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Mem. Inst. Oswaldo Cruz ; 115: e200043, 2020. tab, graf
Article in English | SES-SP, LILACS, SES-SP | ID: biblio-1135250


BACKGROUND The number of malaria cases in Roraima nearly tripled from 2016 to 2018. The capital, Boa Vista, considered a low-risk area for malaria transmission, reported an increasing number of autochthonous and imported cases. OBJECTIVES This study describes a spatial analysis on malaria cases in an urban region of Boa Vista, which sought to identify the autochthonous and imported cases and associated them with Anopheles habitats and the potential risk of local transmission. METHODS In a cross-sectional study at the Polyclinic Cosme e Silva, 520 individuals were interviewed and diagnosed with malaria by microscopic examination. Using a global positional system, the locations of malaria cases by type and origin and the breeding sites of anopheline vectors were mapped and the risk of malaria transmission was evaluated by spatial point pattern analysis. FINDINGS Malaria was detected in 57.5% of the individuals and there was a disproportionate number of imported cases (90.6%) linked to Brazilian coming from gold mining sites in Venezuela and Guyana. MAIN CONCLUSIONS The increase in imported malaria cases circulating in the west region of Boa Vista, where there are positive breeding sites for the main vectors, may represent a potential condition for increased autochthonous malaria transmission in this space.

Humans , Animals , Male , Female , Adult , Plasmodium/isolation & purification , Travel , Miners/statistics & numerical data , Mosquito Vectors/parasitology , Malaria/diagnosis , Malaria/transmission , Anopheles/parasitology , Plasmodium/classification , Urban Population , Venezuela , Brazil/epidemiology , Cross-Sectional Studies , Geographic Information Systems , Spatial Analysis , Gold , Guyana , Malaria/parasitology , Malaria/epidemiology , Anopheles/classification , Middle Aged
Rev. bras. parasitol. vet ; 27(3): 363-376, July-Sept. 2018. tab, graf
Article in English | SES-SP, LILACS, SES-SP | ID: biblio-959200


Abstract The aim of this study was to identify Plasmodium spp. in blood samples from nonhuman primates (NHPs) in the state of Maranhão, using classical and alternative techniques for examination of human malaria. A total of 161 blood samples from NHPs were analyzed: 141 from captive animals at a Wildlife Screening Center (CETAS) and 20 from free-living animals in a private reserve. The techniques used were microscopy, rapid diagnostic test (RDT), Indirect fluorescent antibody test (IFAT) and molecular techniques (semi-nested PCR, quantitative real-time PCR and LAMP). Two serological methods (dot-ELISA and indirect ELISA) were also standardized with rhoptry protein-soluble antigen of P. falciparum and P. berghei. Trophozoite forms of Plasmodium sp. were identified on slides from five different animals. No samples were positive through RDT and LAMP. Four samples were seropositive for P. malariae through IFAT. The samples showed low reactivity to ELISA. Plasmodium sp. was detected in 34.16% (55/161) of the samples using qPCR based on the 18S rRNA gene. After sequencing, two samples showed 100% identityl to P. malariae, one showed 97% identity to Plasmodium sp. ZOOBH and one showed 99% identity to P. falciparum . PCR was shown to be the most sensitive technique for diagnosing Plasmodium in NHP samples.

Resumo Neste estudo objetivamos identificar Plasmodium spp. em amostras sangue de primatas não humanos (PNH) do estado do Maranhão, utilizando técnicas clássicas e alternativas para o exame da malária humana. Foram analisadas 161 amostras de sangue de PNH, sendo 141 de CETAS (cativeiro) e 20 de reserva particular (vida livre), utilizando microscopia, teste de diagnóstico rápido (RDT), imunofluorescência indireta (IFI) e técnicas moleculares (semi-nested PCR, PCR em tempo real quantitativo e LAMP). Dois métodos sorológicos (dot-ELISA e ELISA indireto) também foram padronizados com antígenos solúveis de roptrias de P. falciparum e P. berghei. Formas trofozoíticas de Plasmodium sp. foram identificadas em lâminas de cinco animais diferentes. Nenhuma amostra foi positiva em TDR e LAMP. Quatro amostras foram soropositivas para P. malariae na IFI. Os soros de PNH mostraram baixa reatividade pelo ELISA indireto. Plasmodium sp. foi detectado em 34,16% (55/161) das amostras utilizando a qPCR baseada no gene 18S rRNA. No sequenciamento, duas amostras mostraram identidade com P. malariae (100%), uma com Plasmodium sp. ZOOBH (97%) e uma com P. falciparum (99%). A PCR mostrou ser a técnica mais sensível para diagnósticos de Plasmodium em amostras de PNH.

