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Manifestações clínicas e patogênese da plaquetopenia na malária

Lacerda, Marcus Vinícius Guimarães de
Fonte: Universidade de Brasília Publicador: Universidade de Brasília
Tipo: Tese
POR
Relevância na Pesquisa
46.5%
Tese (doutorado)—Universidade de Brasília, Faculdade de Medicina, 2007.; A plaquetopenia é uma reconhecida complicação hematológica da infecção malárica, porém, sua patogênese ainda é incerta. Os objetivos deste trabalho foram estimar a freqüência e as manifestações clínicas da plaquetopenia na malária, e avaliar o papel dos imunocomplexos circulantes (ICC) e da agregação plaquetária in vitro. O estudo foi realizado em Manaus (Amazonas), entre 2004 e 2006, com seleção aleatória de pacientes com diagnóstico microscópico e molecular de malária vivax (n=142) e malária falciparum (n=26), após exclusão de pacientes com outras doenças. Foram analisadas as características dos pacientes, além da parasitemia, hemograma, exames bioquímicos do sangue e testes de coagulação. Os ICC foram dosados (n=48) e após a eluição da IgG dos ICC, em pacientes com plaquetopenia grave, verificou-se sua capacidade de ligação in vitro a plaquetas normais (n=2), e sua capacidade de destruição plaquetária in vivo, após injeção intraperitoneal em camundongo C57BL/6 sadio (n=1). Plaquetas incubadas com ICC de pacientes com malária e plaquetopenia foram submetidas à fagocitose por células THP-1 (n=3). Avaliou-se também a agregação de plaquetas normais...

Disfunção endotelial e fator de necrose tumoral-α na malária grave

Santos Neto, Leopoldo Luiz dos
Fonte: Universidade de Brasília Publicador: Universidade de Brasília
Tipo: Tese
PT_BR
Relevância na Pesquisa
46.51%
Tese (doutorado)—Universidade de Brasília, Faculdade de Medicina, 1993.; A malária representa atualmente um importante problema de saúde pública. A evolução clínica da infecção pelo P. falciparum é geralmente benigna, mas a mortalidade pode atingir até 50% dos casos. Citocinas como o fator de necrose tumoral-α (FNT-α) e o fenômeno de aderência associado as hemácias parasitadas são os principais mecanismos envolvidos na fisiopatogenia da forma grave de malária. Contudo, ainda existem muitos pontos na patogenia desta infecção, particularmente a contribuição da disfunção endotelial no desenvolvimento da síndrome de inflamação sistêmica da forma grave da malária. Com o objetivo de contribuir para o entedimento da disfunção do endotélio na malária grave foi realizado um estudo envolvendo 42 pacientes infectados pelo Plasmodium falciparum, 6 infectados por P. vivax e 13 indivíduos hígidos. A função endotelial foi avaliada, através da detecção da concentração plasmática da selectina-E e do fator de von Willebrand (FVW). Um total de 19 pacientes foram caracterizados como apresentando a forma grave e 23 a forma moderada, de acordo os critérios da OMS. Nos pacientes com malária houve aumento da concentração de selectina-E e do FVW...

Susceptibilidade genética à malária cerebral em crianças angolanas

Sambo, Maria do Rosário Teixeira de Alva Sequeira Bragança, 1959-
Fonte: Universidade de Lisboa Publicador: Universidade de Lisboa
Tipo: Tese de Doutorado
Publicado em //2009 POR
Relevância na Pesquisa
46.56%
Tese de doutoramento, Medicina (Genética), Universidade de Lisboa, Faculdade de Medicina, 2010; As manifestações neurológicas da infecção pelo Plasmodium falciparum, que culminam com o coma não despertável, configuram a síndroma de malária cerebral. Esta é uma das síndromas mais graves de malária severa que contribui, em larga escala, para a elevada mortalidade da malária em crianças da África subsaariana. A identificação de variantes genéticas do hospedeiro que influenciam a evolução clínica da malária severa e que determinam a fisiopatologia da malária cerebral é um dos desafios que persistem na investigação de factores genéticos da malária. Esta tese teve como principal objectivo investigar variantes genéticas que, de um modo específico, permitissem diferenciar factores de risco de malária cerebral de factores de risco de malária severa não cerebral. Foi desenhado um estudo de associação de casos-controlos, tendo-se analisado dezassete genes previamente correlacionados com a malária severa em 749 crianças angolanas. O estudo compara 130 casos de malária cerebral com 158 controlos de malária severa não cerebral, para detectar factores de risco específicos de malária cerebral. Para confirmar a exclusividade de eventuais factores de risco específicos de malária cerebral...

