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1.
Rev. AMRIGS ; 60(4): 359-362, out.-dez. 2016. ilus
Article in Portuguese | LILACS | ID: biblio-847830

ABSTRACT

A associação entre Vírus da Imunodeficiência Humana (HIV) e Malária é um evento de grande repercussão clínica. A grande importância de tal concomitância de diagnósticos dá-se por sua associação negativa, na qual se observa risco aumentado de infecção por malária em pacientes com HIV e o aumento de replicação viral nesses pacientes em decorrência da coinfecção pela malária. Os achados radiológicos incluem infiltrado intersticial ou alveolar, localizado preferencialmente nas regiões peri-hilares e em bases pulmonares, que pode ser associado a derrame pleural. O caso relatado é de um homem de 40 anos, branco, previamente hígido, que interna por quadro de febre, mialgia difusa e fadiga, após viagem de turismo ao continente africano. Em investigação laboratorial inicial, apresenta hemoconcentração e plaquetopenia importante. No decorrer da internação, tem diagnóstico de malária (demonstração do parasita no esfregaço sanguíneo) e inicia tratamento específico. Solicitou-se sorologia para HIV, a qual se apresentou positiva. O paciente evolui com febre ictero-hemorrágica, confusão mental, vômitos, insuficiência ventilatória e insuficiência renal aguda, sendo transferido para Unidade de Terapia Intensiva. Comprovou-se comprometimento pulmonar grave através da realização de Tomografia Computadorizada de Tórax de Alta Resolução, que evidenciou espessamento de septos interlobulares e de bainhas peribroncovasculares, com áreas esparsas de atenuação em vidro fosco e de consolidações, além de evidência de derrame pleural. Conclui-se que padrão de comprometimento radiológico do paciente foi compatível com os relatos já descritos pela literatura, o que corrobora para unificação de apresentação do quadro nos exames de imagem (AU)


The association between human immunodeficiency virus (HIV) and malaria is an event of great clinical repercussion. The great importance of such concomitance of diagnoses is due to its negative association, where there is an increased risk of malaria infection in patients with HIV and increased viral replication in these patients due to malaria co-infection. Radiological findings include interstitial or alveolar infiltrate, preferably located in the peri-hilar regions and at the lung bases, which may be associated with pleural effusion. The case reported here is of a white 40-year-old man, previously healthy, who was hospitalized for fever, diffuse myalgia and fatigue after a trip to the African continent. In initial laboratory investigation, he presented hemoconcentration and important thrombocytopenia. During the hospitalization, malaria was diagnosed (demonstration of the parasite in the blood smear) and specific treatment was initiated. HIV serology was requested and positive. As the patient progressed with icterohemorrhagic fever, mental confusion, vomiting, ventilatory failure and acute renal failure, he was transferred to the Intensive Care Unit. Severe pulmonary involvement was confirmed by high-resolution computed tomography, which showed thickening of interlobular septa and peribroncovascular sheaths, with sparse areas of ground-glass attenuation and consolidations, as well as evidence of pleural effusion. It was concluded that the patient's radiological involvement pattern was consistent with the reports already described in the literature, which corroborates the unification of the presentation of the picture in the imaging tests (AU)


Subject(s)
Humans , Male , Adult , HIV Infections/complications , Malaria, Falciparum/complications , Pulmonary Edema/etiology , HIV Infections/immunology , Malaria, Falciparum/immunology , Pulmonary Edema/pathology , Risk Factors
2.
Mem. Inst. Oswaldo Cruz ; 110(8): 945-955, Dec. 2015. graf
Article in English | LILACS | ID: lil-769829

ABSTRACT

Asymptomatic Plasmodium infection carriers represent a major threat to malaria control worldwide as they are silent natural reservoirs and do not seek medical care. There are no standard criteria for asymptomaticPlasmodium infection; therefore, its diagnosis relies on the presence of the parasite during a specific period of symptomless infection. The antiparasitic immune response can result in reducedPlasmodium sp. load with control of disease manifestations, which leads to asymptomatic infection. Both the innate and adaptive immune responses seem to play major roles in asymptomatic Plasmodiuminfection; T regulatory cell activity (through the production of interleukin-10 and transforming growth factor-β) and B-cells (with a broad antibody response) both play prominent roles. Furthermore, molecules involved in the haem detoxification pathway (such as haptoglobin and haeme oxygenase-1) and iron metabolism (ferritin and activated c-Jun N-terminal kinase) have emerged in recent years as potential biomarkers and thus are helping to unravel the immune response underlying asymptomatic Plasmodium infection. The acquisition of large data sets and the use of robust statistical tools, including network analysis, associated with well-designed malaria studies will likely help elucidate the immune mechanisms responsible for asymptomatic infection.