Animals , Male , Plasmodium/genetics , Plasmodium/immunology , Platyrrhini/parasitology , Malaria/veterinary , Antibodies, Protozoan/blood , RNA, Ribosomal, 18S/blood , DNA, Protozoan/blood , Fluorescent Antibody Technique, Indirect , Real-Time Polymerase Chain Reaction , Malaria/diagnosis , Malaria/parasitology
Mem. Inst. Oswaldo Cruz ; 113(9): e170522, 2018. tab, graf
Article in English | LILACS | ID: biblio-955127


The Malaria Frontier Hypothesis (MFH) is the current model for predicting malaria emergence in the Brazilian Amazon. It has two important dimensions, 'settlement time' and 'malaria incidence', and its prediction are: malaria incidence peaks five years after the initiation of human settlement and declines towards zero after an estimated 10 years. Although MFH is currently accepted, it has been challenged recently. Herein, we described a novel method for estimating settlement timeline by using remote sensing technology integrated in an open-software geographic information system. Surprisingly, we found that of the majority of the rural settlements with high malaria incidence are more than 10 years old.

Humans , Geographic Information Systems/organization & administration , Malaria/parasitology , Malaria/transmission , Malaria/epidemiology , Rural Population , Brazil/epidemiology , Forests , Conservation of Natural Resources/trends , Parasite Load/statistics & numerical data
Mem. Inst. Oswaldo Cruz ; 111(9): 570-576, Sept. 2016. tab, graf
Article in English | LILACS | ID: lil-794731


Abstract Plasmodium falciparum and Plasmodium vivax have evolved with host switches between non-human primates (NHPs) and humans. Studies on the infection dynamics of Plasmodium species in NHPs will improve our understanding of the evolution of these parasites; however, such studies are hampered by the difficulty of handling animals in the field. The aim of this study was to detect genomic DNA of Plasmodium species from the faeces of New World monkeys. Faecal samples from 23 Alouatta clamitans from the Centre for Biological Research of Indaial (Santa Catarina, Brazil) were collected. Extracted DNA from faecal samples was used for molecular diagnosis of malaria by nested polymerase chain reaction. One natural infection with Plasmodium simium was identified by amplification of DNA extracted from the faeces of A. clamitans. Extracted DNA from a captive NHP was also used for parasite genotyping. The detection limit of the technique was evaluated in vitro using an artificial mixture of cultured P. falciparum in NHP faeces and determined to be 6.5 parasites/µL. Faecal samples of New World primates can be used to detect malaria infections in field surveys and also to monitor the genetic variability of parasites and dynamics of infection.

Animals , Alouatta/parasitology , DNA, Protozoan/genetics , Malaria/veterinary , Monkey Diseases/parasitology , Plasmodium/isolation & purification , Brazil , Feces , Genotype , Malaria/parasitology , Plasmodium/classification
Mem. Inst. Oswaldo Cruz ; 110(4): 560-565, 09/06/2015. graf
Article in English | LILACS | ID: lil-748861


A rapid decrease in parasitaemia remains the major goal for new antimalarial drugs and thus, in vivo models must provide precise results concerning parasitaemia modulation. Hydroxyethylamine comprise an important group of alkanolamine compounds that exhibit pharmacological properties as proteases inhibitors that has already been proposed as a new class of antimalarial drugs. Herein, it was tested the antimalarial property of new nine different hydroxyethylamine derivatives using the green fluorescent protein (GFP)-expressing Plasmodium berghei strain. By comparing flow cytometry and microscopic analysis to evaluate parasitaemia recrudescence, it was observed that flow cytometry was a more sensitive methodology. The nine hydroxyethylamine derivatives were obtained by inserting one of the following radical in the para position: H, 4Cl, 4-Br, 4-F, 4-CH3, 4-OCH3, 4-NO2, 4-NH2 and 3-Br. The antimalarial test showed that the compound that received the methyl group (4-CH3) inhibited 70% of parasite growth. Our results suggest that GFP-transfected P. berghei is a useful tool to study the recrudescence of novel antimalarial drugs through parasitaemia examination by flow cytometry. Furthermore, it was demonstrated that the insertion of a methyl group at the para position of the sulfonamide ring appears to be critical for the antimalarial activity of this class of compounds.