Clinical and molecular aspects of severe malaria

Kirchgatter,Karin; Del Portillo,Hernando A.
Fonte: Academia Brasileira de Ciências Publicador: Academia Brasileira de Ciências
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/09/2005 EN
Relevância na Pesquisa
66.17%
The erythrocytic cycle of Plasmodium falciparum presents a particularity in relation to other Plasmodium species that infect man. Mature trophozoites and schizonts are sequestered from the peripheral circulation due to adhesion of infected erythrocytes to host endothelial cells. Modifications in the surface of infected erythrocytes, termed knobs, seem to facilitate adhesion to endothelium and other erythrocytes. Adhesion provides better maturation in the microaerophilic venous atmosphere and allows the parasite to escape clearance by the spleen which recognizes the erythrocytes loss of deformability. Adhesion to the endothelium, or cytoadherence, has an important role in the pathogenicity of the disease, causing occlusion of small vessels and contributing to failure of many organs. Cytoadherence can also describe adhesion of infected erythrocytes to uninfected erythrocytes, a phenomenon widely known as rosetting. Clinical aspects of severe malaria, as well as the host receptors and parasite ligands involved in cytoadherence and rosetting, are reviewed here. The erythrocyte membrane protein 1 of P. falciparum (PfEMP1) appears to be the principal adhesive ligand of infected erythrocytes and will be discussed in more detail. Understanding the role of host receptors and parasite ligands in the development of different clinical syndromes is urgently needed to identify vaccination targets in order to decrease the mortality rates of this disease.

Platelet profile is associated with clinical complications in patients with vivax and falciparum malaria in Colombia

Martínez-Salazar,Edgar Leonardo; Tobón-Castaño,Alberto
Fonte: Sociedade Brasileira de Medicina Tropical - SBMT Publicador: Sociedade Brasileira de Medicina Tropical - SBMT
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2014 EN
Relevância na Pesquisa
56.4%
Introduction Thrombocytopenia is a common complication in malaria patients. The relationship between abnormal platelet profile and clinical status in malaria patients is unclear. In low and unstable endemic regions where vivax malaria predominates, the hematologic profiles of malaria patients and their clinical utility are poorly understood. The aim of this study was to characterize the thrombograms of malaria patients from Colombia, where Plasmodium vivax infection is common, and to explore the relationship between thrombograms and clinical status. Methods Eight hundred sixty-two malaria patients were enrolled, including 533 (61.8%) patients infected with Plasmodium falciparum, 311 (36.1%) patients infected with Plasmodium vivax and 18 (2.1%) patients with mixed infections. Results The most frequently observed changes were low platelet count (PC) and high platelet distribution width (PDW), which were observed in 65% of patients; thrombocytopenia with <50,000 platelets/µL was identified in 11% of patients. Patients with complications had lower PC and plateletcrit (PT) and higher PDW values. A higher risk of thrombocytopenia was identified in patients with severe anemia, neurologic complications, pulmonary complications, liver dysfunction...

High Levels of Plasmodium falciparum Rosetting in All Clinical Forms of Severe Malaria in African Children