Subject(s)
Humans , Asymptomatic Infections , Antigens, Protozoan/immunology , Carrier State/immunology , Malaria, Falciparum/immunology , Malaria, Vivax/immunology , Plasmodium/immunology , Adaptive Immunity/physiology , Biomarkers , Carrier State/parasitology , Disease Reservoirs/parasitology , Ferritins/immunology , Haptoglobins/immunology , Heme Oxygenase-1/immunology , Immunity, Innate/physiology , /immunology , JNK Mitogen-Activated Protein Kinases/immunology , Malaria, Falciparum/prevention & control , Malaria, Vivax/prevention & control , Parasitemia/immunology , Plasmodium/isolation & purification , Transforming Growth Factor beta/immunology
3.
Mem. Inst. Oswaldo Cruz ; 109(8): 1014-1020, 12/2014. tab, graf
Article in English | SES-SP, LILACS, SES-SP | ID: lil-732596

ABSTRACT

Studies on autochthonous malaria in low-transmission areas in Brazil have acquired epidemiological relevance because they suggest continued transmission in what remains of the Atlantic Forest. In the southeastern portion of the state of São Paulo, outbreaks in the municipality of Juquitiba have been the focus of studies on the prevalence of Plasmodium, including asymptomatic cases. Data on the occurrence of the disease or the presence of antiplasmodial antibodies in pregnant women from this region have not previously been described. Although Plasmodium falciparum in pregnant women has been widely addressed in the literature, the interaction of Plasmodium vivax and Plasmodium malariae with this cohort has been poorly explored to date. We monitored the circulation of Plasmodium in pregnant women in health facilities located in Juquitiba using thick blood film and molecular protocols, as well as immunological assays, to evaluate humoural immune parameters. Through real-time and nested polymerase chain reaction, P. vivax and P. malariae were detected for the first time in pregnant women, with a positivity of 5.6%. Immunoassays revealed the presence of IgG antibodies: 44% for ELISA-Pv, 38.4% for SD-Bioline-Pv and 18.4% for indirect immunofluorescence assay-Pm. The high prevalence of antibodies showed significant exposure of this population to Plasmodium. In regions with similar profiles, testing for a malaria diagnosis might be indicated in prenatal care.


Subject(s)
Adolescent , Adult , Female , Humans , Pregnancy , Young Adult , Antibodies, Protozoan/isolation & purification , Immunity, Humoral/immunology , Malaria, Falciparum/diagnosis , Malaria, Vivax/diagnosis , Pregnancy Complications, Parasitic/diagnosis , Asymptomatic Infections , Brazil/epidemiology , Cohort Studies , Malaria, Falciparum/epidemiology , Malaria, Falciparum/immunology , Malaria, Vivax/epidemiology , Malaria, Vivax/immunology , Plasmodium malariae/immunology , Plasmodium vivax/immunology , Pregnancy Complications, Parasitic/epidemiology , Pregnancy Complications, Parasitic/immunology , Prospective Studies
4.
Mem. Inst. Oswaldo Cruz ; 109(5): 598-601, 19/08/2014. tab, graf
Article in English | LILACS | ID: lil-720422

ABSTRACT

In the Amazon Region, there is a virtual absence of severe malaria and few fatal cases of naturally occurring Plasmodium falciparum infections; this presents an intriguing and underexplored area of research. In addition to the rapid access of infected persons to effective treatment, one cause of this phenomenon might be the recognition of cytoadherent variant proteins on the infected red blood cell (IRBC) surface, including the var gene encoded P. falciparum erythrocyte membrane protein 1. In order to establish a link between cytoadherence, IRBC surface antibody recognition and the presence or absence of malaria symptoms, we phenotype-selected four Amazonian P. falciparum isolates and the laboratory strain 3D7 for their cytoadherence to CD36 and ICAM1 expressed on CHO cells. We then mapped the dominantly expressed var transcripts and tested whether antibodies from symptomatic or asymptomatic infections showed a differential recognition of the IRBC surface. As controls, the 3D7 lineages expressing severe disease-associated phenotypes were used. We showed that there was no profound difference between the frequency and intensity of antibody recognition of the IRBC-exposed P. falciparum proteins in symptomatic vs. asymptomatic infections. The 3D7 lineages, which expressed severe malaria-associated phenotypes, were strongly recognised by most, but not all plasmas, meaning that the recognition of these phenotypes is frequent in asymptomatic carriers, but is not necessarily a prerequisite to staying free of symptoms. .


Subject(s)
Animals , Humans , Antibodies, Protozoan/immunology , /immunology , Erythrocytes/parasitology , Malaria, Falciparum/immunology , Plasmodium falciparum/immunology , Protozoan Proteins/immunology , Asymptomatic Infections , CHO Cells , Cricetulus , Cell Adhesion/genetics , Cell Adhesion/immunology , Erythrocytes/immunology , Flow Cytometry , Gene Expression Profiling , Malaria, Falciparum/parasitology , Protozoan Proteins/genetics , Reverse Transcriptase Polymerase Chain Reaction
5.
Mem. Inst. Oswaldo Cruz ; 109(2): 154-162, abr. 2014. tab, graf
Article in English | LILACS | ID: lil-705821

