection in the immune function and immunomodulation of mother and newborn

Resumen La malaria asociada al embarazo es un evento poco estudiado en América Latina. Los abundantes trabajos sobre el problema en África llevan a pensar que esta infección genera una modulación de la respuesta inmune y alteraciones en el ambiente placentario, eventos cruciales para el adecuado desarrollo del feto y el neonato. La inmunidad contra Plasmodium spp es compleja porque involucra diversos factores que amplían las posibilidades de desenlaces, los que finalmente conducen a los diferentes fenotipos clínicos de la enfermedad. Uno de los desenlaces inmunológicos en infecciones por Plasmodium spp es la modulación de la respuesta inmune hacía un perfil regulador. Esta regulación inducida por la infección malárica resulta ventajosa para la persistencia del parásito en el hospedero, y adicionalmente, podría generar eventos adversos en la respuesta inmune general de los individuos infectados. El objetivo de esta revisión es abordar los mecanismos con los cuales Plasmodium spp modula la respuesta inmune del hospedero y exponer las consecuencias de las infecciones maláricas en el contexto madre-neonato.

Pregnancy-associated malaria is an understudied event in Latin America. Most works about malaria in pregnancy have been conducted in Africa. These studies indicate that the infection generates immune response modulation and alterations in the placental environment, key factors for the proper development of the fetus and neonate. Immunity against Plasmodium spp is complex since involves several factors that increase the possible infection outcomes. One of these immunological outcomes is the immune response modulation towards a regulatory profile, which is advantageous for the persistence of the parasite in the host; additionally, it could generate adverse events in the general immune response of infected individuals. The objective of this review is to address the Plasmodium spp mechanisms of modulation in the host immune response and expose the consequences of malarial infections in the mother-neonate context.

Pathogen-insect interaction candidate molecules for transmission-blocking control strategies of vector borne diseases / Moléculas candidatas para el control de enfermedades transmitidas por vector mediante el bloqueo de interacciones patógeno-insecto

Abstract: Objective: To analyze the current knowledge of pathogen-insect interactions amenable for the design of molecular-based control strategies of vector-borne diseases. Materials and methods: We examined malaria, dengue, and Chagas disease pathogens and insect molecules that participate in interactions during their vectors infection. Results: Pathogen molecules that participate in the insect intestine invasion and induced vector immune molecules are presented, and their inclusion in transmission blocking vaccines (TBV) and in genetically modify insect (GMI) vectors or symbiotic bacteria are discussed. Conclusion: Disruption of processes by blocking vector-pathogen interactions provides several candidates for molecular control strategies, but TBV and GMI efficacies are still limited and other secondary effects of GMI (improving transmission of other pathogens, affectation of other organisms) should be discarded.

Resumen: Objetivo: Analizar el conocimiento actual de las interacciones patógeno-insecto susceptibles a incluirse en el diseño de estrategias moleculares para el control de enfermedades transmitidas por vectores. Material y métodos: Se examinaron los agentes causales de la malaria, el dengue y la enfermedad de Chagas, y las moléculas de insectos que participan en interacciones durante la infección de sus vectores. Resultados: Se presentan moléculas de patógenos que participan en la invasión del intestino del insecto y moléculas inmunes inducidas en los vectores. Se discute su inclusión en vacunas bloqueadoras de transmisión (VBT) y en la modificación genética de vectores (MGI) o de sus bacterias simbióticas. Conclusión: La interrupción de procesos mediante el bloqueo de las interacciones patógeno-vector proporciona varios candidatos para las estrategias de control molecular, pero la eficacia de VBT y MGI es aún limitada y los efectos secundarios de MGI (aumento de la transmisión de otros patógenos y afectación de otros organismos) deben descartase.

The Plasmodium bottleneck: malaria parasite losses in the mosquito vector

Nearly one million people are killed every year by the malaria parasite Plasmodium. Although the disease-causing forms of the parasite exist only in the human blood, mosquitoes of the genus Anopheles are the obligate vector for transmission. Here, we review the parasite life cycle in the vector and highlight the human and mosquito contributions that limit malaria parasite development in the mosquito host. We address parasite killing in its mosquito host and bottlenecks in parasite numbers that might guide intervention strategies to prevent transmission.