Animals , Mice , Rats , Antimalarials/therapeutic use , Malaria/drug therapy , Parasitemia/drug therapy , Plasmodium berghei/drug effects , Disease Models, Animal , Flow Cytometry , Green Fluorescent Proteins , In Vitro Techniques , Malaria/parasitology , Parasitemia/parasitology
Salvador; s.n; 2015. 69 p. ilus, tab.
Thesis in Portuguese | LILACS | ID: biblio-1000983


A malária é uma doença causada por cinco espécies de parasitos do gênero Plasmodium que causa anualmente a morte de milhares de pessoas, principalmente em países pobres da África. Muito antiga, uma diversidade de fármacos já foram empregados na tentativa de erradicação da doença, entretanto o aparecimento de cepas resistentes, bem como efeitos adversos gerados pelo tratamento impossibilitou tal ação. Os quinolínicos configuram uma grande parte destes tratamentos, apresentando uma notável atividade antimalárica. Neste trabalho nós avaliamos o potencial antimalárico de três novos derivados quinolínicos BS 260, BS 318 e BS 373 em culturas de Plasmodium falciparum, cepa w2, cloroquina resistente. BS 373 apresentou melhor atividade contra culturas de Plasmodium falciparum e, assim como o BS 318, foi capaz de inibir a biocristalização de hemozoína pelos parasitos. A microscopia eletrônica de transmissão revelou uma desorganização celular, diminuição do tamanho e quantidade de cristais de hemozoína no vacúolo digestivo, bem como vacuolizações citoplasmáticas e presença de estruturas membranares no vacúolo digestivo, o que indica a ocorrência de um processo autofágico nas células tratadas com 10 LM e 20 LM do BS 373. A presença de cristais citoplasmáticos indica a ocorrência de autólise pela ruptura da membrana do vacúolo digestivo. Por fim, o efeito dos tratamentos se mostrou irreversível nos parasitos com 24 horas de tratamento para BS 318 e BS 373, enquanto que para BS 260 essa irreversibilidade só foi observada após 48 horas. Nossos dados mostram que os derivados quinolínicos testados são efetivos contra culturas de P. falciparum, configurando bons candidatos à novas moléculas antimaláricas.

Malaria is a disease caused by five Plasmodium species that cause deaths of thousands of people annually, mostly in poor countries of Africa. Very anccient, a variety of drugs have been used in an attempt to eradicate the disease, however the emergence of resistant strains, as well as adverse effects caused by treatment prevented such action. The quinoline are a large part of these treatments, presenting a remarkable antimalarial activity. In this paper we evaluate the antimalarial potential of three new quinoline derivative BS 260, BS 318 and BS 373 in Plasmodium falciparum chloroquine resistant, w2 strain, cultures. BS 373 showed the best activity against Plasmodium falciparum cultures, while and analogously to BS 318 was able to inhibit the hemozoin formation by parasites. The transmission electron microscopy revealed a cell disorganization, decreased size and amount of hemozoin crystals in the digestive vacuole, cytoplasmic vacuolization and presence of membrane structures in the digestive vacuole, which indicates an autophagic process in cells treated with 10 LM and 20 LM BS 373. Cytoplasmic being crystals indicate parasite cell autolusis caused by digestive vacuole membrane disrupture. Finally, the effect of treatment proved irreversible on parasites at 24 hours of treatment for BS 318 and BS 373, whereas for BS 260 this irreversibility was only observed after 48 hours. Our data show that the quinoline derivatives tested are effective against P. falciparum cultures, setting good candidates for new antimalarial molecules.

Humans , Oxidative Stress , Oxidative Stress/immunology , Malaria/diagnosis , Malaria/immunology , Malaria/parasitology , Malaria/pathology , Malaria/prevention & control , Malaria/transmission , Plasmodium falciparum , Plasmodium falciparum/parasitology
Salvador; s.n; 2015. 177 p. ilus, tab.
Thesis in Portuguese | LILACS | ID: biblio-1001023


INTRODUÇÃO: A malária é uma das doenças infecto-parasitárias mais incidentes no mundo com grande morbimortalidade. Dentre as espécies infectivas ao ser humano, o Plasmodium vivax é a espécie predominante no Brasil, quase que exclusivamente na Região Amazônica. O espectro clínico da malária abrange desde uma infecção assintomática até casos moderados,com hiperbilirrubinemia isolada ou graves. A produção de mediadores inflamatórios pelo sistema imune, a via de metabolização do heme e os níveis sistêmicos de hepcidina são importantes mecanismos associados afisiopatologia dos diferentes desfechos clínicos da malária. Além disso, coinfecções podem modular ou intensificar a resposta imune de indivíduos infectados pelo plasmódio. OBJETIVO: Neste ínterim, a identificação de biomarcadores confiáveis tanto de gravidade ou resistência são indispensáveis para o auxílio no seguimento, diagnóstico e terapêutica da malária...