ABSTRACT

Haematological and cytokine alterations in malaria are a broad and controversial subject in the literature. However, few studies have simultaneously evaluated various cytokines in a single patient group during the acute and convalescent phases of infection. The aim of this study was to sequentially characterise alterations in haematological patters and circulating plasma cytokine and chemokine levels in patients infected with Plasmodium vivax or Plasmodium falciparum from a Brazilian endemic area during the acute and convalescent phases of infection. During the acute phase, thrombocytopaenia, eosinopaenia, lymphopaenia and an increased number of band cells were observed in the majority of the patients. During the convalescent phase, the haematologic parameters returned to normal. During the acute phase, P. vivax and P. falciparum patients had significantly higher interleukin (IL)-6, IL-8, IL-17, interferon-γ, tumour necrosis factor (TNF)-α, macrophage inflammatory protein-1β and granulocyte-colony stimulating factor levels than controls and maintained high levels during the convalescent phase. IL-10 was detected at high concentrations during the acute phase, but returned to normal levels during the convalescent phase. Plasma IL-10 concentration was positively correlated with parasitaemia in P. vivax and P. falciparum-infected patients. The same was true for the TNF-α concentration in P. falciparum-infected patients. Finally, the haematological and cytokine profiles were similar between uncomplicated P. falciparum and P. vivax infections.


Subject(s)
Adult , Female , Humans , Male , Convalescence , Cytokines/blood , Malaria, Falciparum/blood , Malaria, Vivax/blood , Acute Disease , Brazil , Case-Control Studies , /blood , Chemokines/blood , Granulocyte Colony-Stimulating Factor/blood , Hematocrit , Inflammation , Interferon-gamma/blood , Interleukin-1beta/blood , /blood , /blood , /blood , /blood , /blood , /blood , Malaria, Falciparum/immunology , Malaria, Vivax/immunology , Parasitemia , Plasmodium falciparum/isolation & purification , Plasmodium vivax/isolation & purification , Statistics, Nonparametric , Tumor Necrosis Factor-alpha/blood
6.
Mem. Inst. Oswaldo Cruz ; 108(1): 98-105, Feb. 2013. ilus, graf, tab
Article in English | LILACS | ID: lil-666051

ABSTRACT

The PfCLAG9 has been extensively studied because their immunogenicity. Thereby, the gene product is important for therapeutics interventions and a potential vaccine candidate. Antibodies against synthetic peptides corresponding to selected sequences of the Plasmodium falciparum antigen PfCLAG9 were found in sera of falciparum malaria patients from Rondônia, in the Brazilian Amazon. Much higher antibody titres were found in semi-immune and immune asymptomatic parasite carriers than in subjects suffering clinical infections, corroborating original findings in Papua Guinea. However, sera of Plasmodium vivax patients from the same Amazon area, in particular from asymptomatic vivax parasite carriers, reacted strongly with the same peptides. Bioinformatic analyses revealed regions of similarity between P. falciparum Pfclag9 and the P. vivax ortholog Pvclag7. Indirect fluorescent microscopy analysis showed that antibodies against PfCLAG9 peptides elicited in BALB/c mice react with human red blood cells (RBCs) infected with both P. falciparum and P. vivax parasites. The patterns of reactivity on the surface of the parasitised RBCs are very similar. The present observations support previous findings that PfCLAG9 may be a target of protective immune responses and raises the possibility that the cross reactive antibodies to PvCLAG7 in mixed infections play a role in regulate the fate of Plasmodium mixed infections.


Subject(s)
Animals , Female , Humans , Mice , Antibodies, Protozoan/blood , Antibodies, Protozoan/immunology , Antigens, Protozoan/immunology , Cell Adhesion Molecules/immunology , Malaria, Falciparum/immunology , Malaria, Vivax/immunology , Plasmodium falciparum/immunology , Plasmodium vivax/immunology , Protozoan Proteins/immunology , Brazil , Carrier State , Cross Reactions , Enzyme-Linked Immunosorbent Assay , Erythrocytes/parasitology , Mice, Inbred BALB C , Malaria, Falciparum/parasitology , Malaria, Vivax/parasitology
7.
Mem. Inst. Oswaldo Cruz ; 107(8): 985-992, Dec. 2012. graf
Article in English | LILACS | ID: lil-660644