Doumbo, Ogobara K.; Thera, Mahamadou A.; Koné, Abdoulaye K.; Raza, Ahmed; Tempest, Louisa J.; Lyke, Kirsten E.; Plowe, Christopher V.; Rowe, J. Alexandra
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/2009 EN
Relevância na Pesquisa
46.46%
Plasmodium falciparum rosetting (the spontaneous binding of infected erythrocytes to uninfected erythrocytes) is a well-recognized parasite virulence factor. However, it is currently unclear whether rosetting is associated with all clinical forms of severe malaria, or only with specific syndromes such as cerebral malaria. We investigated the relationship between rosetting and clinical malaria in 209 Malian children enrolled in a case-control study of severe malaria. Rosetting was significantly higher in parasite isolates from severe malaria cases compared with non-severe hyperparasitemia and uncomplicated malaria controls (F2,117 = 8.15, P < 0.001). Analysis of sub-categories of severe malaria (unrousable coma, severe anemia, non-comatose neurological impairment, repeated seizures or a small heterogeneous group with signs of renal failure or jaundice) showed high levels of rosetting in all sub-categories, and no statistically significant differences in rosetting between sub-categories (F4,67 = 1.28, P = 0.28). Thus rosetting may contribute to the pathogenesis of all severe malaria syndromes in African children, and interventions to disrupt rosetting could be potential adjunctive therapies for all forms of severe malaria in Africa.

Haplotypes of IL12B promoter polymorphisms condition susceptibility to severe malaria and functional changes in cytokine levels in Thai adults

Phawong, Chintana; Ouma, Collins; Tangteerawatana, Piyatida; Thongshoob, Jarinee; Were, Tom; Mahakunkijcharoen, Yuvadee; Wattanasirichaigoon, Duangrurdee; Perkins, Douglas Jay; Khusmith, Srisin
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
46.46%
Polymorphic variability in immune response genes, such as IL12B, encoding the IL-12p40 subunit is associated with susceptibility to severe malaria in African populations. Since the role of genetic variation in conditioning severe malaria in Thai adults is largely unexplored, the functional association between IL12B polymorphisms [i.e., IL12Bpro (rs17860508), and IL12B 3’ UTR T/G (rs3212227)], severe malaria, and cytokine production was examined in patients with Plasmodium falciparum infections (n=355) recruited from malaria endemic areas along the Thai-Myanmar border in northwest Thailand. Circulating IL-12p40 (p=0.049) and IFN-γ (p=0.051) were elevated in patients with severe malaria, while only IL-12p40 was significantly higher in severe malaria patients with hyperparasitaemia (p=0.046). Carriage of the IL12Bpro1.1 genotype was associated with enhanced severity of malaria (OR, 2.34; 95% CI, 0.94–5.81; p=0.066) and hyperparasitaemia (OR, 3.42; 95% CI, 1.17–9.87; p=0.025) relative to the IL12Bpro2.2 genotype (wild type). Individuals with the IL12Bpro1.1 genotype also had the lowest IL-12p40 (p=0.002) and the highest IFN-γ (p=0.004) levels. Construction of haplotypes revealed that carriage of the IL12Bpro-2/3’ UTR-T haplotype was associated with protection against severe malaria (OR...

Clinical and Epidemiological Profiles of Severe Malaria in Children from Delhi, India

Kaushik, Jaya Shankar; Gomber, Sunil; Dewan, Pooja
Fonte: International Centre for Diarrhoeal Disease Research, Bangladesh Publicador: International Centre for Diarrhoeal Disease Research, Bangladesh
Tipo: Artigo de Revista Científica
Publicado em /03/2012 EN
Relevância na Pesquisa
46.51%
Plasmodium vivax is traditionally known to cause benign tertian malaria, although recent reports suggest that P. vivax can also cause severe life-threatening disease analogous to severe infection due to P. falciparum. There are limited published data on the clinical and epidemiological profiles of children suffering from ‘severe malaria’ in an urban setting of India. To assess the clinical and epidemiological profiles of children with severe malaria, a prospective study was carried out during June 2008–December 2008 in the Department of Pediatrics, Guru Teg Bahadur Hospital, a tertiary hospital located in East Delhi, India. Data on children aged ≤12 years, diagnosed with severe malaria, were analyzed for their demographic, clinical and laboratory parameters. All patients were categorized and treated as per the guidelines of the World Health Organization. In total, 1,680 children were screened for malaria at the paediatric outpatient and casualty facilities of the hospital. Thirty-eight children tested positive for malaria on peripheral smear examination (2.26% slide positivity rate). Of these, 27 (71%) were admitted and categorized as severe malaria as per the definition of the WHO while another 11 (29%) received treatment on outpatient basis. Most (24/27; 88.8%) cases of severe malaria (n=27) were infected with P. vivax. Among the cases of severe malaria caused by Plasmodium vivax (n=24)...