INTRODUCTION: Malaria is one of the most frequent infectious diseases inthe world with high morbidity and mortality. Among the infective species tohumans, Plasmodium vivax is the most predominant species in Brazil, withdisease incidence almost exclusively observed in the Amazon Region. Theclinical spectrum of malaria can range from asymptomatic infection to mildcases, malaria with isolated hyperbilirubinaemia or severe infection. Theimmune system production of inflammatory mediators, the heme metabolismpathway and systemic levels of hepcidin are important mechanismsassociated with pathophysiology of different malaria clinical outcomes. Inaddition, co-infections can modulate or enhance the immune response ofindividuals infected with P. vivax. OBJECTIVE: In this context, the identification of reliable biomarkers for disease severity and resistance are essential for the diagnosis, treatment and follow-up of malaria...

Humans , Malaria/diagnosis , Malaria/immunology , Malaria/microbiology , Malaria/parasitology , Malaria/pathology , Malaria/prevention & control , Malaria/blood , Malaria/transmission , Plasmodium vivax/parasitology , Plasmodium vivax/pathogenicity
Mem. Inst. Oswaldo Cruz ; 109(7): 955-959, 11/2014. tab, graf
Article in English | LILACS | ID: lil-728802


Malaria in La Guajira, the most northern state of Colombia, shows two different epidemiological patterns. Malaria is endemic in the municipality of Dibulla whereas in Riohacha it is characterised by sporadic outbreaks. This study aimed to establish whether differences in transmission patterns could be attributed to different vector species. The most abundant adult female species were Anopheles aquasalis, exclusive to Riohacha, and Anopheles darlingi, restricted to Dibulla. Anopheles mosquitoes were identified using morphology and the molecular markers internal transcribed spacer 2 and cytochrome c oxidase I. All specimens (n = 1,393) were tested by ELISA to determine natural infection rates with Plasmodium falciparum and Plasmodium vivax. An. darlingi was positive for P. vivax 210, with an infection rate of 0.355% and an entomological inoculation rate of 15.87 infective bites/person/year. Anopheles albimanus larvae were the most common species in Riohacha, found in temporary swamps; in contrast, in Dibulla An. darlingi were detected mainly in permanent streams. Distinctive species composition and larval habitats in each municipality may explain the differences in Plasmodium transmission and suggest different local strategies should be used for vector control.

Animals , Female , Humans , Anopheles/classification , Insect Vectors/classification , Malaria/transmission , Plasmodium , Anopheles/anatomy & histology , Biomarkers , Cities , Colombia , DNA, Intergenic , Enzyme-Linked Immunosorbent Assay , Geography , Malaria/parasitology , Species Specificity
Indian J Exp Biol ; 2014 Aug; 52(8): 781-786
Article in English | IMSEAR | ID: sea-153759


The hunt for an effective vaccine against malaria still continues. Several new target antigens as candidates for vaccine design are being explored and tested for their efficacy. In the present study the sera from mice immunized with 24,000 × g fraction of Plasmodium berghei has been used to identify highly immunogenic blood stage antigens. The protective antibodies present in immune sera were covalently immobilized on CNBr activated sepharose 4B and used for affinity chromatography purification of antigens present in blood stages of P. berghei. Two polypeptides of 66 and 43 kDa molecular weights proved to be highly immunogenic. They exhibited a strong humoral immune response in mice as evident by high titres in ELISA and IFA. Protective immunity by these two antigens was apparent by in vivo and in vitro studies. These two proteins could further be analysed and used as antigens in malaria vaccine design.

Animals , Histocompatibility Antigens Class II/blood , Humans , Immunity, Humoral/immunology , Immunization , Malaria/blood , Malaria/parasitology , Malaria/prevention & control , Malaria Vaccines/immunology , Mice , Plasmodium berghei/immunology , Plasmodium berghei/pathogenicity
Mem. Inst. Oswaldo Cruz ; 109(5): 546-552, 19/08/2014. tab, graf
Article in English | LILACS | ID: lil-720416