ABSTRACT

Human immunodeficiency virus (HIV)-1 infection has an important impact on malaria. Plasmodium falciparum and HIV-1 co-infected patients (Pf/HIV) present with a high degree of anaemia, enhanced parasitaemia and decreased CD4+ T cell counts, which increase the risk of developing severe malaria. In addition, infection with either Pf or HIV-1 alone causes extensive immune activation. Our hypothesis was that lymphocyte activation is potentiated in Pf/HIV co-infected patients, consequently worsening their immunosuppressed state. To test this hypothesis, 22 Pf/HIV patients, 34 malaria patients, 29 HIV/AIDS patients and 10 healthy controls without malaria or HIV/acquired immune deficiency syndrome (AIDS) from Maputo/Mozambique were recruited for this study. As expected, anaemia was most prevalent in the Pf/HIV group. A significant variation in parasite density was observed in the Pf/HIV co-infected group (110-75,000 parasites/µL), although the median values were similar to those of the malaria only patients. The CD4+ T cell counts were significantly lower in the Pf/HIV group than in the HIV/AIDS only or malaria only patients. Lymphocyte activation was evaluated by the percentage of activation-associated molecules [CD38 expression on CD8+ and human leukocyte antigen-DR expression on CD3+ T cells]. The highest CD38 expression was detected in the Pf/HIV co-infected patients (median = 78.2%). The malaria only (median = 50%) and HIV/AIDS only (median = 52%) patients also exhibited elevated levels of these molecules, although the values were lower than those of the Pf/HIV co-infected cases. Our findings suggest that enhanced T-cell activation in co-infected patients can worsen the immune response to both diseases.


Subject(s)
Adult , Female , Humans , Male , Anemia/parasitology , /immunology , HIV Infections/immunology , Lymphocyte Activation/immunology , Malaria, Falciparum/immunology , Parasitemia/immunology , Acquired Immunodeficiency Syndrome/complications , Acquired Immunodeficiency Syndrome/immunology , Case-Control Studies , Cross-Sectional Studies , HIV Infections/complications , Mozambique , Malaria, Falciparum/complications , Severity of Illness Index
8.
Mem. Inst. Oswaldo Cruz ; 107(8): 1035-1041, Dec. 2012. graf
Article in English | LILACS | ID: lil-660652

ABSTRACT

The haematological changes and release of soluble mediators, particularly C-reactive protein (CRP) and nitric oxide (NO), during uncomplicated malaria have not been well studied, especially in Brazilian areas in which the disease is endemic. Therefore, the present study examined these factors in acute (day 0) and convalescent phase (day 15) patients infected with Plasmodium falciparum and Plasmodium vivax malaria in the Brazilian Amazon. Haematologic parameters were measured using automated cell counting, CRP levels were measured with ELISA and NO plasma levels were measured by the Griess reaction. Our data indicate that individuals with uncomplicated P. vivax and P. falciparum infection presented similar inflammatory profiles with respect to white blood cells, with high band cell production and a considerable degree of thrombocytopaenia during the acute phase of infection. Higher CRP levels were detected in acute P. vivax infection than in acute P. falciparum infection, while higher NO was detected in patients with acute and convalescent P. falciparum infections. Although changes in these mediators cannot predict malaria infection, the haematological aspects associated with malaria infection, especially the roles of platelets and band cells, need to be investigated further.


Subject(s)
Adult , Female , Humans , Male , Blood Platelets/immunology , C-Reactive Protein/analysis , Inflammation Mediators/blood , Malaria, Falciparum/blood , Malaria, Vivax/blood , Neutrophils/immunology , Nitric Oxide/blood , Acute Disease , Convalescence , Enzyme-Linked Immunosorbent Assay , Malaria, Falciparum/diagnosis , Malaria, Falciparum/immunology , Malaria, Vivax/diagnosis , Malaria, Vivax/immunology
9.
Biomédica (Bogotá) ; 32(supl.1): 106-120, ene.-mar. 2012. tab
Article in Spanish | LILACS | ID: lil-639832

ABSTRACT

Se presentan los mecanismos patogénicos más conocidos en la infección por Plasmodium falciparum durante la fase eritrocitaria y extraeritrocitaria. La obstrucción vascular, explicada por los fenómenos de secuestro de glóbulos rojos parasitados y la formación de rosetas, mediados por diversos ligandos y receptores endoteliales, además de los procesos inflamatorios instaurados ante la presencia del parásito, son aspectos centrales en la patogenia de la malaria que permiten explicar. A partir de eventos como la lesión y la destrucción de eritrocitos, hepatocitos y células endoteliales, la pérdida de integridad del endotelio y la activación de promotores de daño celular y de apoptosis, se explican alteraciones como el aumento de la permeabilidad vascular, la hipoxia y el metabolismo anaerobio, que conducen tanto a lesiones localizadas en órganos como cerebro y pulmón, como a un estado de acidosis generalizada y falla multisistémica.


The most recognized pathogenic mechanisms of the infection with Plasmodium falciparum, during both the erythrocytic and exo-erithrocytic stages are presented. Vascular obstruction explained by the sequestration of parasitized red blood cells and erythrocyte rosetting, mediated by different endothelial ligands and receptors, in addition to the inflammatory processes induced by the presence of the parasite, are central aspects in the pathogenesis of malaria that explain the processes of damage, dysfunction and cell death in various organs. Alterations such as increased vascular permeability, hypoxia and anaerobic metabolism leading to localized lesions in organs such as brain and lung, as well as to a generalized acidotic state with multisystem failure can be explained by events such as the injury and destruction of erythrocytes, hepatocytes and endothelial cells, the loss of endothelial integrity, and the activation of cell damage and apoptosis promoters.