Plasmodium falciparum erythrocyte membrane protein 1 domain cassettes 8 and 13 are associated with severe malaria in children

Lavstsen, Thomas; Turner, Louise; Saguti, Fredy; Magistrado, Pamela; Rask, Thomas S.; Jespersen, Jakob S.; Wang, Christian W.; Berger, Sanne S.; Baraka, Vito; Marquard, Andrea M.; Seguin-Orlando, Andaine; Willerslev, Eske; Gilbert, M. Thomas P.; Lusingu,
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
46.48%
The clinical outcome of Plasmodium falciparum infections ranges from asymptomatic parasitemia to severe malaria syndromes associated with high mortality. The virulence of P. falciparum infections is associated with the type of P. falciparum erythrocyte membrane protein 1 (PfEMP1) expressed on the surface of infected erythrocytes to anchor these to the vascular lining. Although var2csa, the var gene encoding the PfEMP1 associated with placental malaria, was discovered in 2003, the identification of the var/PfEMP1 variants associated with severe malaria in children has remained elusive. To identify var/PfEMP1 variants associated with severe disease outcome, we compared var transcript levels in parasites from 88 children with severe malaria and 40 children admitted to the hospital with uncomplicated malaria. Transcript analysis was performed by RT-quantitative PCR using a set of 42 primer pairs amplifying var subtype-specific loci covering most var/PfEMP1 subtypes. In addition, we characterized the near-full-length sequence of the most prominently expressed var genes in three patients diagnosed with severe anemia and/or cerebral malaria. The combined analysis showed that severe malaria syndromes, including severe anemia and cerebral malaria...

Plasmodium falciparum Infection Patterns Since Birth and Risk of Severe Malaria: A Nested Case-Control Study in Children on the Coast of Kenya

Lundblom, Klara; Murungi, Linda; Nyaga, Victoria; Olsson, Daniel; Rono, Josea; Osier, Faith; Ogada, Edna; Montgomery, Scott; Scott, J. Anthony G.; Marsh, Kevin; Färnert, Anna
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 13/02/2013 EN
Relevância na Pesquisa
46.46%
Children in malaria endemic areas acquire immunity to severe malaria faster than to mild malaria. Only a minority of children suffers from severe malaria and it is not known what determines this. The aim of this study was to establish how P. falciparum infections during the first years of life affect the risk of severe malaria. A matched case-control study was nested within a large birth cohort set up to study the immunoepidemiology of pneumococci on the Kenyan coast. Infection patterns in three-monthly blood samples in cohort children admitted to hospital with severe malaria were compared to controls matched on age, residential location and time of sampling. P. falciparum detected at least once from birth conferred an increased risk of severe malaria and particularly if multiclonal infections, as characterized by genotyping of a polymorphic antigen gene, were ever detected. The results show for the first time that children with severe malaria have more infections early in life compared to community controls. These findings provide important insights on the immunity to severe disease, knowledge essential for the development of a vaccine against severe malaria.

Incidence of Severe Malaria Syndromes and Status of Immune Responses among Khat Chewer Malaria Patients in Ethiopia

Ketema, Tsige; Bacha, Ketema; Alemayehu, Esayas; Ambelu, Argaw
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 14/07/2015 EN
Relevância na Pesquisa
46.47%
Although more emphasis has been given to the genetic and environmental factors that determine host vulnerability to malaria, other factors that might have a crucial role in burdening the disease have not been evaluated yet. Therefore, this study was designed to assess the effect of khat chewing on the incidence of severe malaria syndromes and immune responses during malaria infection in an area where the two problems co-exist. Clinical, physical, demographic, hematological, biochemical and immunological data were collected from Plasmodium falciparum mono-infected malaria patients (age ≥ 10 years) seeking medication in Halaba Kulito and Jimma Health Centers. In addition, incidences of severe malaria symptoms were assessed. The data were analyzed using SPSS (version 20) software. Prevalence of current khat chewer malaria patients was 57.38% (95%CI =53-61.56%). Malaria symptoms such as hyperpyrexia, prostration and hyperparasitemia were significantly lower (P<0.05) among khat chewer malaria patients. However, relative risk to jaundice and renal failure were significantly higher (P<0.05) in khat chewers than in non-khat chewer malaria patients. Longer duration of khat use was positively associated with incidence of anemia. IgM and IgG antibody titers were significantly higher (P<0.05) among khat chewer malaria patients than among malaria positive non-chewers. Although levels of IgG subclasses in malaria patients did not show significant differences (P>0.05)...