Use and Effects of Malaria Control Measures in Pregnancy in Lagos, Nigeria

In Nigeria, malaria causes up to 11% of maternal mortality. Our main aim was to find out the most common mosquito control measures employed by the pregnant women in Lagos and their effects on malaria infection. The study was carried out over a period of 6 months during which trained interviewers administered questionnaires to 400 pregnant women. The prevalence of malaria was 8.4%. There was no significant association between the prevalence of malaria and age, level of education, or occupation of the participants. Pregnant women in the age range 26-30 had the mean parasite density (409.9+/-196.80). Insecticide spray (32.8%), mosquito coil (27.5%), and insecticide-treated nets (ITN) (15.5%) were the major mosquito control measures employed by the participants while the prevalence of infection among them were 2.3%, 6.2%, and 3.2%, respectively (P<0.05). Only 18.3% of the women had taken more than one dose of intermittent preventive treatment (IPT), while another 11.8% had taken a single dose. The infection rate among them was 4.1% and 6.4%, respectively. Malaria prevalence was highest among those who had not received any dose of IPT (10%). This study showed that the use of ITN and IPT among the pregnant women were still unacceptably low. It also showed that the use of insecticide spray which was the most common malaria control measure adopted by the participants was effective despite the fact that it is not a National Malaria Control Policy. We recommend that a sustained integrated mosquito management and public education should be strengthened in Nigeria.

Análisis proteómico de Plasmodium, el agente causal de la malaria / Proteomic analysis of Plasmodium, the causal agent of Malaria

Los plasmodios son protozoarios cuyo complejo ciclo de vida se lleva a cabo en dos hospederos, el vertebrado y el mosquito. La infección de los seres humanos produce la enfermedad conocida como malaria. La secuenciación del genoma de Plasmodium falciparum y el desarrollo de la proteómica han permitido un gran avance en el conocimiento de la biología de este letal parásito. La presente revisión se centra en describir los logros recientes en el estudio del proteoma de Plasmodium falciparum y algunas de las implicaciones en la búsqueda de nuevos fármacos antimaláricos, así como en la generación de vacunas para el control de la enfermedad.

Plasmodia are protozoa whose complex life cycle takes place in two different hosts, the vertebrate and the mosquito. The human infection produces the malaria disease. The genome sequence of Plasmodium falciparum and the proteomic tools have enabled a huge advance in knowledge of the biology of this parasite. This review will focus on the recent advances in proteomic studies of Plasmodium falciparum and some implications for the search of new antimalarial drugs as well as vaccines for the control of the disease.

Coadaptation and malaria control

Malaria emerges from a disequilibrium of the system 'human-plasmodium-mosquito' (HPM). If the equilibrium is maintained, malaria does not ensue and the result is asymptomatic plasmodium infection. The relationships among the components of the system involve coadaptive linkages that lead to equilibrium. A vast body of evidence supports this assumption, including the strategies involved in the relationships between plasmodium and human and mosquito immune systems, and the emergence of resistance of plasmodia to antimalarial drugs and of mosquitoes to insecticides. Coadaptive strategies for malaria control are based on the following principles: (1) the system HPM is composed of three highly complex and dynamic components, whose interplay involves coadaptive linkages that tend to maintain the equilibrium of the system; (2) human and mosquito immune systems play a central role in the coadaptive interplay with plasmodium, and hence, in the mainten-ance of the system's equilibrium; the under- or overfunction of human immune system may result in malaria and influence its severity; (3) coadaptation depends on genetic and epigenetic phenomena occurring at the interfaces of the components of the system, and may involve exchange of infectrons (genes or gene fragments) between the partners; (4) plasmodia and mosquitoes have been submitted to selective pressures, leading to adaptation, for an extremely long while and are, therefore, endowed with the capacity to circumvent both natural (immunity) and artificial (drugs, insecticides, vaccines) measures aiming at destroying them; (5) since malaria represents disequilibrium of the system HPM, its control should aim at maintaining or restoring this equilibrium; (6) the disequilibrium of integrated systems involves the disequilibrium of their components, therefore the maintenance or restoration of the system's equilibrium depend on the adoption of integrated and coordinated measures acting on all components,...