Subject(s)
Humans , Malaria, Falciparum/parasitology , Plasmodium falciparum/pathogenicity , Erythrocytes/parasitology , Hemolysis , Inflammation/parasitology , Malaria, Falciparum/immunology
10.
Mem. Inst. Oswaldo Cruz ; 106(supl.1): 34-43, Aug. 2011. ilus, graf, tab
Article in English | LILACS | ID: lil-597242

ABSTRACT

The glutamate-rich protein (GLURP) is an exoantigen expressed in all stages of the Plasmodium falciparum life cycle in humans. Anti-GLURP antibodies can inhibit parasite growth in the presence of monocytes via antibody-dependent cellular inhibition (ADCI), and a major parasite-inhibitory region has been found in the N-terminal R0 region of the protein. Herein, we describe the antiplasmodial activity of anti-GLURP antibodies present in the sera from individuals naturally exposed to malaria in a Brazilian malaria-endemic area. The anti-R0 antibodies showed a potent inhibitory effect on the growth of P. falciparum in vitro, both in the presence (ADCI) and absence (GI) of monocytes. The inhibitory effect on parasite growth was comparable to the effect of IgGs purified from pooled sera from hyperimmune African individuals. Interestingly, in the ADCI test, higher levels of tumour necrosis factor alpha (TNF-α) were observed in the supernatant from cultures with higher parasitemias. Our data suggest that the antibody response induced by GLURP-R0 in naturally exposed individuals may have an important role in controlling parasitemia because these antibodies are able to inhibit the in vitro growth of P. falciparum with or without the cooperation from monocytes. Our results also indicate that TNF-α may not be relevant for the inhibitory effect on P. falciparum in vitro growth.


Subject(s)
Adolescent , Adult , Aged , Humans , Middle Aged , Young Adult , Antibodies, Protozoan/immunology , Malaria, Falciparum , Plasmodium falciparum/growth & development , Protozoan Proteins/immunology , Endemic Diseases , Enzyme-Linked Immunosorbent Assay , Fluorescent Antibody Technique, Indirect , Immunoglobulin G/immunology , Malaria, Falciparum/blood , Malaria, Falciparum/immunology , Parasitemia , Plasmodium falciparum/immunology , Protozoan Proteins , Tumor Necrosis Factor-alpha/blood
11.
Mem. Inst. Oswaldo Cruz ; 106(supl.1): 64-69, Aug. 2011. ilus, graf
Article in English | LILACS | ID: lil-597245

ABSTRACT

Malaria during pregnancy can be severe in non-immune women, but in areas of stable transmission, where women are semi-immune and often asymptomatic during infection, malaria is an insidious cause of disease and death for mothers and their offspring. Sequelae, such as severe anaemia and hypertension in the mother and low birth weight and infant mortality in the offspring, are often not recognised as consequences of infection. Pregnancy malaria, caused by Plasmodium falciparum, is mediated by infected erythrocytes (IEs) that bind to chondroitin sulphate A and are sequestered in the placenta. These parasites have a unique adhesion phenotype and distinct antigenicity, which indicates that novel targets may be required for development of an effective vaccine. Women become resistant to malaria as they acquire antibodies against placental IE, which leads to higher haemoglobin levels and heavier babies. Proteins exported from the placental parasites have been identified, including both variant and conserved antigens, and some of these are in preclinical development for vaccines. A vaccine that prevents P. falciparum malaria in pregnant mothers is feasible and would potentially save hundreds of thousands of lives each year.


Subject(s)
Female , Humans , Pregnancy , Chondroitin Sulfates , Erythrocytes , Malaria, Falciparum/immunology , Pregnancy Complications, Parasitic/immunology , Antibodies, Protozoan/immunology , Antigens, Protozoan/immunology , Cell Adhesion/immunology , Erythrocytes/immunology , Erythrocytes/physiology , Malaria Vaccines , Malaria, Falciparum/blood , Malaria, Falciparum , Placenta , Placenta , Pregnancy Complications, Parasitic/blood , Pregnancy Complications, Parasitic
12.
Mem. Inst. Oswaldo Cruz ; 106(supl.1): 70-78, Aug. 2011. ilus, graf
Article in English | LILACS | ID: lil-597246

ABSTRACT

Malaria remains a major infectious disease that affects millions of people. Once infected with Plasmodium parasites, a host can develop a broad range of clinical presentations, which result from complex interactions between factors derived from the host, the parasite and the environment. Intense research has focused on the identification of reliable predictors for exposure, susceptibility to infection and the development of severe complications during malaria. Although most promising markers are based on the current understanding of malaria immunopathogenesis, some are also focused more broadly on mechanisms of tissue damage and inflammation. Taken together, these markers can help optimise therapeutic strategies and reduce disease burden. Here, we review the recent advances in the identification of malarial biomarkers, focusing on those related to parasite exposure and disease susceptibility. We also discuss priorities for research in biomarkers for severe malaria.