The Role of Animal Models for Research on Severe Malaria

Craig, Alister G.; Grau, Georges E.; Janse, Chris; Kazura, James W.; Milner, Danny Arnold; Barnwell, John W.; Turner, Gareth; Langhorne, Jean
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
56.28%
In light of the recent controversies over the role of animal models for research into the development of new treatments for severe malaria, particularly cerebral disease, a group of scientists came together to discuss the relative merits of a range of animal models and their overlap with the complex clinical syndromes of human disease. While it was not possible to fully resolve differences over the utility of the Plasmodium berghei ANKA model of experimental cerebral malaria, the meeting did bring the two research communities closer together to identify further work to provide information needed to validate the model and revitalise the development of other animal models displaying features of human pathology. The driving force behind this was the desire to ensure better translation of experimental findings into effective treatments for severe malaria.

Pre-Referral Rectal Artesunate to Prevent Death and Disability in Severe Malaria : A Placebo-Controlled Trial

Gomes, M. F.; Faiz, M. A.; Gyapong, J. O.; Warsame, M.; Agbenyega, T.; Babiker, A.; Baiden, F.; Yunus, E. B.; Binka, F.; Clerk, C.; Folb, P.; Hassan, R.; Hossain, M. A.; Kimbute, O.; Kitua, A.; Krishna, S.; Makasi, C.; Mensah, N.; Mrango, Z.; Olliaro, P.;
Fonte: Banco Mundial Publicador: Banco Mundial
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
56.3%
BACKGROUND: Most malaria deaths occur in rural areas. Rapid progression from illness to death can be interrupted by prompt, effective medication. Antimalarial treatment cannot rescue terminally ill patients but could be effective if given earlier. If patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate can be given before referral and acts rapidly on parasites. We investigated whether this intervention reduced mortality and permanent disability. METHODS: In Bangladesh, Ghana, and Tanzania, patients with suspected severe malaria who could not be treated orally were allocated randomly to a single artesunate (n=8954) or placebo (n=8872) suppository by taking the next numbered box, then referred to clinics at which injections could be given. Those with antimalarial injections or negative blood smears before randomisation were excluded, leaving 12 068 patients (6072 artesunate, 5996 placebo) for analysis. Primary endpoints were mortality, assessed 7-30 days later, and permanent disability, reassessed periodically. All investigators were masked to group assignment. Analysis was by intention to treat. This study is registered in all three countries, numbers ISRCTN83979018, 46343627, and 76987662. RESULTS: Mortality was 154 of 6072 artesunate versus 177 of 5996 placebo (2.5%vs 3.0%...

The Use of Placebo in a Trial of Rectal Artesunate as Initial Treatment for Severe Malaria Patients En Route to Referral Clinics : Ethical Issues

Kitua, A.; Folb, P.; Warsame, M.; Binka, F.; Faiz, A.; Ribeiro, I.; Peto, T.; Gyapong, J.; Yunus, E. B.; Rahman, R.; Baiden, F.; Clerk, C.; Mrango, Z.; Makasi, C.; Kimbute, O.; Hossain, A.; Samad, R.; Gomes, M.
Fonte: Banco Mundial Publicador: Banco Mundial
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
56.22%
Placebo-controlled trials are controversial when individuals might be denied existing beneficial medical interventions. In the case of malaria, most patients die in rural villages without healthcare facilities. An artesunate suppository that can be given by minimally skilled persons might be of value when patients suddenly become too ill for oral treatment but are several hours from a facility that can give injectable treatment for severe disease. In such situations, by default, no treatment is (or can be) given until the patient reaches a facility, making the placebo control design clinically relevant; alternative bioequivalence designs at the facility would misrepresent reality and risk incorrect conclusions. We describe the ethical issues underpinning a placebo-controlled trial in severe malaria. To protect patients and minimise risk, all patients were referred immediately to hospital so that each had a higher chance of prompt treatment through participation. There was no difference between artesunate and placebo in patients who reached clinic rapidly; among those who could not, a single artesunate suppository significantly reduced death or permanent disability, a finding of direct and indirect benefit to patients in participating villages and elsewhere.