Due to the recent advances of atovaquone, a naphthoquinone, through clinical trials as treatment for malarial infection, 19 quinone derivatives with previously reported structures were also evaluated for blood schizonticide activity against the malaria parasite Plasmodium falciparum. These compounds include 2-hydroxy-3-methylamino naphthoquinones (2-9), lapachol (10), nor-lapachol (11), iso-lapachol (12), phthiocol (13) and phenazines (12-20). Their cytotoxicities were also evaluated against human hepatoma and normal monkey kidney cell lines. Compounds 2 and 5 showed the highest activity against P. falciparum chloroquine-resistant blood-stage parasites (clone W2), indicated by their low inhibitory concentration for 50% (IC50) of parasite growth. The therapeutic potential of the active compounds was evaluated according to the selectivity index, which is a ratio of the cytotoxicity minimum lethal dose which eliminates 50% of cells and the in vitro IC50. Naphthoquinones 2 and 5, with activities similar to the reference antimalarial chloroquine, were also active against malaria in mice and suppressed parasitaemia by more than 60% in contrast to compound 11 which was inactive. Based on their in vitro and in vivo activities, compounds 2 and 5 are considered promising molecules for antimalarial treatment and warrant further study.

Animals , Humans , Mice , Antimalarials/pharmacology , Malaria/drug therapy , Naphthoquinones/pharmacology , Phenazines/pharmacology , Plasmodium berghei/drug effects , Plasmodium falciparum/drug effects , Antimalarials/chemistry , Cell Line , Disease Models, Animal , Malaria/parasitology , Naphthoquinones/chemistry , Parasitic Sensitivity Tests , Parasitemia/drug therapy , Phenazines/chemistry
Mem. Inst. Oswaldo Cruz ; 109(5): 589-597, 19/08/2014. graf
Article in English | LILACS | ID: lil-720424


Metabolomics uses high-resolution mass spectrometry to provide a chemical fingerprint of thousands of metabolites present in cells, tissues or body fluids. Such metabolic phenotyping has been successfully used to study various biologic processes and disease states. High-resolution metabolomics can shed new light on the intricacies of host-parasite interactions in each stage of the Plasmodium life cycle and the downstream ramifications on the host’s metabolism, pathogenesis and disease. Such data can become integrated with other large datasets generated using top-down systems biology approaches and be utilised by computational biologists to develop and enhance models of malaria pathogenesis relevant for identifying new drug targets or intervention strategies. Here, we focus on the promise of metabolomics to complement systems biology approaches in the quest for novel interventions in the fight against malaria. We introduce the Malaria Host-Pathogen Interaction Center (MaHPIC), a new systems biology research coalition. A primary goal of the MaHPIC is to generate systems biology datasets relating to human and non-human primate (NHP) malaria parasites and their hosts making these openly available from an online relational database. Metabolomic data from NHP infections and clinical malaria infections from around the world will comprise a unique global resource.

Animals , Humans , Host-Parasite Interactions , Metabolomics , Malaria/parasitology , Plasmodium/chemistry , Computational Biology , Mass Spectrometry , Plasmodium/metabolism , Plasmodium/pathogenicity
Mem. Inst. Oswaldo Cruz ; 109(5): 641-653, 19/08/2014. tab, graf
Article in English | LILACS | ID: lil-720431


Blood infection by the simian parasite, Plasmodium simium, was identified in captive (n = 45, 4.4%) and in wild Alouatta clamitans monkeys (n = 20, 35%) from the Atlantic Forest of southern Brazil. A single malaria infection was symptomatic and the monkey presented clinical and haematological alterations. A high frequency of Plasmodium vivax-specific antibodies was detected among these monkeys, with 87% of the monkeys testing positive against P. vivax antigens. These findings highlight the possibility of malaria as a zoonosis in the remaining Atlantic Forest and its impact on the epidemiology of the disease.

Animals , Alouatta/parasitology , Malaria/veterinary , Monkey Diseases/epidemiology , Plasmodium/classification , Antibodies, Protozoan/blood , Brazil/epidemiology , Forests , Malaria/epidemiology , Malaria/parasitology , Monkey Diseases/parasitology , Polymerase Chain Reaction
Mem. Inst. Oswaldo Cruz ; 109(1): 21-28, 02/2014. tab, graf
Article in English | LILACS | ID: lil-703648


The polymerase chain reaction (PCR)-based methods for the diagnosis of malaria infection are expected to accurately identify submicroscopic parasite carriers. Although a significant number of PCR protocols have been described, few studies have addressed the performance of PCR amplification in cases of field samples with submicroscopic malaria infection. Here, the reproducibility of two well-established PCR protocols (nested-PCR and real-time PCR for the Plasmodium 18 small subunit rRNA gene) were evaluated in a panel of 34 blood field samples from individuals that are potential reservoirs of malaria infection, but were negative for malaria by optical microscopy. Regardless of the PCR protocol, a large variation between the PCR replicates was observed, leading to alternating positive and negative results in 38% (13 out of 34) of the samples. These findings were quite different from those obtained from the microscopy-positive patients or the unexposed individuals; the diagnosis of these individuals could be confirmed based on the high reproducibility and specificity of the PCR-based protocols. The limitation of PCR amplification was restricted to the field samples with very low levels of parasitaemia because titrations of the DNA templates were able to detect < 3 parasites/µL in the blood. In conclusion, conventional PCR protocols require careful interpretation in cases of submicroscopic malaria infection, as inconsistent and false-negative results can occur.

Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Carrier State/parasitology , DNA, Protozoan/analysis , Malaria/parasitology , Plasmodium/genetics , Polymerase Chain Reaction/methods , Chi-Square Distribution , Carrier State/diagnosis , Coinfection/diagnosis , Genes, rRNA/genetics , Microscopy , Malaria/diagnosis , Parasitemia/diagnosis , Parasitemia/parasitology , Plasmodium/classification , Reproducibility of Results , Real-Time Polymerase Chain Reaction/methods , Sensitivity and Specificity
Indian J Exp Biol ; 2014 Jan; 52(1): 67-72
Article in English | IMSEAR | ID: sea-150334


The present work deals with the development of Plasmodium falciparum stages in mouse model and its potential for the study of efficacy of antimalarial drugs. C57BL/6J mice were infected with multidrug resistant P. falciparum strain then treated with arteether and artesunate. A response was observed to antimalarial drugs in terms of decrease in parasitemia. Mice infected with P. falciparum strain were successfully cured after treatment with either arteether or artesunate. The speed of parasite clearance time and burden of parasitemia differed for each drug and matched the previously reported observations, hence stressing the relevance of the model. These findings thus suggest that P. falciparum. infected human RBC (iRBC) – C57BL/6J mice can provide a valuable in vivo system and should be included in the short list of animals that can be used for the evaluation of P. falciparum responses to drugs.

Animals , Artemisinins/administration & dosage , Disease Models, Animal , Drug Resistance, Multiple/genetics , Female , Humans , Malaria/drug therapy , Malaria/metabolism , Malaria/parasitology , Mice , Mice, Inbred C57BL , Parasitemia/drug therapy , Plasmodium falciparum/growth & development , Plasmodium falciparum/pathogenicity
Rev. chil. obstet. ginecol ; 79(4): 288-293, 2014. ilus
Article in Spanish | LILACS | ID: lil-724829


Los mecanismos fisiopatológicos de la malaria placentaria son hasta el momento poco comprendidos, y el daño placentario derivado de la infección por Plasmodium spp se ha relacionado con eventos adversos del embarazo que afectan directamente el desarrollo del feto. Las concentraciones placentarias de algunas citocinas como la IL-10, TNF-alfa y TGF-beta y glicosaminoglicanos como el CSA, HA y HS podrían estar participando de forma reguladora en los eventos inflamatorios placentarios durante la infección por Plasmodium spp.

The pathophysiological mechanisms of placental malaria are until now poorly understood and the placental damage resulting from infection by Plasmodium spp has been linked to adverse pregnancy events that directly affect fetal development. Placental concentrations of some cytokines such as IL-10, TNF-alpha and TGF-beta and glycosaminoglycans such as CSA, HA and HS could be involved in a regulatory role in placental inflammation during infection by Plasmodium spp.

Humans , Female , Pregnancy , Glycosaminoglycans , Malaria/immunology , Malaria/parasitology , Placenta/immunology , Placenta/parasitology , Plasmodium , Pregnancy Complications, Parasitic
Mem. Inst. Oswaldo Cruz ; 108(8): 974-982, 6/dez. 2013. tab, graf
Article in English | LILACS | ID: lil-697147


Infusions of Aspidosperma nitidum (Apocynaceae) wood bark are used to treat fever and malaria in the Amazon Region. Several species of this family are known to possess indole alkaloids and other classes of secondary metabolites, whereas terpenoids, an inositol and the indole alkaloids harmane-3 acid and braznitidumine have been described in A. nitidum . In the present study, extracts from the wood bark, leaves and branches of this species were prepared for assays against malaria parasites and cytotoxicity testing using human hepatoma and normal monkey kidney cells. The wood bark extracts were active against Plasmodium falciparum and showed a low cytotoxicity in vitro, whereas the leaf and branch extracts and the pure alkaloid braznitidumine were inactive. A crude methanol extract was subjected to acid-base fractionation aimed at obtaining alkaloid-rich fractions, which were active at low concentrations against P. falciparum and in mice infected with and sensitive Plasmodium berghei parasites. Our data validate the antimalarial usefulness of A. nitidum wood bark, a remedy that can most likely help to control malaria. However, the molecules responsible for this antimalarial activity have not yet been identified. Considering their high selectivity index, the alkaloid-rich fractions from the plant bark might be useful in the development of new antimalarials.