Subject(s)
Animals , Humans , Biomarkers , Malaria, Falciparum/transmission , Malaria, Vivax/transmission , Anopheles , Disease Susceptibility , Insect Vectors , Malaria, Falciparum , Malaria, Falciparum/immunology , Malaria, Vivax , Malaria, Vivax/immunology , Plasmodium falciparum/immunology , Plasmodium falciparum/physiology , Plasmodium vivax/immunology , Plasmodium vivax/physiology , Severity of Illness Index
13.
Mem. Inst. Oswaldo Cruz ; 106(supl.1): 202-211, Aug. 2011. tab
Article in English | LILACS | ID: lil-597262

ABSTRACT

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


Subject(s)
Animals , Humans , Antibodies, Protozoan/immunology , Antigens, Protozoan/immunology , Malaria Vaccines/immunology , Malaria, Falciparum , Malaria, Vivax , Latin America , Malaria, Falciparum/immunology , Malaria, Falciparum , Malaria, Vivax/immunology , Malaria, Vivax , Plasmodium falciparum/immunology , Plasmodium vivax/immunology , Protozoan Proteins/immunology
14.
Article in English | IMSEAR | ID: sea-135712

ABSTRACT

Background & objectives: Severe anaemia in Plasmodium falciparum (Pf) associated malaria is a leading cause of death despite low levels of parasitaemia. In an effort to understand the pathogenesis of anaemia we studied expression level of RBC complement regulatory proteins, CR1 (CD35), CD55 and CD59 with haemoglobin status in a group of malaria cases from Assam, Goa and Chennai, and in healthy controls. Methods: Flowcytometry was used to study expression of CR1, CD55 and CD59 in 50 Pf cases and 30 normal healthy volunteers. Giemsa stained thick and thin blood films were used for microscopic detection and identification of malarial parasites and parasite count. Results: No correlation was found between degree of expression of RBC surface receptors CR1, CD55 and CD59 with haemoglobin level. However, expression of CD55 was less in malaria cases than in healthy controls. Interpretation & conclusions: The present findings indicate that malaria infection changes the expression profile of complement regulatory protein CD55 irrespective of severity status of anaemia. Further studies are needed to explore the pathophysiology of anaemia in malaria cases in Assam where expression of RBC complement receptors appears to be low even in normal healthy population.


Subject(s)
Adolescent , Adult , Aged , Anemia/blood , Anemia/immunology , Anemia/microbiology , CD55 Antigens/immunology , CD59 Antigens/immunology , Child , Child, Preschool , Erythrocytes/immunology , Female , Humans , India , Infant , Malaria, Falciparum/blood , Malaria, Falciparum/immunology , Male , Middle Aged , Receptors, Complement 3b/immunology , Young Adult
15.
Mem. Inst. Oswaldo Cruz ; 103(6): 522-527, Sept. 2008. ilus
Article in English | LILACS | ID: lil-495725

ABSTRACT

Rhoptry-associated protein 2 (RAP2) is known to be discharged from rhoptry onto the membrane surface of infected and uninfected erythrocytes (UEs) ex vivo and in vitro and this information provides new insights into the understanding of the pathology of severe anemia in falciparum malaria. In this study, a hexahistidine-tagged recombinant protein corresponding to residues 5-190 of the N-terminal of Plasmodium falciparum RAP2 (rN-RAP2) was produced using a new method of solubilization and purification. Expression was induced with D-lactose, a less expensive alternative inducer to the more common isopropyl-²-D-thio-galactopyranosidase. The recombinant protein was purified using two types of commercially-available affinity columns, iminodiacetic and nitrilotriacetic. rN-RAP2 had immunogenic potential, since it induced high titers of anti-RAP2 antibodies in mice. These antibodies recognized full-length RAP2 prepared from Triton X-100 extracts from two strains of P. falciparum. In fact, the antibody recognized a 29-kDa product of RAP2 cleavage as well as 82 and 70-kDa products of RAP1 cleavage. These results indicate that the two antigens share sequence epitopes. Our expressed protein fragment was shown to contain a functional epitope that is also present in rhoptry-derived ring surface protein 2 which attaches to the surface of both infected and UEs and erythroid precursor cells in the bone marrow of malaria patients. Serum from malaria patients who developed anemia during infection recognized rN-RAP2, suggesting that this protein fragment may be important for epidemiological studies investigating whether immune responses to RAP2 exacerbate hemolysis in falciparum malaria patients.