The Roll Back Malaria Partnership : Defining the role of the World Bank

World Bank
Fonte: Washington, DC Publicador: Washington, DC
Relevância na Pesquisa
56.33%
Malaria kills over one million people and causes 300-500 million episodes of illness each year. The majority of the 3,000 deaths each day and ten new cases every second occur in Africa. The disease not only takes a high human toll; it also impedes development. Malaria has economic impacts through labor efficiency and land use; adversely affects school attendance, performance and cognitive ability; and translates in monetary costs in terms of expenditures by households and the public health sector. The poor are affected most, as they have less access to services, information and protective measures (e.g. nets, screens, prophylaxis), and have less power to avoid living or working within malaria-affected areas. Malaria is on the rise. While efforts to control malaria in the past fifty years have achieved a decline in malaria mortality and morbidity in some regions, the gains have often not been sustained (e.g. Madagascar, Sri Lanka, Central Asia). Emerging drug and pesticide resistances threaten to reduce the availability of effective and affordable prevention and treatment of malaria. Recent epidemics indicate a resurgence of the disease in previously low-risk areas (e.g. the highlands of Kenya)...

Quantitative trait locus analysis of parasite density reveals that HbS gene carriage protects severe malaria patients against Plasmodium falciparum hyperparasitaemia

do Sambo, Maria Rosário; Penha-Gonçalves, Carlos; Trovoada, Maria Jesus; Costa, João; Lardoeyt, Roberto; Coutinho, António
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em 07/10/2015 ENG
Relevância na Pesquisa
66.37%
Haemoglobin S (HbS) is the gene known to confer the strongest advantage against malaria morbidity and mortality. Multiple HbS effects have been described resulting in protection against parasitaemia and reduction of severe malaria risk. This study aimed to explore HbS protection against severe malaria and Plasmodium falciparum parasitaemia in Angolan children exhibiting different severe malaria syndromes.; Instituto Gulbenkian de Ciência.

Using the PfEMP1 Head Structure Binding Motif to Deal a Blow at Severe Malaria

Patarroyo, Manuel E; Patricia Alba, Martha; Curtidor, Hernando
Fonte: Universidade do Rosário Publicador: Universidade do Rosário
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/acceptedVersion Formato: application/pdf
Publicado em /02/2014 ENG
Relevância na Pesquisa
56.34%
Plasmodium falciparum (Pf) malaria causes 200 million cases worldwide, 8 million being severe and complicated leading to similar to 1 million deaths and similar to 100,000 abortions annually. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) has been implicated in cytoadherence and infected erythrocyte rosette formation, associated with cerebral malaria; chondroitin sulphate-A attachment and infected erythrocyte sequestration related to pregnancy-associated malaria and other severe forms of disease. An endothelial cell high activity binding peptide is described in several of this similar to 300 kDa hypervariable protein's domains displaying a conserved motif (GACxPxRRxxLC); it established H-bonds with other binding peptides to mediate red blood cell group A and chondroitin sulphate attachment. This motif (when properly modified) induced PfEMP1-specific strain-transcending, fully-protective immunity for the first time in experimental challenge in Aotus monkeys, opening the way forward for a long sought-after vaccine against severe malaria.

Mild Plasmodium falciparum Malaria following an Episode of Severe Malaria Is Associated with Induction of the Interferon Pathway in Malawian Children