Animals , Humans , Mice , Antimalarials/pharmacology , Aspidosperma/chemistry , Plant Bark/chemistry , Plant Extracts/pharmacology , Plasmodium berghei/drug effects , Plasmodium falciparum/drug effects , Antimalarials/isolation & purification , Malaria/drug therapy , Malaria/parasitology , Parasitic Sensitivity Tests , Plant Extracts/isolation & purification
Mem. Inst. Oswaldo Cruz ; 108(5): 644-650, ago. 2013. tab, graf
Article in English | LILACS | ID: lil-680765


During the season of high malaria transmission, most children are infected by Plasmodium, which targets red blood cells (RBCs), affecting haematological parameters. To describe these variations, we examined the haematological profiles of two groups of children living in a malaria-endemic area. A cross-sectional survey was conducted at the peak of the malaria transmission season in a rural area of Burkina Faso. After informed consent and clinical examination, blood samples were obtained from the participants for malaria diagnosis and a full blood count. Of the 414 children included in the analysis, 192 were not infected with Plasmodium, whereas 222 were asymptomatic carriers of Plasmodium infection. The mean age of the infected children was 41.8 months (range of 26.4-57.2) compared to 38.8 months (range of 22.4-55.2) for the control group (p = 0.06). The asymptomatic infected children tended to have a significantly lower mean haemoglobin level (10.8 g/dL vs. 10.4 g/dL; p < 0.001), mean lymphocyte count (4592/µL vs. 5141/µL; p = 0.004), mean platelet count (266 x 103/µL vs. 385 x 103/µL; p < 0.001) and mean RBC count (4.388 x 106/µL vs. 4.158 x 106/µL; p < 0.001) and a higher mean monocyte count (1403/µL vs. 1192/µL; p < 0.001) compared to the control group. Special attention should be applied when interpreting haematological parameters and evaluating immune responses in asymptomatic infected children living in malaria-endemic areas and enrolled in vaccine trials.

Child, Preschool , Female , Humans , Male , Asymptomatic Infections/epidemiology , Malaria/epidemiology , Parasitemia/epidemiology , Plasmodium/classification , Burkina Faso/epidemiology , Case-Control Studies , Cross-Sectional Studies , Malaria/parasitology , Prevalence , Plasmodium/isolation & purification , Rural Population , Seasons
Indian J Exp Biol ; 2013 Apr; 51(4): 273-279
Article in English | IMSEAR | ID: sea-147592


Malaria is a complex disease that afflicts human today. Malaria epidemiology is associated with drug resistance in parasite and differential distribution and insecticide resistance in vector. Efforts are being made to eradicate malaria but burden of malaria is still increasing. Vector control is essential for malaria prevention strategies. Knowledge of population genetic structure is pre-requisite for determining prevention strategies, particularly using transgenic mosquitoes. Population genetic study can predict level of gene flow between different populations. Anopheles stephensi Liston is urban vector of malaria in Indo-Pakistan subcontinent. About 12% of malaria cases of malaria in India are contributed by A. stephensi. Studies conducted on population genetics of A. stephensi using various markers in different parts of the world are discussed in this communication.

Animals , Anopheles/genetics , DNA, Mitochondrial/genetics , DNA, Ribosomal/genetics , Genetic Markers/genetics , Genetics, Population , Geography , Humans , India , Insect Vectors/genetics , Insecticide Resistance/genetics , Malaria/parasitology , Malaria/prevention & control , Microsatellite Repeats/genetics , Pakistan , Random Amplified Polymorphic DNA Technique
Mem. Inst. Oswaldo Cruz ; 107(3): 410-415, May 2012. ilus, graf, tab
Article in English | LILACS | ID: lil-624024