Subject(s)
Animals , Mice , Anemia/parasitology , Malaria, Falciparum/complications , Plasmodium falciparum/immunology , Protozoan Proteins/biosynthesis , Recombinant Proteins/biosynthesis , Anemia/immunology , Base Sequence , Molecular Sequence Data , Malaria, Falciparum/immunology , Protein Denaturation , Plasmodium falciparum/genetics , Protozoan Proteins/genetics , Protozoan Proteins/isolation & purification
16.
J Vector Borne Dis ; 2008 Mar; 45(1): 1-20
Article in English | IMSEAR | ID: sea-117932

ABSTRACT

The observation that inactivated Plasmodium sporozoites could protect against malaria is about a hundred years old. However, systematic demonstration of protection using irradiated sporozoites occurred in the nineteen-sixties, providing the impetus for the development of a malaria vaccine. In 1983, the circumsporozoite protein (CSP), a major sporozoite surface antigen, became the first Plasmodium gene to be cloned, and a CSP-based vaccine appeared imminent. Today, 25 years later, we are still without an effective malaria vaccine, despite considerable information regarding the genomics and proteomics of the malaria parasites. Although clinical immunity to malaria has been well-documented in adults living in malaria endemic areas, our understanding of the host-immune responses operating in such malaria immune persons remains poor, and limits the development of immune control of the disease. Currently, several antigen and adjuvant combinations have entered clinical trials, in which efficacy against experimental sporozoite challenge and/or exposure to natural infection is evaluated. This review collates information on the recent status of the field. Unresolved challenges facing the development of a malaria vaccine are also discussed.


Subject(s)
Animals , Child , Child, Preschool , Clinical Trials as Topic , Female , Humans , Infant , Malaria Vaccines , Malaria, Falciparum/immunology , Malaria, Vivax/immunology , Mice , Plasmodium falciparum/immunology , Plasmodium vivax/immunology , Pregnancy , Pregnancy Complications, Parasitic/immunology , Protozoan Proteins/immunology
17.
Mem. Inst. Oswaldo Cruz ; 102(8): 943-951, Dec. 2007. mapas, tab
Article in English | LILACS | ID: lil-471861

ABSTRACT

To infer recent patterns of malaria transmission, we measured naturally acquired IgG antibodies to the conserved 19-kDa C-terminal region of the merozoite surface protein (MSP)-1 of both Plasmodium vivax (PvMSP-1(19)) and Plasmodium falciparum (PfMSP-1(19)) in remote malaria-exposed populations of the Amazon Basin. Community-based cross-sectional surveys were carried out between 2002 and 2003 in subjects of all age groups living along the margins of the Unini and Jaú rivers, Northwestern Brazil. We found high prevalence rates of IgG antibodies to PvMSP-1(19) (64.0 - 69.6 percent) and PfMSP-1(19) (51.6 - 52.0 percent), with significant differences in the proportion of subjects with antibodies to PvMSP-1(19) according to age, place of residence and habitual involvement in high-risk activities, defining some groups of highly exposed people who might be preferential targets of malaria control measures. In contrast, no risk factor other than age was significantly associated with seropositivity to PfMSP-1(19). Only 14.1 percent and 19.3 percent of the subjects tested for antibodies to PvMSP-1(19) and PfMSP-1(19) in consecutive surveys (142 - 203 days apart) seroconverted or had a three fold or higher increase in the levels of antibodies to these antigens. We discuss the extent to which serological data correlated with the classical malariometric indices and morbidity indicators measured in the studied population at the time of the seroprevalence surveys and highlight some limitations of serological data for epidemiological inference.


Subject(s)
Adolescent , Adult , Animals , Child , Child, Preschool , Humans , Antibodies, Protozoan/blood , Malaria, Falciparum/immunology , Malaria, Vivax/immunology , Merozoite Surface Protein 1/immunology , Plasmodium falciparum/immunology , Plasmodium vivax/immunology , Brazil/epidemiology , Epidemiologic Methods , Immunoglobulin G/blood , Malaria, Falciparum/epidemiology , Malaria, Vivax/epidemiology
18.
Mem. Inst. Oswaldo Cruz ; 102(3): 405-410, June 2007. tab
Article in English | LILACS | ID: lil-452520

ABSTRACT

Antibody responses directed against the Plasmodium falciparum antigens, total extract, anti-merozoite surface protein-3 (MSP3b) and glutamate-rich protein (Glurp-R0) were studied in 42 children exposed to both Schistosoma haematobium and P. falciparum infections. The association between levels of the anti-malaria IgG subclasses and IgM with host age, sex, schistosome infection intensity and schistosome specific antibodies was studied before chemotherapeutic treatment of schistosome infections. This showed a significant negative association between schistosome infection intensity and levels of IgG1, IgG3, and IgG4 directed against malaria total extract antigen, and a positive association between levels of anti-schistosome soluble egg antigen IgG2, IgG3, and IgG4 and levels of the same subclasses directed against malaria total extract antigens. The effect of treating schistosome infections with praziquantel on malaria specific responses was also studied. This treatment resulted in increases in significant IgG4 levels against MSP3b and IgM against Glurp R0. Treatment also resulted in a significant decrease in IgG4 levels against Glurp R0. Host age, sex or pre-treatment infection intensity was not associated with the magnitude of change in the two IgG4 responses while males showed a significantly higher increase in levels of IgM. The results suggest cross reactivity between schistosome and malaria antigens in this population.