Krupka, Malkie; Seydel, Karl; Feintuch, Catherine M.; Yee, Kenny; Kim, Ryung; Lin, Chang-Yun; Calder, R. Brent; Petersen, Christine; Taylor, Terrie; Daily, Johanna
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /03/2012 EN
Relevância na Pesquisa
46.47%
Infection with Plasmodium falciparum can lead to a range of severe to minimal symptoms, occasionally resulting in death in young children or nonimmune adults. In areas of high transmission, older children and adults generally suffer only mild or asymptomatic malaria infections and rarely develop severe disease. The immune features underlying this apparent immunity to severe disease remain elusive. To gain insight into host responses associated with severe and mild malaria, we conducted a longitudinal study of five children who first presented with severe malaria and, 1 month later, with mild malaria. Employing peripheral blood whole-genome profiling, we identified 68 genes that were associated with mild malaria compared to their expression in the severe malaria episode (paired Students t test, P < 0.05). These genes reflect the interferon (IFN) pathway and T cell biology and include IFN-induced protein transcripts 1 to 3, oligoadenylate synthetases 1 and 3, and the T cell markers cathepsin W and perforin. Gene set enrichment analysis identified Gene Ontology (GO) pathways associated with mild malaria to include the type I interferon-mediated signaling pathway (GO 0060337), T cell activation (GO 0042110), and other GO pathways representing many aspects of immune activation. In contrast...

Candidate Human Genetic Polymorphisms and Severe Malaria in a Tanzanian Population

Manjurano, Alphaxard; Clark, Taane G.; Nadjm, Behzad; Mtove, George; Wangai, Hannah; Sepulveda, Nuno; Campino, Susana G.; Maxwell, Caroline; Olomi, Raimos; Rockett, Kirk R.; Jeffreys, Anna; ; Riley, Eleanor M.; Reyburn, Hugh; Drakeley, Christopher
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 29/10/2012 EN
Relevância na Pesquisa
46.48%
Human genetic background strongly influences susceptibility to malaria infection and progression to severe disease and death. Classical genetic studies identified haemoglobinopathies and erythrocyte-associated polymorphisms, as protective against severe disease. High throughput genotyping by mass spectrometry allows multiple single nucleotide polymorphisms (SNPs) to be examined simultaneously. We compared the prevalence of 65 human SNP's, previously associated with altered risk of malaria, between Tanzanian children with and without severe malaria. Five hundred children, aged 1–10 years, with severe malaria were recruited from those admitted to hospital in Muheza, Tanzania and compared with matched controls. Genotyping was performed by Sequenom MassArray, and conventional PCR was used to detect deletions in the alpha-thalassaemia gene. SNPs in two X-linked genes were associated with altered risk of severe malaria in females but not in males: heterozygosity for one or other of two SNPs in the G6PD gene was associated with protection from all forms of severe disease whilst two SNPs in the gene encoding CD40L were associated with respiratory distress. A SNP in the adenyl cyclase 9 (ADCY9) gene was associated with protection from acidosis whilst a polymorphism in the IL-1α gene (IL1A) was associated with an increased risk of acidosis. SNPs in the genes encoding IL-13 and reticulon-3 (RTN3) were associated with increased risk of cerebral malaria. This study confirms previously known genetic associations with protection from severe malaria (HbS...

Evidence of IL-17, IP-10, and IL-10 involvement in multiple-organ dysfunction and IL-17 pathway in acute renal failure associated to Plasmodium falciparum malaria

Herbert, Fabien; Tchitchek, Nicolas; Bansal, Devendra; Jacques, Julien; Pathak, Sulabha; Bécavin, Christophe; Fesel, Constantin; Dalko, Esther; Cazenave, Pierre-André; Preda, Cristian; Ravindran, Balachandran; Sharma, Shobhona; Das, Bidyut; Pied, Sylvia
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em 24/11/2015 ENG
Relevância na Pesquisa
56.34%
Plasmodium falciparum malaria in India is characterized by high rates of severe disease, with multiple organ dysfunction (MOD)-mainly associated with acute renal failure (ARF)-and increased mortality. The objective of this study is to identify cytokine signatures differentiating severe malaria patients with MOD, cerebral malaria (CM), and cerebral malaria with MOD (CM-MOD) in India. We have previously shown that two cytokines clusters differentiated CM from mild malaria in Maharashtra. Hence, we also aimed to determine if these cytokines could discriminate malaria subphenotypes in Odisha.; Indo-French Centre for the Promotion of Advanced Research (IFCPAR project No 3703), International Associated Laboratory Systems Immunology and Genetics of Infectious Diseases (LIA SIGID, CNRS, Lille University and the Department of Biotechnology (DBT), Ministry of Science and Technology of India and the ANR LAbEx Parafrap).