Immune effector mechanisms of the nitric oxide pathway in malaria: cytotoxicity versus cytoprotection

Nitric oxide (NO) is thought to be an important mediator and critical signaling molecule for malaria immunopathology; it is also a target for therapy and for vaccine. Inducible nitric oxide synthase (iNOS) is synthesized by a number of cell types under inflammatory conditions. The most relevant known triggers for its expression are endotoxins and cytokines. To date, there have been conflicting reports concerning the clinical significance of NO in malaria. Some researchers have proposed that NO contributes to the development of severe and complicated malaria, while others have argued that NO has a protective role. Infection with parasites resistant to the microbicidal action of NO may result in high levels of NO being generated, which could then damage the host, instead of controlling parasitemia. Consequently, the host-parasite interaction is a determining factor for whether the parasite is capable of stimulating NO production; the role of NO in resistance to malaria appears to be strain specific. It is known that NO and/or its related molecules are involved in malaria, but their involvement is not independent of other immune events. NO is an important, but possibly not an essential contributor to the control of acute-phase malaria infection. The protective immune responses against malaria parasite are multifactorial; however, they necessarily involve final effector molecules, including NO, iNOS and RNI.

Assessing the effects of global warming and local social and economic conditions on the malaria transmission

Objetivo: Apresenta-se um modelo matemático mostrando como esse instrumento pode ser importante para descrever a transmissäo da malária. Métodos: Baseado no modelo proposto previamente, foram quantificados os efeitos de dois fatores que podem afetar a transmissäo da malária: a temperatura ambiente e as condiçöes socioeconômicas locais. Resultados/Conclusöes: A quantificaçäo foi feita estudando o modelo proposto no estado estacionário e na sua dinâmica. Dependendo do nível de risco de malária, os principais efeitos na transmissäo de malária säo devidos à temperatura ambiente ou às condiçöes socioeconômicas

Malaria transmission model for different levels of acquired immunity and temperature-dependent parameters (vector)

Objetivo: Propöe-se um modelo compartimental para descrever a transmissäo de malária, levando em consideraçäo duas populaçöes envolvidas: o hospedeiro humano e o vetor mosquito. Métodos: Desenvolveu-se um modelo matemático baseado nas seguintes características: em relaçäo ao hospedeiro humano, assumiu-se a existência de imunidade adquirida e de memória imunológica que, em uma reinfecçäo, leva ao reforço da resposta imune; em relaçäo ao vetor mosquito, levou-se em consideraçäo que o período médio de desenvolvimento desde ovo até mosquito adulto e o período de incubaçäo extrínseco de parasitas (transformaçäo de mosquitos infectados mas näo-infecciosos em mosquitos infecciosos) säo dependentes de temperatura ambiente. Resultados: Foram obtidos os valores do equilíbrio no estado estacionário do modelo proposto. Da análise da estabilidade dos pontos de equilíbrio, foi determinada a razäo de reprodutibilidade basal. Conclusöes: Foi obtida uma variável epidemiológica importante, razäo de reprodutibilidade basal, que foi analisada em funçäo dos parâmetros do modelo

Current trends in research on tissue stage of malaria.

The tissue stage or the exoerythrocytic (EE) stage of the malaria parasite, for many years remained the most neglected form mainly because of its inaccessibility being located in the liver. The advent of in vitro techniques resulting in the successful cultivation of these forms in primary hepatocyte cultures and a variety of cell lines has greatly augmented research on these stages and have provided unique in vitro systems which can be used as primary screens for candidate chemotherapeutic and immunoprophylactic agents and have facilitated better understanding of the sporozoite-hepatocyte interactions. Sensitive and specific nucleic acid probes (DNA and ribosomal RNA) have been developed to quantify EE stages in infected livers. Efforts to establish SCID mouse as a model for cultivation of EE stages of human malaria parasites have been encouraging. The earlier assumptions that these tissue stages are free from immune attack have been proven wrong and the hepatic phase itself now appears to be essential for the induction of protection against the pre-erythrocytic stages. Liver stage specific antigens have been identified in recent years. Despite its intracellular position, this 'hidden' form has been found to constitute a target for antibodies, cytokines, and cytotoxic T cells. The present review focuses on the advances in research on the 'silent' stage of malaria parasites.

Urban malaria vector biology.