Subject(s)
Humans , Animals , Male , Female , Child , Adolescent , Immunoglobulin G/immunology , Malaria, Falciparum/immunology , Peptide Fragments/immunology , Protozoan Proteins/immunology , Schistosomiasis haematobia/immunology , Antibody Specificity , Anthelmintics/therapeutic use , Antibodies, Protozoan/immunology , Antigens, Protozoan/immunology , Cross Reactions , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G/blood , Immunoglobulin G/classification , Malaria, Falciparum/complications , Malaria, Falciparum/drug therapy , Plasmodium falciparum/immunology , Praziquantel/therapeutic use , Schistosoma haematobium/immunology , Schistosomiasis haematobia/complications , Schistosomiasis haematobia/drug therapy
19.
Mem. Inst. Oswaldo Cruz ; 102(3): 421-425, June 2007. tab, ilus
Article in English | LILACS | ID: lil-452522

ABSTRACT

The antibody response to Plasmodium falciparum parasites of naturally infected population is critical to elucidate the role of polymorphic alleles in malaria. Thus, we evaluated the impact of antigenic diversity of repetitive and family dimorphic domains of the merozoite surface protein 2 (MSP-2) on immune response of 96 individuals living in Peixoto de Azevedo (MT-Brazil), by ELISA using recombinant MSP-2 proteins. The majority of these individuals were carrying FC27-type infections. IgG antibody responses were predominantly directed to FC27 parasites and were correlated to the extension of polymorphism presented by each MSP-2 region. This finding demonstrated the impact of the genetic polymorphism on antibody response and therefore, its importance on malaria vaccine efficacy.


Subject(s)
Humans , Animals , Adult , Middle Aged , Antibody Specificity , Antibodies, Protozoan/immunology , Antigens, Protozoan/genetics , Malaria, Falciparum/parasitology , Protozoan Proteins , Plasmodium falciparum/genetics , Plasmodium falciparum/immunology , Acute Disease , Alleles , Antibodies, Protozoan/blood , Brazil/epidemiology , Endemic Diseases , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G/blood , Immunoglobulin G/immunology , Malaria, Falciparum/epidemiology , Malaria, Falciparum/immunology , Polymerase Chain Reaction , Polymorphism, Genetic , Polymorphism, Single-Stranded Conformational
20.
IJI-Iranian Journal of Immunology. 2007; 4 (1): 44-49
in English | IMEMR | ID: emr-102543

ABSTRACT

Sickle cell disease [HbSS] is a major health problem in Nigeria and malaria has been implicated as a leading cause of morbidity/mortality in sickle cell disease patients. Few reasons were put forward to explain the observed morbidity/mortality of HbSS subjects due to Plasmodium falciparum [P. falciparum] malaria. To determine the level of immunoglobulin classes [IgM, IgA, and IgG] and regulators of complement system [C1 inhibitor and C3 activator] in Nigerian HbSS patients with and without P. falciparum parasitemia. A total of 64 subjects were considered, including 10 HbSS genotypic subjects with P. falciparum parasitemia [HbSS+PfM], 18 HbAA genotypic subjects with P. falciparum parasitemia [HbAA+PfM], 20 HbSS without P. falciparum parasitemia [HbSS-PfM], and 16 HbAA genotypic subjects without P. falciparum parasitemia [HbAA-PfM]. IgM, IgA, IgG, C1 inhibitor, and C3 activator titers were quantified by single radial immunodiffusion method. The mean levels of IgG in HbSS+PfM [2373.90 +/- 1772.81mg/dl] and HbAA+PfM [1868.80 +/- 0.00mg/dl] were significantly higher compared with HbSS-PfM [644.55 +/- 171.15mg/dl] or HbAA-PfM [659.75 +/- 158.01mg/dl] patients. HbAA-PfM subjects had the lowest level of IgM [67.27 +/- 63.7mg/dl], though no significant difference was observed comparing mean levels of IgM between the four groups. IgA titer was significantly higher in HbSS-PfM patients [249.00 +/- 94.8mg/dl] compared with HbAA-PfM [p<0.05], HbAA+PfM [p<0.05], or HbSS+PfM [p<0.05]. The mean values of C1 inhibitor were lower in HbSS+PfM and HbAA+PfM compared with HbSS-PfM or HbAA-PfM. However, HbAA+PfM had a significantly lower value of C1 inhibitor compared with HbAA-PfM [p<0.01]. C3 activator was highest in HbSS-PfM [17.10 +/- 7.35mg/dl] and was significantly higher compared with HbSS+PfM [p<0.05]. Increased C1 inhibitor and decreased C3 activator in HbSS+PfM compared with HbAA+PfM shows that deranged regulation of complement factors may be responsible for increased susceptibility of HbSS to P. falciparum malaria


Subject(s)
Humans , Malaria/immunology , Complement C1 Inhibitor Protein , Complement C3-C5 Convertases , Immunoglobulin A, Secretory , Immunoglobulin M , Immunoglobulin G , Complement System Proteins , Plasmodium falciparum/immunology , Immunoglobulin A , Malaria, Falciparum/immunology
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