The spleen plays a crucial role in the development of immunity to malaria, but the role of pattern recognition receptors (PRRs) in splenic effector cells during malaria infection is poorly understood. In the present study, we analysed the expression of selected PRRs in splenic effector cells from BALB/c mice infected with the lethal and non-lethal Plasmodium yoelii strains 17XL and 17X, respectively, and the non-lethal Plasmodium chabaudi chabaudi AS strain. The results of these experiments showed fewer significant changes in the expression of PRRs in AS-infected mice than in 17X and 17XL-infected mice. Mannose receptor C type 2 (MRC2) expression increased with parasitemia, whereas Toll-like receptors and sialoadhesin (Sn) decreased in mice infected with P. chabaudi AS. In contrast, MRC type 1 (MRC1), MRC2 and EGF-like module containing mucin-like hormone receptor-like sequence 1 (F4/80) expression decreased with parasitemia in mice infected with 17X, whereas MRC1 an MRC2 increased and F4/80 decreased in mice infected with 17XL. Furthermore, macrophage receptor with collagenous structure and CD68 declined rapidly after initial parasitemia. SIGNR1 and Sn expression demonstrated minor variations in the spleens of mice infected with either strain. Notably, macrophage scavenger receptor (Msr1) and dendritic cell-associated C-type lectin 2 expression increased at both the transcript and protein levels in 17XL-infected mice with 50% parasitemia. Furthermore, the increased lethality of 17X infection in Msr1 -/- mice demonstrated a protective role for Msr1. Our results suggest a dual role for these receptors in parasite clearance and protection in 17X infection and lethality in 17XL infection.

Animals , Female , Mice , Lectins, C-Type/immunology , Malaria/parasitology , Mannose-Binding Lectins/immunology , Plasmodium chabaudi/immunology , Plasmodium yoelii/immunology , Receptors, Cell Surface/immunology , Receptors, Scavenger/immunology , Spleen/parasitology , Toll-Like Receptors/immunology , Flow Cytometry , Lectins, C-Type/genetics , Mice, Inbred BALB C , Microarray Analysis , Malaria/immunology , Mannose-Binding Lectins/genetics , Parasitemia/immunology , Receptors, Cell Surface/genetics , Receptors, Scavenger/genetics , Spleen/immunology , Toll-Like Receptors/genetics
Biomédica (Bogotá) ; 32(supl.1): 79-94, ene.-mar. 2012. ilus, tab
Article in Spanish | LILACS | ID: lil-639830


Introducción. El pronto reconocimiento de los signos de peligro en los pacientes con malaria puede reducir las complicaciones y muertes. Sin embargo, se conoce poco sobre su valor pronóstico para la malaria complicada, especialmente en las zonas de transmisión baja e inestable de la enfermedad. Objetivo. Estimar el valor pronóstico de gravedad que tienen diversos signos clínicos y parasitológicos en los pacientes con malaria. Materiales y métodos. Se hizo un estudio en una cohorte prospectiva con pacientes de cinco municipios de Colombia, con diagnóstico de malaria por Plasmodium falciparum y P. vivax, en quienes se estudió la asociación de los signos clínicos y los parasitológicos con la malaria complicada. Resultados. Se obtuvo un modelo de predicción con una sensibilidad de 47,4 % y especificidad de 92,8 %, valor pronóstico positivo de 63,2 % y valor pronóstico negativo de 87,1 %, el cual incluye ictericia, orina oscura, hiperpirexia y signos de deshidratación. Conclusiones. Con el fin de causar un impacto en la morbilidad complicada de la malaria, se propone una estrategia de reconocimiento de los signos de peligro por el personal no médico, que se acompañe de otros elementos de la atención, como el suministro de un tratamiento antipalúdico adecuado y oportuno. Se proponen los criterios del diagnóstico de complicación moderada.

Prognostic value of clinical and parasitological signs for severe malaria in patients from Colombia.

Introduction. Early recognition of danger signs in patients with malaria can reduce complications and deaths, but little is known about their prognostic value for severe malaria, especially in areas of low transmission and unstable malaria. Objective. To assess the prognostic value for severity of different clinical and parasitological signs in patients with malaria. Materials and methods. A prospective cohort of patients from five municipalities in Colombia with diagnosis of Plasmodium falciparum or P. vivax malaria in whom the association between clinical and parasitological signs with complicated malaria was studied. Results. A predictive model with 47.4% sensitivity, 92.8% specificity, 63.2% positive predictive value and 87.1% negative predictive value was obtained which includes jaundice, dark urine, hyperpyrexia and signs of dehydration. Conclusions. To impact the morbidity of complicated proposed a strategy is proposed for the early recognition of danger signs by non-medical personnel, which could be complemented by other elements of health care, such as providing adequate and appropriate antimalarial treatment. Diagnostic criteria for moderate complication are also proposed.

Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Young Adult , Malaria/diagnosis , Malaria/parasitology , Colombia , Prognosis , Prospective Studies , Severity of Illness Index