One of the main reasons for the set-back in the urban malaria control programme is the peculiar biobehaviour of the principal urban malaria vector Anopheles stephensi. Certain relevant facts such as incrimination as the vector of malaria, sibling or biological species, resting habitat, manlanding behaviour, seasonal prevalence, blood meal analysis, longevity, parity status, daily survival and mortality rates of adults, breeding habitats and vertical distribution of larvae of An. stephensi have been discussed. Determination of density of the vector using various parameters and their relation to malaria endemicity in an urban situation have been reviewed. An. stephensi has become resistant to DDT, HCH, malathion and propoxur in many places in India. Hence for control source reduction, use of predators such as fish and biolarvicides such as Bacillus thuringiensis var israelensis H14 and B. sphaericus, personal protection, i.e., use of appropriate clothing, bed nets, indigenous repellents, etc., information, education and communication (IEC) are to be stressed.

Anopheline species complexes & malaria control.

Species complexes comprising morphologically indistinguishable biological species that are reproductively isolated, are of common occurrence among anophelines. A list of anopheline species complexes identified so far in the world has been given. To demonstrate the importance of species complexes in malaria control, we report the Anopheles culicifacies complex as a case study. An. culicifacies is a major vector of malaria in India and neighbouring countries. This complex comprises four sibling species, A, B, C and D. Stratification of U.P. state and district Allahabad has been shown taking into consideration the biological differences among sibling species, viz., sibling species composition and vectorial potential- species B is a non-vector while others are vectors. To achieve cost effective vector control, microlevel stratification at least at the block level has been suggested. Implications of differential responses of sibling species to DDT and malathion in field operations have been discussed. To achieve selective and sustainable control, and to reduce the unnecessary selection pressure of insecticides, an insecticide spray strategy to control An. culicifacies has been provided.

Culex saltanensis Dyar, 1928: natural vector of Plasmodium juxtanucleare in Rio de Janeiro, Brazil

Searching for the natural vector of Plasmodium juxtanucleare in an enzootic locality: Granjas Calábria (33% of the chickens infected), Jacarepaguá, in Rio de Janeiro, Brazil, 13 comparative captures of mosquitoes were carried out, simultaneously on man (out-doors) and on chiken ( in a poultry-yard), between 6 and 9 p.m., from September to March 1989. Culex saltanensis was the most frequent species in captures on chicken, accounting for 41.7% of the mosquitoes collected on this bait, showing to be highly ornithophilic (90% captured on chicken versus 10% on man). Seven specimens of Cx. saltanensis were found naturally infected in granjas Calábria: five with mature pedunculate oocysts and two with sporozoites (on in the haemocoele and one in the salivary glands). These sporozoites porudced an infection by P. juxtanucleare in a chick, which had parasitemia on day 41 after inoculation. One Cx. coronator was found with mature pedunculate oocysts. Culex saltanensis was regarded as primary vector of P. juxtanucleare in Rio de Janeiro for being highly ornithophilic and in enough density to maintain the transmission, having been found with infective sporozoites in its salivary glands, and being susceptible to the parasite and able to transmit experimentally it by th bite

Malaria as anthropo-ecosystem (MAES): Part V. Self-regulation and stability of MAES.

In biological ecosystems, population tends to fluctuate above or below asymptotic level or the 'carrying capacity'. Self-regulation is achieved by extrinsic, that is, environmental limiting factors and intrinsic, that is, physiological and genetic factors. In Malaria Anthropo-Ecosystem (MAES) which is much more intricate and complex system, Plasmodium being endoparasite is required not only to interact with intrinsic factors of its vertebrate and invertebrate host but also to regulate itself to environmental factors to which its both the hosts are subjected. Attempt has been made to provide, on the basis of present knowledge, the probable explanation of self-regulatory mechanisms from molecular, cell, organ/organism, population/community levels of vertebrate and invertebrate hosts which give stability to MAES as a whole system.

Malaria as Anthropo-Ecosystem. Part IV. Adaptation of elements of MAES.

Adaptations have been recognized as an essential facets of evolution. These broadly cover two types exemplified by change (adjustments) and that leads to creation of new species. The former is generally in response to environmental factors, while the others are genetic and heritable and enable the population to continue its existence. These are also accompanied by biological and behavioural changes. In the study of MAES, adaptations appear to be main mechanism which facilitate the dynamics of the malaria system in time and space. Schematically, three broad groups of resultant factors of adaptations within MAES. viz. genetical, biological and environmental have been identified and briefly discussed with regard to their diversity in all the three elements of MAES.